Causes of and predisposing factors for anemia during pregnancy.
\r\n\t
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"dc069c307f12ff3436be837ed7d2252a",bookSignature:"Dr. Selcan Karakuş",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10264.jpg",keywords:"Click Chemistry, Nanostructures, Microstructures, Controllable Click Synthesis, Nanoparticle, Nanocomposite, Drug Delivery Nanosystems, Release Kinetic, Bionanoconjugation, Environmental Applications, Removal of Pollutants, Sensor",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 8th 2020",dateEndSecondStepPublish:"July 29th 2020",dateEndThirdStepPublish:"September 27th 2020",dateEndFourthStepPublish:"December 16th 2020",dateEndFifthStepPublish:"February 14th 2021",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 years",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Dr. Karakuş worked as a visiting researcher at the Department of Polymer Science and Engineering, University of Massachusetts, USA where she gained research experience in molecular adsorption, self-assembled polymeric nanostructures and nanocomposites, and copolymer blends.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"206110",title:"Dr.",name:"Selcan",middleName:null,surname:"Karakuş",slug:"selcan-karakus",fullName:"Selcan Karakuş",profilePictureURL:"https://mts.intechopen.com/storage/users/206110/images/system/206110.jpeg",biography:"Assoc. Prof. Selcan Karakuş is currently working at the Department of Chemistry, Istanbul University - Cerrahpasa, Turkey. She obtained her Master of Science degree in Physical Chemistry from Istanbul University (IU) in 2006. She obtained her Doctor of Philosophy degree in Physical Chemistry from IU in 2011. She has worked as a visiting researcher at the University of Massachusetts, Department of Polymer Science and Engineering. She has research experience in nanoparticles, nanocomposites, nanoemulsions, metal oxide nanostructures, and sensors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"50716",title:"Anemia During Pregnancy",doi:"10.5772/63211",slug:"anemia-during-pregnancy",body:'\nAnemia in pregnancy is a major public health problem, where it has been estimated that 41.8% of pregnant women worldwide are anemic [1]. The majority (at least half) of this burden is due to iron deficiency [2]. However, there is a significant variation in prevalence of anemia, both within and between countries. Because of physiological changes during pregnancy, pregnant women are at higher risk of anemia and in particular iron deficiency anemia, which is the most common type of anemia during pregnancy. Hematological changes during pregnancy, especially expansion of blood volume, often confuse the diagnosis of anemia and its treatment. Because of increased iron and folic acid demands during pregnancy, pregnant women are more susceptible to develop anemia. Moreover, pregnant women are more susceptible to the other types of anemia that affect other women of childbearing age such as hereditary anemia, sickle cell disease and aplastic anemia. Anemia during pregnancy, particularly the severe form, is associated with increased maternal morbidity and mortality and contributes to 20% of the maternal mortality in Africa [2–5]. Anemia in pregnancy is associated with negative consequences for both the woman and neonate. Therefore, great effort is needed to develop/reassess and implement programs to control and prevent anemia during pregnancy.
\nDuring pregnancy, there is a considerable increase in plasma volume, which increases by 40–45% above the level of nonpregnant women. The blood volume expands by 15% compared with non-pregnancy levels. The disproportionate amount of blood creates the physiological and dilution anemia during pregnancy [5, 6]. However, these changes are of great importance and may protect pregnant woman against supine hypotension, guard against the adverse effects of the expectant blood loss during labor, and meet the demand for increased blood flow to the uterus and fetus [5, 7–9]. Despite this hemodilution, there is usually minimal change in mean corpuscular volume (MCV) or mean corpuscular hemoglobin (Hb) concentration (MCHC). The increase in iron demand during pregnancy is met by increased iron absorption. The maternal plasma erythropoietin level increases during pregnancy and reaches its peak in the third trimester [5, 7–9]. This accelerates erythropoiesis, but hemoglobin concentration and hematocrit decrease.
\nIn adult men, there is usually little iron loss from the body. Because females lose iron during menses, their iron needs are greater. Usually only around 4% of the ingested iron is absorbed in the upper part of the small intestine, mainly in the ferrous state, while the majority is ingested in the ferric state. Many metal-binding proteins bind not only to iron but the other metals such as zinc and copper. After crossing the intestinal cells, most of the absorbed iron is bound to apoferritin forming ferritin. Usually around 35% of the transferritin is saturated with iron. The details of the process, involving intestine, plasma, liver, and bone marrow are shown in the Figure 1.
\nIron metabolism
The daily requirement of iron is around 1.5 mg in nonpregnant women. This requirement increases dramatically during pregnancy to reach 6–7 mg/day (total 1000 mg) with advanced gestational age. Pregnancy causes a twofold to threefold increase in the requirement for iron and a 10- to 20-fold increase in folate requirement. The increase in demand for iron is mainly due to fetal requirement, placenta, blood volume, tissue accretion, and the intra-partum potential for blood loss [5, 10]. This sixfold increase in need is quite difficult to meet with diet alone, especially in situations of poverty. In many underdeveloped countries, pregnant woman may have depleted iron stores and/or iron-deficiency anemia and, therefore, are at increased risk of becoming anemic during pregnancy and developing the adverse consequences of iron deficiency and anemia. For this reason iron supplementation during pregnancy is very important to keep the maternal hemoglobin within the normal range. It was previously thought that even in the absence of sufficient iron supplementation, fetal hemoglobin production was not impaired because the fetus obtains iron even if the mother suffers from severe anemia. This is now an obsolete theory, and maternal anemia may lead to fetal anemia and many other perinatal adverse effects.
\nThe normal level of folic acid is not sufficient to prevent megaloblastic changes in bone marrow in about 25% of pregnant women. Moreover, folic acid deficiency is more likely to occur in twin pregnancy, and in women taking anti-convulsion and sulfa-containing drugs. All pregnant women in developing countries should receive daily supplementation of 60 mg iron and 40 mg folic acid. Folate level is affected by sickle cell disease, malaria, and hemolytic anemia. The issue of folate deficiency has received global attention due to its association with neural tube defects.
\nThe World Health Organization (WHO) defines anemia during pregnancy as a hemoglobin concentration <11 g/dl. However, this cutoff value for hemoglobin concentration is affected by many factors such as ethnicity, altitude, and smoking [10]. Anemia in pregnancy is further classified as mild/moderate (Hb 7–10.9 g/dl) and severe (Hb < 7 g/dl) [2]. The Centers for Disease Control and Prevention (1990) defined anemia as hemoglobin <11 g/dl in the first and second trimesters and <10.5 g/dl in the third trimester. This is based on the reduction in hemoglobin level during pregnancy caused by the disproportion in volume expansion between the plasma and erythrocytes. This disproportion is considerably greater during the second trimester. Postpartum anemia is defined by the WHO as hemoglobin <10 g/dl [10].
\nThere are several different factors responsible for anemia. The most common is iron deficiency anemia (IDA), which is generally assumed to represent 50% of cases [11]. Among the various risk factors for IDA nutritional or low iron intake together with acute blood loss are the leading causes. During pregnancy, symptoms such as nausea and vomiting together with other contributing factors may cause maternal anemia; the other factors include history of heavy menstruation, high parity, short birth spacing, lack of antenatal nutritional education, and multiple pregnancy. Malabsorption interferes with iron absorption and parasitic infestation such as hookworm may also lead to low hemoglobin levels. Iron absorption is enhanced by ascorbic acid and inhibited by phytic acid and tannins present in tea, coffee, and chocolate.
\nThe second common leading cause of anemia in pregnancy is folic acid deficiency. Other micronutrient deficiency such as vitamin A, B12, and riboflavin, zinc, and copper may also contribute to anemia. Malaria, hookworm infestation, infection, and deficiency of a number of micronutrients are leading causes of anemia during pregnancy. The relative contribution of each of these factors to anemia during pregnancy varies greatly by geographical location. Iron deficiency in anemic subjects in poor communities may be complicated by one or more additional micronutrient deficiencies. The etiologic pattern of anemia during pregnancy is often complex such that, for example, infection and nutritional deficiencies coexist.
\nObstetric/gynecologic | \n
Previous history of menorrhagia/metrorrhagia | \n
History of miscarriage | \n
Fibroid | \n
Multiple pregnancies | \n
Teenagers | \n
Infections | \n
Infections, for example, urinary tract infection | \n
Parasitic infections, for example | \n
Malaria, schistosomiasis, and hookworms | \n
HIV | \n
| \n
Bleeding from other site | \n
Peptic ulcer | \n
Hemorrhoids | \n
General | \n
Pica, for example, eating mud | \n
Nutrition habits, for example, vegetarian | \n
Causes of and predisposing factors for anemia during pregnancy.
Other etiologies for anemia in pregnancy include malaria, chronic infection including HIV/AIDS, hemolytic anemia, thalassemia, and sickle cell disease.
\nPregnancy is suggested as a possible cause for aplastic anemia due to the suppression of hematopoiesis by placental lactogens [12]. This is supported by the clinical observation that pregnancy-associated aplastic anemia is frequently self-limiting, ending with delivery. Pregnancy is one cause of bone marrow suppression, and aplastic anemia is likely to be immune-mediated since pregnancy is a state of hypo-immunity, likely involving suppression by cytotoxic T lymphocytes. In patients with aplastic anemia, CD4 and HLA-DR+ are detectable in both blood and bone marrow. The cells produce inhibitory cytokines such as tumor necrosis factor and gamma interferon, which affect the mitotic cells and induce nitric oxide synthase and nitric oxide production by bone marrow cells, related to immune-mediated cytotoxicity and elimination of hematopoietic cells.
\nTable 1. shows causes and predisposing factors for anemia in pregnancy.
\nWhile mild anemia is usually asymptomatic and may be detected during routine prenatal check up for hemoglobin, moderate and severe anemia may present with different symptoms, including fatigue, dizziness, tiredness, lethargy, fainting, palpitation, symptoms of congestive heart failure, and leg swelling. In severe cases, there may be difficulty in swallowing and/or blindness if there is a vitamin A deficiency. It is worth mentioning that some of these symptoms can overlap and hence be attributed to symptoms detected in normal pregnancy (\nTable 2\n).\n
\nFatigue | \n
Dizziness | \n
Tiredness | \n
Lethargy | \n
Fainting | \n
Palpitation | \n
Symptoms of congestive heart failure | \n
Legs swelling | \n
Symptoms of anemia during pregnancy.
Pallor and physical findings of iron deficiency may also be present, such as angular stomatitis, smooth tongue, and koilonychias, in the Figure 2.
\nSigns of IDA (iron deficiency anemia)
An abdominal examination to rule out enlarged spleen and/or liver is mandatory in approaching anemic pregnant woman. A complete blood picture (include peripheral blood film) is the first step in tailoring the next investigations aimed at determining etiology as shown in the Figure 3.
\nPeripheral blood picture in IDA
These may include stool examination for hookworms, hemoglobin electrophoresis, and tests for infectious organisms such as malaria, tuberculosis, and HIV. Bone marrow aspirate or biopsy may be needed to diagnose the underlying cause of anemia.
\nThe definition and identification of iron deficiency have been problematic, especially in situations in which chronic inflammation is present. The gold standard for identifying iron deficiency anemia has been the examination of suitably stained bone marrow aspirates for storage iron as hemosiderin. Biochemical measurement of iron status is influenced by inflammation and clearly defined and validated cutoffs for diagnosing iron deficiency in pregnancy in the presence of coexisting infection have been lacking. A lowered MCV is the most sensitive indicator of iron deficiency, where serum iron is low and the total binding capacity raised. Macrocytosis with megaloblastic changes in bone marrow in an indicator of folate deficiency anemia (\nTable 3\n).
\nFactor | \nLower cutoff | \n
---|---|
Hemoglobin | \n11 g/dl | \n
Hematocrit | \n30% | \n
Mean corpuscular volume | \n80 fl | \n
Mean cell hemoglobin | \n28 pg | \n
Mean cell hemoglobin concentration | \n32 g/dl | \n
Serum ferritin | \n12 μg/l | \n
Total iron binding capacity | \n15% | \n
The lower cut off points of the hematological indices during pregnancy.
Anemia during pregnancy is associated with increased maternal morbidity and mortality. Anemia in pregnancy is associated with negative consequences for both the woman and neonate. Fetal anemia, low birth weight, preterm birth, and stillbirth have been associated with anemia [13]. Anemia was observed as a predictor for poor perinatal outcomes such as fetal anemia and low birth weight deliveries [13, 14]. A meta-analysis showed that anemia during early pregnancy, but not late pregnancy, is associated with slightly increased risk of preterm delivery and low birth weight [15]. Interestingly, recent reports revealed that the prevalence of preeclampsia and eclampsia was significantly higher in women with severe anemia [16]. In some African countries, anemia was reported to be associated with stillbirth [17, 18]. In addition, there is also association between anemia and postpartum hemorrhage and pulmonary edema.
\n\n | \n
Anemic heart failure | \n
Maternal death | \n
Septicemia | \n
Preterm labor | \n
Low tolerance to systemic diseases, for example, heart disease | \n
Postpartum hemorrhage | \n
Lack of tolerance of minimal bleeding | \n
Impaired ability to push during the second stage of labor | \n
Impaired lactation | \n
Breast milk of low nutritional value | \n
Deep venous thrombosis | \n
Puerperal psychosis | \n
Cognitive abnormalities | \n
\n | \n
Intrauterine growth restriction | \n
Intrauterine fetal death | \n
Low birth weight | \n
Fetal anemia | \n
Low APGAR score | \n
Increased perinatal motility | \n
Increased infant death | \n
Complications/adverse effects of anemia during pregnancy.
As physiological iron requirements are several times higher in pregnancy than they are in the nonpregnant women, the recommended daily intake of iron for the second half of pregnancy is 30 mg with iron absorption increasing threefold. The amount of iron absorbed depends upon the following factors: (1) amount of iron in the diet, (2) its bioavailability, and (3) physiological requirements. Dietary heme iron is found mainly in red meats, fish, and poultry. Heme iron absorption is twofold to threefold greater than non-heme iron. Moreover, meat contains organic compounds (including peptides), which promote the absorption of iron from other less bioavailable non-heme iron sources. While heme iron is more readily absorbed than non-heme iron, the latter still forms approximately 95% of dietary iron intake. Ascorbic acid significantly increases iron absorption from non-heme sources, with the magnitude of this effect concordant with the increase in quantity of vitamin C in the meal. The bioavailability of non-heme iron is enhanced by germination and fermentation of cereals and legumes which results in a decrease in the phytate content, a food constituent that hinders iron absorption. Tannins in tea and coffee hinder iron absorption on consumption with or shortly after a meal.
\nNutritional education is the main objective of antenatal care to assist in the prevention of anemia. In addition, family planning and control of birth spacing is another preventive measure that should be considered by health-care providers. The WHO jointly with the International Nutritional Anemia Consultative Group and the United Nations Children’s Fund recommend routine supplements of 60 mg iron per day and 400 μg folate per day to all pregnant women for at least 6 months. This guideline also recommends continuation until 3 months postpartum in areas of high prevalence of anemia (>40%). The standard oral preparation, Fefol, comprising 100 mg iron and 350 μg folate, is suitable for both prevention and treatment. Parenteral iron does not provide rapid correction of hemoglobin levels compared with oral form but is an option for those with poor compliance and who cannot tolerate the oral formulation. It is also suitable in cases of malabsorption. The maximum rise in hemoglobin achievable with either oral or parenteral formulations is 0.8 g/dl/week. Blood transfusion is indicated in cases of severe anemia (Hb% < 7 g/dl) and anemia in late pregnancy when delivery is due.
\nReferral to secondary care level should be considered if any of the following situations exist:
\nSignificant symptoms and/or severe anemia (Hb < 70 g/l), or
Advanced gestation (>34 weeks), or
If there is no rise in Hb at 2 weeks.
In non-anemic women who are at increased risk of iron depletion such as those with:\n
Previous anemia,
Multiple pregnancy,
Consecutive pregnancies with <1 year’s interval between
Vegetarians
Women at high risk of bleeding
Pregnant teenagers
Jehovah’s witnesses.
The WHO definition for postnatal anemia is Hb < 10 g/dl. Complete blood count should be checked within 48-hour post-delivery in all women with an estimated blood loss >500 ml and in women with uncorrected anemia in the prenatal period or symptoms suggestive of postpartum anemia. Elemental iron 100–200 mg daily for at least 3 months should be offered to women with Hb < 100 g/l, who are hemodynamically stable, asymptomatic, or have mild symptoms, and a repeat complete blood count and ferritin level assessment should be undertaken to ensure hemoglobin and iron stores are replete [17].
\nIndications for parenteral iron therapy [19]:
\nabsolute noncompliance with oral iron therapy
intolerance to oral iron therapy
proven malabsorption.
Parenteral iron therapy bypasses the natural gastrointestinal regulatory mechanisms to supply nonprotein-bound iron to the red blood cells. It is characterized by fast increases in Hb and better replenishment of iron stores compared with oral therapy, particular iron sucrose. However, issues concerning its safety are waiting to be addressed.
\nContraindications for parenteral iron use are as follows:
\nhistory of anaphylaxis or reactions to parenteral iron therapy
first trimester of pregnancy
active acute or chronic infection
chronic liver disease.
Appropriate setting and staff trained in management of anaphylaxis should be available on contemplating usage of parenteral iron.
\nWith good practice, this situation should generally be avoided; nonetheless, there are instances when women book late have recently arrived from abroad or have not engaged with antenatal care. In such circumstances, it may be essential to take active measures to minimize blood loss at parturition. Attention should be paid to delivery in hospital, securing an intravenous access and blood group and save, and consideration of active management of the third stage of labor to reduce postpartum blood loss.
\nThere are multiple potential hazards from blood transfusions but most arise from clinical and laboratory errors. Moreover, specific risks for women of child-bearing age include the potential for transfusion-induced sensitization to red blood cell antigens, creating a future risk of fetal hemolytic disease. Massive obstetric hemorrhage is widely appreciated as an important cause of morbidity and mortality and necessitates prompt use of blood and components as part of appropriate management.
\nBoth clinical assessment and hemoglobin concentration are of immense significance postpartum to decide on the optimum method of iron replacement. In the absence of bleeding, the decision to transfuse blood should be made on an informed individual basis.
\nBlood transfusion should be reserved for women with:
\ncontinued bleeding or at risk of further bleeding,
imminent cardiac compromise
significant symptoms requiring urgent correction.
If, after careful consideration, elective blood transfusion is needed, women should be fully counseled about potential risks and given written information, and consent should be obtained.
\nEfforts aimed at preventing iron deficiency and iron deficiency anemia among pregnant women include iron supplementation, fortification of staple foods with iron, increasing health and nutritional awareness, combating parasitic infections, and improvement in sanitation [20]. A prophylactic dose of 300 μg (0.3 mg) daily during pregnancy was proposed in 1968 by the WHO.
\nDuring pregnancy, women need iron supplementation to ensure they have sufficient iron stores to prevent iron deficiency [21]. Hence, in most developing countries, iron supplements are used extensively during pregnancy to prevent and correct iron deficiency and anemia during gestation.
\nA dose of 60 mg of elemental iron was accepted as standard supplemental dose in 1959, depending on estimates of iron needs during pregnancy [22]. This has since been endorsed by several experts [23, 24]. Gastrointestinal discomfort is a common observation among women consuming large amounts of supplemental iron, especially if taken on an empty stomach. Gastrointestinal side effects are recognized as the critical adverse effect on which the tolerable upper limit of intake for iron is determined. Use of high-dose iron supplements commonly leads to gastrointestinal manifestations, such as constipation nausea, vomiting, and diarrhea, with the frequency and severity being determined by the amount of elemental iron released in the stomach.
\nFollowing publication of a number of studies supporting the periconceptional use of folic acid in the prevention of neural tube defects, the supplemental dose was increased to 400 μg (0.4 mg) of folic acid daily in 1998. This dose was considered to provide more folic acid than needed to produce an optimal hemoglobin response in pregnant women. If supplementation is delayed till after the first trimester of pregnancy, it will not contribute to preventing birth defects [25]. Interestingly, a recent Cochrane review showed that supplement with folic acid, alone or in combination with vitamins and minerals, prevents neural tube defects, but it does not have a clear effect on other birth defects [26].
\nLikewise, it has been found that folic acid alone, or in combination with vitamin and mineral supplements during pregnancy, improved iron status in women without affecting perinatal anemia, perinatal mortality or other infant outcomes [27, 28].
\nHemoglobinopathies such as thalassemias and sickle cell diseases should be considered during pregnancy because of their impact on maternal and perinatal outcomes. They are genetic disorders of hemoglobin structure and synthesis and may transmit to the offspring. The main clinical manifestation of these disorders during pregnancy is anemia. Usually the iron store is quite normal necessitating folate supplementation without iron to avoid iron overload. Pre-conceptual counseling is a very important issue in patients with hemoglobinopathies. It allows establishment of the hemoglobin status of the parents and prediction of the likelihood of an affected offspring [29].
\nSickle cell disease is caused by the substitution of glutamic acid by valine at position 6 of the globin chain. It includes sickle cell anemia, sickle hemoglobin C disease, sickle beta thalassemias, and sickle cell anemia with alpha thalassemia. Sickling and crystallization of the hemoglobin are induced by de-oxygenated states such hypoxia, acidosis, and dehydration. Almost always the patients are already diagnosed prior to pregnancy, but the diagnosis is made by hemoglobin electrophoresis. Sickle cell disease substantially increases maternal and perinatal mortality. It leads to miscarriage, intrauterine growth restriction, preterm labor, preeclampsia, abruptio placentae, and thrombosis [29]. There is also an increased incidence of infection, and the sickle cell crisis should be managed as aggressively as in nonpregnant women. The management of sickle cell disease in pregnancy should be in collaboration with hematologist. Folic acid supplementation with avoidance of iron is very important together with penicillin prophylaxis. The patient should be removed from factors that may have triggered the crisis. These may include dehydration in early pregnancy (hyperemesis gravidarum) and during labor. Regular antenatal monitoring, serial growth scans, and intrapartum avoidance of dehydration, hypoxia, acidosis, and infection are very important, as are consideration of analgesia and anesthesia. The routine use of prophylactic blood transfusion is controversial in this situation.
\nThe genetically determined hemoglobinopathies termed thalassemias are characterized by impaired production of one or more of the normal globin peptide chains. Thalassemias occur according to which globin chain is deficient.
\nAlpha thalassemia minor (three normal alpha gene) is usually asymptomatic, but the patient may become anemic. Alpha thalassemia major is incompatible with life, and the fetus is severely hydropic. Beta thalassemia minor may also be a symptomatic but may present with iron deficiency anemia with lowered MCV, MCH, and MCHC. The patient will need oral folate and iron supplementation. Beta thalassemia major in adults presents with iron overload.
\nThis is an uncommon type of anemia and is either primary or secondary. It is usually due to antibody production. Secondary hemolytic anemia may be due to chronic infection, drugs, or connective tissue disease. Typically both direct and indirect Coombs tests are positive and spherocytosis and reticulocytosis are the typical characteristics of a peripheral blood smear. Steroids are usually effective treatment (prednisolone 1 mg/kg/day). The presentation and symptoms depend on the severity of hemolysis. Very rarely, as in gestational thrombocytopenia, there is pregnancy-induced hemolytic anemia. However, usually the condition is benign and resolves spontaneously. Some obstetric conditions such as pre-eclampsia and eclampsia may induce micro-angiopathic hemolysis, and this might progressed to hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome [29].
\nHeavy metal exposure has long been associated with major health care concerns pertaining to human health. The metals responsible for these adverse changes in human health need to include and focus on their role in carcinogenicity. As a premise, and for obvious reasons, there has been long-standing research and clinical focus among scientists and oncologists that has produced an extensive database. Using a variety of research engines, such as the National Institute of Medicine database (PubMed) and Google Search to explore the various aspects of heavy metals and their ability to induce cancer, we have attempted to review the reported studies in this area. Importantly, the information presented in the following pages represents linking heavy metal exposure to cancer, and specific human systems most susceptible to heavy metal carcinogenesis.
Aluminum is unique based upon the various mechanisms of action whereby it is listed based on its carcinogenic activity. More often, human exposure to aluminum is the result of contamination of food, interestingly in the process of manufacturing vaccines for human use, and when added as a chemical salt during a variety of processes used in industry for manufactured products for commercial purposes [1, 2]. The commercial products most susceptible are those in which aluminum salts are included in the list of added ingredients such as antacid tablets and antiperspirant deodorants [1, 2, 3].
Exposure to aluminum has had a direct link to the induction of human cancer, specifically breast cancer. Experimental studies performed in mice exposed to AlCl3, which interestingly is the identical form of aluminum used in the manufacture of antiperspirant deodorants for humans, demonstrated an induction of malignant transformation of epithelial cells located within mammary glands [1]. Similar results were observed following exposure to human breast tissue epithelial cells [1, 2, 3]. Aluminum has been implicated in the development of neoplasia, specifically in the development of sarcomas [4]. In the same report it was noted that one patient, following consistent chronic exposure to aluminum, developed an atypical transformation resulting in a neuroectodermal malignancy [4].
Regarding the carcinogenicity of aluminum, it was of importance to best identify the potential or possible mechanism(s) of action responsible for the induction of tumors following exposure. In research studies performed
When other body tissues were examined following aluminum exposure, in this specific case, the development of bladder cancer, it was revealed the bladder cancer cells had higher levels of aluminum compared to other heavy metals [5]. Although these studies were not able to directly link a cause and effect between aluminum and the induction of bladder cancer, it did provide suggestive evidence that aluminum exposure may play in the development of such cancers. This hypothesis lead to a formative therapeutic modality and that is to remove the aluminum. Use of chemical chelators has been recommended standard therapeutic procedure to be performed whenever aluminum exposure, thus poisoning, has been implicated in any physiological or cellular transformation. Physiological studies have demonstrated that when introduced into the human body, aluminum accumulates in both the soft and skeletal tissues. These are the target tissues for aluminum chelation [6]. The most common chelating agent used to detoxify aluminum exposure is desferrioxamine [6]. This chelator has proven very effective in removing the heavy metal aluminum from tissues, even though use of desferrioxamine is associated with its own level of toxicity that is associated with its clinical use in humans [6]. In order to address desferrioxamine toxicity, other chelating agents have been identified that show promise as candidates to replace desferrioxamine; however, the level of chelation associated with these agents has not yet equaled what has been demonstrated using desferrioxamine. Another option in order to reduce aluminum especially if is measured to be present in high amounts in public consumption, e.g., drinking water [7]. The method used in these conditions is reverse osmosis filtration. The procedure has been demonstrated to reduce significant aluminum levels when applied in a variety of industrial settings such as in the mining of copper and in other areas of industrial usages [7].
Arsenic is a heavy metal with known cytotoxicity in human tissues following exposure that can result in serious illnesses to those who are exposed. In a majority of cases, the path of exposure results from ingestion of foods and sources of drinking water contaminated with arsenic [8, 9, 10, 11]. There are also examples of arsenic exposure that are the result of occupational exposure through environmental pollution [8, 9, 10, 11]. Examples of occupations that provide direct risks are smelting and arsenic based pesticide industries [12]. Another well documented source of heavy metal arsenic is through contact with contaminated soil thus consumption occurs through the food chain [13].
The correlation between heavy metal arsenic exposure and human cancers is relevant because arsenic detection within tumor tissue. Specific examples of arsenic and cancer development comes from research studies demonstrating a role for arsenic in the development of bladder, lung and skin malignancies [8, 11, 12]. An additional positive correlation linking arsenic with the development of human cancers focused on the relationship between arsenic exposure and mortality rates in patients diagnosed with a variety of cancers – colon, gastric, kidney, lung and nasopharyngeal cancers [13]. Importantly, based on epidemiological data from several studies shows a clear association between the induction of both pancreatic and non-Hodgkin’s lymphoma following chronic arsenic low-level exposure [14, 15].
As with all heavy metals the question is what is/are the mechanism(s) responsible for the carcinogenic activity? As it pertains to arsenic, several studies have clearly demonstrated the mechanisms responsible for arsenic induced carcinogenicity involve the formation of reactive oxygen species (ROS) that indues critical epigenetic changes leading to damaging DNA repair mechanisms [8, 9, 12]. Specifically, these important epigenetic changes induced by arsenic have included alterations in DNA methylation, histones, and miRNA, all potentially responsible for the tumorgenicity associated with arsenic exposure [9, 12]. Another postulated mechanism of action for arsenic associated carcinogenicity is arsenic’s ability to induce abnormal cell growth cycles in specific cell types such as macrophages and lung epithelial [16]. This was of particular concern because in lung epithelial cells, arsenic promoted a key and significant mechanism of action inducing carcinogenesis. In this cell population arsenic was demonstrated to alter the gene expression of the tumor suppressor protein
In studies conducted to further understand the association between arsenic and tumor cell initiation, another important activity was attributed to arsenic. Based upon further examination, it became clear that in co-existence with changes in cell transformation, intracellular levels of glutathione, a potent ant-oxidant agent, were reduced [18]. Lowering glutathione levels thereby reduces its antioxidant activity, thus allowing altered or transformed cells to escape from being removed by suppressor T-cell lymphocytes and NK cells [18].
Another postulated mechanism of action explaining the tumorgenicity of arsenic was proposed. This alternative mechanism was identified following arsenic exposure to human bladder cells. The mechanism was attributed to the ability of chronic exposure of arsenic to inhibit proper cellular morphology attributed to altered gene expression responsible for base excision repair [19]. The key enzymatic component here is the rate limiting step catalyzed by the enzyme DNA polymerase beta, an active enzyme in the process [19]. In the presence of arsenic, the enzymatic activity was reduced in a dose-dependent manner, meaning higher concentrations of arsenic, correlating with the lack of enzymatic activity [19]. These studies demonstrated chronic exposure to arsenic influenced changes in cellular morphology and altered the gene expression for specific proteins that control cellular proliferation [20].
In order to remove arsenic from the body the use of specific chelating agents have been shown to be most effective [21]. One such example of a very effective chelating agent is 2,3-dimercaptopropanol, otherwise known as British anti-lewisite. The molecule contains 2 functional thiol groups [21]. Significant clinical data has been accumulating over the past several years demonstrating the effective chelating action of this compound. 2,3-dimercaptopropane-1-sulphonate was administered effectively with minimum side-effects to a patient diagnosed with arsenic exposure [22]. This one study provided the clear and effective use of chelators to remove excess amounts of heavy metals [22]. Based on these observations, it was proposed that incorporation of antioxidants as a component of one’s dietary consumption should be recommended in order to maximize anti-cancer and reduced oxidative stress [23]. Both rice and apple juice have been found to reduce cellular stress by the presence of antioxidant compounds, in part because they contain levels of vitamin C, a potent antioxidant. Oxidative stress is a major factor leading to a number of cellular disease pathologies.
As mentioned above, safety regulators have identified apple juice and rice as two food stuffs that can often serve as source of arsenic exposure in children. The level of 5 μg/L arsenic has been set as the lowest level of toxicity exposure [24]. With these dietary links identified other alternative methods to curb the toxicity linked to food stuffs have been presented to limit arsenic uptake using genetic modifications to rice that would inhibit the absorption of arsenic [24]. Another strategy has been to use specific micro-organisms that when co-existing with arsenic in the environment reduce metal uptake [24]. Alternatively, in the cultivation of rice, use of certain watering methods in agricultural would ultimately reduce the concentration of the heavy metal when present in the environment [24, 25].
The heavy metal beryllium is associated with human use through its application tied to industrial processes. Thus, human consumption is linked to environmental contamination documented to most often occur from its association in power plants where it is often found in dust [26, 27]. Thus, human contact occurs via inhalation as the most common method of contact. As an environmental contaminant, it has been linked to a number of respiratory ailments including carcinogenesis of the lung [27, 28, 29]. Initially the relationship between beryllium and lung cancer was suspect, but additional studies demonstrated a clear association between exposure, especially following higher levels of beryllium exposure [28, 29, 30]. Subsequently it was shown that use of beryllium in the dental industry was another opportunity for exposure through occupational risk [29]. Thus, the intervention of personal protective equipment (PPE) had a marked ability to reduce occupational exposure related to dentistry [31]. Importantly, patients diagnosed with stage III breast cancer were found to have elevated levels of beryllium [32]. However, in this study, beryllium was not the only heavy metal to be detected thus limiting a direct cause effect situation [32]. Another cancer, osteosarcoma has also been implicated to be the result of beryllium exposure [33].
There has been a paucity of defined experimental studies conducted to determine cause and effect between beryllium and the conduction of cancer and the mechanisms involved. Much of the focus has been to address issues correlated with lung exposure. One carcinogenic mechanism studied was the link between the elevated levels of tumor necrosis factor alpha (TNF-α), which is a cytokine secreted from a specific type of T-cell (CD4+) that are present in the lung [30, 34]. This factor plays an important role in the development and induction of inflammation [30, 34]. The association between TNF-α and beryllium implicates a direct link to the action of chronic inflammation exposure [30, 34].
Genetic changes are associated with beryllium exposure and have been observed to methylate the
The heavy metal cadmium is a toxic element related to significant health consequences as an environmental contaminant. The sources of environmental exposure are generally associated with industries where it is present in their emissions. The element is used in industries such as mining, research with metallurgy, battery development, and preventing pigment precipitation when used in textiles [41]. A very serious issue regarding environmental cadmium exposure is soil contamination, as human exposure of cadmium most often is the result of ingesting contaminated food and water, inhalation and/or smoking [41, 42]. Regarding soil contamination, a specific source of cadmium contamination occurs as a result of landfills. High levels of cadmium have been found in landfills at concentrations that are much higher than recommended as tolerable in the maintenance of human health [43].Given that landfills are a major source of soil and water contamination, human exposure to cadmium more often is associated with the ingestion of contaminated foods [14, 44].
The main health issue associated with cadmium is the carcinogenicity following toxic exposure in humans, in particular, cancers of the breast, esophagus, intestines, lungs, stomach, testes [41, 45, 46], and possibly the gallbladder. The link to the gallbladder is identified in studies where gallstones have been associated as a pre-cancerous situation in many cases, when analyzed for the heavy metal contact in patients with cancer of the gallbladder [47]. When analyzed statistically significant levels of heavy metal content, cadmium and other heavy metals were found to be elevated [47]. The link between cadmium and carcinogenicity is still a significant human health concern. In other types of studies, in particular laboratory generated experiments, the results of liver cells cultured in the presence of cadmium demonstrated the oncogenic transformation of these liver cells [44]. In patients with gliomas (cancer of the brain) heavy metal analysis detected high levels of cadmium, indicating cancer of the brain may be linked to heavy metal exposure [48].
Another body organ that has also been linked to cancer following cadmium exposure is the pancreas [15, 49]. Cadmium has also been linked to the development of blood disorders, in particular, the development of chronic myeloid and lymphoblastic leukemia. When analyzed compared to controls, patients with leukemia when tested were found to have increased concentrations of cadmium in the presence of reduced levels of magnesium in both blood and serum [50]. Another significant correlation between increased levels of cadmium and carcinogenicity is the association between cadmium in urine and the development of cancer of the gastrointestinal system [51].
As was observed with other heavy metals, the overall effects correlated with the development of a variety of cancers, focused attention to determine what were the exact mechanisms involved that led to initiation of the carcinogenic processes. With respect to cadmium, the focus of the carcinogenic mechanism involved the generation of reactive oxygen species (ROS) and epigenetic changes. Both contributed to the restriction of repair mechanisms that generated altered or damaged DNA. Both also contributed to the loss of apoptosis in affected cells [41, 46, 52, 53]. Whether the exposure to cadmium is either acute or chronic, the result targets the altered signal transduction mechanisms that induce altered gene regulation, which collectively contribute to the initiation of tumor growth [44]. In this key sequence of intracellular changes that takes place following cadmium exposure, important proteins are dysregulated either via upregulation or enhanced activity or perhaps via suppression of key molecular pathways. Such an example is the inhibition of EGR-1, which is a key protein that regulates cell destructive pathways, such as transcription [44].
Adverse toxic human exposure resulting from cadmium poisoning unfortunately is not associated with any standard therapeutic measures designed to address cadmium toxicity, if presented following acute or chronic exposure [54]. With that said, research has developed compounds that upon co-administration would be effective in reducing the toxicity of cadmium exposure. Examples of compounds developed to reduce cadmium toxicity are peptide ligands that have specificity for cadmium [54]. Importantly because of their widespread availability, meaning they occur naturally are flavonoid compounds that are present widely in fruits and in fact in most plants. Collectively whether they are fruits or vegetables, they all contain flavonoids. Flavonoids are potent antioxidants, thus chemically they reduce the development of ROS and also, they can assist in cadmium chelation [55]. With that said, it is still important to more fully understand how flavonoids, specifically via their structure inhibit the development of cadmium toxicity [55].
There is experimental evidence exploring whether the use of stem cells would be effective in ameliorating the cellular damage associated with cadmium toxicity. In a study performed using rats, the testicles were exposed to cadmium causing tissue damage [56]. Following the toxic exposure, animals received bone marrow derived mesenchymal stem cells. Upon clinical treatment it was observed that within the testes the levels of proteins responsible for apoptosis reached appropriate levels to restore apoptosis, thus effecting cell regulation [56]. Within the affected tissue there was evidence that the damaged tissue had been repaired. The implications of these observations suggested that the target of recovery delivered by mesenchymal stem cells was the restoration of mitochondrial apoptosis [56].
One of the most researched heavy metals, in part because of its well-established effects on human health is lead. It has long been recognized as a significant environmental pollutant. There have been a number of pathways that either singularly or in concert attribute to impairing human health especially after chronic lead exposure [57, 58, 59].
A very common method of human lead exposure is the result of environmental contamination that involves soil and water contamination, especially sources of drinking water. Lead levels accumulate in deposits and exposure is manifested through the human food chain, thus its eventual presence in consumed food [57, 58, 59]. Another common source of lead that contributed to its exposure to humans was the presence of lead added as additive to gasoline. However, since 1995 lead has been banned as additive to gasoline for use in automobiles, yet it is still added to the fuel used for aviation purposes [59]. Another alarming link to human lead exposure was the discovery that lead was present in cigarette smoke; therefore, the lead levels in blood of smokers was reported to be high, as there is no safe concentration of lead regarding impact on human health [60]. Other occupational hazards also exist such as mining that contributes to the presence of lead exposure in those workers [57].
What have been the studies conducted to determine the overall level of toxicity of lead exposure to human health? A number of epidemiological studies have been conducted to determine the impact of lead on human health that has implicated the heavy metal as a causative factor in a number of human cancers. Whether lead exposure functions in terms of a direct cause vs. effect on inducing a specific cancer type is still under investigation [61]. In particular, interest has centered on a supportive, perhaps an additive, role in the maintenance of cancer rather than an initiating agent [61]. Lead has been detected along with other heavy metals that are also known for their impact on human health especially in children where it can impact the development of myelin, thus causing impairment in neurological development. An example was the detection of very high levels of lead in the water systems of Flint, MI and along with cadmium when analyzed in patients with gliomas (brain cancer) [61]. This observation demonstrated an increased toxic consequence to human health when such heavy metal contaminants are found together in human tissue or body fluids [61].
A study of patients with kidney cancer came to the conclusion that the cancer developed associated with high levels of lead [58]. This observation was later supported by evidence linking the development of renal cell carcinoma as associated with the presence of lead in the blood [60]. A link to the development of liver disease as the result of high lead concentrations levels along with a number of other heavy metals when tested in gallstones [47] suggested there may be a correlation between lead levels and disease of the gallbladder, perhaps inducing a pre-cancerous lesion [47]. When examined in workers exposed to high levels of lead, it was clearly demonstrated there was a significant positive correlation between the heavy metal and the presence of cancer in the lungs, along with a positive correlation linking lead exposure to the development of cancer of the brain, larynx, and bladder tissues [62]. In patients detected with pancreatic cancer, increased levels of lead in addition to several other heavy metals were measured, suggesting heavy metal exposure may contribute to the overall carcinogenicity of these heavy metals [15, 61].
The scientific literature has been devoid of studies devoted to the understanding of the mechanisms of lead induced carcinogenicity; however, several potential mechanisms have been proposed. Based on the current understanding of how lead can be carcinogenetic, one hypothesis has implicated lead as effectively disrupting internal genetic processes that result in the inability of tumor regulatory genes to function, inducing damage to DNA, and at the same time inhibiting repair of DNA damage [63]. In animal studies using mice exposed to lead, they showed that the heavy metal was capable of inducing reactive oxygen species (ROS) and by doing so the exposure effectively altered the sequence of specific gene function [63]. Another critical observation related to the ability of lead to disrupt normal cellular physiological processes were the results showing lead was effective in normal reactions controlling transcription. The reaction that mediates this transition was the substitution of lead for zinc that serves as a metal catalyst for several key enzymatic reactions that control DNA transcription [63]. Along with this observation was the important association of calcium in these enzymatic reactions based on epidemiological studies showing an increase in calcium correlated with a lower risk level for developing renal cell cancer. Consequently, as pointed out by the investigators, it clearly showed the need to have a clinical trial to determine the overall significance when these important cations and heavy metals come into contact with one another [60].
For clinical cases where heavy metals such as in lead poisoning are implicated in disease etiology and pathology, the therapeutic remedy recommended is chelation [64]. The most common chelators being used for reducing elevated lead levels are British, Anti-Lewsite, calcium disodium ethylenediaminetetraacetic acid (EDTA), D-penicillamine and Meso-2,3-dimercaptosuccinic acid. The use of any specific chelator depends on the individual clinical case [64]. Unfortunately, several of these chelating agents are associated with their own level of toxicity. Thus, to reduce the toxicity potential of these chelating agents, substitution using garlic in the clinically was found to effectively reduce blood levels of lead when lead toxicity was at moderate levels and also restricted lead associated symptoms when used clinically [64]. With the collective results, it goes worth saying the most effective treatment is to prevent lead exposure [58]. To achieve such a goal requires that all industries known to be associated with lead toxicity must address emissions of the toxic metal to the environment as well as to reduce with the goal to completely eliminate emissions such that workers are not exposed, which implies factories need to have established quality control guidelines for limiting lead exposure [64]. It stands to reason that the best and most effective way to remove lead contamination is to eliminate the sources of lead contamination [64]. In communities such as has been the case in Flint, MI that have been impacted because of lead leaching from old water pipes, the only remedy is to completely remove the old lead-based pipes for modern substitutes.
Another heavy metal that has shown severe health consequences in humans following exposure is mercury. A minor portion of the heavy metal is found as a mineral in trace amounts with the major portion of mercury exposure the result of the environmental exposure following industrial use [65]. There are many different areas where mercury use has caused environmental problems. Common usage includes the long-term use of mercury in thermometers, dental fillings, in the manufacture of certain types of batteries, and in the burning of medical waste [65, 66]. Burning of fossil fuels has also been identified as a source of mercury pollution [65, 66]. Another contributing factor to environmental pollution and mercury is the fact that mercury often will be vaporized thus entering the atmosphere along with the other substances that when in the atmosphere, can then be incorporated into the soils and water systems [65, 67]. Regarding foods, consumption of large amounts of seafood, e.g., tuna and shellfish has been identified as another link to environmental exposure especially methyl mercury [65, 68, 69]. Collectively these sources have contributed to the environmental contamination associated with mercury.
Regarding the association between the development of cancer and mercury, there has been suggestive evidence linking mercury exposure and kidney cancer. This association is based on the physiological role of kidney in removing toxic substances when present in the body, especially within the blood [65]. Several other cancers associated with mercury are both liver and gastric cancers [70]. Also related to liver and gastric cancers, in patients with cancer of the gallbladder, mercury has been detected in gallstones at significant concentrations [47].
As has been mentioned when discussing the other heavy metals, mercury has the potential to be associated with the development of malignancies that utilize specific mechanisms that regulate the control of tumor development. The mechanisms implicated are the capacity to generate free radicals (ROS), in addition to the disruption of DNA, whether it be related to transcription events, changes in or maintenance of its molecular structure [66]. With that said there are reported other carcinogenic mechanisms that are unique to mercury. One such mechanism that addresses the carcinogenic potential of mercury is its ability to reduce levels of glutathione [71]. As mentioned earlier, glutathione is a naturally occurring antioxidant and as such it can reduce the antioxidant activity of mercury via reactive oxidant species, by inhibiting the development of oxidative stress mediated through reactive oxidant production, thus minimizing its carcinogenic potential [71]. Cells that are exposed to oxidative stress have been demonstrated to have increased rates of peroxidation of lipids, which has been proposed as another functional mechanism inducing cancer [65]. Within cells mercury has been implicated to influence the function of microtubules, which by their very nature can disrupt cellular mitosis [66].
As was stated with the other heavy metals previously mentioned, the use of chelators has been a common therapeutic approach for removing mercury from the body. For mercury two of the most effective chelating agents are dimercaptosuccinic acid (DMSA) and dimercaptopropane (DMPS) [72, 73]. With that said, there are substances that have been untested in terms of their chelating abilities for their effect against mercury. Two of these substances, desferairox and deferiprone, were tested experimentally in rats where it was observed that the combination was able to effectively chelate mercury and reduce toxic effects of mercury [74]. An experimental chelating agent that has been postulated is thiol-modified nanoporous, a silica material [75]. When tested experimentally in animals, it was observed that this substance had the potential to chelate mercury with minimal toxicity [75].
The heavy metal nickel originally discovered as a major component constituting the earth’s core has in recent years been the focal point of investigations to determine if its exposure, occupational or environmental, is involved in any carcinogenic action that compromises human health, through occupational exposure occurring primarily in the mining and refinement of nickel ore and producing metal alloys [76, 77, 78]. Nickel pollution of the environment results in its accumulation in organs and tissues within exposed organisms. As an example, nickel can enter the food chain through fish [79]. Alternatively, another route can take occur once contamination of the soil takes place [76]. On an industrial scale, nickel is often present in emissions released from oil refineries that have been identified as significant sources of environmental exposure and pollution, thus increasing the risk of exposure to those residents living close to these refineries [80].
Nickel exposure in humans has been associated with the development of a variety of cancers. Through epidemiological studies, evidence has shown there is a correlation between nickel exposure and the induction of cancer development in the lungs and in nasal and sinus tissues [13, 17, 81, 82]. In a study performed in breast cancer patients, when blood serum was analyzed for nickel it was found to be elevated significantly suggesting a potential relationship between the high nickel levels and the induction of breast cancer [83]. The correlation between nickel exposure and cancer has also been linked to the development of acute myeloid and lymphoblastic leukemia [84]. Additionally, when the urine was analyzed in patients with childhood leukemia, elevated levels of both nickel and 8-hydroxydehydrogenase implicating a causative role for nickel in inducing this childhood disease [84]. The role of nickel as a carcinogenic agent is implicated because of its ability to induce oxidative cellular damage as a primary mechanism of action [84].
Patients with pancreatic cancer, when measured for nickel levels, demonstrated elevated levels suggesting there is a positive correlation, even though other heavy metals were detected [15]. In addition, a study came to the conclusion that there may be a link between chronic nickel exposure, along with concomitant exposure of other heavy metals, to the development of T-cell lymphoma [85] and also liver cancer [13]. Collectively, the implications of these reports suggest the carcinogenic action of nickel.
Discussion of nickel and cancer addresses the need to focus on potential mechanisms of action. Several have been implicated. One mechanism involves the ability of nickel to influence noncoding RNA expression. A study demonstrated that nickel was effective in inducing materially expressed gene regulation (gene 3 MEG3) by its ability to influence the methylation of its associated promoter element [81]. This process was an effective inhibitor of PHLPPI and up-regulator of hypoxia-inducible factor-1α. Both are proteins recognized for their effective role in the processes involved in carcinogenesis [81]. As has been reported for other heavy metals, nickel as well can induce the formation of free radicals, a known carcinogenic action [86]. Exposure to nickel has been demonstrated to influence the status of the transcription and regulation status of mRNAs and also involve microRNAs [78]. Implicated in these reactions is the ability of nickel to influence immunity and the immune response, especially when it involves inflammation and the immune response, which in itself has also been implicated as having a significant role in carcinogenicity [78]. Nickel and its role in influencing the inflammatory response has been researched using animals and in combination with human cells [82]. These studies came away with the observation that there is an association between nickel exposure and cancer [78].
In addition to nickel’s association with cancer, inflammation has also been investigated when tested using both animal and human cells. After dose–response studies were conducted it was determined that exposure to nickel increased the expression of certain proteins, specifically SQSTM1 and TNF. Both are known to have specific functions in the inflammation process [82]. As was observed with other heavy metals, nickel has been suggested to induce cellular following exposure epigenetic changes, an example is alteration in DNA methylation [82]. This conclusion is suggested from results that demonstrated exposure to nickel induced histone H3K4 tri-methylation [87]. The reactions associated with nickel exposure have been correlated with faulty transcriptional activation that can be a blueprint for the development of cancer [87].
Although chelation has been widely applied as a mechanism to remove heavy metal contamination, when applied to alleviate nickel contamination has produced different results. A very effector for chelating nickel, especially the cancer-linked nickel carbonyl, sodium diethyldithiocarbamate to the extent that it is the recommended remedy in the clinical setting [88]. With respect to environmental contamination, the compound ethylene diaminetetraacetic acid (EDTA) was shown to decrease the uptake of nickel when exposed to soil [89], indicating the potential for EDTA to be considered as an effective remedy for experimental exposure. The chelating compound CaNa(2+)-EDTA effectively removed nickel [90].
The heavy metal radium has had a long association with negative effects on human health. The harmful fact associated with radium is its radioactivity. Radium releases ionizing radiation through the decaying of radium into a toxic gas [91]. Radon contamination in the form of ionizing radiation can be associated through environmental and occupational exposure. Occupational exposure to radium is often associated with coal mining [92]. Coal mining exposure also implies radium contamination of any water or liquid residue used in the mining process [93]. The occupational exposure of radium can be associated with exposure through contact with building materials, soil and water systems. An Italian study demonstrated radium can accumulate when associated with confined space, such as in buildings, basements and other storage facilities [91]. Another overlooked substance that can contribute to the increased presence and concentration of radium in confined spaces is cigarette smoke [93]. This observation clearly implicates smoking and radium exposure that collectively could synergistically impact human health [93].
The development of several types of cancer have linked to radium, thus labeling it as a known carcinogen. Because the main occupational exposure of radium comes from occupations where inhalation is the primary method of exposure, the predominate form of cancer is lung cancer [91]. As a significant agent responsible for inducing cancer following radium exposure is the release of the ionizing radiation. With that said, when under controlled conditions, radium is used in the clinical treatment for human ankylosing spondylitis [94]. However, careful administration is critical because injection of radium has been associated with the development of several types of leukemia [94]. In animals, radium injections were demonstrated to induce the formation of osteosarcomas [94]. In a clinical case report, a patient being treated with radium-223 developed a cutaneous squamous cell carcinoma indicating such patients need to be followed clinically by a dermatologist [95].
Aluminum is known for its genotoxic profile in cosmetics, especially underarm anti-perspirant products [96]. Aluminum prevents perspiration by blocking the sweat ducts; it also absorbs through the skin. This environmental carcinogen accumulates in the human breast, transforming MCF-10A human mammary epithelial cells and inducing DNA double strand breaks (DSB). These effects have been exhibited
To repair DSB is intrinsically mutagenic; once aluminum was removed from the culture medium, however, DSB were not reversible, therefore suggesting that mammary epithelial cells cultured in the presence of aluminum acquire mutations. In addition,
Aluminum is a metalloestrogen, a type of inorganic xenoestrogen that is capable of binding to cellular estrogen receptors and mimicking the actions of physiological oestrogens [99]. The most commonly used aluminum-based compounds in underarm cosmetic products (UCP) are aluminum chloride and aluminum chlorohydrate. Not only do aluminum salts trigger DNA DSB, they can lead to oxidative stress, proliferation, and interference in estrogen action before and with metastasis.
A 1:1 age-matched hospital-based case–control study was performed to examine the impacts that self-reported UCP use had on breast cancer. Between a large series of breast cancer patients (aged 20–85 years) and healthy individuals, the aluminum concentrations in their breast tissue were measured and compared. The study participants were interviewed about their UCP application; their answers were categorized under “never”, “1-4 times per month”, “2-6 times per week”, “daily” and “several times per day.” A positive family history of breast cancer resulted in being the most prominent risk factor. However, self-reported use of UCP several times per day during early ages (< 30 years) showed a significant association with an increased risk of breast cancer. In addition, the aluminum in breast tissue was significantly associated with self-reported UCP use [98].
Another study showed that in an aqueous solution with a pH of 7.0, aluminum chloride and aluminum chlorohydrate yield aluminum hydroxide and are absorbed through the human skin. This suggests that with daily application of UCPs to the underarm’s skin indicates a pronounced source of exposure to aluminum for the human mammary epithelium.
Aluminum has a transforming effect that is followed by the dose-dependent appearance of DNA DSB. The altered phenotype of MCF-10A cells that were cultured in the presence of aluminum chloride is not reversed by withdrawing the salt, however. These results reveal that a mutagenic effect is at least partly responsible for aluminum’s transforming effect. The salt causes mutations in genes that regulate cellular proliferation, migration, metastasis and apoptosis. Mutations are also found in the genes monitoring the Max-binding protein MNT and T-lymphoma invasion and metastasis-inducing protein 2 (
Arsenic is a naturally deposited metalloid that is widely distributed throughout the Earth’s crust. Most arsenic-containing compounds are classified as organic and inorganic forms, with the inorganic form, specifically the trivalent arsenic (As3+), being much more toxic and carcinogenic. Studies have shown that As3+ is an environmental etiological factor for a certain number of human cancers. There has shown to be a significant correlation between human lung cancer and environment As3+ exposure, either from drinking water contamination or air pollution. When As3+ is ingested through drinking water, it is absorbed into the bloodstream; its metabolic products, especially the methylated As3+, is potentially deposited in the lung tissues due to the high partial pressure of oxygen [102].
The exact pathophysiological mechanism through which arsenic induces carcinogenesis is still to be determined; however, the increasing of oxidative stress, chromosome abnormalities (with uncontainable growth), and abnormal immune developments, are likely mechanisms. Reactive oxygen species, 8-Hydroxy-2-deoxyguanosine, is a major form of oxidative DNA damage that was acquired from the urine and skin tissue of individuals exposed by arsenic. DNA strand breaks, micronuclei in cord blood, and nitrative DNA damage were some of the early genetic effects discovered in the arsenic exposed patients. Studies have shown that arsenic also affects DNA repair machinery, which therefore causes oxidative DNA damage and mutations by the impairment of nucleotide excision repair, DNA ligase, DNA base excision repair, and DNA strand break rejoining.
Arsenic additionally affects epigenetic regulations. Chanda
Recent evidence has been reported to show that arsenic can alter miRNA expression patterns in
In immortalized human keratinocytes (HaCaT cells), miR-21, miR-200a, and miR-141 are overexpressed after a 4-week treatment with 500 nM sodium arsenic. For miR-21 and miR-141, these microRNAs have exhibited strong associations with the majority of human tumors. The miR-200 family has been reported to have a role in the epithelial-mesenchymal transition and cancer progression. For lung cancer development, the overexpression of miR-155 in normal cells has been a leading cause. Results indicate that urothelial human cancer is induced by miR-200 family members; the expression of miR-200a, miR-200b, and miR-200c was down-regulated in arsenic-exposed human urothelial cells (HUC1) in comparison to nonexposed HUC1 cells. The levels of these miR-200 family members in the urine of arsenic-exposed patients were also decreased [105].
Beginning in 1952, a collection of case reports in the Beryllium Case Registry at the Massachusetts General Hospital and cohort studies established the basis for several overlapping epidemiological reports on how beryllium induces cancer. Elevated ratios of lung cancer were shown among workers who had experienced acute berylliosis; however, the results were not similar in workers with chronic berylliosis [107]. Acute beryllium disease is mostly considered an irritative chemical phenomenon associated with high exposures; on the other hand, chronic beryllium disease is an immune-mediated granulomatous reaction to beryllium [108]. Studies showed that the increased cancer death started to occur 15 years after the onset of beryllium exposure.
Experiments were conducted by injecting zinc beryllium silicate in rabbits intravenously. Results indicated that the administration produces consistently metastasizing osteosarcomas in the long bones. Outcomes parallel to these results were obtained with the injection of beryllium oxide, beryllium phosphate, and beryllium metal into the medullary cavity of bones. This route of administration was the only route that led to the formation of osteosarcomas. Splenectomy was additionally shown to increase carcinogenicity with the IV-injected beryllium in bones; the spleen, being an important storage organ, most likely allowed the retention of a higher proportion in the reticuloendothelial system and bone.
Exposing the rats to beryllium sulfate, beryllium phosphate, beryllium fluoride, zinc beryllium manganese silicate, and beryl ore, through inhalation also produced carcinogenic properties. Throughout the duration of a 35-hour week exposure schedule, 10 micrograms of BeSO4 was determined to be threshold for the induction of pulmonary adenocarcinoma in rats. The majority of malignancies were adenocarcinomas with a predominantly alveolar pattern.
In Chinese hamster V79 cells (lung fibroblasts) and in Chinese hamster ovary (CHO) cells, the induction of 8-azaguanine-resistant mutants by BeCl2 and by BeSO4, respectively, has demonstrated beryllium’s ability to inflict gene mutations in cultured mammalian cells. BeSO4 did not cause chromatid or chromosomal aberrations in Chinese hamster lung cells. In CHO cells and cultured human lymphocytes, however, BeSO4 produced chromosomal breaks and sister-chromatid exchanges [107].
With a soluble beryllium compound and upon incubation of a continuous human cell line, there was shown to be a reduction of the expression of messenger RNA coding for DNA repair proteins. This observation was suggested to be a relevant mechanism for potential carcinogenicity of beryllium. To further study this claim, the DNA of rat primary hepatocytes was purposely damaged by incubation with a known DNA damaging agent, 2-acetylaminofluorene. In addition, the DNA was co-incubated with beryllium metal extracts. In the results, there was a reduction in DNA repair synthesis with the beryllium metal extract. Beryllium metal has not been confirmed to directly damage the DNA of cells; nevertheless, there is strong evidence that the metal can cause morphological cell transformation and the inhibition of DNA repair synthesis [109].
The carcinogenic properties of beryllium have been mostly demonstrated when in its metal form, some of its alloys, and a variation of its compounds. Lung cancer induced by beryllium is a main result from pulmonary instillation or inhalation with consequent direct action on the lung. The bone tumors that beryllium stimulates, a characteristic of osteogenic sarcoma, reflects the metal’s bone seeking propensities [110].
Cadmium is a dangerous metal for humans as the human body is limited in its response to cadmium exposure; the metal is incapable of metabolic degradation to less toxic species [111]. Cadmium is a toxic heavy metal that is commonly known as a human carcinogen. Their main sources of exposure include food, cigarette smoking, and cadmium related industry. Reactive oxygen species (ROS) are measured to be the most prominent mechanism in cadmium-induced carcinogenesis. The intracellular oxidative stress that reactive oxygen species induce potentially damage macromolecules and eventually grow responsible in the formation of cancer.
There are two stages referred to when discussing cadmium-induced carcinogenesis. In the first stage, normal cells transition into transformed cells. The reactive oxygen species contribute in the malignant cell transformation of BEAS-2B (human bronchial epithelial) cells in their exposure to cadmium. For the second stage, morphologically transformed cells advance into tumorigenesis. Cadmium-transformed cells,
Cadmium exposure is shown to induce consistent low levels of ROS production, which causes endoplasmic reticulum stress that causes defective autophagy, which protects cadmium exposed damaged cells and encourages malignant transformation in prostate carcinogenesis. In order to maintain the quality of intracellular components, autophagy, a highly complex lysosomal-mediate degradation process, is accountable for the removal and recycling of damaged organelles. This deficient form of this activity assists in cancer cell survival as autophagy protects the cells from hypoxia and oxidative damage, in addition to promoting chemoresistance [113].
The
Similar to metal arsenic, cadmium is weakly genotoxic and mutagenic. To determine whether cadmium exposure induces properties analogous to cancer stem cells, researchers exposed immortalized human pancreatic ductal epithelial (HPDE) cells to low dose cadmium for 29 weeks. Using suspension culture spheroid formation assay, the chronic cadmium-exposed HPDE cells exhibited significantly higher levels of molecular markers for cancer stem cells, yielding 3-fold more suspension spheres than the controlled cells [115].
Cadmium does not form adducts with DNA; however, it is capable of inflicting oxidative stress that could indirectly attack DNA. This process is not instigated through participation in Fenton type chemical reactions [111]. The Fenton reaction is defined by a redox pair of ferrous ion and hydrogen peroxide (H2O2) that ultimately generates a reactive hydroxyl radical [116]. The potential mechanisms for cadmium-carcinogenesis include aberrant gene activation and signal transduction, suppressed apoptosis and disruption of E-cadherin-mediated-cell–cell adhesion, and altered DNA repair [111].
Lead is a metal that can be classified as an environmental pollutant and is commonly known for its usage in many industrial settings worldwide. With high lead exposure, health effects can include damage to the brain and nervous system, gastrointestinal problems, anemia, liver and kidney damage, fertility problems, and developmental delays. Inorganic lead is also suggested to be a carcinogen; epidemiological evidence for carcinogenicity in industrial workers that have been exposed to inorganic lead indicates a significant relationship with cancers of the stomach, lung, kidney, brain, and meninges.
The two primary routes through which lead enters and accumulates in the body is inhalation and oral ingestion. With this being said, even though lead has the capacity to enter the bloodstream and impact other organs of the body, the lungs and stomach are what first come into contact with lead. Due to lead’s ability to pass through the blood–brain barrier, the brain and nervous system are especially vulnerable to the potential toxic effects of lead. The mechanisms that lead uses in playing a role in carcinogenesis include oxidative damage, induction of apoptosis, altered cell-signaling pathways, inhibition of DNA synthesis and repair of damage, and interaction with DNA-binding proteins [117].
In one study, results provided support for an association between occupational lead exposure and brain cancer risk. Among industrial workers who were potentially exposed to lead, the brain cancer mortality rates were greater as compared to unexposed subjects, with indications of an exposure-response trend [118]. Results, however, of many studies have showed inconsistency in determining the relationship between lead exposure and brain tumors. For results that support the association, the results suggest that lead can cross the blood–brain barrier and concentrate in the brain parenchyma due to its ability to replace calcium ions. Once the lead is absorbed, it is generally allocated to plasma, the nervous system, and soft tissues, therefore potentially developing micronucleus formation, chromosomal aberrations, and DNA damage in most mammals.
Lead’s mechanism in which it causes brain cancer remains unclear; nevertheless, studies suggest the most probable mechanism is the metal’s inhibiting of DNA synthesis and repair and the interacting with binding proteins that eventually hinder tumor suppressor proteins [119].
Mercury is one of the most toxic heavy metals due to its persistence in the environment. Mercury inflicts oxidative stress and induces apoptosis. Methylmercury (MeHg) is a metalloestrogen, a small ionic metal that activates the estrogen receptor. Studies indicate that once metalloestrogens activate the estrogen receptor, there is an increase in transcription and expression of estrogen-regulated genes, therefore inducing proliferation of estrogen-dependent breast cancer [120].
The phases of cancer development are initiation, latency, promotion, and then progression. In the promotion phase, mercury has shown to cause an imbalance in the reactive oxygen species homeostasis through selectively inhibiting selenocysteine antioxidant enzymes. Mercury fulfills both the capacity to induce an inhibition of the gap junction intercellular communication and the proinflammatory cytokine release. These two mechanisms have potential to isolate cells from tissue-specific homeostasis, promoting their proliferation. In addition, they have potential to overcome the immune system defenses, checkmating the entire organism. The International Agency Research Cancer (IARC) does not classify mercury as an identified carcinogen to humans; nevertheless, if the toxic compound inhibits the gap junction intercellular communication, mercury is suggested to be a potential cancer “promoter” [121].
Animal experiments were performed to investigate the carcinogenic effects that methylmercury had on mice. They were fed with 10 mg/kg of methylmercury, and as a result, chronic kidney failure, adenoma, and carcinoma were observed. With these results, rodents that were exposed to methylmercury were reported to show a higher incidence of kidney cancer. The International Agency for Research on Cancer claims there is a satisfactory amount of evidence for methylmercury’s impact in cancer on experimental animals, only classifying it as a possible carcinogenic to humans. On the other hand, the U.S. Environmental Protection Agency (EPA) judges that evidence of methylmercury’s carcinogenic potential in humans was insufficient and the justification of the carcinogenicity in experimental animals was limited. Therefore, they classified methylmercury as a Group C material (possible human carcinogen) [122].
Mercury can affect multiple organ systems, especially the nervous and renal systems. One particular study wanted to determine mercury’s capacity to induce centrosome amplification. Centrosomes, microtubule organizing centers of the cell, play a crucial role in cell division; they aid in the proper segregation of chromosomes into the resulting daughter cells. When metals induce cellular and genotoxic stress, however, this can interfere with the strict coordination between the centrosome and DNA cycles that ensures the cell to enter mitosis with only two chromosomes. This disrupted linkage stimulates centrosome amplification, potentially resulting in chromosome segregation and aneuploidy. For the aneuploid cells that survive, they can eventually lead to tumor formation and cancer. The study reported that methylmercury, but not inorganic mercury, prompted both a mitotic arrest and centrosome amplification in mitotic cells, therefore suggesting a possible carcinogenic mechanism [123].
Nickel is considered a major carcinogenic heavy metal, mainly through the mechanism of DNA damage. Demonstrated by
With reactive oxygen species, when they excessively attack the DNA, this results in genomic instability, a promoter of tumorigenesis. This oxidative stress or genomic instability, being a major driving force of oncogenesis, is the basic toxicological mechanism of nickel overexposure [124]. Oxidative stress is known to occur as a result of overproduction of reactive oxygen and nitrogen species through endogenous and exogenous insults. The production of these reactive oxygen species is enabled by nickel’s capacity to bind with amino acids, peptides, and proteins [125].
The metal has the ability to dissolve in the human body, releasing ionic nickel, an active and occasionally genotoxic carcinogenic form of nickel. When a carcinogen is classified as ‘genotoxic’, this refers to chemicals that are capable of directly altering genetic material, opposed to ‘non-genotoxic’ carcinogens that produce cancer through indirect or secondary mechanisms. Most of the chemical carcinogens that induce direct DNA damage are therefore categorized as ‘genotoxic’ in their carcinogenic mechanisms. Nickel’s carcinogenic potential also originates from its capacity to raise the intracellular concentration of nickel ions [126]. The nickel ions exhaust intracellular iron by hindering the membrane ion transporters, in addition to displacing iron from the active site of dioxygenase enzymes. This all leads to the inhibition of their catalytic activity [127].
DNA hypermethylation and subsequent silencing of tumor suppressor genes potentially serve as an epigenetic mechanism responsible for nickel’s carcinogenicity. Promoter hypermethylation induced by nickel was observed
Along with X-rays, radium has a carcinogenic effect of ionizing radiation in humans. The danger of ionizing radiation involves the risk of developing cutaneous squamous cell carcinoma. Additionally, studies suggest that radium treatment for the benign skin lesions may only increase the risks of sarcoma of the bone. For example, in one particular case, a patient developed a mixed tumor of carcinoma and sarcoma at the specific site where she had received radium treatment; a malignancy that developed in the same location supports the notion that the previous radium treatment caused it [129].
At elevated concentrations, naturally occurring dissolved radium can potentially be classified as carcinogenic to the human body. Following digestion, the radium can become deposited within the body where its radioactive characteristic threatens human health through cell damage, therefore increasing the overall risk of cancer [130].
Other experiments show that intra-uterine radium application or X-irradiation of the uterus can induce rat malignant uterine tumors, usually endometrial adenocarcinomas. One rat subject’s uterus was exposed to direct X-irradiation and a composite endometrial tumor, also classified as an adeno-sarcoma, was produced. The tumor was not structurally similar to the mixed endometrial tumors seen in women; nevertheless, the composite structure and the potential that the tumor may also exhibit carcinomatous areas, implies that it may strongly represent the rat counterpart of the human neoplasm. Results of the experiment strengthened the suspicion that pelvic radiation can lead to an increase in long-term incidence of uterine cancer, particularly mixed tumors [131].
In recent years the legalization of producing marijuana (cannabis and cannabis-derived products) especially in certain specific states within the United States has caused a level of alarm in part because of the presence of heavy metals within these products. As the result of the expansion in the commercialization of these products, has created the challenge to now measure heavy metals in cannabis and cannabis-infused commodities. Marijuana is now legal and approved for both medical and recreational use in 33 states within the United States and the District of Columbia (Washington, DC) [132]. However, the raw materials (cannabis and hemp plants) are known to be hyperaccumulators of contaminants such as heavy metals that may be present in the medium used to cultivate the plants, whether it is the soil, the fertilizers used, and in any other growth promoting substances used to supply needed nutrients. With that said, the alarm has been sounded to critically monitor the levels of heavy metal contaminants present in any part of the growing process to ensure that the marijuana-cannabis material and its food-associated products are safe to consume [133].One of the major remaining issues, at least in the United States, is the lack of federal government oversight regarding measuring contaminants in marijuana (cannabis and cannabis-prepared food products) produced in the United States. The U.S. federal government has removed itself from this oversight and in doing so they have delegated regulatory issues to the individual states to regulate the use of marijuana cannabis and cannabis-prepared products. This adds a financial burden to states that are often financially stressed to meet these demands.
What individual states have emphasized has been to focus on the manufacturers of these marijuana (cannabis and cannabis-prepared food products) to show regulation by measuring for the following four major heavy metals: lead (Pb), arsenic (As), cadmium (Cd), and mercury (Hg). The levels of metals must be below maximum limits, based mainly on regulations set by the pharmaceutical industry in USP Chapter 232 and ICH Q3D guidelines [134, 135]. The state of California is usually the state that places severe restrictions on levels allowed. This policy is considered to be the gold standard in regulating cannabis and hemp. It determines the levels allowable in both the oral (edibles) and inhaled (vapes) cannabis products to be to safe to consume only if these four heavy metals are present at levels below those shown in Tables 1 and 2, based on typical consumption of 10 g/day of cannabis material [137].
Element | Maximum limit (edibles) mg/m | Maximum limit (inhaled) mg/g |
---|---|---|
Arsenic | 1.5 | 0.2 |
Cadmium | 0.5 | 0.2 |
Lead | 0.5 | 0.5 |
Mercury | 3.0 | 0.1 |
Heavy metal limits (cannabis & cannabis-hemp) by state of California [136].
Element | Maximum limit (soil) mg/kg | Maximum limit (plant) mg/kg |
---|---|---|
Cadmium | 0.8 | 0.02 |
Chromium | 100 | 1.3 |
Lead | 85 | 2 |
Lead (water) | 0.01/children, 0.015/adult | |
Mercury | 50 | 200 |
Nickel | 35 | 10 |
Heavy metal limits according to the World Health Organization (https://www.who.int/ceh/capacity/heavy_metals.pdf?ua=1).
For analytical measurements of heavy metal contaminants, the state of California requires that at least half a gram of sample must be used for testing purposes. The analytical testing methodology recommends that inductively coupled plasma mass spectrometry (ICP-MS) serve as the method of choice [136]. ICP-MS is a sophisticated multi-element analytical technique, capable of measuring levels to parts per trillion (ppt) using mass spectrometry to identify and measure positively charged ions. The testing methods occur in an extremely energetic argon plasma at approximately 6,000-7,000°C [138]. However, this method requires a solution technique, meaning any solid samples must be dissolved/digested before being analyzed. Most cannabis-related samples are solid materials, powders, concentrates and extracts, which invites several challenges. In addition, cannabinoid oils, which are mainly hydrophobic (not miscible with water), must also be digested prior to analysis.
As mentioned previously in the United States within the federal government exists the Environmental Protection Agency (EPA). The function of the EPA is to set federal standards for a variety of compounds and substances in terms of determining their presence in the environment, which includes the air, soil, ground water, lakes, and rivers. Over the past several years, based upon political influences, the minimum acceptable levels for a variety of substances such as heavy metals have been increased for no other reason than to reduced regulations without factoring the environmental impact. These changes come at the expense of potentially reducing the overall quality of air, soil, ground water, lakes and rivers, thus imposing potential harm to people (children and adults). As mentioned earlier in the discussion of sources of lead contamination, recent incidence of dramatically higher levels of lead present in the drinking water of those living in the Flint, Michigan area is an example of political incompetence when the politicians in the community changed the source of the community drinking water from Lake Michigan to the Detroit River, which was highly contaminated because of age of the lead pipes used to pump the water from the river. The rationale for the change was to reduce the overall costs of providing usable water for the community. Based upon the excessive negligence involved in this case, compensation costs to the citizens of the community has been in the hundreds of millions of dollars not to mention the total costs involved to completely remove and install a new water delivery system devoid of metal pipes of any kind. The long-term consequence of this unfortunate and unnecessary change on the overall sustained health of the community is yet to be determined.
In Europe the European Environment Agency (EEA), controls the level of pollutants such as heavy metals [139]. Regarding heavy metal emissions, across the 33 European countries the following is a short summary of recent achievements in the EU with respect to reducing heavy metals concentrations: (a) Since 1990 across all 33 countries, lead admissions decreased by 93%, mercury by 72%, and cadmium by 64%; (b) Reductions in levels of lead have occurred by 2004 due in part to the removal lead from gasoline; (c) Reductions in levels of mercury have occurred as the result of changes in energy use both in industries and other processes used in industry; and (d) Reductions in levels of cadmium are attributed to operational changes in industries across the board.
A remaining issue in a select set of areas of Europe is the continued presence of unacceptable levels of arsenic, cadmium, lead, mercury and nickel as the result of the presence of these substances still in the atmosphere [140]. The collective set of excessive metal excesses due cause local health issues, in part, because of the presence of localized industrial plants that release emissions of the pollutants. With that said, even though the emissions are concentrated in localized areas, this does not limit nor restrict the impact on health concerns because the pollutants are able to enter the food chain through ground soil and water contamination. Across the EU member countries there is the political will to do what is necessary and needed to sustain the momentum to continue to reduce pollutants in the environment.
One could deduce that the presence of heavy metals in the environment combined with occupational exposure is a problem for human health. A pertinent question to ask then is “what can be done to reduce human heavy metal exposure?” Several remedies or actions can be considered that have been shown to be effective, they are:
Antioxidants - consume foods high in Vitamin C. Fruits and vegetables high in vitamin C can reduce the damage caused by heavy metal toxins by acting as an antioxidant. Vitamin C helps to convert toxins into a water-soluble form that can be easily eliminated from the body [141].
Porphyra. A logical approach would be to use naturally occurring organisms to monitor and remove toxic metals from aquatic systems. Such organisms could be harvested at regular intervals, dried and disposed of as contaminated solid waste or used to recover valuable heavy metals. It is the feasibility and future optimization of this approach using marine macroalgae that forms the basis of the proposed studies. Bioavailability of heavy metals is highly dependent upon several environmental factors. Biomonitors utilizing plants growing under “natural” conditions where biotic and abiotic factors are intercalated reduces the need for making assumptions regarding bioavailability of metals. Plants themselves can alter the microenvironment around them, thus altering the amount of metals that are biologically available. Bulk water analysis may not measure the conditions at the membrane level where changes occur. Benthic plants can provide valuable information regarding past environmental conditions over weeks and months. This is particularly important in plants growing within the intertidal zones where the metal content of water may fluctuate continuously [142].
Integrated Processes. Addressing heavy metal pollution is one of the productive areas of environmental research. Despite natural existence, various anthropomorphic sources have contributed to an unusually high concentration of heavy metals in the environment. The central problem is often these metals are characterized by their long persistence in natural environment leading to serious health consequences in humans, animals, and plants even at very low concentrations (only 1 or 2 μg in some cases). Failure of restrict regulations by government authorities is also to be blamed for heavy metal pollution. Several individual treatments, namely, physical, chemical, and biological are being implied to remove heavy metals from the environment; but they all face challenges in terms of expensiveness and
Phytoremediation. Soil heavy metal pollution has become a worldwide environmental problem that has attracted considerable public attention. This attention stems largely from the increasing concern regarding the overall security of agricultural products. In this area, heavy metals refer to several metals and metalloids that possess toxicity on biological systems. The heavy metals of most concern are arsenic, cadmium, chromium, lead, and mercury. These metals pollutants enter the soil agricultural ecosystem through natural processes derived from parent materials and anthropogenic activities. As stated previously, heavy metal pollution poses a great threat to the health and well-being of all organisms not just human beings due to the risk of increased accumulation potential that takes place through bioaccumulation via the food chain. Remediation from heavy metal exposure using chemical, physical, and biological methods has been recommended to best solve the overall problem of toxic exposure in the environment. Phytoremediation has proven to be a promising alternative to conventional approaches as it is cost effective, environmentally friendly, and esthetically pleasing. According to studies conducted, based on the natural ability of extraction, approximately 500 plants and other organisms have been identified as hyperaccumulators of one or more the heavy metals. In addition, further research integrating biotechnological approaches with comprehensive multidisciplinary research is needed to improve plant tolerance and reduce the accumulation of toxic metals in soils [144].
Other. As stated, heavy metals endanger overall human health. Of importance are the conditions especially when as the result of testing identifies heavy metal levels to be significantly above required standards for each. What still remains as an important factor regarding overall human health is that sustained elevated levels of heavy metals are indeed carcinogenic. The majority of studies performed designed to determine the pathway of heavy metal exposure that results in the carcinogenic effect of heavy metals in human exposure takes place via heavy metal contamination the overall food chain thereby impacting the quality agriculture, specifically the generation of agricultural products such as food and food by-products. In addition to the exposures that account for heavy metal contamination, there are additional factors that account for human exposure. This additional exposure can occur through the use of pesticides directly contaminating soil and also through waste-water run-off contamination. There are natural remediation methods that can help remediate areas of heavy metal contamination such as the presence of geological specific rock formations. With that said, it is still necessary to employ methods that address the heavy metal remediation especially when the sites of contamination are present in food products - fruits and vegetables. In addition, remediation of soil areas and water may also must be considered because these factors also contribute to heavy metal food contamination. Thus, it is imperative heavy metal remediation methods be used constructively in order to maintain overall public health [145].
The heavy metals have been shown to be responsible for a variety of human illnesses. These illnesses develop as the result of unwanted exposure whether by internal or external processes. One of the major health problems associated with heavy metal exposure is the development of a variety of cancers. The most common risk factors for developing cancer are exposure to heavy metals in the form of industrial based carcinogens, in cigarette smoke, and through foods consumed, thus via the diet. The toxicity associated with heavy metal poisoning can vary from minor conditions to major diseases, such as cancer. Both are capable of compromising overall human health. It is a fact that the major pathway responsible for human exposure, more often than not, is linked to both environmental and occupational exposure. Comparable studies have demonstrated higher levels of heavy elements, such as arsenic, aluminum, cadmium, lead, and nickel were present in cancerous tissue when compared and measured against non-heavy metal exposure in tissue from controls. Thus, limiting human exposure to heavy metals is sound public health policy; however, successful health policy must include cooperation from local, regional and national government agencies to develop, approve, implement, and then enforce those policies in order to reduce the links between heavy metal exposure and the major health concerns associated with exposure. The challenge seen for local, state, national and/or federal governments is to take these health concerns seriously and devise suitable and cost effective remedies to reduce the overall impact of heavy metals on the health consequences for its citizens.
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They accumulate in the sera of patients with chronic kidney disease (CKD) and have been associated with CKD progression and cardiovascular and all-cause mortality. Therapeutic strategies for lowering IS and PCS include increased clearance (enhanced dialysis), gastrointestinal sequestration (oral adsorbents), reduced synthesis (dietary protein restriction, dietary fibre augmentation and pre-, pro- or synbiotics), antioxidants and organic anion transporter modulators. This review will discuss the roles of IS and PCS as therapeutic targets and examine the clinical evidence for different treatment options and their effects on CKD and cardiovascular disease risk. We will include our group’s research with pre-, pro- and synbiotic interventions to mitigate serum uraemic toxin accumulation and modify cardiovascular and renal risk.",book:{id:"5955",slug:"chronic-kidney-disease-from-pathophysiology-to-clinical-improvements",title:"Chronic Kidney Disease",fullTitle:"Chronic Kidney Disease - from Pathophysiology to Clinical Improvements"},signatures:"Melissa Nataatmadja, Yeoungjee Cho, Katrina Campbell and David\nW. Johnson",authors:[{id:"50425",title:"Prof.",name:"David",middleName:null,surname:"Johnson",slug:"david-johnson",fullName:"David Johnson"},{id:"183338",title:"Dr.",name:"Yeoungjee",middleName:null,surname:"Cho",slug:"yeoungjee-cho",fullName:"Yeoungjee Cho"},{id:"205845",title:"Dr.",name:"Melissa",middleName:null,surname:"Nataatmadja",slug:"melissa-nataatmadja",fullName:"Melissa Nataatmadja"},{id:"205846",title:"Dr.",name:"Katrina",middleName:null,surname:"Campbell",slug:"katrina-campbell",fullName:"Katrina Campbell"}]},{id:"56960",doi:"10.5772/intechopen.70611",title:"Inflammation in Nonimmune-Mediated Chronic Kidney Disease",slug:"inflammation-in-nonimmune-mediated-chronic-kidney-disease",totalDownloads:1421,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Regardless of its etiology, chronic kidney disease (CKD) is characterized by proteinuria, serum creatinine retention, glomerulosclerosis (GS), and tubulointerstitial damage. Notably, the last one has been correlated more closely with the evolution to kidney failure than the extent of glomerular injury. Tubulointerstitial inflammation comprises the activation of tubular epithelial cells, which release inflammatory mediators and chemokines promoting the influx of leukocytes in the renal parenchyma and the activation/proliferation of resident fibroblasts, leading to excessive production of extracellular matrix (EM), fibrosis, and renal function loss. Therefore, inflammation exerts a key role in the pathogenesis of CKD, although the mechanisms by which this process is activated and perpetuated, even when the initial insult is not immune-mediated, such as in the hypertensive nephrosclerosis, in the diabetic nephropathy, and in the crystal-induced renal disease, remain unclear. This chapter provides an overview on inflammation and CKD development not related to autoimmunity or caused by presence of foreign antigens. Cellular and molecular mechanisms involved in different pathways and its potential therapeutic targets to detain the progression of inflammation and fibrosis in CKD are also presented ahead as a contribution in this book.",book:{id:"5955",slug:"chronic-kidney-disease-from-pathophysiology-to-clinical-improvements",title:"Chronic Kidney Disease",fullTitle:"Chronic Kidney Disease - from Pathophysiology to Clinical Improvements"},signatures:"Camilla Fanelli, Ayman Noreddin and Ane Nunes",authors:[{id:"55270",title:"Prof.",name:"Ane",middleName:null,surname:"Claudia Fernandes Nunes",slug:"ane-claudia-fernandes-nunes",fullName:"Ane Claudia Fernandes Nunes"},{id:"202420",title:"Dr.",name:"Camilla",middleName:null,surname:"Fanelli",slug:"camilla-fanelli",fullName:"Camilla Fanelli"},{id:"211577",title:"Prof.",name:"Ayman",middleName:null,surname:"Noreddin",slug:"ayman-noreddin",fullName:"Ayman Noreddin"}]},{id:"55757",doi:"10.5772/intechopen.69298",title:"Disorders in the System of Mineral and Bone Metabolism Regulators—FGF-23, Klotho and Sclerostin—in Chronic Kidney Disease: Clinical Significance and Possibilities for Correction",slug:"disorders-in-the-system-of-mineral-and-bone-metabolism-regulators-fgf-23-klotho-and-sclerostin-in-ch",totalDownloads:1145,totalCrossrefCites:5,totalDimensionsCites:5,abstract:"The chapter discusses the current understanding of the system of mineral and bone metabolism regulators—FGF-23, Klotho and sclerostin—disturbances in chronic kidney disease (CKD). In the chapter we presented the date, including our own results, which allow to suggest the change in the ratio of FGF-23-Klotho-sclerostin in CKD as an early biomarker not only for the chronic kidney damage but also for high cardiovascular (CV) risk. Results of studies show that disorders in FGF-23-Klotho-sclerostin ratio correlate with the frequency and severity of hypertension, vascular calcification, cardiac remodelling, anaemia, malnutrition, inflammation and strong aggravate CV risk in CKD. It was found independent from blood pressure (BP) action of increased serum FGF-23 on the myocardium as well as the correlation of serum high-sensitive troponin I with increased serum FGF-23 and low Klotho levels in CKD patients. At the same time, it was shown that renoprotective therapy, including renin-angiotensin blockers, low-protein diet with amino/keto acid supplementation and phosphate binders, erythropoiesis stimulators, vitamin D metabolites used to get the target levels of BP, serum phosphorus, haemoglobin, parathyroid hormone and nutritional status disorders correction can reduce the risk of CV events, as the major cause of death in CKD patients.",book:{id:"5955",slug:"chronic-kidney-disease-from-pathophysiology-to-clinical-improvements",title:"Chronic Kidney Disease",fullTitle:"Chronic Kidney Disease - from Pathophysiology to Clinical Improvements"},signatures:"Ludmila Y. Milovanova, Victor V. Fomin, Lidia V. Lysenko\n(Kozlovskaya), Nikolay A. Mukhin, Svetlana Y. Milovanova, Marina\nV. Taranova, Yuriy S. Milovanov, Vasiliy V. Kozlov and Aigul Zh.\nUsubalieva",authors:[{id:"64184",title:"Dr.",name:"Ludmila",middleName:"Urievna",surname:"Milovanova",slug:"ludmila-milovanova",fullName:"Ludmila Milovanova"},{id:"200575",title:"Prof.",name:"Yuriy",middleName:null,surname:"Milovanov",slug:"yuriy-milovanov",fullName:"Yuriy Milovanov"},{id:"207619",title:"Prof.",name:"Nikolay",middleName:null,surname:"Mukhin",slug:"nikolay-mukhin",fullName:"Nikolay Mukhin"},{id:"207620",title:"Dr.",name:"Svetlana",middleName:null,surname:"Milovanova",slug:"svetlana-milovanova",fullName:"Svetlana Milovanova"},{id:"207621",title:"Dr.",name:"Marina",middleName:null,surname:"Taranova",slug:"marina-taranova",fullName:"Marina Taranova"},{id:"207622",title:"Prof.",name:"Victor",middleName:null,surname:"Fomin",slug:"victor-fomin",fullName:"Victor Fomin"}]},{id:"58425",doi:"10.5772/intechopen.72716",title:"Inflammation and Chronic Kidney Disease: Current Approaches and Recent Advances",slug:"inflammation-and-chronic-kidney-disease-current-approaches-and-recent-advances",totalDownloads:2107,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"Despite being a “silent epidemic” disease, chronic kidney disease (CKD) is considered one of the major causes of mortality, together with its main complication, the cardiovascular disease, which contributes to the poor prognosis of these patients. Inflammation has been recognized as an essential part of CKD and is closely linked to cardiovascular complications. The identification of novel biomarkers using omics technologies is rapidly advancing and could improve the early detection in renal diseases. Omics approaches, including proteomics, could provide novel insights into disease mechanisms, identifying at the same time accurate inflammatory biomarker panels with an essential role in disease monitoring and follow-up. Recent advances highlight the gut microbiota as an important source of inflammation in kidney diseases. An increasing body of evidence reveals the cross talk between microbiota and host in CKD; in addition, gut dysbiosis may represent an underappreciated cause of inflammation and subsequently could lead to malnutrition, accelerated cardiovascular disease and CKD progression. This chapter discusses the relationship between inflammation and CKD and highlights the novel approaches regarding microbiota involvement in CKD pathology, as well as their potential to facilitate improving the quality of life.",book:{id:"5955",slug:"chronic-kidney-disease-from-pathophysiology-to-clinical-improvements",title:"Chronic Kidney Disease",fullTitle:"Chronic Kidney Disease - from Pathophysiology to Clinical Improvements"},signatures:"Simona Mihai, Elena Codrici, Ionela Daniela Popescu, Ana-Maria\nEnciu, Laura Georgiana Necula, Gabriela Anton and Cristiana\nTanase",authors:[{id:"76152",title:"Dr.",name:"Cristiana",middleName:null,surname:"Pistol-Tanase",slug:"cristiana-pistol-tanase",fullName:"Cristiana Pistol-Tanase"},{id:"80114",title:"Dr.",name:"Gabriela",middleName:null,surname:"Anton",slug:"gabriela-anton",fullName:"Gabriela Anton"},{id:"215418",title:"Dr.",name:"Ana-Maria",middleName:null,surname:"Enciu",slug:"ana-maria-enciu",fullName:"Ana-Maria Enciu"},{id:"216223",title:"Dr.",name:"Elena",middleName:null,surname:"Codrici",slug:"elena-codrici",fullName:"Elena Codrici"},{id:"216226",title:"Dr.",name:"Ionela Daniela",middleName:null,surname:"Popescu",slug:"ionela-daniela-popescu",fullName:"Ionela Daniela Popescu"},{id:"216227",title:"Dr.",name:"Simona",middleName:null,surname:"Mihai",slug:"simona-mihai",fullName:"Simona Mihai"},{id:"223988",title:"Dr.",name:"Laura Georgiana",middleName:null,surname:"Necula",slug:"laura-georgiana-necula",fullName:"Laura Georgiana Necula"}]},{id:"57259",doi:"10.5772/intechopen.71194",title:"Subjective Wellbeing Assessment in People with Chronic Kidney Disease Undergoing Hemodialysis",slug:"subjective-wellbeing-assessment-in-people-with-chronic-kidney-disease-undergoing-hemodialysis",totalDownloads:2126,totalCrossrefCites:4,totalDimensionsCites:4,abstract:"The aim of this study was to analyze the relationship between satisfaction with life in general and the sociodemographic and emotional factors and components of quality of life in people with chronic kidney disease undergoing hemodialysis. A cross-sectional and correlational study was performed on a sample of 171 people with chronic kidney disease in two hemodialysis units at a Clinic in Lisbon between May and June 2015. Subjective wellbeing (personal wellbeing index) is positively related with subjective happiness, positive affect, and quality of life and is negatively associated with negative affect. Subjective happiness, negative affect, and the physical component of quality of life influence subjective wellbeing. These conclusions can assist us in understanding that people with chronic kidney disease (CKD) encounter greater feelings of wellbeing, mainly related to pleasant affect (subjective happiness and positive affect).",book:{id:"5955",slug:"chronic-kidney-disease-from-pathophysiology-to-clinical-improvements",title:"Chronic Kidney Disease",fullTitle:"Chronic Kidney Disease - from Pathophysiology to Clinical Improvements"},signatures:"Luís Manuel Mota de Sousa, Ana Vanessa Antunes, Cristina Rosa\nSoares Lavareda Baixinho, Sandy Silva Pedro Severino, Cristina\nMaria Alves Marques-Vieira and Helena Maria Guerreiro José",authors:[{id:"220206",title:"Ph.D.",name:"Luís",middleName:"Manuel Mota",surname:"Sousa",slug:"luis-sousa",fullName:"Luís Sousa"},{id:"220843",title:"Prof.",name:"Ana Vanessa",middleName:null,surname:"Antunes",slug:"ana-vanessa-antunes",fullName:"Ana Vanessa Antunes"},{id:"220844",title:"Dr.",name:"Sandy",middleName:"S P",surname:"Severino",slug:"sandy-severino",fullName:"Sandy Severino"},{id:"220847",title:"Prof.",name:"Cristina M. A.",middleName:null,surname:"Marques-Vieira",slug:"cristina-m.-a.-marques-vieira",fullName:"Cristina M. A. Marques-Vieira"},{id:"220848",title:"Prof.",name:"Cristina R. S. L.",middleName:null,surname:"Baixinho",slug:"cristina-r.-s.-l.-baixinho",fullName:"Cristina R. S. L. Baixinho"},{id:"220849",title:"Prof.",name:"Helena M. G.",middleName:null,surname:"José",slug:"helena-m.-g.-jose",fullName:"Helena M. G. José"}]}],mostDownloadedChaptersLast30Days:[{id:"61976",title:"Metabolic Alkalosis",slug:"metabolic-alkalosis",totalDownloads:1458,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Metabolic alkalosis is a disorder where the primary defect, an increase in plasma bicarbonate concentration, leads to an increase in systemic pH. Here we review the causes of metabolic alkalosis with an emphasis on the inherited causes, namely Gitelman syndrome and Bartter syndrome and syndromes which mimic them. We detail the importance of understanding the kidney pathophysiology and molecular genetics in order to distinguish these syndromes from acquired causes. In particular we discuss the tubular transport of salt in the thick ascending limb of the loop of Henle, the distal convoluted tubule and the collecting duct. The effects of salt wasting, namely an increase in the renin-angiotensin-aldosterone axis are discussed in order to explain the biochemical phenotypes and targeted treatment approaches to these conditions.",book:{id:"6790",slug:"fluid-and-electrolyte-disorders",title:"Fluid and Electrolyte Disorders",fullTitle:"Fluid and Electrolyte Disorders"},signatures:"Holly Mabillard and John A. Sayer",authors:null},{id:"62184",title:"Hyponatremia and Psychotropic Drugs",slug:"hyponatremia-and-psychotropic-drugs",totalDownloads:1924,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Given the widespread use of psychotropic drugs in the population, it’s important to consider hyponatremia as an avoidable and reversible adverse effect and include the detection of high-risk subjects to establish safer medications, as well as early detection measures in routine clinical practice. Although hyponatremia has been especially associated with serotonergic antidepressants (SSRIs), there is also an elevated risk with tricyclics, duals and heterocyclic antidepressants, due to the different mechanisms of action at the renal tubular level and the release of ADH. Hyponatremia secondary to tricyclics with slow CYP2D6 metabolizers have higher plasma concentrations of antidepressants metabolized by CYP2D6. Hyponatremia secondary to SSRIs appears in the first week of treatment, it is “not dose-dependent” and normalization of natremia occurs between 2 and 20 days after stopping the medication. Bupropion, trazodone, mianserin, reboxetine and agomelatine are a safe alternative. Also antiepileptics have been related to hyponatremia. Both typical and atypical antipsychotics have been exposed to an increased risk of hyponatremia, even after adjusted factors such as age, sex and comorbidity. Other factors that favor the onset of hyponatremia act synergistically with psychotropic drugs, such as: advanced age, female sex, concomitant diuretic intake, low body weight and low sodium levels; NSAID, ACEIs, and warm.",book:{id:"6790",slug:"fluid-and-electrolyte-disorders",title:"Fluid and Electrolyte Disorders",fullTitle:"Fluid and Electrolyte Disorders"},signatures:"Mireia Martínez Cortés and Pedro Gurillo Muñoz",authors:null},{id:"62743",title:"Fluids and Sodium Imbalance: Clinical Implications",slug:"fluids-and-sodium-imbalance-clinical-implications",totalDownloads:1996,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Fluids and electrolytes are basic components of the human body and essential for the survival of most species. Any imbalance can potentially lead to serious conditions and death. The replacement of fluids and electrolytes has been used since the ancient age. Modern medicine still requires certain degree of expertise in these areas, which ranges from simple replacement in patients with mild illness to a more complex management in critically ill or hospitalized patients. Training and education in the evaluation and management of patients with fluids and electrolyte abnormalities are fundamental for patient’s outcomes. Severe sodium abnormalities are associated with increased morbidity and mortality, and they are markers of poor outcomes. This review presents a concise discussion of frequently asked questions in the evaluation and management of patients with fluids and sodium abnormalities.",book:{id:"6790",slug:"fluid-and-electrolyte-disorders",title:"Fluid and Electrolyte Disorders",fullTitle:"Fluid and Electrolyte Disorders"},signatures:"Gilda Diaz-Fuentes, Bharat Bajantri and Sindhaghatta Venkatram",authors:null},{id:"55595",title:"Fluid Overload in Peritoneal Dialysis",slug:"fluid-overload-in-peritoneal-dialysis",totalDownloads:1685,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The prevalence of end-stage renal disease (ESRD) has increased globally to 10% due to diabetes mellitus, hypertension, and stroke. When chronic kidney disease (CKD) maintenance therapy fails, patients require renal replacement therapy (RRT) to survive, such as peritoneal dialysis (PD), hemodialysis, and renal transplantation. The most common therapy in Mexico is PD because it is a feasible, low-cost, and easy-to-perform procedure; however, fluid overload is a frequent condition in patients with this RRT modality. The usual adverse comorbidities in patients with PD are cardiovascular diseases (CVD) associated to atherosclerosis, uremia, inflammation, and oxidative stress. Fluid overload is intimately associated to hypertension, left ventricular hypertrophy, heart failure, and worsening of kidney failure, leading to increased hospital admissions, higher cardiovascular mortality, and reduced life expectancy. Two main pathologies are involved in the deterioration of both heart and kidney functions, namely, cardiorenal syndrome and uremic cardiomyopathy. Along with these phenomena, patients in PD with rapid peritoneal transport have reduced ultrafiltration, increased glucose absorption, and albumin loss in the dialysate, which lead to overhydration, hypertension, dyslipidemia, and malnutrition. This review focuses on the clinical, physiological, and biochemical mechanisms involved in fluid overload of patients with CKD undergoing PD.",book:{id:"5955",slug:"chronic-kidney-disease-from-pathophysiology-to-clinical-improvements",title:"Chronic Kidney Disease",fullTitle:"Chronic Kidney Disease - from Pathophysiology to Clinical Improvements"},signatures:"Leonardo Pazarin-Villaseñor, Francisco Gerardo Yanowsky-Escatell,\nJorge Andrade-Sierra, Luis Miguel Roman-Pintos and Alejandra\nGuillermina Miranda-Diaz",authors:[{id:"178033",title:"Dr.",name:"Alejandra Guillermina",middleName:null,surname:"Miranda-Diaz",slug:"alejandra-guillermina-miranda-diaz",fullName:"Alejandra Guillermina Miranda-Diaz"},{id:"184047",title:"Dr.",name:"Luis Miguel",middleName:null,surname:"Roman-Pintos",slug:"luis-miguel-roman-pintos",fullName:"Luis Miguel Roman-Pintos"},{id:"202793",title:"Dr.",name:"Leonardo",middleName:null,surname:"Pazarín-Villaseñor",slug:"leonardo-pazarin-villasenor",fullName:"Leonardo Pazarín-Villaseñor"},{id:"202794",title:"Prof.",name:"Francisco",middleName:null,surname:"Yanowski-Escatell",slug:"francisco-yanowski-escatell",fullName:"Francisco Yanowski-Escatell"},{id:"202798",title:"Dr.",name:"Jorge",middleName:null,surname:"Andrade-Sierra",slug:"jorge-andrade-sierra",fullName:"Jorge Andrade-Sierra"}]},{id:"58425",title:"Inflammation and Chronic Kidney Disease: Current Approaches and Recent Advances",slug:"inflammation-and-chronic-kidney-disease-current-approaches-and-recent-advances",totalDownloads:2107,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"Despite being a “silent epidemic” disease, chronic kidney disease (CKD) is considered one of the major causes of mortality, together with its main complication, the cardiovascular disease, which contributes to the poor prognosis of these patients. Inflammation has been recognized as an essential part of CKD and is closely linked to cardiovascular complications. The identification of novel biomarkers using omics technologies is rapidly advancing and could improve the early detection in renal diseases. Omics approaches, including proteomics, could provide novel insights into disease mechanisms, identifying at the same time accurate inflammatory biomarker panels with an essential role in disease monitoring and follow-up. Recent advances highlight the gut microbiota as an important source of inflammation in kidney diseases. An increasing body of evidence reveals the cross talk between microbiota and host in CKD; in addition, gut dysbiosis may represent an underappreciated cause of inflammation and subsequently could lead to malnutrition, accelerated cardiovascular disease and CKD progression. This chapter discusses the relationship between inflammation and CKD and highlights the novel approaches regarding microbiota involvement in CKD pathology, as well as their potential to facilitate improving the quality of life.",book:{id:"5955",slug:"chronic-kidney-disease-from-pathophysiology-to-clinical-improvements",title:"Chronic Kidney Disease",fullTitle:"Chronic Kidney Disease - from Pathophysiology to Clinical Improvements"},signatures:"Simona Mihai, Elena Codrici, Ionela Daniela Popescu, Ana-Maria\nEnciu, Laura Georgiana Necula, Gabriela Anton and Cristiana\nTanase",authors:[{id:"76152",title:"Dr.",name:"Cristiana",middleName:null,surname:"Pistol-Tanase",slug:"cristiana-pistol-tanase",fullName:"Cristiana Pistol-Tanase"},{id:"80114",title:"Dr.",name:"Gabriela",middleName:null,surname:"Anton",slug:"gabriela-anton",fullName:"Gabriela Anton"},{id:"215418",title:"Dr.",name:"Ana-Maria",middleName:null,surname:"Enciu",slug:"ana-maria-enciu",fullName:"Ana-Maria Enciu"},{id:"216223",title:"Dr.",name:"Elena",middleName:null,surname:"Codrici",slug:"elena-codrici",fullName:"Elena Codrici"},{id:"216226",title:"Dr.",name:"Ionela Daniela",middleName:null,surname:"Popescu",slug:"ionela-daniela-popescu",fullName:"Ionela Daniela Popescu"},{id:"216227",title:"Dr.",name:"Simona",middleName:null,surname:"Mihai",slug:"simona-mihai",fullName:"Simona Mihai"},{id:"223988",title:"Dr.",name:"Laura Georgiana",middleName:null,surname:"Necula",slug:"laura-georgiana-necula",fullName:"Laura Georgiana Necula"}]}],onlineFirstChaptersFilter:{topicId:"1396",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:16,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:4,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"June 20th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",isOpenForSubmission:!0,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. His research interests include biomaterials, nanomaterials, bioengineering, biosensors, drug delivery systems, and tissue engineering.",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:23,paginationItems:[{id:"82392",title:"Nanomaterials as Novel Biomarkers for Cancer Nanotheranostics: State of the Art",doi:"10.5772/intechopen.105700",signatures:"Hao Yu, Zhihai Han, Cunrong Chen and Leisheng Zhang",slug:"nanomaterials-as-novel-biomarkers-for-cancer-nanotheranostics-state-of-the-art",totalDownloads:0,totalCrossrefCites:null,totalDimensionsCites:null,authors:null,book:{title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering - Annual Volume 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11405.jpg",subseries:{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering"}}},{id:"82184",title:"Biological Sensing Using Infrared SPR Devices Based on ZnO",doi:"10.5772/intechopen.104562",signatures:"Hiroaki Matsui",slug:"biological-sensing-using-infrared-spr-devices-based-on-zno",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hiroaki",surname:"Matsui"}],book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82122",title:"Recent Advances in Biosensing in Tissue Engineering and Regenerative Medicine",doi:"10.5772/intechopen.104922",signatures:"Alma T. 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He is currently a consultant at Endocrinology Metabolism Consulting, LLC, Anthem, AZ, USA.",institutionString:"Endocrinology Metabolism Consulting, LLC",institution:null},{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/198499/images/system/198499.jpeg",biography:"Dr. Daniel Glossman-Mitnik is currently a Titular Researcher at the Centro de Investigación en Materiales Avanzados (CIMAV), Chihuahua, Mexico, as well as a National Researcher of Level III at the Consejo Nacional de Ciencia y Tecnología, Mexico. His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. in Chemistry in July 2000, and his Ph.D. in Physical Chemistry in 2007 from the University of Khartoum, Sudan. In 2009 he joined the Dr. Ron Clarke research group at the School of Chemistry, Faculty of Science, University of Sydney, Australia as a postdoctoral fellow where he worked on the Interaction of ATP with the phosphoenzyme of the Na+, K+-ATPase, and Dual mechanisms of allosteric acceleration of the Na+, K+-ATPase by ATP. He then worked as Assistant Professor at the Department of Chemistry, University of Khartoum, and in 2014 was promoted to Associate Professor ranking. In 2011 he joined the staff of the Chemistry Department at Taif University, Saudi Arabia, where he is currently active as an Assistant Professor. His research interests include:\r\n(1) P-type ATPase Enzyme Kinetics and Mechanisms; (2) Kinetics and Mechanism of Redox Reactions; (3) Autocatalytic reactions; (4) Computational enzyme kinetics; (5) Allosteric acceleration of P-type ATPases by ATP; (6) Exploring of allosteric sites of ATPases and interaction of ATP with ATPases located in the cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. 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The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine"},{id:"8",title:"Bioinspired Technology and Biomechanics",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation"},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 24th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:314,numberOfPublishedBooks:31,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/194517",hash:"",query:{},params:{id:"194517"},fullPath:"/profiles/194517",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()