\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"3510",leadTitle:null,fullTitle:"Evolution of the Molecular Biology of Brain Tumors and the Therapeutic Implications",title:"Evolution of the Molecular Biology of Brain Tumors and the Therapeutic Implications",subtitle:null,reviewType:"peer-reviewed",abstract:"A dramatic increase in knowledge regarding the molecular biology of brain tumors has been established over the past few years. In particular recent new avenues regarding the role of stem cells and microRNAs along with further understanding of the importance of angiogenesis, immunotherapy and explanations for the resistance of the tumors to chemotherapeutic agents and radiation therapy has been developed. It is hopeful that this new information will lead to efficacious treatment strategies for these tumors which remain a challenge. In this book a review of the latest information on these topics along with a variety of new therapeutic treatment strategies with an emphasis on molecular targeted therapies is provided.",isbn:null,printIsbn:"978-953-51-0989-1",pdfIsbn:"978-953-51-7099-0",doi:"10.5772/50198",price:159,priceEur:175,priceUsd:205,slug:"evolution-of-the-molecular-biology-of-brain-tumors-and-the-therapeutic-implications",numberOfPages:650,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"55fec67e081aaf4092d93187b20ab6d1",bookSignature:"Terry Lichtor",publishedDate:"February 27th 2013",coverURL:"https://cdn.intechopen.com/books/images_new/3510.jpg",numberOfDownloads:47536,numberOfWosCitations:41,numberOfCrossrefCitations:20,numberOfCrossrefCitationsByBook:3,numberOfDimensionsCitations:56,numberOfDimensionsCitationsByBook:3,hasAltmetrics:1,numberOfTotalCitations:117,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 13th 2012",dateEndSecondStepPublish:"May 4th 2012",dateEndThirdStepPublish:"August 8th 2012",dateEndFourthStepPublish:"November 6th 2012",dateEndFifthStepPublish:"December 6th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"37886",title:"Dr.",name:"Terry",middleName:null,surname:"Lichtor",slug:"terry-lichtor",fullName:"Terry Lichtor",profilePictureURL:"https://mts.intechopen.com/storage/users/37886/images/3428_n.jpg",biography:"Dr. Lichtor is a practicing neurosurgeon. He has a number of research interests, and his brain tumor work is largely focused on the development of a DNA vaccine for treatment of primary and metastatic intracerebral tumors. In particular Dr. Lichtor has shown that vaccines prepared by transfer of DNA from the tumor into a highly immunogenic cell line can encompass the array of tumor antigens that characterize the patient’s neoplasm. Poorly immunogenic tumor antigens, characteristic of malignant cells, can become strongly antigenic if they are expressed by highly immunogenic cells. The introduction of the vaccine directly into the tumor bed of animals with an intracerebral tumor stimulates a systemic cellular anti-tumor immune response associated with a prolongation of survival. It is hopeful that this vaccine strategy will be efficacious in the treatments of patients with brain tumors. Dr. Lichtor is a member of the neurosurgery faculty at Rush University Medical Center in Chicago, Illinois.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Rush University Medical Center",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1085",title:"Neuro-Oncology",slug:"neuro-oncology"}],chapters:[{id:"43049",title:"Brain Tumor Invasion and Angiogenesis",doi:"10.5772/52309",slug:"brain-tumor-invasion-and-angiogenesis",totalDownloads:1790,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Almos Klekner",downloadPdfUrl:"/chapter/pdf-download/43049",previewPdfUrl:"/chapter/pdf-preview/43049",authors:[{id:"155547",title:"Associate Prof.",name:"Almos",surname:"Klekner",slug:"almos-klekner",fullName:"Almos Klekner"}],corrections:null},{id:"42916",title:"Gliomas Biology: Angiogenesis and Invasion",doi:"10.5772/53487",slug:"gliomas-biology-angiogenesis-and-invasion",totalDownloads:2202,totalCrossrefCites:1,totalDimensionsCites:5,hasAltmetrics:0,abstract:null,signatures:"Maria Caffo, Valeria Barresi, Gerardo Caruso, Giuseppe La Fata, Maria Angela Pino, Giuseppe Raudino, Concetta Alafaci and Francesco Tomasello",downloadPdfUrl:"/chapter/pdf-download/42916",previewPdfUrl:"/chapter/pdf-preview/42916",authors:[{id:"36309",title:"Dr.",name:"Gerardo",surname:"Caruso",slug:"gerardo-caruso",fullName:"Gerardo Caruso"},{id:"54267",title:"Prof.",name:"Mariella",surname:"Caffo",slug:"mariella-caffo",fullName:"Mariella Caffo"},{id:"54268",title:"Prof.",name:"Concetta",surname:"Alafaci",slug:"concetta-alafaci",fullName:"Concetta Alafaci"},{id:"60567",title:"Dr.",name:"Giuseppe",surname:"Raudino",slug:"giuseppe-raudino",fullName:"Giuseppe Raudino"},{id:"159267",title:"Dr.",name:"Francesca",surname:"Granata",slug:"francesca-granata",fullName:"Francesca Granata"},{id:"160023",title:"Prof.",name:"Valeria",surname:"Barresi",slug:"valeria-barresi",fullName:"Valeria Barresi"},{id:"160024",title:"Prof.",name:"Mario",surname:"Venza",slug:"mario-venza",fullName:"Mario Venza"}],corrections:null},{id:"42918",title:"Hypoxia, Angiogenesis and Mechanisms for Invasion of Malignant Gliomas",doi:"10.5772/53298",slug:"hypoxia-angiogenesis-and-mechanisms-for-invasion-of-malignant-gliomas",totalDownloads:1988,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:null,signatures:"Paula Province, Corinne E. 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World Health Organization (WHO) defines diabetes mellitus as a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with alterations of carbohydrate absorption, fat and protein metabolism. DM is one of the four major non-communicable diseases along with cardiovascular disease (CVD), cancer and chronic respiratory diseases. Once a disease of affluence, it is now increasingly common among the poor countries [1]. The morbidity and mortality associated with DM arises from minor and macrovascular complications, ischemic heart disease (IHD) and peripheral vascular disease (PVD) [2]. Metformin acts by several mechanisms of action but the major mechanism is inhibiting hepatic gluconeogenesis [3]. The drug may antagonize the action of glucagon, and reduces fasting blood glucose (FBG) [4]. In addition, metformin increases insulin action at target sites, increases peripheral glucose uptake, enhances fatty acid oxidation and reduces glucose absorption from gastrointestinal tract [5]. Diabetes mellitus and statins have a complex association and are the attention of patient and healthcare debate. Statins are widely used as a part of diabetes mellitus care due to that patients with DM have a greater CVD [6]. At the early stage, the heart only showed transcriptional and metabolic altercations, including enhanced inflammation, oxidative stress, depletion of antioxidant proteins, and changes in energy metabolism. Use of statins in diabetes is a controversial when compared with metformin. Although the potential detrimental effects of statin on muscle and liver have been known for a long time, new concerns have emerged regarding the risk of new onset diabetes (NOM). This often leads to discontinuation of statin, non-adherence to therapy, or concerns correlating with initiating statin therapy.
There are several CVD risk factors, including hypertension, dyslipidemia, diabetes mellitus (DM), smoking and obesity, as well as platelet dysfunction. Certain drugs are currently available for treating these risk factors, whereas drug combinations are frequently needed to achieve therapeutic goals especially in hypertension, DM and coronary heart disease (CHD). Based on these considerations our objectives were 1) to assess whether combination therapy shows clinical effectiveness for cognition and functional benefits in a well-characterized prospective cohort of patients with T2DM treated over years with metformin; 2) to determine the magnitude and duration of benefit; 3) to characterize the long-term treatment of patients who receive combination therapy compared to those who were never treated with statins and those who only received metformin as monotherapy; and 4) to use modeling methods to make predictions about the mechanism and clinical course in different treatment groups and dose levels.
Both metformin and statins thus act on glucose—as well as lipid metabolism which is why metformin–statin combination therapy is prescribed to many T2DM patients. Since both drugs act on glucose as well as lipid metabolism, it is important to understand in detail the interactions between metformin and statin mechanism of action on treatment design with different dose level and optimal safety/efficacy profiles. This chapter is therefore designed to provide insight in the mechanism of combined effect of statin/metformin not only on DM and CVD but also with different types of cancer and other diseases. This chapter also explain the interaction of both drugs on preclinical and clinical studies to determine an optimal dosing strategy of both drugs.
Metformin is an oral antidiabetic drug, discovered in 1922, came on the market as late as 1979 [7]. The drug is belongs to the biguanide classification and derivative from guanidine found in
Oral administration of metformin transported into the small intestine across the apical membrane into the enterocytes via several transporter proteins. The main proteins are the plasma monoamine transporter (PMAT; SLC29A4), organic cation transporter 1 (OCT1; SLC22A1) and serotonin transporter protein (SERT; SLC6A4) [11].
Metformin accumulated majorly in the intestine, and in the stomach, liver, kidney and lesser extent in muscle. The accumulation of metformin in intestine and stomach is because of these organs are most exposed to high concentrations of metformin after oral administration. A recent study confirmed the high metformin levels are accumulated in these organs [12]. These concentrations are tenfold higher than metformin concentrations in the liver, indicating that the intestine is probably an important site of action. In fact, the metformin effects in the intestine may be rather different than the effects in the liver. The concentration of metformin in human jejunum has been shown to be 30 to 300 fold greater than in plasma, and earlier studies demonstrating accumulation of metformin in the intestinal mucosa. Metformin navigates to the liver via the portal vein and is taken up predominantly by organic cation transporter (OCT1) as well as by Thiamine transporter (THTR-2). In this chapter, the effects of metformin on the lipid metabolism are highlighted, thereby creating a special focus on the effects on lipids related to the activation of AMPK by metformin (Figure 1) [13].
Schematic diagram of the anti-hyperglycaemic action of metformin on the liver cell.
Metformin is transported into hepatocytes mainly via OCT1, and inhibited the mitochondrial respiratory chain (complex I) through a currently unknown mechanism(s). The deficit in energy production is balanced by reducing gluconeogenesis in the liver. This is mediated in two main ways. First, a decrease in ATP and a concomitantly increase in AMP concentration. Second, increased AMP levels function as a key signaling mediator to (1) allosterically inhibit cAMP–PKA signaling by suppression of adenylatecyclase, (2) allosterically inhibit FBPase, (3) activates AMPK. This leads to inhibition of gluconeogenesis (1 and 2) and lipid/cholesterol synthesis (3).
Metformin is present for over 99% in the mono protonated form in all tissues of the body except in the stomach. The sparse data showed, that metformin is mostly distributed in the cytosolic fraction (~ 70%) of rat hepatic cells compared to mixed membranes (12%), nucleus (~ 5%), and mitochondrial and lysosomal fractions (8%). A low binding affinity of metformin to mitochondrial membranes was seen, and this may be because of the two methyl groups present in metformin structure [14]. Previous study concludes that, the mitochondrial membrane potential may promote entry of metformin (positively charged) [15], which will then concentrate inside the mitochondria (negatively charged) [16]. Molecular modeling of the metformin distribution and validation study confirmed the presence of high concentrations of the drug in the endoplasmic reticulum (ER) and in the mitochondria, based on its membrane potential [17].
The main mechanisms of metformin involved in decreasing the endogenous glucose production and plasma glucose have all been extensively reviewed and critically discussed in earlier studies [18]. Metformin shows beneficial effects on the glucose and lipid metabolism, even though the pathways are not fully understood [19]. In patient studies, the variations of metformin efficacy may be due to the presence of responders and non-responders to the drug treatment [20], racial and ethnic background [21], and personal variation in the adaptation of metformin treatment. Sonne et al., [22] proposed a pathway inducing reduction of LDL cholesterol by the. Inhibition of the intestinal absorption of bile acids is caused by metformin. It causes an increased synthesis of bile acids in the liver, and cholesterol is used for this process [23], thereby causing a decreased amount of cholesterol in the hepatic cells. Upregulation of the LDL-C receptor may increase the uptake of lipoproteins, to restore a sufficient level of cholesterol in the liver. Hence, metformin indirectly decrease the LDL-C concentration and plasma total cholesterol concentrations.
A decreased β cell mass is an important factor in the development of T2DM. High glucose and FFA induce damaging effects on β cells (e.g. decreased insulin secretion and β cell mass) [24]. It is therefore of interest to consider possible beneficial effects of metformin on β cell function. Lipase and amylase are secreted by the pancreas and are often measured to monitor the condition of the pancreas. There were no changes observed in the enzyme levels, and the pancreas volume when metformin (1950 mg/day) was given to T2DM patients for 24 weeks. This works suggesting that metformin does not repair damaged β cells [25].
Statins, block an enzyme called HMG-CoA reductase (3-hydroxy-3-methylglutaryl coenzyme A reductase) that is involved in the synthesis of mevalonate, a naturally occurring substance that is then used by the body to make cholesterol. By inhibiting this enzyme, LDL-cholesterol and cholesterol production is decreased. Statins also increase the number of LDL receptors on liver cells, which increases the uptake and breakdown of LDL-cholesterol. Most of the effects of statins, including the blocking of the HMG-CoA reductase enzyme occur in the liver. Many research have shown that elevated levels of total cholesterol, LDL-cholesterol, triglycerides, and apolipoprotein B increase a person’s risk of developing heart disease or having a stroke.
Statins are classified based on different criteria, including: 1) how they are obtained, 2) liver metabolism, 3) physicochemical properties, and 4) specific activity. Some of the statins are obtained after fungal fermentation: lovastatin, pravastatin and simvastatin, others by synthesis: fluvastatin, atorvastatin, and cerivastatin. Only five statins are, at this moment, in clinical use: lovastatin, simvastatin, pravastatin, atorvastatin and fluvastatin. Pravastatin is extremely hydrophilic, fluvastatin has intermediate characteristics, lovastatin, simvastatin, atorvastatin and cerivastatin are hydrophobic.
Statins differ in their potency at lowering total cholesterol, triglycerides, LDL-cholesterol, or increasing HDL-cholesterol; their propensity for drug interactions; and their reported safety in people with kidney disease.
Reduce a person’s risk of having a heart attack or stroke or developing angina
Reduce the risk of further heart disease in people with type 2 diabetes or coronary artery disease.
Simvastatin and atorvastatin produce the greatest percentage change in LDL cholesterol levels. Fluvastatin and atorvastatin are also preferred in hypocholesteremic patients with kidney disease.
Pravastatin and fluvastatin have a lower risk of drug interactions because they are not metabolized by cytochrome p450 3A4.
Pitavastatin has a similar effectiveness to atorvastatin but reportedly produces greater increases in HDL-cholesterol that are sustained over the long-term. It is effective at low dosages and has minimal drug interactions.
Statins are a major class of drugs that decrease plasma cholesterol levels and are prescribed as first choice to patients suffering from CVD [26]. Simvastatin and atorvastatin are often given as a first choice to patients with cardiovascular risk factors/cardiovascular disease. In earlier studies reported that low dose (20 mg/day) of atorvastatin given to patients with myocardial infarction showed improved lipid, adipokine, and pro-inflammatory markers and decreased insulin resistance. Higher dose (40 mg/day) of atorvastatin showed hyperglycemia, increased leptin levels and ghrelin deficiency [27, 28] in diabetic patient. It was also discovered that the reduction in LDL-C by statins is an important indicator of increased T2DM risk [29]. Genetic factors and/orange-related factors could as well lead to the development of T2DM during statin treatment.
Several mechanisms possibly involved in the effect of statins on glucose metabolism are summarized in Figure 2. Statin signaling pathway that stimulates endogenous glucose production (EGP) by activation of gluconeogenic genes in human liver cells. Statin activates the pregnaneX receptor (PXR) in the cytoplasm. Many functions are exerts by PXR, such as the stimulation of the expression of proteins involved in regulation of hepatic glucose and removal of xenobiotics, and lipid metabolism [17].
Hypercholesterolemia enhance the entry of LDL particles into sub endothelial space at lesion-prone arterial sites. Monocyte chemotactic protein-1 (MCP-1) and oxidized-LDL act as chemoattractants to direct accumulation of monocytes and their migration to the subendothelial space, where monocytes undergo phenotypic transformation into macrophages. Oxygen free radicals concurrently modify LDL. Oxidatively modified LDL is taken up by nondownregulating macrophage receptors to form lipid-rich foam cells. The foam cells develop into fatty streaks that is the, precursor of atherosclerotic plaques. Statins exhibit pleiotropic effects on many components of atherosclerosis that accompany hypercholesterolemia, abnormal endothelial function and including platelet coagulation abnormalities, and determinants of plaque thrombogenicity such as plaque inflammation and proliferation.
Statin mechanism may contribute to a decreased insulin secretion in the β cell, possibly contributing to the progress of T2DM. The upregulation of LDL-C receptor seen upon inhibition of HMG-CoA reductase are one of the directly affected processes, which results in increased uptake of plasma LDL-C into the β cell [30]. The increased amount of cholesterol within the cell causes interference with translocation of glucokinase, to the mitochondria [31]. A decreased glucose transporter (GLUT2) expression level was observed in simvastatin treated mouse MIN6 cells which resulted in a reduction of ATP levels. This may be the mechanism of inhibition of the KATP channel closure, membrane depolarization and calcium channel opening all leading to reduced insulin secretion [32]. Inhibition of the ATP-dependent potassium channel, depolarization and the decreased influx of intracellular calcium, and calcium concentrations were observed and were related to a decreased insulin secretion. In an ex vivo study, intracellular calcium levels were not affected even though intact with single-islets were treated with simvastatin [33]. Statin treatment may cause inactivation of Ras and Rho molecules, hence the activation and membrane translocalization of GLUT-4 is inhibited. Experiments with atorvastatin treatment in mouse adipocytes confirmed that GLUT-4 located on the plasma membrane moved to the cytosol during treatment and this may result in an increased insulin resistance [34].
Since 1959, evidence from many studies had revealed that there was an association between T2DM and cancer, and patients who had T2DM were more likely to be diagnosed with cancer than patients who had not [35, 36]. A lot of evidence has also shown its beneficial effects in cancers, including prostate, breast, lung, and colorectal cancers [37]. Experimental results in vitro have suggested the effect of statins on growth, migration, apoptosis, and autophagy of cancer cells [38, 39]. The data from in vivo cell culture studies, statins may act as a preventive drug for hepatocellular carcinoma, malignant glioma and bladder cancer [40]. However, the role of statins on the incidence of cancer in patients with T2DM has not been well documented. Fei et al., [41] performed a meta-analysis to evaluate the impact of different types of statins on the risk of cancers with T2DM.The study was systematically searched with the Cochrane Library, PubMed, Embase, and Wanfang databases from January 1999 to March 2017. A pairwise meta-analysis used to estimate the pooled ratios (ORs) and 95% confidence intervals (CIs). NMA was performed to compare different types of statins. In pairwise meta-analysis result showed that, the incidence of cancer in T2DM patients was reduced when simvastatin, atorvastatin, pravastatin, fluvastatin, lovastatin, rosuvastatin, and pitavastatin were used. The analyses suggest that rosuvastatin may be more effective than others.
Previous studies on diabetic rats (200–220 g) reported that after 2 weeks of metformin–atorvastatin combination therapy (500 mg metformin and 20 mg atorvastatin per 70 kg body weight), reduced blood glucose, lipid-lowering effects, and reduced in elevated oxidative stress, and positive effects on cardiovascular hypertrophy occurred [42]. The reduction of oxidative stress and liver protection (blood analysis and liver histology studies, e.g. CRP, TNF-α, IL-6, protein carbonyl levels) was also seen in T2DM rats treated with metformin and atorvastatin [43].
Statins consistently showed a protective role in the setting of diabetes cardiomyopathy (DCM) due to their roles of anti-inflammation, anti-oxidation, and antiapoptosis effects [44]. In previous animal experiments, statins could prevent DCM by all evicting left ventricular dysfunction and inhibiting myocardial fibrosis through anti-apoptosis and anti-inflammation pathways. It seems that statins may facilitate the onset of diabetes by impacting peripheral insulin sensitivity and islet b-cell function, while statins can effectively modify the promotive factors and promoting DCM, including inflammation and oxidative stress, thereby protecting the heart against diabetic conditions [45].
An animal study was designed to evaluate the effectiveness safety and mechanism of an atorvastatin/metformin combination therapy in a rabbit atherosclerosis model induced by a high-cholesterol diet. At the end of the experiment, all rabbits were sacrificed by injection of an overdose of sodium pentobarbital solution and the aortas were separated from the surrounding tissues. From the initiation of the aortic arch, 0.5 cm sections were excised for paraffin treatment [46] and the remaining aortas were soaked in 4%paraformaldehyde and then stained with Oil Red O solution, to evaluate the atherosclerotic lesion area of the aorta by image-processing software (ImageJ). One portion stained with hematoxylin and eosin (H&E) before quantification using ImageJ software. In an animal study 12-week high-cholesterol diet induced a significant increase in atherosclerotic lesion area in rabbits in the control (Ctrl) group; after 10 weeks of atorvastatin or metformin treatment, the atherosclerotic lesion area was significantly reduced by 51% and 35%, respectively.
Atorvastatin/metformin combination therapy resulted in an 80% reduction of atherosclerotic plaques compared with the control group. The combination therapy showed which was more effectively than each monotherapy. Compared with control group, the treatment of atorvastatin or metformin significantly reduced the lesion size by 68% and 42%, respectively, while atorvastatin/metformin combination therapy further reduced atherosclerotic lesion size by 86%. It was reported that large HDL is inversely associated with cardiovascular disease [47]. The results suggest that atorvastatin and metformin combination therapy is superior to atorvastatin monotherapy for the treatment of atherosclerosis and the underlying mechanisms might be associated with cholesterol efflux in macrophages. The study results demonstrated that atorvastatin/metformin combination therapy did not show a better lipid-lowering effect than atorvastatin, which is similar with the recent clinical and preclinical data [48]. The CAMERA study revealed that metformin did not affect the lipid profile in statin-treated patients [49]. Forouzandeh
In a clinical study a great number of patients are selected and treated with metformin–atorvastatin combination tablet administered as a single daily dose [52]. There is only a minor chance for toxic drug interactions when treated with metformin and statin together because metformin is not metabolized and is the mechanism for most statins are via the cytochrome P450 system [53]. Since metformin shows beneficial effects on both dyslipidemia and glycemic control and has been shown to reduce CVD risk while statins may have an added beneficial effect on CVD risk. Hence the combined treatment with both drugs seems a good option. Clinical studies on the effects of metformin and statin combination therapy have been carried out but for different diabetic complications [54, 55, 56]. Each of these studies had different objectives and included different patients groups, i.e. either with T2DM, dyslipidemia, treated (different doses), untreated, or newly diagnosed T2DM. This criteria were compared in these studies to arrive at overall results of metformin statin combination therapy. The lowest dose of metformin (500 mg) and atorvastatin (10 mg) once daily resulted in the highest reduction of fasting plasma glucose (−35%). Atorvastatin 20 mg showed to attenuate the glucose and HbA1c-lowering effect in combination with 1000 and 2000 mg metformin.
In another clinical trial, a total of 50 newly diagnosed patients with T2DM with age range of 47.8 ± 7.4 years and prescribed 850 mg/day of metformin (sustained release), with dietary restriction, were enrolled in open-label multi center pilot study. WHO criteria was followed for the selection of newly diagnosed patients [57] and underwent a physical examination and information about their medical history, demographic parameters, and medication history were obtained by questionnaire. The patients received a constant dose regimen of metformin during the 90-day study period. In that study, the use of metformin in newly diagnosed T2DM patients, improves body weight and glycemic control; however, the addition of low-dose atorvastatin did not improve these conditions. Metformin, in a long-term study, reduces the risk of macrovascular disease after a follow-up period of 4 years [58], and this beneficial effect supports to continue metformin treatment with T2DM patients unless contraindicated. The result of this study is consistent with that reported in an experimental animal model, which indicates that the combination of atorvastatin with metformin did not produce a better lipid-lowering effect than atorvastatin [59]. In addition, the study indicated that 10 mg/day did not increase the HbA1c and serum glucose levels, but there was no additional significant improvement in the studied markers when compared with the metformin-treated group.
The effects of metformin on lipid homeostasis discussed earlier in this chapter, indicate that lipid metabolism is positively affected in the intestine and liver leading to decreased plasma triglycerides, LDL-C, and total cholesterol. Metformin effects on lipid metabolism seem to be localized to the intestine. Statins mainly act on plasma cholesterol via activation of the LDL-receptor suggesting that combination therapy should show an additional effect on plasma lipids. Combination therapy with statins and metformin demonstrated beneficial effects in patients with other disease(s)/disorder(s) than T2DM and dyslipidemia [60].
In earlier studies, the effect of metformin alone on the lipid profile was studied, and the result analysis showed that only TG levels and LDL/HDL ratio were significantly improved. Whereas these effects were not significantly different compared with its combination with atorvastatin that improves all lipid profile components. These results indicated that the addition of atorvastatin with metformin did not influence the lipid-lowering effects of monotherapy in newly diagnosed T2DM patients with metformin. In previous studies, although metformin moderately improves the lipid profile, there were inconsistencies in its effects on the lipid parameters [61]. Accordingly, the addition of atorvastatin to metformin treatment in newly diagnosed T2DM patients showed relatively normal lipid profile may be irrational and cost ineffective and the emergence of adverse effects may be highly expected with long-term use.
Diabetic patients receiving metformin have been shown to have a reduced cancer incidence and a decrease in cancer-specific mortality [62]. Statin use was also found to be associated with a reduction in the risk of biochemical recurrence in patients with prostate cancer and a decreased risk of cancer mortality [63, 64]. Based on epidemiologic evidence and the preclinical data for metformin and atorvastatin individually in prostate cancer, the author concluded the beneficial effects of metformin and atorvastatin alone or in combination on SCID mice and cultured prostate cancer cells. Metformin and atorvastatin in combination exhibited potent inhibitory effect on the growth of prostate cancer cells
In T2DM patients with non-alcoholic fatty liver disease (NAFLD) the combination therapy was found to be benefited. Whereas, statin therapy associates negatively with non-alcoholic steatohepatitis and found to be significant fibrosis while a safe use of metformin in patients with T2DM and NAFLD was demonstrated [68]. Combination therapy consisting of metformin and statin treatment is frequently prescribed to women with polycystic ovary syndrome (PCOS). This syndrome increases the risk of T2DM and cardiovascular morbidity as it is associated with abnormal increased lipid levels, insulin resistance, endothelial dysfunction and systemic inflammation [69]. Meta-analysis showed that combined therapy in women with PCOS resulted in improved inflammation and lipid markers but it did not improve insulin sensitivity [70].
Treatments using statins, and combined statins and metformin can effectively improve IR, fasting insulin (F-INS), insulin sensitivity index, hyperandrogenemia, acne, hirsutism, testosterone and decreasing C reactive protein (CRP) [71, 72, 73]. Pre-treatment with atorvastatin for 3 months followed by metformin in patients with PCOS improves insulin and homeostasis model assessment of IR (HOMA-IR) indices and reduces CRP level but does not improve the lipid profile compared with placebo treatment. Hence, atorvastatin pre-treatment enhances the effects of metformin in improving IR, whereas inflammatory markers are not affected by decreased total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) after cessation of atorvastatin [74].
The lipid-lowering effect of statins administered with or without metformin in PCOS patients remains ambiguous. This finding is also supported with the meta-analysis performed by Gao et al. [75]. A clinical trial demonstrated that insulin secretion was found to be increased after 6 weeks of statin therapy in women with PCOS [76]. The meta-analysis found that statins fail to improve F-INS and HOMA-IR in single or in combination with metformin. This finding may be due to the following reasons. First, statins may damage endothelial function through loss of the protective anti-proliferative and anti-angiogenic effects of adiponectin, resulting in impaired insulin sensitivity [77]. Second, statins decrease the levels of cholesterol mediated by the farnesoid X receptor (FXR), the deficiency of which is related to IR [78]. The activation of FXR can lower the levels of glucose-6-phosphatase, reduce phosphoenol pyruvate carboxykinase in gluconeogenesis, and increase glycogen synthesis [79]. Hence, induced IR caused by statin therapy may be related to the low expression of FXR [80]. Third, statins (lipophilic) are possibly absorbed by extra-hepatic cells; these statins can deregulate cholesterol metabolism, thus deteriorating IR and attenuating β-cell function [81].
Combination therapy could also be considered for T2DM patients with diabetic retinopathy. Diabetic retinopathy (DR) is a microvascular complication of diabetes caused by hyperglycemia and hyperosmolarity. In T2DM patients and pre-existing DR patients, the use of statin showed a protective effect against development of diabetic macular edema [82]. In T2DM patients receiving statin therapy in combination with increased levels of cholesterol remnants and triglycerides were associated with slight decreased in left ventricular systolic function. Targeting cholesterol remnants might be beneficial for finding cardiac function in T2DM patients receiving statins [83].
A high daily dose of metformin (3000 mg) and simvastatin (40 mg) resulted in an improved insulin resistance, but fasting plasma glucose decreased only by 5%, and observed minor changes on lipid metabolism parameters. This may probably due to the fact that metformin was given on top of simvastatin treatment. The patients involved in these studies had an impaired fasting glucose, dyslipidemia, newly diagnosed T2DM and/or dyslipidemia. However, it could be used for hypothesis-generation rather than making rigid decisions, considering the lack of multiple dose dependent combination studies.
The combination of metformin with insulin may be a better therapeutic option for patients with DM whose hyperglycemia is poorly controlled on insulin treatment. Aviles et al. [84] stated that increased frequency of dosage of insulin causes more improvement in glycemic control and significantly reduce HbA1c which was compared with a combination therapy of insulin and metformin. Furthermore, unchanged FBG and PPBG and HbA1c in patients on metformin and insulin compared to combination of metformin, insulin and simvastatin treated patients. The HbA1c of diabetic patients on simvastatin showed a slight elevation as compared to other groups. Previous studies reported that statin use is associated with a rise of FPG in patients with and without DM [85]. Sattar et al., have identified deterioration in glucose homoeostasis in patients treated with statins and this depends on lipid solubility of statins. Simvastatin can enter easily extra hepatic cells because of its high lipid solubility and may suppress isoprenoid protein synthesis, thus attenuating the action of insulin. The abnormal level of FBG may translate into clinical syndrome of DM with rise in HbA1c is not excluded. The combination of metformin and insulin may be an attractive therapeutic option for patients with DM whose hyperglycemia is poorly controlled on insulin [86].
The mechanism of metformin is a controversial along with the use of statins in diabetes. Although the potential detrimental effects of statin therapy on muscle and liver have been known for a long time, new concerns have emerged regarding the risk of new onset diabetes (NOM) that often leads to discontinuation of statin, concerns correlating with initiating statin therapy or non-adherence to therapy.
Metformin is generally to exert its beneficial effects on glucose metabolism mainly in the liver. In line with recent research articles on the topic we conclude that the drug acts primarily in the intestine. This is due to the at least one order of magnitude higher concentrations of metformin in the intestine than in the liver. The drug present in the liver and its effects may be localized to this organ most probably via its effects on gluconeogenesis. A newly diagnosed patient with T2DM who show inadequate response to metformin may need better treatment approaches to lower atherogenic lipids. Supplementation with niacin or high-dose omega-3 fatty acid could be used in newly diagnosed T2DM patients with borderline values of lipid profile, secondary to lifestyle modifications before using a potent statin such as atorvastatin as the first treatment priority.
The effects of metformin on lipid metabolism as discussed in this chapter indicate that lipid level is positively affected in the intestine and liver leading to decreased LDL-C, plasma triglycerides and total cholesterol. Metformin effects on lipid metabolism seem to be localized to the intestine. Statins mainly act on plasma cholesterol levels via activation of the LDL-receptor suggesting that combination therapy should show an additional effect on plasma lipids. This may influence glucose homeostasis primarily by inhibition of insulin secretion in pancreatic β cells. T2DM patients receiving statin therapy in combination, with increased levels of cholesterol remnants and triglycerides were associated with slight decreased in left ventricular systolic function. Targeting cholesterol remnants in addition to T2DM patients receiving statins might be shown beneficial effect on patient’s cardiac function. To treat T2DM and its secondary complications, the combination therapy of metformin with statins seems well placed and may act as a double-sided sword particularly in the case of statins. Whereas, statins alone increases the risk on T2DM particularly in pre-diabetic subjects, and co-treatment with metformin might reduce this risk.
We have concluded that, previous studies investigated possible sites of interaction of metformin and statins and they act on largely parallel pathways. Many studies suggested that the benefits of statin therapy for diabetes far outweigh any real or perceived risks, not suggested/recommended for discontinuation of statins for diabetic patients. In conclusion, both metformin and atorvastatin can protect DCM via the mechanism of anti-inflammation and anti-apoptosis activities. The combined administration of metformin and atorvastatin resulted in superior protective effects on DCM than a single drug treatment. In this chapter, we have compiled the possible sites of interaction of metformin and statins and conclude that they act on largely parallel pathways.
The authors declare no conflict of interest among themselves.
BA | bile acids |
BMI | body mass index |
CVD | cardiovascular disease |
DCM | Diabetes cardiomyopathy |
DI | disposition indices |
DR | diabetic retinopathy |
DM | Diabetes mellitus |
EGP | endogenous glucose |
FBG | Fasting blood glucose |
FAS | fatty acid synthase |
FFA | free fatty acid |
GLUT | glucose transporter |
HbA1c | glycated hemoglobin |
HDL-C | high-density lipoprotein cholesterol |
HMGCR | 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase |
HMGCS | HMG-CoA synthase |
IFG | impaired fasting glucose |
IHD | Ischemic heart disease |
LDL-C | low-density lipoprotein |
NOM | Non onset diabetes |
OCT | organic cation transporter |
PDX | insulin promoter factor |
PMAT | Plasma monoamine transporter |
PXR | pregnane X receptor |
RCT | Reverse cholesterol transport |
RXR | retinoid X receptor |
SERT | sodium-dependent serotonin transporter |
TNF | Tumor necrosis factor |
T2DM | type 2 diabetes mellitus |
TG | triglycerides |
THTR | thiamine transporter |
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All published Book Chapters are licensed under a Creative Commons Attribution 3.0 Unported License. Monographs are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license granted to all others. Our Copyright Policy aims to guarantee that original material is published while at the same time giving significant freedom to our Authors. IntechOpen upholds a flexible Copyright Policy meaning that there is no copyright transfer to the publisher and Authors hold exclusive copyright to their work.
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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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This chapter reviews the results of 20 PTSD clinical trials funded by the United States Department of Defense and Department of Veterans Affairs on the treatment of combat-related PTSD. All of the studies were conducted under the leadership and management of two research consortia: the South Texas Research Organizational Network Guiding Studies on Trauma and Resilience (STRONG STAR) Consortium and the Consortium to Alleviate PTSD.",book:{id:"9563",slug:"current-topics-on-military-medicine",title:"Current Topics on Military Medicine",fullTitle:"Current Topics on Military Medicine"},signatures:"Alan L. Peterson, Barbara L. Niles, Stacey Young-McCaughan and Terence M. Keane",authors:[{id:"340047",title:"Prof.",name:"Alan L.",middleName:null,surname:"Peterson",slug:"alan-l.-peterson",fullName:"Alan L. Peterson"},{id:"345787",title:"Prof.",name:"Barbara L.",middleName:null,surname:"Niles",slug:"barbara-l.-niles",fullName:"Barbara L. 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This is followed by a modified theoretical framework, M-31000, taking into account OHS risk management practice. The results of 42/149 key informants selected as part of a purposive sampling strategy identified three main advantages of ISO 31000, including acting as a good starting point for risk management, supplementing other risk management strategies, and allowing for easier integration with other similar strategies. The two main shortfalls identified in this pilot included the standard being vague and difficult to implement. The study also revealed that M-31000 was much simpler and more consistent with safety management practice.",book:{id:"6480",slug:"occupational-health-and-safety-a-multi-regional-perspective",title:"Occupational Health and Safety",fullTitle:"Occupational Health and Safety - A Multi-Regional Perspective"},signatures:"Manikam Pillay",authors:[{id:"199145",title:"Dr.",name:"Manikam",middleName:null,surname:"Pillay",slug:"manikam-pillay",fullName:"Manikam Pillay"}]}],mostDownloadedChaptersLast30Days:[{id:"71988",title:"Introductory Chapter: Safety and Health for Workers - Theory and Applications",slug:"introductory-chapter-safety-and-health-for-workers-theory-and-applications",totalDownloads:827,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"7620",slug:"safety-and-health-for-workers-research-and-practical-perspective",title:"Safety and Health for Workers",fullTitle:"Safety and Health for Workers - Research and Practical Perspective"},signatures:"Bankole K. 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Nevertheless, the recent changes of the labor market underline that new risks to the health and well-being of workers should be considered. In this context, a vast amount of studies have analyzed the relationship between work conditions, social inequalities, and health, suggesting a complex net of causation. Only recently, it has been shown that people in lower socioeconomic positions incur higher working risks. The 2008–2013 economic crisis also introduced a reduction of the number of workers in full-time permanent employment with a steady expansion of atypical and precarious workers. The latter have generally been associated with more insecure and unhealthy working conditions. Another important aspect of safety in the workplace is gender differences. Although nowadays there is more information than before about the types of health problems and accidents women incur at the workplace, the gender-related questions are still open issues that require a careful evaluation of work-related risks of men and women. In this chapter, we focused on the current state of the art in the field of occupational health and examined the aspects that are still being debated.",book:{id:"7620",slug:"safety-and-health-for-workers-research-and-practical-perspective",title:"Safety and Health for Workers",fullTitle:"Safety and Health for Workers - Research and Practical Perspective"},signatures:"Anna Maria Giammarioli",authors:[{id:"175022",title:"Dr.",name:"Anna Maria",middleName:null,surname:"Giammarioli",slug:"anna-maria-giammarioli",fullName:"Anna Maria Giammarioli"}]},{id:"72308",title:"Hand Hygiene Practices in Public Restrooms: Effects and Proposed Solutions",slug:"hand-hygiene-practices-in-public-restrooms-effects-and-proposed-solutions",totalDownloads:994,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Human safety is a popular ongoing research area in personal hygiene. Researchers are mostly apprehensive about how to protect humans from different hazards in the environment. Thus, guidelines developed for good hand wash practices in the public restrooms have showed little or no impact on human behavior. This research examined hand wash acts in the public restrooms and proposed possible solutions to improve the practice. There are 427 people who participated in the study. Participant age ranged from 18 years old and upward: statistically, female, 63%; male, 35%; and unidentified, 2%. Descriptive statistics revealed 99.5% respondents approved restroom redesign for appropriate hand hygiene practice, while 49% suggested restroom device automation. Inferential statistics results on redesign with a Welsh t-test were statistically significant (t=1.967, df=300, p<0.0001; t=1.990, df=80, p<0.0001; t=1.9746, df=163, p<0.0001). Findings showed that hand hygiene guidelines and recommendations are insufficient to ensure proper promotion of hand wash practices in restrooms. This study concluded that good hand wash practices in public restrooms could be ergonomically redesigned to include a visual and auditory alert that reminds users to wash their hands after restroom usage and to include hand wash practice in school curriculum. The findings from this study could be applicable in restaurants, schools, and bars, to manage and control transmission of disease through direct hands contacted with infectious diseases in the restrooms.",book:{id:"7620",slug:"safety-and-health-for-workers-research-and-practical-perspective",title:"Safety and Health for Workers",fullTitle:"Safety and Health for Workers - Research and Practical Perspective"},signatures:"Bankole K. Fasanya, Moruf Adegbite, Maged Mikhail and George L. 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Dr. Bobek is also a co-founder of the Academy of Regional Management in Slovenia.",institutionString:"Universities of Applied Sciences FH Joanneum, Austria",institution:null},editorTwo:{id:"293992",title:"Dr.",name:"Tatjana",middleName:null,surname:"Horvat",slug:"tatjana-horvat",fullName:"Tatjana Horvat",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hXb0hQAC/Profile_Picture_1642419002203",biography:"Tatjana Horvat works as a professor for accountant and auditing at the University of Primorska, Slovenia. She is a Certified State Internal Auditor (licensed by Ministry of Finance RS) and Certified Internal Auditor for Business Sector and Certified accountant (licensed by Slovenian Institute of Auditors). 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She specializes in the subject of brands, brand equity, and brand management in production, service, and trade enterprises. She combines this subject with marketing and marketing management in both theoretical and practical aspects. Prof. Hanna Górska-Warsewicz also analyzes brands in the context of trademarks, legal regulations and the protection of intangible. She is an author or co-author of over 200 publications in this field, including 8 books. She works with the business sector and has participated in projects for the Ministry of Agriculture and Rural Development and the Ministry of Education and Science in Poland.",institutionString:null,institution:{name:"Warsaw University of Life Sciences",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:45,paginationItems:[{id:"82135",title:"Carotenoids in Cassava (Manihot esculenta Crantz)",doi:"10.5772/intechopen.105210",signatures:"Lovina I. Udoh, Josephine U. 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Military Reserve Officer serving with the 100 Support Command, 100 Troop Command, 40 Infantry Division, CA National Guard.",institutionString:null,institution:{name:"Loma Linda University",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"6925",title:"Endoplasmic Reticulum",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6925.jpg",slug:"endoplasmic-reticulum",publishedDate:"April 17th 2019",editedByType:"Edited by",bookSignature:"Angel Català",hash:"a9e90d2dbdbc46128dfe7dac9f87c6b4",volumeInSeries:2,fullTitle:"Endoplasmic Reticulum",editors:[{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",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",institutionURL:null,country:{name:"Argentina"}}}]},{type:"book",id:"6924",title:"Adenosine Triphosphate in Health and Disease",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6924.jpg",slug:"adenosine-triphosphate-in-health-and-disease",publishedDate:"April 24th 2019",editedByType:"Edited by",bookSignature:"Gyula Mozsik",hash:"04106c232a3c68fec07ba7cf00d2522d",volumeInSeries:3,fullTitle:"Adenosine Triphosphate in Health and Disease",editors:[{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",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. 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He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. 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He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. 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She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. 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Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"38",type:"subseries",title:"Pollution",keywords:"Human activity, Pollutants, Reduced risks, Population growth, Waste disposal, Remediation, Clean environment",scope:"
\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11966,editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",biography:"Ismail Md. Mofizur Rahman (Ismail M. M. Rahman) assumed his current responsibilities as an Associate Professor at the Institute of Environmental Radioactivity, Fukushima University, Japan, in Oct 2015. He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). The research focus of Dr. Zinnat includes the effect of the relative stability of metal-chelator complexes in the environmental remediation process designs and the development of eco-friendly soil washing techniques using biodegradable chelators.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null,series:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713"},editorialBoard:[{id:"252368",title:"Dr.",name:"Meng-Chuan",middleName:null,surname:"Ong",slug:"meng-chuan-ong",fullName:"Meng-Chuan Ong",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRVotQAG/Profile_Picture_2022-05-20T12:04:28.jpg",institutionString:null,institution:{name:"Universiti Malaysia Terengganu",institutionURL:null,country:{name:"Malaysia"}}},{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed",profilePictureURL:"https://mts.intechopen.com/storage/users/63465/images/system/63465.gif",institutionString:null,institution:{name:"Aswan University",institutionURL:null,country:{name:"Egypt"}}},{id:"187907",title:"Dr.",name:"Olga",middleName:null,surname:"Anne",slug:"olga-anne",fullName:"Olga Anne",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBE5QAO/Profile_Picture_2022-04-07T09:42:13.png",institutionString:null,institution:{name:"Klaipeda State University of Applied Sciences",institutionURL:null,country:{name:"Lithuania"}}}]},onlineFirstChapters:{paginationCount:6,paginationItems:[{id:"82135",title:"Carotenoids in Cassava (Manihot esculenta Crantz)",doi:"10.5772/intechopen.105210",signatures:"Lovina I. 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