Differential diagnosis in vomiting infants.
\r\n\t
",isbn:"978-1-83881-111-2",printIsbn:"978-1-83880-992-8",pdfIsbn:"978-1-83881-112-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"acb2875b3bfc189c9881a9b44b6a5184",bookSignature:"Dr. Abdo Abou Jaoudé",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11865.jpg",keywords:"Linear Operators, Normal Operators, Spectral Theorem, Applications, Differential Operators, Integral Operators, Functional Calculus, Complex Variables, Complex Analysis, Theory, Recent Advances, Latest Trends",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 13th 2022",dateEndSecondStepPublish:"June 21st 2022",dateEndThirdStepPublish:"August 20th 2022",dateEndFourthStepPublish:"November 8th 2022",dateEndFifthStepPublish:"January 7th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Abdo Abou Jaoudé is a pioneering Associate Professor of Mathematics and Statistics at Notre Dame University-Louaizé. He holds two PhDs in Mathematics and Prognostics from the Lebanese University and Aix-Marseille University. His research interests are in the field of mathematics.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"248271",title:"Dr.",name:"Abdo",middleName:null,surname:"Abou Jaoudé",slug:"abdo-abou-jaoude",fullName:"Abdo Abou Jaoudé",profilePictureURL:"https://mts.intechopen.com/storage/users/248271/images/system/248271.jpg",biography:"Abdo Abou Jaoudé has been teaching for many years and has a passion for researching and teaching mathematics. He is currently an Associate Professor of Mathematics and Statistics at Notre Dame University-Louaizé (NDU), Lebanon. He holds a BSc and an MSc in Computer Science from NDU, and three PhDs in Applied Mathematics, Computer Science, and Applied Statistics and Probability, all from Bircham International University through a distance learning program. He also holds two PhDs in Mathematics and Prognostics from the Lebanese University, Lebanon, and Aix-Marseille University, France. Dr. Abou Jaoudé's broad research interests are in the field of applied mathematics. 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Thus, age-related androgen deficiency, known as late-onset hypogonadism (LOH), is a risk factor for erectile dysfunction (ED) [1, 2]. Several studies have reported that androgen replacement therapy mitigates the symptoms of LOH and ED. In this context, bioidentical or synthetic testosterone facilitates erectile function by maintaining an adequate supply of nitric oxide (NO), penile structure, and the endothelial functioning of the corpus cavernosum. Thus, reduced NO bioavailability is believed to be the main cause of ED in individuals with testosterone deficiency [6]; however, the pathophysiological mechanisms underlying this process remain unclear and require further study. This chapter summarizes relevant basic research reports examining the effects of testosterone on erectile function.
\nAndrogens are well established as being essential for erectile function, and their deficiency is considered a risk factor for ED. LOH is a result of the normal aging process and is responsible for androgen deficiency [7, 8]. In recent years, epidemiologic studies have suggested that metabolic syndrome and diabetes mellitus are also associated with the development of androgen deficiency [9, 10, 11, 12].
\nErectile function is regulated by complex mechanisms [13]. When sexual stimulation occurs, NO is released in the penis, causing corporal smooth muscle relaxation through the activation of the cGMP/protein kinase G signaling cascade. ED results when the relaxant system is weakened; therefore, many studies have focused on smooth muscle relaxation. In contrast, in the flaccid state, corporal smooth muscle contraction is controlled by constrictors such as noradrenaline. Recent studies have indicated that the balance between smooth muscle relaxation and contraction is disturbed by abnormal activation of the RhoA/Rho-kinase signaling pathway. In some syndromes causing ED, such as diabetes mellitus or metabolic syndrome, the RhoA/Rho-kinase signaling pathway is enhanced [14, 15, 16]. Additionally, enhancement of the RhoA/Rho-kinase signaling pathway is known to occur in aged individuals, and a Rho-kinase inhibitor (Y-27632) has been shown to improve erectile function in aged rats [17, 18]. As contractility may play a significant role in erectile function, its role in ED should be considered along with contraction. Thus, the balance between smooth muscle contraction and relaxation is important for normal erectile function.
\nMost animal studies have shown that castration causes ED by reducing arterial inflow [19]. Further, endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) are important in erectile functioning. In castrated animals, testosterone administration restores the erectile response and NOS expression in the penis [20]. Li et al. showed that testosterone deficiency decreases eNOS activity (phosphor-eNOS/eNOS ratio) by upregulating reactive oxygen species production [21], and the decreased eNOS activity decreases cGMP levels in the penis.
\nSome studies found that testosterone changes phosphodiesterase type 5 (PDE-5) expression in the penis. Traish et al. showed that castration decreased PDE-5 activity in rabbit penises [22], whereas Zhang et al. showed that testosterone deficiency decreased PDE-5 expression in the rat penis and that testosterone administration increased PDE-5 expression [23]. These results suggest that testosterone is essential not only for regulating eNOS activity but also for regulating PDE-5 activity. Traish et al. also suggested that while these actions may seem paradoxical, in which androgens are upregulating both signal initiators (NOS) and signal terminators (PDE-5), they may be interpreted to be part of a homeostatic mechanism that maintains a relatively constant ratio of critical pathway enzymes [3]. They also postulated that PDE-5 expression may be controlled by NO. Androgen-mediated upregulation of NOS may lead to increased NO synthesis, which may then upregulate PDE-5 expression and activity. Conversely, androgen deprivation-mediated NOS downregulation also results in the downregulation of PDE-5 expression and activity. More studies are needed to define this delicate and crucial mechanism of testosterone action.
\nTestosterone also affects the smooth muscle of the corpus cavernosum. Reilly et al. showed that castration reduced the number of α-adrenergic-1 receptors on smooth fascia [24]. They also showed that testosterone modulated the adrenergic response of the corpus cavernosum vascular smooth muscle [25]. Their results indicate that when testosterone levels decrease, smooth muscle contractility also decreases. On the other hand, Wingard et al. showed that castration increased the levels of Rho-A and Rho-kinase proteins in rats. RhoA, a small monomeric GTPase, activates the Rho-associated protein kinase, a serine/threonine kinase, which phosphorylates the myosin-binding subunit of myosin light chain phosphatase, thereby deactivating it and promoting contraction [26]. Their results indicate that when testosterone levels decline, smooth muscle contractility increases, leading not only to the development of ED but also to the hypertension. Thus, although testosterone deficiency might increase contraction, additional research is required to fully elucidate its impact on smooth muscle contraction.
\nInterestingly, testosterone also directly affects smooth muscle relaxation. Yue et al., using an isometric tension study, showed that testosterone relaxed the smooth muscle of rabbit coronary arteries and aortas [27]. Others also showed that testosterone induces the relaxation of isolated human corpora cavernosa strips by activating smooth muscle ATP-sensitive K+ channels [28]. These findings suggest that testosterone, in addition to its known endothelial action, might regulate erectile function locally by acting on human corpus cavernosum smooth muscle. These results indicate that testosterone might affect both the genomic and nongenomic actions of erectile function.
\nSome studies demonstrated that testosterone also impacts the structure of the penis. One group showed that castrated rats show smooth muscle loss and fibrosis [29], and another group reported that castration increases the collagen content of the internal pudendal arteries and decreases α-actin expression [30]. These testosterone effects suggest that testosterone deprivation results in programmed trabecular smooth muscle cell death (apoptosis) and increased development of extracellular matrix [22]. Traish et al. also proposed that testosterone deprivation is associated with the accumulation of fat-containing cells (fibroblasts or preadipocyte-like cells), especially in the subtunical region of the corpus cavernosum, contributing to impaired veno-occlusion [31]. Interestingly, Wang et al. showed that castration attenuates erectile function and induces corporeal fibrosis by inhibiting autophagy and promoting apoptosis of the corpus cavernosum smooth muscle cells in rats [32]. Their study has limitations, but they highlighted the important role of androgens in maintaining the structural integrity and functioning of the corpus cavernosum. This resulted from androgens mediating the counter-regulation of autophagy and apoptosis through regulation of the BECN 1-Bcl-2 (key dual regulators of autophagy and apoptosis) interaction [33, 34].
\nED has relationships between not only cardiovascular diseases but also neurological diseases. Yang et al. found the hazard risk for Alzheimer’s disease and non-Alzheimer dementia to be greater in patients with ED [35]. They also found that log-rank test revealed that patients with ED had significantly higher cumulative incidence rates of dementia than those without. Yang et al. found the incidence density rate of Parkinson’s disease (PD) was higher in the ED cohort than in the non-ED cohort [36]. Balsamo et al. reported that men with multiple sclerosis had high risk of ED [37]. Interestingly, testosterone deficiency is often observed in these neurological disease patients relative to age-matched controls [38, 39, 40].
\nIn basic study, there are some reports on the relationship between testosterone deficiency and neurogenic factors. Baba et al. reported the mean number of NOS-containing nerve fibers in the corpora cavernosa and in both dorsal nerves of castrated rats [41]. Others also showed that castration decreased nNOS protein expression in the corpus cavernosum [32]. However, reports regarding nNOS responses differ significantly; some studies show increased activity but no change in protein expression [42] in rats, whereas others report no effects in rabbits [43]. Thus, more research into the relationship between nNOS and testosterone is required.
\nOn the other hand, Suzuki et al. measured the ICP during electrical stimulation of the preoptic area and cavernous nerve in castrated male rats with and without testosterone replacement [44]. They showed the actions of testosterone and its metabolites on both the central and peripheral neural pathways are crucial for maintaining and restoring erectile capacity. Syme et al. reported that castration resulted in a decreased erectile response to electrostimulation following nerve grafting due to decreased graft neuronal nitric oxide synthase-positive axonal regeneration [45]. Armagan et al. indicated that testosterone had a neuroprotective role in the nerve fibers of the dorsal nerve and testosterone deficiency led to different forms of nerve degeneration resulting in anatomic alterations [46]. Baba et al. also reported that castration decreased the number of nicotinamide adenine dinucleotide phosphate diaphorase-staining nerve fibers not only in corpus cavernosum but also in dorsal nerve [47]. These results indicate that testosterone deficiency would cause neurogenic dysfunction of erectile tissues; however, future study needs to unravel the mechanism of testosterone action to the nerve systems.
\nObesity has become a major public health issue that is associated with increased mortality primarily due to increased risks of cardiovascular disease and type 2 diabetes mellitus (T2DM) [1, 48, 49]. Obesity is also considered a strong risk factor for ED [4, 5]. In men, visceral adipose tissue causes arteriosclerosis and vessel endothelial dysfunction [12]. Therefore, men with T2DM have a high incidence of ED [5, 48, 50, 51].
\nIn recent years, epidemiologic studies have suggested that obesity is also associated with multiple alterations in the gonadal endocrine system, including low testosterone levels [1, 48, 52, 53]. Low testosterone levels have also been reported in animals with T2DM, including two seminal research papers that reported testosterone replacement therapy (TRT) in such animal models [54, 55]. Davis et al. administered TRT to obese Zucker rats, resulting in improved cholesterol parameters and insulin sensitivity [54]. On the other hand, others administered TRT to rabbits with high-fat diet-associated hypogonadotropic hypogonadism [55]. TRT partially ameliorated the animals’ blood glucose levels and improved CC sensitivity to acetylcholine and eNOS.
\nWe also reported that T2DM increased inflammatory biomarker (inducible NO synthase, interleukin-6, and tumor necrosis factor alpha) mRNA expression levels in the CC, but TRT decreased them [56]. Ota et al. reported an in vitro study that demonstrated testosterone prevented inflammation caused by hydrogen peroxide in blood vessel cells by upregulating the sirtuin-1 (Sirt1)/eNOS pathway [57, 58]. In one of our studies, testosterone administration upregulated Sirt1 and eNOS mRNA transcription, possibly preventing CC inflammation in T2DM rats (Figures 1 and 2). Interestingly, serum asymmetric dimethylarginine (ADMA) levels were also increased in T2DM rats, and rats receiving TRT were observed to have decreased ADMA levels. ADMA is an endogenous arginine compound that rises in individuals demonstrating some disease states [59]; in particular, several reports have suggested a potential relationship between ADMA levels and ED [60, 61]. ADMA has NOS inhibitory activity, and the elevation of ADMA levels contributes to decreased NO bioactivity and decreased endothelial functioning of vessel tissues. Zhang et al. also reported that testosterone treatment improved nNOS activity using streptozotocin-induced diabetic rat [62].
\nThe mechanism of erectile dysfunction caused by T2DM.
The mechanism of ART for T2DM.
TRT is widely used to effectively treat patients with testosterone deficiencies. It has also been applied to animal models for investigating the mechanisms of testosterone action. However, Burns-Cox et al. pointed out that testosterone (testosterone enanthate) injections cause extremely high levels of testosterone after a few days [63]. Similarly, we injected testosterone enanthate into rats, and the animals demonstrated serum testosterone level increases that rose in a dose-dependent manner (Figure 3).
\nTestosterone levels after testosterone injection in rat.
Amano et al. reported that the therapeutic administration of testosterone ointment to patients with LOH successfully kept testosterone at normal levels [64]. We administered low-dose testosterone (similar to applying testosterone ointment) to rats, as previous report [65], 4 weeks after castration. Interestingly, this TRT did not improve erectile functioning over the first 4 weeks of administration. However, after 8 weeks of TRT, partial ED improvements were observed (Figure 4). Baba et al. reported that delayed TRT improved ED, in rats, for 4 weeks [41]. However, they used high-dose testosterone administrations and the testosterone levels were ≥10 times normal. These results suggest that low-dose testosterone treatments may require longer treatment periods to overcome testosterone deficiency. Currently, testosterone undecanoate, a drug that is applied over a long period (about 3 months), is widely used in European countries. The medication has been shown to be a safe and effective treatment for patients with testosterone deficiencies [66]. However, some countries have not approved the medication, and there are no basic science reports addressing its use. These results demonstrate the need to investigate differences between various testosterone administration methods.
\nDifferent effects of TRT periods for delayed treatment.
Erectile functioning is a complex process, with an underlying mechanism that is affected by several factors [4, 67, 68, 69]. Recent studies have suggested that one of these factors may be endogenous estrogen levels [70, 71, 72, 73, 74, 75, 76, 77]. For example, Baser et al. suggested that serum estrogen levels are correlated with aging in men and that estrogen may, therefore, play an important role in the expression of the symptoms of aging [70]. Further, Greco et al. reported that tadalafil treatment suppresses estrogen levels in some obese men and improved their erectile function domain scores [71]. Another group reported high estrogen levels in elderly patients with ED and sexual disinterest; therefore, they suggested that pathophysiological estrogen-testosterone imbalance is involved in these conditions among elderly men [72, 73]. In a basic study, Goyal et al. reported that estrogen caused developmental disorders of the rat penis and that it decreased penile testosterone levels [74, 75]. Others reported that estrogen caused pathophysiological changes in the corpus cavernosum and a decline in erectile function in rats [76]. These authors also reported that estrogen induction enhanced corpus cavernosum smooth muscle contraction and decreased smooth muscle relaxation in rabbits [77]. We reported the use of TRT in a rat model of testosterone deficiency induced by estrogen injections. Interestingly, TRT is not an effective ED treatment in the high-estrogen level model [78]. Thus, attention needs to be given not only to the testosterone levels but also to the levels of other hormones.
\nAlthough TRT is an effective treatment for testosterone deficiency, some reports have reported a new treatment approach based on the use of testosterone deficiency models that consider the mechanism of testosterone action on erectile function. PDE-5 inhibitors are the first choice for ED patients, but they are not always effective in patients with testosterone deficiencies [79, 80]. One of the reasons for the lack of efficacy might be the PDE-5 expression changes induced by testosterone. A combination therapy involving both testosterone and PDE-5 inhibitors is one choice, but it is the one that is being vigorously debated, with strong reasons being presented for and against its use. PDE-5 inhibitors are also effective, but regardless of their pharmacokinetics or the regimen used, none has been shown to cure ED [2].
\nMoody et al. showed that L-arginine administration also improves ED in castrated rats [81]. Similarly, we demonstrated that L-citrulline supplementation improves erectile function and penile structure in castrated rats [82]. L-arginine and L-citrulline are amino acids present in free form in the human body. When L-citrulline is orally administered, it is converted to L-argininosuccinate and, subsequently, to L-arginine by renal argininosuccinate lyase [83]. L-arginine is then converted to NO and L-citrulline by NOS [84]. Orally administered L-arginine is known to be extensively metabolized by autochthonous gut bacteria and by arginases in the gut and liver [3]. However, oral L-citrulline administrations were shown to avoid such metabolism [85]. Accordingly, oral L-citrulline supplementation was reported to increase L-arginine levels more efficiently than oral L-arginine administration; L-citrulline also increased NO production [86]. In addition, we conducted a similar study using an acute arteriogenic ED model [87]. In that study, oral L-citrulline supplementation improved erectile function and increased NO production, without side effects (e.g., decreased mean arterial pressure) [87].
\nFukuhara et al. showed that resveratrol and vardenafil improved erectile responses in rats with streptozotocin-induced diabetes [88]. Recently, Dalaklioglu et al. also reported that resveratrol improved sildenafil-induced corpus cavernosum relaxation in both diabetic and nondiabetic aged rats, probably by potentiating NOS activity [89]. Oral supplementation might improve the vasculogenic condition, considering our previous study, though this is just speculation and needs to be examined.
\nTestosterone levels affect several organs, including the functioning of male erectile tissue. Many studies have described the mechanism of testosterone deficiency effects on erectile function as well as the impact of TRT. Testosterone affects NO production and PDE-5 expression in the corpus cavernosum through molecular pathways. It also preserves smooth muscle contractility by regulating both contraction and relaxation. Further, testosterone maintains the structure of the corpus cavernosum. TRT is widely used to treat patients with testosterone deficiencies; however, the present discussion has also documented some problems associated with this therapeutic approach. Basic research has also identified other potentially effective therapeutic methods for treating testosterone deficiency. Among these, PDE-5 inhibitors, L-citrulline, and resveratrol might be options for treating testosterone deficiency-induced ED. Future research should confirm these findings in more specific experiments that use molecular tools. Such additional research may shed more light on possible treatments for endocrine-mediated ED and its treatment.
\nThe authors declare no conflict of interest.
The prevalence of congenital heart disease (CHD) is known to be approximately 0.5–0.8% in all live births [1]. It is estimated that approximately 30–35% of children with CHD require medical treatment, interventional procedures, or surgical treatment [2]. Over the last 30 years, significant advances in surgical techniques and medical treatment have been made in the treatment of CHD in the world [3]. Nutritional status of CHD patients in the first year has an important role in growth and neurodevelopmental functions. GERD, which is closely related to nutrition and malnutrition, should be considered in these patients [4].
Gastroesophageal reflux is a common condition in children in all age groups, with gastric contents retrograde passage to the esophagus, even pharynx and mouth. This condition is defined as gastroesophageal reflux disease (GERD) if it continues more frequently and continuously and causes worrisome symptoms and undesirable consequences [5]. Especially, it results in esophagitis or other esophageal symptoms or symptoms of the respiratory system.
Gastroesophageal reflux is a physiological condition that may occur in healthy infants, children, and adults. It usually occurs in very short episodes (<3 minutes) and in the postprandial period without any symptom, esophageal damage, or complications. If these reflux processes cause worrisome symptoms and unwanted conditions, GERD is in question [6, 7].
Regurgitation refers to reflux in the oropharynx, while vomiting refers to the gastric contents coming out of the mouth. There is no need to be with repetition and any coercion. The use of these terms is intertwined in clinical practice, and no definite distinction is made. They are perceived as different states of the same process. Symptoms occur for many reasons (Table 1).
Causes of vomiting | ||
---|---|---|
Gastrointestinal obstruction Pyloric stenosis Malrotation Intestinal duplication Hirschsprung’s disease Antral/duodenal web Foreign body | Hydrocephalus Subdural hematoma Intracranial hemorrhage Intracranial mass Infant migraine Chiari malformation | Obstructive uropathy Renal insufficiency |
The lead Iron Vitamins A and D | ||
Other gastrointestinal causes Achalasia Gastroparesis Gastroenteritis Peptic ulcer Eosinophilic esophagitis gastroenteritis Food allergy | Sepsis Meningitis Urinary infection Pneumonia Otitis media | Congestive heart failure Vascular ring |
Galactosemia Hereditary fructose intolerance Urea cycle defects Amino and organic acidemias Congenital adrenal hyperplasia |
Differential diagnosis in vomiting infants.
A study of 948 infants in the United States reported a prevalence of reflux in the 4–6 months of life as 67% which has decreased to 5% by 10–12 months of age. Similarly in the study with 602 babies in India, it showed that the prevalence of gastroesophageal reflux, which was 55% in the first 6 months of life, decreased to 4% at 1 year of age [8, 9]. Epidemiological studies suggest that gastroesophageal reflux in infancy with CHD can be seen from the first month of life and the frequency of occurrence reaches to the peak around the fourth month, most of them recover after the age of 1 year, almost all of them at the age of 2 [10].
There is also a genetic predisposition to GERD. In addition to known GERD symptoms in some families, the incidence of endoscopic esophagitis, hiatus hernia, Barrett’s esophagus, and adenocarcinoma has been shown [11, 12]. Genetic factors which the 9q22-9q31 gene was mapped with infantile gastroesophageal reflux were thought to play a role in the concordance of gastroesophageal reflux in monozygotic twins compared to dizygotic twins [13].
Regurgitation is common in infants. However, typically around 1 year of age, it decreases or completely recovers. Regurgitation usually occurs in late infancy, but there is a weak relationship with GERD that occurs later in life. For example, frequent regurgitation in infancy and GERD in the mother (not the father) are risk factors that increase the occurrence of reflux-related symptoms in childhood [14]. In addition, it has been shown in a recent study that the psychopathological personality traits of the mother negatively affect the baby’s eating behavior and are effective in the development of reflux [15].
In a prospective study, it was found that babies with frequent vomiting more than 90 days in the first 2 years of life showed more adult symptoms of reflux at the age of 8–9 years [16].
The lower esophageal sphincter forms a functional barrier between the stomach and the esophagus and prevents the retrograde passage of stomach contents (acid, pepsin, sometimes bile) to the esophagus [17]. In addition, factors facilitating gastroesophageal reflux in CHD infants are the following:
Antireflux barrier dysfunction
Inadequate clearance mechanism of the esophagus
Impairment of esophageal mucosal resistance
Delay in gastric emptying
The physiological structure formed by the circular muscles, diaphragm cruses, and phrenoesophageal ligament in the esophagogastric junction forms the lower esophageal sphincter (LES) which acts as the primary barrier function for reflux. In addition, the His angle between the esophagus and fundus and the intraabdominal segment of the esophagogastric junction are other components of the antireflux barrier.
The main problem leading to primary gastroesophageal reflux is not the loose of the lower esophageal sphincter; it is known that there are transient relaxations lasting longer than 5 seconds, independent of swallowing [17, 18]. Also some hormones (cholecystokinin, glucagon, vasoactive intestinal peptide (VIP), nitric oxide (NO), dopamine, secretin, and estrogen), drugs (atropine), and nutrients (peppermint, and cocoa) may contribute to GERD by reducing LES pressure [17]. In addition, the presence of stress associated with intensive treatment periods and interventions in complicated CHD patients may lead to increased catecholamine levels. Therefore, it may increase the expression of acid secretion and cause reflux formation [19].
Physiological reflux attacks return the secretions and nutrients that escaped from the stomach to the esophagus for a very short period of time with the effect of normal esophageal peristalsis and gravity. In this way, acid, pepsin, and bile which may cause inflammation when it comes into contact with the esophageal mucosa are removed. However, the acid which has not been cleared from the esophageal mucosa is neutralized by swallowing saliva at the alkaline pH. The aim is to remove the gastric contents that will cause inflammation in the esophageal mucosa. Disruption of these natural mechanisms increases the exposure to reflux [20].
The mucus layer and bicarbonate concentration covering the esophageal epithelium, the connections between epithelial cell membrane and cells, intra- and extracellular buffers, blood flow at the postepithelial level, and acid-base balance in the tissue are the factors that provide the resistance of the esophageal mucosa.
Breast milk is known to have a healing effect on the intestinal mucosa and is well absorbed from the mucosa. However, it cannot provide sufficient energy support alone in infants with CHD. Therefore, high-energy density formulas used in patients receiving nutritional support due to increased energy support cause reflux by delaying gastric emptying. Increased fluid and sodium load, especially in patients with heart failure, increases the existing failure and therefore leads to malnutrition and increased metabolic consumption. In the presence of hepatomegaly and ascites, gastric emptying is delayed due to the compression of the stomach, and this delay causes gastroesophageal reflux [3, 21, 22].
Impaired gastrointestinal motility, the presence of protein-losing enteropathy, and the presence of mucosal atrophy secondary to decreased splanchnic blood flow significantly slow the frequency of food elimination and gastric emptying in infants with CHD [1, 4]. Heart failure, especially in infants with critical congenital heart disease, causes some gastrointestinal problems in addition to the findings of the present disease. It causes intestinal edema, malabsorption, steatorrhea, and protein-losing enteropathy, which cause malnutrition. If the clinical situation cannot be controlled and progresses, it forms the basis for gastroesophageal reflux disease [4, 10, 23].
Animasahun et al. reported in their study that cyanosis was the most common presentation of congenital heart disease in children [14]. In a survey based on the frequency of GERD in CHD infants, cyanosis was found to be more frequent in favor of reflux in the group with cyanotic CHD. However, it was stated that this finding is not specific for reflux in CHD infants because this may also be caused by disease [10].
As a result insufficiency of lower esophageal sphincter, transient LES loosening, deterioration of esophageal dysmotility and esophageal clearance, stress and hormonal factors that increase gastric acidity, as well as delayed emptying of the stomach and using high-energy density formulas play a role in reflux pathophysiology of CHD patients.
A thorough history, a detailed physical examination, and warning symptoms to exclude differential diagnoses are sufficient to make a clinical diagnosis of uncomplicated infant reflux. Regurgitation is the most frequent symptoms of infantile gastroesophageal reflux. In contrast to gastroesophageal reflux that occurs after birth, regurgitation may not be pronounced until the second or third week of life. The typical symptom of physiological reflux is effortless and painless regurgitation which is called “happy spitter” [24]. A detailed nutritional history including the frequent amount of vomiting and regurgitation, feeding type (breastfeeding or formula), turning blue/purple in feeding time, hiccups, and behavior of the baby during feeding should be obtained.
In order to protect the airway from reflux during infancy, the dystonic posture formed by throwing back the baby’s head and sometimes the body can be mistakenly perceived as “seizure.” This condition, known as “Sandifer syndrome,” protects the airways from reflux or reduces abdominal pain caused by acid reflux. This position regresses with antireflux therapy [25, 26].
Unexplained crying attacks and restless behaviors during the day are associated with various conditions in infants. Healthy infants have crying attacks and restlessness on an average between 0 and 2 hours during the day. Excessive crying attacks and increased restlessness expressed by the family should be considered [27]. Feranchak and colleagues showed during video and pH monitoring study that infants had excessive crying attacks during reflux episodes [28].
Regurgitation, vomiting, irritability, and refusal of feeding which are common in infants may be clinical signs of reflux although food allergies that may develop with the same clinical presentation especially in infant children should be included in the differential diagnosis. Remember that vomiting/regurgitation during infancy may be the first sign of systemic infection, sepsis, or many metabolic diseases other than reflux [29]. Alarm symptoms should be questioned, especially in infants with vomiting under 1 year of age (Table 2).
Alarm symptoms in a vomiting baby | |
---|---|
Presence of bile Gastrointestinal bleeding Presence of force vomiting Failure to thrive Presence of blood Abdominal distension | Diarrhea Fever Lethargy Hepatosplenomegaly Bulging fontanel Macro/microcephaly Seizure Suspected genetic/metabolic syndrome |
Alarm symptoms requiring further investigation in infants with regurgitation and vomiting.
The first step in making a definitive diagnosis in gastroesophageal reflux disease is to suspect. The findings should be questioned with careful and detailed history. Anamnesis and physical examination are the basis of the treatment. A specific diagnostic test is not required to diagnose reflux in the presence of recurrent postprandial vomiting with typical history, especially in infants under 1 year of age. However, if symptoms are not typical or if reflux-related complications are suspected, specific methods should be used. Many methods are used for the diagnosis of GER. Each of these methods is important in obtaining different information [10, 30, 31, 32].
The diagnosis of GERD in adults can generally be made by anamnesis and clinical history [33]. Since the complaints are difficult to identify in children under 12 years of age, the history is less reliable [34, 35]. The questionnaire forms are aimed at increasing the reliability of the history rather than making the diagnosis. It is widely accepted surveys that I-GERQ-R developed by Orenstein et al. and GSQ-I and GSQ-YC prepared by Deal et al. could be used in infants with gastroesophageal reflux [10, 35, 36, 37].
An upper gastrointestinal (GI) series are not sensitive and specific for the diagnosis of GERD. Especially in studies comparing esophageal pH studies, sensitivity, specificity, and positive predictive values were found to be very low [38, 39]. Therefore, radiological evaluation is not an appropriate method to confirm or exclude GERD. However, it can be used especially in the evaluation of selected cases with atypical or severe symptoms such as dysphagia or odynophagia. In these patients provides recognition of anatomical disorders such as achalasia, tracheoesophageal fistula, esophageal stricture, hiatal hernia, antral web, pyloric stenosis, intestinal malrotation or peptic strictures [33, 39].
Nuclear scintigraphy is a method of demonstrating the spread of isotope in the esophagus, stomach, and lung by ingestion of technetium-labeled food or food. The potential advantage when compared with the esophageal pH study is that it also shows reflux of nonacidic gastric contents and determines gastric emptying rate [40, 41]. However, its sensitivity and specificity are lower than the pH study. Therefore, its place in the diagnosis of GERD is limited and is not routinely recommended [24, 42].
The important advantages of 24 hr monitoring that can show the relationship between GERD and the patient’s symptoms and allow the baby to be monitored for a long time (night, day, according to the position of the body) in the physiological environment [5]. It is used frequently in the diagnosis of patients with non-gastrointestinal symptoms (such as stridor, cough, hoarseness, chest pain) and in the evaluation of the response to medical treatment in patients with refractory gastroesophageal reflux [43, 44].
24 hr monitoring in esophagitis shows the duration, frequency of acidic reflux, and the degree of pH to which the esophagus is exposed [45]. Since it is a useful method in finding and evaluating reflux, it is widely accepted as the gold standard [43, 46, 47]. However, problems such as breast milk shifting the pH of the stomach to the alkaline side, the amount of reflux cannot be determined, and the pH probe cannot be fully inserted into the lower end of the esophagus are disadvantages of this method [45, 47].
Esophageal endoscopy and biopsy are other valuable methods for the diagnosis of GERD. Endoscopy is used to diagnose complications such as erosive esophagitis, stricture, and Barrett’s esophagus. Esophageal biopsy can be used in the histological diagnosis of reflux esophagitis in the absence of erosion and in the differentiation of allergic and infection-induced esophagitis. It also helps to exclude diseases such as allergic or infectious esophagitis.
The normal appearance of the esophagus on endoscopy does not exclude histopathological esophagitis. Minimal mucosal changes such as erythema and pallor may occur without esophagitis [48]. In one study, 87% of 62 patients with esophagitis had normal or mild mucosal changes endoscopically [49]. There are no eosinophils and neutrophils in the esophageal epithelium in healthy infants and children [50]. Intraepithelial eosinophilia, which is one of the diagnostic criteria for reflux esophagitis, shows that the esophagus is associated with long-term reflux injury [51].
Physiological reflux should be considered in the approach to gastroesophageal reflux for infants with congenital heart disease, and patients should be followed up closely (1–2 month periods). Treatment decisions should be made according to the current clinical situation and follow-up [10]. GERD treatment in infants consists of three main topics.
Conservative measures
Pharmacological treatment
Surgical treatment
Lifestyle changes or regulation may vary according to age in infants, young children, and older children/adolescents. However, what is known is that lifestyle changes are effective in the prevention of GERD in infants as well as in adults. Education of parents and awareness raising of reflux, nutritional and positional changes are involved in the management of physiological reflux [52, 53, 54]. Lifestyle changes in non-pathological reflux should be made before aggressive treatment approaches in infants with CHD such as healthy infants [10].
Antireflux conservative measures recommended during infancy are not to feed the baby in a supine position, to allow time to release gas for decompression of the stomach in the middle of the feeding, to place the baby in an anti-Trendelenburg position at 30° after feeding, and not to allow constipation [54, 55]. Many studies have shown that infants lying in the prone position significantly reduce acid reflux compared to the flat supine position [56]. Although keeping the head higher in the prone position was found to reduce reflux further, no such difference was found in the supine position. Despite its positive effect on prevention of reflux, finding a relationship between prone position and sudden infant death prevented this method to be recommended. However, if the child is still observed, this position can be applied after feeding [57, 58].
Since breast-fed infants are less likely to have GERD than infants who take formula, the importance of breastfeeding should be explained and encouraged them. In this age group, cow’s milk allergy symptoms (regurgitation, vomiting, sometimes refusal to feed, and restlessness) may not be distinguished from physiological reflux [59, 60, 61]. Therefore, in infants with persistent reflux symptoms, cow milk elimination should be performed for 2–3 weeks, and the patient should be followed up. The significant reduction in vomiting and other symptoms during this period and recurrence of symptoms when the diet is impaired suggest cow’s milk allergy [62].
It has been shown that the thickening of formulas and nutrients prevents weight loss by reducing vomiting and regurgitation rather than reflux episodes. For this purpose, adding the products containing thickeners (rice cereal, corn or potato starch, and carob bean gum) to thickeners may reduce the frequency and volume of regurgitation [63].
Pharmacotherapy therapy is not indicated in infants with CHD who has uncomplicated gastroesophageal reflux because physiological reflux tends to improve over time. Pharmacotherapy should be considered in the treatment of gastroesophageal reflux disease in patients who do not respond despite thickened feedings, lifestyle changes, and nutritional recommendations [64, 65].
This group prevents acid secretion by inhibiting Na+ - K+ ATPase, called proton pump, which is responsible for acid secretion in parietal cells. Proton pump inhibitors, which have a stronger acid suppressant and mucosal curative effect than H2RAs, maintain gastric pH above 4 and inhibit food-borne acid secretion. It is also more effective in healing erosive esophagitis. It is also more effective in healing erosive esophagitis. Their efficacy is 24 hours, so they have the advantage of using a single dose per day. Proton pump inhibitors, omeprazole, lansoprazole, and esomeprazole, which can be used in the treatment of infants with gastroesophageal reflux, should be appropriately adjusted: omeprazole (infants: 3–<5 kg, 2.5 mg/day; 5–<10 kg, 5 mg/day; ≥10 kg, 10 mg/day), esomeprazole (infants: 3–<5 kg, 2.5 mg/day; 5–<10 kg, 5 mg/day; ≥10 kg, 10 mg/day), and lansoprazole (infants and children: 1 mg/kg/day [maximum 15 mg/day]) [38, 65].
There are potential risks of acid suppression due to PPI treatment in young children, which can be evaluated in four categories: idiosyncratic reactions, drug-drug interactions, drug-induced hypergastrinemia, and drug-induced hypochlorhydria [66]. The most common idiosyncratic reactions were detected in 14% of children receiving PPI and showed effects such as headache, diarrhea, constipation, and nausea. They can be improved by reducing the dose or replacing it with a different preparation [67, 68].
The mechanism of action of H2 receptor antagonists, which is mainly used in children under 1 year of age, is to reduce acid secretion by inhibiting histamine 2 receptors in gastric parietal cells [53, 66]. Cimetidine, ranitidine, nizatidine, and famotidine are drugs in this group used in the treatment of reflux esophagitis. The frequency and dosage of use of these drugs in children are as follows: cimetidine (children: 30–40 mg/kg/day divided into four doses); ranitidine (children: 5–10 mg/kg/day divided into two to three doses), which is the most preferred drug in the treatment of infants and children; famotidine (children: 1 mg/kg/day divided into two doses); and nizatidine (children: 10–20 mg/kg/day divided into two doses) [38]. Although H2 receptor antagonists reduce pepsin and gastric acid secretion, they do not reduce the frequency of gastroesophageal reflux and are less effective than proton pump inhibitors.
If they are used in reflux treatment for a long time (>14 days), tachyphylaxis and hypochlorhydria which can lead to bacterial colonization may occur. Common adverse events include increased risk of enteritis infection, especially
The mechanism of action of antacids containing a combination of magnesium, aluminum hydroxide, or calcium carbonate is shown by neutralizing gastric acid. The use of aluminum-containing antacids in infants can cause osteopenia, microcytic anemia, and neurotoxicity, so it is not suitable for use in infants [72].
Alginate and sucralfate are used as surface protection agents in reflux treatment [24, 73]. According to the results of the meta-analysis in 2017, alginates have been shown to be less effective than H2 receptor antagonists and proton pump inhibitors. Alginates are water-soluble salts of alginic acid and act as protective agents for the mucosal surface. Sodium and magnesium alginate preparations have been shown to significantly reduce vomiting symptoms even in preterm and term infants by pH/MMI studies [74]. Sucralfate, composed of sucrose sulfate aluminum, converts into a gel form with gastric acid and adheres to the mucosa, which is exposed to peptic erosion. Its efficacy has been shown in children in a limited number of studies, but there are not enough studies in terms of its efficacy and side effects and safety [75, 76].
Metoclopramide, cisapride, domperidone, and baclofen are among the drugs in this group and can be used in the treatment of gastroesophageal reflux disease. However, cohort studies have shown that prokinetic drugs are not helpful in treatment of reflux [77]. In addition, these agents are not recommended for use in infants and children as they have important side effects such as lethargy, irritability, gynecomastia, galactorrhea, ventricular arrhythmias, QT prolongation, extrapyramidal reactions, and persistent tardive dyskinesia [78, 79].
Surgical procedures such as fundoplication (Nissen) are rarely performed under 1 year of age for indications such as recurrent pneumonia and life-threatening reactive airway disease. It is a method that can be applied in the case of cardiopulmonary insufficiency, which is unresponsive to medical treatment in patients with CHD [80, 81].
The authors disclose that they received no financial support for this work. The authors declare no conflict of interest.
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These physiological events occur smoothly in normal healthy individual and/or under normal conditions. However, in certain cases, these molecular events are retarded resulting in hard-to-heal or chronic wounds arising from several factors such as poor venous return, underlying physiological or metabolic conditions such as diabetes as well as external factors such as poor nutrition. In most cases, such wounds are infected and infection also presents as another complicating phenomenon which triggers inflammatory reactions, therefore delaying wound healing. There has therefore been recent interests and significant efforts in preventing and actively treating wound infections by directly targeting infection causative agents through direct application of antimicrobial agents either alone or loaded into dressings (medicated). These have the advantage of overcoming challenges such as poor circulation in diabetic and leg ulcers when administered systemically and also require lower amounts to be applied compared to that required via oral or iv administration. This chapter will review and evaluate various antimicrobial agents used to target infected wounds, the means of delivery, and current state of the art, including commercially available dressings. Data sources will include mainly peer-reviewed literature, clinical trials and reports, patents as well as government reports where available.",book:{id:"5290",slug:"wound-healing-new-insights-into-ancient-challenges",title:"Wound Healing",fullTitle:"Wound Healing - New insights into Ancient Challenges"},signatures:"Omar Sarheed, Asif Ahmed, Douha Shouqair and Joshua Boateng",authors:[{id:"183108",title:"Dr.",name:"Joshua",middleName:null,surname:"Boateng",slug:"joshua-boateng",fullName:"Joshua Boateng"},{id:"183399",title:"Dr.",name:"Omar",middleName:null,surname:"Sarheed",slug:"omar-sarheed",fullName:"Omar Sarheed"},{id:"188082",title:"Mr.",name:"Asif",middleName:null,surname:"Ahmed",slug:"asif-ahmed",fullName:"Asif Ahmed"},{id:"188083",title:"Ms.",name:"Douha",middleName:null,surname:"Shouqair",slug:"douha-shouqair",fullName:"Douha Shouqair"}]},{id:"51825",doi:"10.5772/64611",title:"Roles of Matrix Metalloproteinases in Cutaneous Wound Healing",slug:"roles-of-matrix-metalloproteinases-in-cutaneous-wound-healing",totalDownloads:3629,totalCrossrefCites:20,totalDimensionsCites:39,abstract:"Wound healing is a complex process that consists of hemostasis and inflammation, angiogenesis, re-epithelialization, and tissue remodeling. Matrix metalloproteinases (MMPs) play important roles in wound healing, and their dysregulation leads to prolonged inflammation and delayed wound healing. There are 24 MMPs in humans, and each MMP exists in three forms, of which only the active MMPs play a role in the pathology or repair of wounds. The current methodology does not distinguish between the three forms of MMPs, making it challenging to investigate the roles of MMPs in pathology and wound repair. We used a novel MMP-inhibitor-tethered affinity resin that binds only the active form of MMPs, from which we identified and quantified active MMP-8 and active MMP-9 in a murine diabetic model with delayed wound healing. We showed that up-regulation of active MMP-9 plays a detrimental role whereas active MMP-8 is involved in repairing the wound in diabetic mice. These studies identified MMP-9 as a novel target for therapeutic intervention in the treatment of chronic wounds. A selective inhibitor of MMP-9 that leaves MMP-8 unaffected would provide the most effective therapy and represents a promising strategy for therapeutic intervention in the treatment of diabetic foot ulcers.",book:{id:"5290",slug:"wound-healing-new-insights-into-ancient-challenges",title:"Wound Healing",fullTitle:"Wound Healing - New insights into Ancient Challenges"},signatures:"Trung T. Nguyen, Shahriar Mobashery and Mayland Chang",authors:[{id:"183405",title:"Prof.",name:"Mayland",middleName:null,surname:"Chang",slug:"mayland-chang",fullName:"Mayland Chang"},{id:"191152",title:"Mr.",name:"Trung",middleName:null,surname:"Nguyen",slug:"trung-nguyen",fullName:"Trung Nguyen"},{id:"191153",title:"Prof.",name:"Shahriar",middleName:null,surname:"Mobashery",slug:"shahriar-mobashery",fullName:"Shahriar Mobashery"}]},{id:"63675",doi:"10.5772/intechopen.81208",title:"Wound Healing: Contributions from Plant Secondary Metabolite Antioxidants",slug:"wound-healing-contributions-from-plant-secondary-metabolite-antioxidants",totalDownloads:1331,totalCrossrefCites:7,totalDimensionsCites:20,abstract:"Plants by their genetic makeup possess an innate ability to synthesize a wide variety of phytochemicals that help them to perform their normal physiological functions and/or to protect themselves from microbial pathogens and animal herbivores. The synthesis of these phytochemicals presents the plants their natural tendency to respond to environmental stress conditions. These phytochemicals are classified either as primary or secondary metabolites. The secondary metabolites have been identified in plants as alkaloids, terpenoids, phenolics, anthraquinones, and triterpenes. These plant-based compounds are believed to have diverse medicinal properties including antioxidant properties. Plants have therefore been a potential source of antioxidants which have received a great deal of attention since increased oxidative stress has been identified as a major causative factor in the development and progression of several life-threatening diseases, including neurodegenerative and cardiovascular diseases and wound infection. Consequently, many medicinal plants have been cited and known to effect wound healing and antioxidant properties. This chapter briefly reviews antioxidant properties of medicinal plants to highlight the important roles medicinal plants play in wound healing.",book:{id:"7046",slug:"wound-healing-current-perspectives",title:"Wound Healing",fullTitle:"Wound Healing - Current Perspectives"},signatures:"Victor Y.A. Barku",authors:[{id:"261027",title:"Prof.",name:"Victor Y. A.",middleName:null,surname:"Barku",slug:"victor-y.-a.-barku",fullName:"Victor Y. A. Barku"}]},{id:"66793",doi:"10.5772/intechopen.85020",title:"The Impact of Biofilm Formation on Wound Healing",slug:"the-impact-of-biofilm-formation-on-wound-healing",totalDownloads:1434,totalCrossrefCites:7,totalDimensionsCites:16,abstract:"Chronic wounds represent an important challenge for wound care and are universally colonized by bacteria. These bacteria can form biofilm as a survival mechanism that confers the ability to resist environmental stressors and antimicrobials due to a variety of reasons, including low metabolic activity. Additionally, the exopolymeric substance (EPS) contained in biofilm acts as a mechanical barrier to immune system cells, leading to collateral damage in the surrounding tissue as well as chronic inflammation, which eventually will delay healing of the wound. This chapter will discuss current knowledge on biofilm formation, its presence in acute and chronic wounds, how biofilm affects antibiotic resistance and tolerance, as well as the wound healing process. We will also discuss proposed methods to eliminate biofilm and improve wound healing despite its presence, including basic science and clinical studies regarding these matters.",book:{id:"7046",slug:"wound-healing-current-perspectives",title:"Wound Healing",fullTitle:"Wound Healing - Current Perspectives"},signatures:"Rafael A. Mendoza, Ji-Cheng Hsieh and Robert D. Galiano",authors:[{id:"253607",title:"M.D.",name:"Rafael",middleName:null,surname:"Mendoza",slug:"rafael-mendoza",fullName:"Rafael Mendoza"},{id:"254018",title:"Dr.",name:"Robert",middleName:null,surname:"Galiano",slug:"robert-galiano",fullName:"Robert Galiano"},{id:"271116",title:"Mr.",name:"Ji-Cheng",middleName:null,surname:"Hsieh",slug:"ji-cheng-hsieh",fullName:"Ji-Cheng Hsieh"}]},{id:"63086",doi:"10.5772/intechopen.80215",title:"Medicinal Plants in Wound Healing",slug:"medicinal-plants-in-wound-healing",totalDownloads:2901,totalCrossrefCites:7,totalDimensionsCites:15,abstract:"Wound healing process is known as interdependent cellular and biochemical stages which are in trying to improve the wound. Wound healing can be defined as stages which is done by body and delayed in wound healing increases chance of microbial infection. Improved wound healing process can be performed by shortening the time needed for healing or lowering the inappropriate happens. The drugs were locally or systemically administrated in order to help wound healing. Antibiotics, antiseptics, desloughing agents, extracts, etc. have been used in order to wound healing. Some synthetic drugs are faced with limitations because of their side effects. Plants or combinations derived from plants are needed to investigate identify and formulate for treatment and management of wound healing. There is increasing interest to use the medicinal plants in wound healing because of lower side effects and management of wounds over the years. Studies have shown that medicinal plants improve wound healing in diabetic, infected and opened wounds. The different mechanisms have been reported to improve the wound healing by medicinal plants. In this chapter, some medicinal plants and the reported mechanisms will be discussed.",book:{id:"7046",slug:"wound-healing-current-perspectives",title:"Wound Healing",fullTitle:"Wound Healing - Current Perspectives"},signatures:"Mohammad Reza Farahpour",authors:[{id:"253340",title:"Prof.",name:"Mohammadreza",middleName:null,surname:"Farahpour",slug:"mohammadreza-farahpour",fullName:"Mohammadreza Farahpour"}]}],mostDownloadedChaptersLast30Days:[{id:"55736",title:"Haemodynamic Monitoring in the Intensive Care Unit",slug:"haemodynamic-monitoring-in-the-intensive-care-unit",totalDownloads:3369,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Monitoring is a cognitive aid that allows clinicians to detect the nature and extent of pathology and helps assessment of response to therapy. The cardiovascular system is the most commonly monitored organ system in the critical care setting. It helps identify the presence and nature of shock and guides response to resuscitation by detection of cardiac rate and rhythm, evaluation of volume state, cardiac contractility and systemic vascular resistance. Newer technologies allow greater assessment of oxygen delivery to vulnerable tissues. We discuss the nature, history, modalities and interpretation of the most commonly available haemodynamic monitoring methods in clinical use currently.",book:{id:"5756",slug:"intensive-care",title:"Intensive Care",fullTitle:"Intensive Care"},signatures:"Mainak Majumdar",authors:[{id:"86678",title:"Dr.",name:"Mainak",middleName:null,surname:"Majumdar",slug:"mainak-majumdar",fullName:"Mainak Majumdar"}]},{id:"51825",title:"Roles of Matrix Metalloproteinases in Cutaneous Wound Healing",slug:"roles-of-matrix-metalloproteinases-in-cutaneous-wound-healing",totalDownloads:3628,totalCrossrefCites:20,totalDimensionsCites:37,abstract:"Wound healing is a complex process that consists of hemostasis and inflammation, angiogenesis, re-epithelialization, and tissue remodeling. Matrix metalloproteinases (MMPs) play important roles in wound healing, and their dysregulation leads to prolonged inflammation and delayed wound healing. There are 24 MMPs in humans, and each MMP exists in three forms, of which only the active MMPs play a role in the pathology or repair of wounds. The current methodology does not distinguish between the three forms of MMPs, making it challenging to investigate the roles of MMPs in pathology and wound repair. We used a novel MMP-inhibitor-tethered affinity resin that binds only the active form of MMPs, from which we identified and quantified active MMP-8 and active MMP-9 in a murine diabetic model with delayed wound healing. We showed that up-regulation of active MMP-9 plays a detrimental role whereas active MMP-8 is involved in repairing the wound in diabetic mice. These studies identified MMP-9 as a novel target for therapeutic intervention in the treatment of chronic wounds. A selective inhibitor of MMP-9 that leaves MMP-8 unaffected would provide the most effective therapy and represents a promising strategy for therapeutic intervention in the treatment of diabetic foot ulcers.",book:{id:"5290",slug:"wound-healing-new-insights-into-ancient-challenges",title:"Wound Healing",fullTitle:"Wound Healing - New insights into Ancient Challenges"},signatures:"Trung T. Nguyen, Shahriar Mobashery and Mayland Chang",authors:[{id:"183405",title:"Prof.",name:"Mayland",middleName:null,surname:"Chang",slug:"mayland-chang",fullName:"Mayland Chang"},{id:"191152",title:"Mr.",name:"Trung",middleName:null,surname:"Nguyen",slug:"trung-nguyen",fullName:"Trung Nguyen"},{id:"191153",title:"Prof.",name:"Shahriar",middleName:null,surname:"Mobashery",slug:"shahriar-mobashery",fullName:"Shahriar Mobashery"}]},{id:"63086",title:"Medicinal Plants in Wound Healing",slug:"medicinal-plants-in-wound-healing",totalDownloads:2898,totalCrossrefCites:7,totalDimensionsCites:15,abstract:"Wound healing process is known as interdependent cellular and biochemical stages which are in trying to improve the wound. Wound healing can be defined as stages which is done by body and delayed in wound healing increases chance of microbial infection. Improved wound healing process can be performed by shortening the time needed for healing or lowering the inappropriate happens. The drugs were locally or systemically administrated in order to help wound healing. Antibiotics, antiseptics, desloughing agents, extracts, etc. have been used in order to wound healing. Some synthetic drugs are faced with limitations because of their side effects. Plants or combinations derived from plants are needed to investigate identify and formulate for treatment and management of wound healing. There is increasing interest to use the medicinal plants in wound healing because of lower side effects and management of wounds over the years. Studies have shown that medicinal plants improve wound healing in diabetic, infected and opened wounds. The different mechanisms have been reported to improve the wound healing by medicinal plants. In this chapter, some medicinal plants and the reported mechanisms will be discussed.",book:{id:"7046",slug:"wound-healing-current-perspectives",title:"Wound Healing",fullTitle:"Wound Healing - Current Perspectives"},signatures:"Mohammad Reza Farahpour",authors:[{id:"253340",title:"Prof.",name:"Mohammadreza",middleName:null,surname:"Farahpour",slug:"mohammadreza-farahpour",fullName:"Mohammadreza Farahpour"}]},{id:"67217",title:"Nursing Implications in the ECMO Patient",slug:"nursing-implications-in-the-ecmo-patient",totalDownloads:2528,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Effective care and positive outcomes of the extracorporeal membrane oxygenation (ECMO) patient necessitate optimal interdisciplinary management from the healthcare team, including expert care from specially trained registered nurses (RNs). It is incumbent upon the RN caring for the ECMO patient to excel in both time management and assessment skills, as this population often demands care delivery at the pinnacle of intensive care unit (ICU) acuity. Astute and nuanced monitoring of neurological status, bleeding risk with potential (often massive) transfusions, poor hemodynamics, and integrity of the ECMO pump itself are only the few specialized areas of focus that must share priority with traditional nursing considerations involving the critically ill, such as prevention of pressure injuries and bloodstream infections. These high-intensity medical foci must be balanced with ethical considerations, as the ultimate goal of returning the patient to their normal life is not always possible. These demands highlight the dynamic proficiency of the RN caring for the ECMO patient. The following chapter will highlight the importance of specialized nursing care in the critically ill patient supported with ECMO.",book:{id:"7878",slug:"advances-in-extracorporeal-membrane-oxygenation-volume-3",title:"Advances in Extracorporeal Membrane Oxygenation",fullTitle:"Advances in Extracorporeal Membrane Oxygenation - Volume 3"},signatures:"Alex Botsch, Elizabeth Protain, Amanda R. Smith and Ryan Szilagyi",authors:[{id:"298623",title:"Mr.",name:"Alexander",middleName:null,surname:"Botsch",slug:"alexander-botsch",fullName:"Alexander Botsch"}]},{id:"66239",title:"Echocardiography Evaluation in ECMO Patients",slug:"echocardiography-evaluation-in-ecmo-patients",totalDownloads:2184,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Extracorporeal membrane oxygenation (ECMO) is a special form of organ support for selected cases of cardiovascular and severe respiratory failure. Echocardiography is a diagnostic and monitoring tool widely used in all aspects of ECMO support. The pathophysiology of ECMO, and its distinct effects on cardiorespiratory physiology, requires an echocardiographer with high skills to understand the interaction between the ECMO and the patient. In this chapter, we present the main application of echocardiography in ECMO patients and some general concepts on the ECMO working. ECMO, such as the standard cardiopulmonary bypass employed in cardiac surgery, V-V (veno-venous), can support the insufficient respiratory system by oxygenating and removing carbon dioxide from the blood. VA-ECMO (venous-arterial) can support haemodynamics by providing mechanical circulatory assistance. Today, ECMO can be used as bridge to decision, waiting for the development of the clinical conditions to support with other devices the evolution of cardiorespiratory failure or stop the assistance. Echocardiography (transthoracic (TTE) or transoesophageal (TOE)) can be used primarily to take decisions regarding appropriateness of ECMO support, therefore to control cannula insertion and confirm final position, to modify number and position of the cannulae in case of malfunctioning of these, and, finally, to assess clinical progress and suitability for weaning from ECMO.",book:{id:"7878",slug:"advances-in-extracorporeal-membrane-oxygenation-volume-3",title:"Advances in Extracorporeal Membrane Oxygenation",fullTitle:"Advances in Extracorporeal Membrane Oxygenation - Volume 3"},signatures:"Luigi Tritapepe, Ernesto Greco and Carlo Gaudio",authors:[{id:"284893",title:"Prof.",name:"Luigi",middleName:null,surname:"Tritapepe",slug:"luigi-tritapepe",fullName:"Luigi Tritapepe"},{id:"294005",title:"Prof.",name:"Ernesto",middleName:null,surname:"Greco",slug:"ernesto-greco",fullName:"Ernesto Greco"},{id:"294006",title:"Prof.",name:"Carlo",middleName:null,surname:"Gaudio",slug:"carlo-gaudio",fullName:"Carlo Gaudio"}]}],onlineFirstChaptersFilter:{topicId:"173",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{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"}}}},{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"}}}}]},series:{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:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:33,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-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"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:42,paginationItems:[{id:"82914",title:"Glance on the Critical Role of IL-23 Receptor Gene Variations in Inflammation-Induced Carcinogenesis",doi:"10.5772/intechopen.105049",signatures:"Mohammed El-Gedamy",slug:"glance-on-the-critical-role-of-il-23-receptor-gene-variations-in-inflammation-induced-carcinogenesis",totalDownloads:15,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}},{id:"82875",title:"Lipidomics as a Tool in the Diagnosis and Clinical Therapy",doi:"10.5772/intechopen.105857",signatures:"María Elizbeth Alvarez Sánchez, Erick Nolasco Ontiveros, Rodrigo Arreola, Adriana Montserrat Espinosa González, Ana María García Bores, Roberto Eduardo López Urrutia, Ignacio Peñalosa Castro, María del Socorro Sánchez Correa and Edgar Antonio Estrella Parra",slug:"lipidomics-as-a-tool-in-the-diagnosis-and-clinical-therapy",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82440",title:"Lipid Metabolism and Associated Molecular Signaling Events in Autoimmune Disease",doi:"10.5772/intechopen.105746",signatures:"Mohan Vanditha, Sonu Das and Mathew John",slug:"lipid-metabolism-and-associated-molecular-signaling-events-in-autoimmune-disease",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82483",title:"Oxidative Stress in Cardiovascular Diseases",doi:"10.5772/intechopen.105891",signatures:"Laura Mourino-Alvarez, Tamara Sastre-Oliva, Nerea Corbacho-Alonso and Maria G. Barderas",slug:"oxidative-stress-in-cardiovascular-diseases",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Importance of Oxidative Stress and Antioxidant System in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/11671.jpg",subseries:{id:"15",title:"Chemical Biology"}}}]},overviewPagePublishedBooks:{paginationCount:33,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science\nand Technology from the Department of Chemistry, National\nUniversity of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013.\nShe relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the\nNational Institute of Fundamental Studies from April 2013 to\nOctober 2016. She was a senior lecturer on a temporary basis at the Department of\nFood Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is\ncurrently Deputy Principal of the Australian College of Business and Technology –\nKandy Campus, Sri Lanka. 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