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\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
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\\n\\nInfectious Diseases, ISSN 2631-6188
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\\n\\nNote: Edited in October 2021
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\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
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\n\nNote: Edited in October 2021
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As such, SAW based micro sensors, actuators and communication electronic devices are well known applications of SAW technology. For example, SAW based passive micro sensors are capable of measuring physical properties such as temperature, pressure, variation in chemical properties, and SAW based communication devices perform a range of signal processing functions, such as delay lines, filters, resonators, pulse compressors, and convolvers. In recent decades, SAW based low-powered actuators and microfluidic devices have significantly added a new dimension to SAW technology. This book consists of 20 exciting chapters composed by researchers and engineers active in the field of SAW technology, biomedical and other related engineering disciplines. The topics range from basic SAW theory, materials and phenomena to advanced applications such as sensors actuators, and communication systems. As such, in addition to theoretical analysis and numerical modelling such as Finite Element Modelling (FEM) and Finite Difference Methods (FDM) of SAW devices, SAW based actuators and micro motors, and SAW based micro sensors are some of the exciting applications presented in this book. 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In METAVIR, only interface hepatitis and lobular necrosis determine the grade of activity, while in Ishak, portal infiltrate and confluent necrosis are included with the two previous parameters. Confluent necrosis is very rare in chronic hepatitis C, that in most patients the actual score limit is 12 instead of 18 (Ishak score), that mostly underscore the actual necroinflammation. Also, portal inflammatory infiltrate may reflect immunological response rather than necroinflammation. This may explain the discrepancy between enzyme elevation and necroinflammatory score as determined by Ishak score (modified HAI) in assessment of chronic hepatitis C biopsy specimens. On the other hand, no study has clearly tested such discrepancy in applying METAVIR.
Some of the terminologies applied in METAVIR are in need of revision or declaration. For example; the term “septa” is used to mean actual fibrous bridges, while in Ishak score both terms; septa and bridges; are applied by different meaning. Ishak et al, 1995, in their system, applied both terminologies (septa & bridges), however in completely different meaning. Septa, means expansion of portal tract edges without formation of bridges or actual connection between portal areas or portal area and central vein (1). On the other hand, the term bridge was applied to actual fibrous connection between two portal areas or portal area and central vein. Because of this confusion, some studies comparing both scoring systems have committed some mistakes.
Some studies have compared both Ishak and METAVIR systems, but they included small number of patients or included hepatitis B and hepatitis C. Therefore, the objectives of this chapter are:
Revision of histological grading and staging in chronic hepatitis C.
Clarification of the METAVIR terminology for future applications.
Establishing an Ishak to METAVIR fibrosis score conversion table.
The new approach to classify chronic hepatitis C involves three separate considerations. The first is a comment on etiology. Frequently, this cannot be determined on the basis of histological appearance alone, and the diagnosis is made on the basis of other laboratory investigations. The second assessment relates to the severity and distribution of necroinflammatory activity (histological “grade”). Thirdly, an attempt should be made to assess the degree of fibrosis (histological “stage”) (2).
Inflammatory activity in the liver can be divided into two main components. The first involves portal tracts (portal hepatitis) with variable extension into the adjacent periportal regions (periportal hepatitis). The second involves liver parenchyma (lobular hepatitis). These different patterns of inflammation are probably related to the different pathways whereby circulating inflammatory cells can gain access to the liver (3).
Inflammatory cells migrating across the endothelium of portal vessels pass into portal connective tissue which is rich in antigen presenting dendritic cells. A predominantly portal inflammatory infiltrate is one of the characteristic histological features of chronic hepatitis. However it should kept in mind that portal hepatitis by itself does not necessarily indicate a diagnosis of chronic hepatitis. Mild portal inflammatory changes, indistinguishable from low-grade chronic viral hepatitis, can be seen in a variety of conditions including systemic illness, nearby space-occupying lesion and even in some livers, which otherwise would be considered as normal. Furthermore, a predominantly portal inflammatory infiltrate is sometimes present in cases of acute viral hepatitis, without any implication of chronicity (4).
Considerable attention has focused on the extension of portal inflammatory cells into the adjacent liver parenchyma associated with destruction of the limiting plate and damage to periportal hepatocytes (interface hepatitis) (5).
Inflammatory cells migrating across the endothelium of hepatic sinusoids can gain direct access to the liver parenchyma causing lobular inflammation. Typically this presents as “spotty” inflammation dispersed randomly throughout the liver parenchyma. In some cases inflammatory changes are more pronounced in perivenular (acinar zone 3) region and are associated with areas of confluent necrosis. When areas of zone 3 necrosis link vascular structures, in particular portal tracts to hepatic venules, the term “bridging necrosis” is used. Rarely in severe cases, there may be complete destruction of hepatocytes in one or more acini (panacinar necrosis or multiacinar necrosis) (6).
The main purpose in identifying different patterns of necroinflammatory activity is that these may have different functional and prognostic significance in terms of progression to fibrosis and ultimately cirrhosis.
Interface hepatitis has long been considered as an important lesion in the evolution of chronic hepatitis to cirrhosis. In the original classification proposed by De Groote et al, 1968 (7), chronic persistent hepatitis (portal inflammation without piecemeal necrosis) was thought to have a favorable prognosis, whereas chronic active hepatitis (portal inflammation with piecemeal necrosis) was regarded as having substantial risk for progression to cirrhosis. Interface hepatitis with associated periportal liver cell loss and collapse of the reticulin framework can readily be visualized as a mechanism for the development of periportal fibrosis (2).
There have been few attempts to validate this lesion as a prognostic feature in serial biopsies. One study showed that the presence of interface hepatitis in initial biopsies from patients with chronic hepatitis correlate with subsequent development of cirrhosis (8). Two other studies have demonstrated an association between the severities of necroinflammatory activity (including interface hepatitis as a major component) in an initial biopsy and the development of fibrosis or cirrhosis in follow up biopsies (9).
Bursts of lobular inflammatory activity are thought to be particularly important in pathogenesis of chronic hepatitis C infection, where progression to cirrhosis is common despite the lack of interface activity (10). For these reasons it has been suggested that the pattern and severity of lobular inflammation should be taken in account in assessing the outcome in cases of chronic hepatitis (11).
In the majority of cases fibrosis begins as expansion of portal tracts occurring in association of interface hepatitis. As fibrosis progresses, there is formation of septa with the development of portal-portal linkage. Eventually hepatocyte nodules are completely surrounded by fibrous tissue. Development of established cirrhosis usually takes several years. However, in some situations (e.g. viral hepatitis recurring following liver transplantation) cirrhosis can develop much more quickly. Parenchymal fibrosis can also occur in presence of lobular inflammation, particularly in areas of bridging necrosis (12). This may be responsible of for formation of portal-central septa, which have been regarded as more significant in the development of cirrhosis than portal-portal linkages (13).
The work of the two decades preceding the Knodell HAI provided the foundation for our current understanding of the histopathology of chronic hepatitis. Early descriptions and classifications focused on differentiating acute and chronic hepatitis and on lesions that predicted disease progression. The first histological classification, which was published by De Groote in 1968 (7), codified the terminology,
Popper and Schaffner (1971) (14) affirmed the value of liver biopsy for diagnosis and prognosis and recommended use of “topographic” descriptors for hepatitis, that is,
The explosion of scientific information on viral and non-viral hepatitis in the last decades of the 20th century led pathologists to question the conventional nomenclature of chronic persistent and chronic active (aggressive) hepatitis because of a growing understanding that etiology may be more significant than morphological classification in predicting the natural history of liver disease. This shift in thinking was driven largely by the apparent dissociation between the mild histology of non A-non B hepatitis (hepatitis C) and its progressive clinical course. It was found that, in many cases, the lesions of this form of viral hepatitis fell between those described as chronic persistent and chronic active hepatitis and could not be clearly categorized (15).
The lack of severe piecemeal necrosis and confluent lobular necrosis resulted in the diagnosis of chronic persistent hepatitis, implying a benign course. At the same time, the lobular component was being recognized as more significant than portal lesions with respect to disease progression. Also, confluent necrosis, which when present in severe autoimmune hepatitis and hepatitis B confers an ominous prognosis, is uncommon in hepatitis C, and yet progression to fibrosis or cirrhosis occurs in all 3 diseases (2).
For a system to be effective in every day diagnostic practice, it must be simple to understand, simple to apply, communicate effectively to the treating clinician, and clinically relevant (16). The system that is most appropriate for clinical practice may not be the most informative for investigative work (17).
This scheme represents an extension of the original Knodell system, with a number of minor modifications. Firstly, a continuous scale is used for scoring each of the features assessed. Secondly, necroinflammatory activity and fibrosis are considered as separate categories. Thirdly, confluent necrosis is separated from periportal hepatitis and is included as a separate category of necroinflammatory activity. The term interface hepatitis was used in place of ‘‘piecemeal necrosis,’’ to reflect the growing evidence that apoptosis, not necrosis, occurs at the limiting plate.
The fibrosis scores are defined as follows: 0, no fibrosis; 1, fibrous expansion of some portal areas, with or without short fibrous septa; 2, fibrous expansion of most portal areas, with or without short fibrous septa; 3, fibrous expansion of most portal areas with occasional portal to portal bridging; 4, fibrous expansion of most portal areas with marked bridging (portal to portal as well as portal to central); 5, marked bridging with occasional nodules (incomplete cirrhosis); 6, cirrhosis, probable or definite (1).
Difficulties with the Ishak system have been noted. Use of the X10 objective for the evaluation of necroinflammatory foci raises concerns of reproducibility, because the size of the field may vary among microscopes. In addition, definitions of a “focus” of lymphocytic aggregates, apoptotic hepatocytes, or confluent necrosis may vary among pathologists (18).
The French METAVIR Cooperative Study Group stated that another possible approach for grading the necroinflammatory activity is to consider that periportal and intra-lobular necroinflammatory lesions are related to the same pathologic mechanism and that they must be globally assessed. A panel decided to define activity according to its potential predictive value for the occurrence of liver fibrosis. They chose to include in algorithm only two features (piecemeal necrosis and lobular necrosis) (19).
Portal inflammation was excluded from the algorithm, because this feature is a prerequisite for the definition of chronic hepatitis even without activity. Furthermore they observed a strong correlation with piecemeal necrosis, making these two features redundant criteria.
Piecemeal necrosis was chosen as the first decision criterion because of its proven potential value in other types of chronic hepatitis. It was then suspected that another feature, lobular necrosis, was of major importance in the prediction of liver fibrosis. It is believed that aggravation of chronic hepatitis C occurs through a burst of lobular necrosis, a lesion that is frequently present in chronic hepatitis C. The two lesions were therefore combined to propose a simple algorithm that defined activity.
In several existing classifications, the degree of piecemeal and lobular necrosis was independently assessed and their scores then added, thus giving each of these two lesions the same weight in the definition of activity. The METAVIR system included both piecemeal necrosis and lobular necrosis in the definition of activity, but with different values. The rationale for overweighting the piecemeal necrosis item by comparison with lobular necrosis is that piecemeal necrosis is the major discriminating factor used to grade activity, as shown by stepwise discriminate analysis.
The fibrosis scores are defined as follows: F0, no fibrosis; F1, portal fibrosis without septa; F2, portal fibrosis with rare septa; F3 numerous septa without cirrhosis; F4, cirrhosis (19).
The METAVIR system has the advantage of simplicity, reproducibility and application to a large number of biopsies (20). This score is composed of a two-letter and two-number coding system: A= histological activity and F= fibrosis (Table 2).
The METAVIR System.
There are a number of problems which apply to all the scoring systems currently in use.
Lack of scientific validation:
A fundamental problem with histological “scoring” is that the numbers which are generated do not represent measurement of continuous variable. Instead, they simply represent different categories of severity. This contrasts with biochemical measurements, for example, serum transaminases, for which a true numerical progression can be more readily justified (21).
Observer variation:
There are problems in obtaining reproducible results, even when scoring system is applied by experts in the field of liver pathology. In general, better reproducibility has been obtained for scoring fibrosis than for scoring inflammatory activity. This is probably due to imprecise terminology which is used in individual histological features. Terms such as “occasional”, “some”, or “mild’, “moderate and “severe” are used without defining precisely what these mean (22).
Sampling Variation:
Much of the knowledge regarding this problem has come from the examination of hepatectomy specimens obtained at liver transplantation. Sampling variation exist, both for the grade of necroinflammatory activity and for the stage of fibrosis. For example, small areas of multiacinar necrosis can often be found in a liver which otherwise show a relatively inactive cirrhosis. These areas are typically subcapsular in location but may be also present elsewhere. If a needle biopsy is taken from one of these areas, a “falsely high” inflammatory score may be obtained. Chronic viral hepatitis may affect the liver uniformly, but considerable variation in the severity of fibrosis can be seen when whole liver are available for examination (2).
Etiological considerations:
The scoring systems currently in common use incorporate histological features which may be seen in all types of chronic hepatitis. However, different types of chronic hepatitis have marked differences in natural history and response to therapy. These differences in behavior may be reflected by different patterns of histological damage. For example, ballooning, rosetting, and giant cell transformation may be regarded as signs of severe damage in cases of autoimmune hepatitis, even in the absence of conspicuous inflammatory activity. Direct cytopathic damage (e.g. ballooning or fatty change) may be important in the pathogenesis of fibrosis in chronic hepatitis C infection (2).
Terminology in METAVIR as regard fibrosis stage assessment is not clear and confusing; with narrow range (F0-F4). F3 indicates numerous septa, however, in practical application early (developing) cirrhosis is included too, irrespective of being not described in the score details. On the other hand, Ishak fibrosis score is wider (0-6), more sensitive, as well clearly separate incomplete (developing, early) cirrhosis from established cirrhosis (1,20,23).
Rozario and Ramakrishna, 2003(24) have built their analysis, tables and comparison on the inaccurate idea that F2 of METAVIR (rare septa) is equal to stage 2 of Ishak. However, the correct is that, F1 stage of METAVIR is equal to stages 1&2 of Ishak, and F2 of METAVIR is equal to stage 3 of Ishak (occasional bridging fibrosis). This resulted in a defect that may affect the idea and the conclusion (4).
Applying semi-quantitative terminology reflecting grades of necroinflammatory injury as recorded by Ishak may underestimate the severity of these changes. In Ishak scoring, 6 points out of the 18 are related to confluent necrosis, which is a rare event in chronic hepatitis C.
Elzbieta and Marek, 2005 (25) reported that, the comparison of three histological scoring systems used to evaluate chronic hepatitis (Batts and Ludwig, Ishak
Goodman in his review 2007(26), considered Ishak stage 5 (incomplete cirrhosis) to be included in METAVIR F4 stage, that is different from the opinion of Bedossa and others of METAVIR group. This is a pitfall that may affect the results of some research studies.
In assessment of regression of fibrosis after autoimmune hepatitis treatment, Abdalla et al, 2009 have reported higher sensitivity of Ishak compared with METAVIR in detection of fibrosis regression (27). They also found statistically higher sensitivity for quantitative assessment of fibrosis by analysis of digitalized pictures of sirus red. Czaja and Carpente 2004, reported a sensitivity of Ishak in assessment of fibrosis regression (28). Esmat et al, 2007 (applying Ishak fibrosis score) have demonstrated a correlation between fibrosis score and hyaluronic acid level (29). Tsochatzis1 et al 2011, in their meta-analysis of diagnostic accuracy of elastography for the diagnosis of severity of fibrosis in chronic liver disease, the different stages of fibrosis (scoring systems) were converted to comparable stages in METAVIR (30). Goodman 2007, suggested application of METAVIR in routine work, and Ishak score in clinical trials, because of higher sensitivity in fibrosis assessment (28). Lefkowitch 2007 and Guido et al, 2011, suggested application of any of the scoring systems, that is not home made, and the clinicians with whom they work prefer (31,32).
Although liver biopsy has long been regarded as a gold standard procedure, it has obvious limitations. It represents an approximation of liver fibrosis for the whole liver and is, therefore, not the gold standard for fibrosis assessment. Nevertheless, it is the best procedure currently available (33). Germani et al 2010 recommend liver pathologists to perform computer-assisted digital analysis of Sirius red-stained histological sections in addition to the scoring system established to describe the stage of the liver disease (34).
Ishak and METAVIR are nearly identical; however, Ishak is of a wider scale.
The term “Septa” in METAVIR is equal to “bridging fibrosis” in Ishak.
F3 stage in METAVIR score includes incomplete (developing) cirrhosis.
METAVIR is more sensitive to severe activity and more reproducible. However, without numerical scoring that let it less effective for monitoring minor changes.
Ishak modified HAI has a wider scale. However, 6 points of it (confluent necrosis) are nearly out of the chronic hepatitis C scope. This minimizes the actual scoring to 12 points instead of 18 in practical application.
The proposed table is advised for unidirectional converting fibrosis scores from Ishak to METAVIR.
METAVIR F3 stage may better be subdivided into F3a: Marked bridging fibrosis and F3b: incomplete (early cirrhosis) (developing cirrhosis).
More work is needed in:
Assessing the validity of the current scoring systems in post-liver transplant patients with recurrent HCV especially those with a back ground of graft pathologies such as rejection and those with associated HBV or cytomegalovirus and HIV infections.
Convertibility of the results of these scoring systems and image pattern of contrast enhanced ultrasound of the liver.
Modified and reprinted (
Portal tract expansion by fibrosis, Masson trichrom stain.
Bridging fibrosis, Masson trichrom stain.
Multiple portal-portal bridges,, Masson trichrom stain.
Regenerating nodules rimmed by fibrosis, Masson trichrom stain.
Regenerating nodules rimmed by dense fibrosis, Masson trichrom stain.
Interface hepatitis, H&E stain.
Evident interface hepatitis with apoptosis, H&E stain.
Confluent necrosis, reticulin collapse, sirus red stain. [
Canine parvovirus (CPV-2) is a member of the
CPV-2 causes 100 percent morbidity and mortality rate of 10 percent and 91 percent in adult and young dogs respectively [9]. However, a mortality of 91 percent was reported in experimentally infected dogs that were not treated [10]. CPV-2 affects predominately the younger dogs between 6 weeks and 6 months [8] with an increased susceptibility to puppies less than 6 months. In dogs over the age of 6 months, sexually intact males are more likely (twice) to develop canine parvovirus enteritis (CPVE) in comparison to intact females [11]. The CPV-2 antibody titer transmitted to the newborn via absorbed colostral antibody is 50–60% of the mother’s titer. The half-life of paroviral maternal antibodies is around 10 days [12]. Therefore, puppies are highly susceptible to the CPV-2 infection as the maternal antibody titres start declining. CPVE affects dogs of all ages, although it is more severe in puppies. Puppies can succumb to shock and die within two days after being sick. The most striking symptom of CPV-2 myocarditis is the abrupt mortality in young puppies, generally around the age of 4 weeks [13].
In recent years, CPVE outbreaks caused by multiple CPV-2 variants have been recorded in diverse geographical locations throughout the world. Previously, CPV-2, which could not infect cats, has been replaced by CPV-2 variants that can now infect cats, suggesting that CPV-2 may be capable of spreading between species [14]. Since CPV-2 infects a wide range of wild animals in the order Carnivora, subclinical infection appears to be prevalent. As a result, significant CPV-2 reservoirs in wildlife appear to exist, and transmission of virus between domestic dogs and wildlife appears to be common and bidirectional [15]. Despite the availability of a wide range of immunoprophylactic and antiviral agents to control CPV-2 infections in dogs, many outbreaks have been reported throughout the world, and the disease has remained a major veterinary and economic concern due to the presence of unvaccinated dogs, intervention of active immunization by maternally derived antibodies, and the emergence of a different antigenic variants of CPV-2.
Canine parvovirus infection is caused by
Schematic representation of
The virus is nonenveloped having icosahedral symmetry and is 25 nm in diameter. The CPV virus is made up of the sixty protein subunits containing VP1 (5–6 units) and VP2 (54–55 units). The protein structure is made up of antiparallel β-barrel (8-stranded) capsid. The viral replication occurs inside the nucleus of multiplying cells and therefore the intranuclear inclusion bodies are formed during the infection. The viral capsid structure is made up of spike at the three-fold axes of the icosahedral unit, a 15-Å depression around the five-fold axes and two-fold axes is formed. Antigenic determinant regions have been plotted to the three-fold protrusion and the two-fold depression are related to the host cell features [17]. The surface of the capsid is composed of four loops inserted between the strands, resulting in spike-like protrusions around threefold axes of approximately 22 Å. The antigen neutralization site, also known as epitope A, is composed of loops 1 and 2 of one VP2 and loop 4 of a threefold related molecule [21]. The molecular weight (MW) is around 5.5 to 6.2 × 106 Da. There is an equal ratio of protein to nucleic acid.
NS1 is the largest non structural protein in CPV-2, and it is primarily involved in viral replication and pathogenicity [22]. NS1 is a key mediator of cytotoxicity of CPV and can selectively cause tumor cell lysis by inducing an antitumor immune response in different tumor models [23]. A recent study demonstrated the amino acid residues of T598 and T601 in the C-terminal phosphorylation sites of NS1 protein, involved in replication and pathogenicity of CPV-2 [24].
In the 1970s, CPV-2 emerged as a novel pathogen in dogs. Since then, CPVE has been reported across all the continents [25, 26]. Other related viruses such as Feline panleukopenia virus (FPV), Mink enteritis virus (MEV), Raccoon parvovirus (RPV) are closely related to the CPV-2 [27]. Mutations in the canine transferrin receptor (TfR) type-1 lead to adaptation of CPV-2 in different species 2 [28, 29]. There is more than 98% genome homology reported in the CPV and FPV nonetheless infect different species and have typical antigenic capsid and haemagglutination (HA) properties [28, 30]. The mutations in different amino acid positions have led to the effective adaptation in the new hosts [30]. There are over five to six mutations in the VP2 residue of the CPV-2 and FPV and also 375 and 323 amino acid position regulates the pH functionality of HA [31, 32]. CPV-2a (Asn CPV-2a) replaced CPV 2 in 1980s in the USA and various European countries. CPV 2a can infect the cats which was not a feature of CPV 2. CPV 2a has been displaced by the CPV-2b (426Asp) which was first reported in USA in 1982 and CPV-2c (426Glu) variant in Italy [31, 33]. Although two variants, CPV-2a and 2b had been identified much earlier, however, the third variant CPV-2c had been recognized in early 2000 [33]. Thereafter it has been reported frequently from many different countries. In addition, new CPV-2a and new CPV-2b have also been documented due to non-synonymous substitution at 297 residues (Ser to Ala) of VP2 protein [34]. In India, CPV-2a has recently become the most prevailing antigenic type among all variants. Recent emergence of new antigenic variants that differ significantly from the current vaccine strains is a matter of concern for efficacy of vaccine [35].
The CPV is of two types: CPV-1, commonly known as minute virus of canine and accountable for gastrointestinal and respiratory infection of dogs whereas, CPV-2, most pathogenic type and is responsible for severe gastroenteritis/hemorrhagic gastroenteritis, in young puppies as well as adult dogs.
It is quite difficult to distinguish the clinical diseases caused by CPV-2 variants owing to its overlapping nature of signs and symptoms. These variants are believed to produce similar pathogenicity however; some studies showed that severity of clinical manifestations is influenced by variants of CPV-2 based on clinical, hematological, serological and histopathological examinations [36, 37].
Although puppies under 6 months of age are highly susceptible, adult dogs with insufficient immunity are also considered as high risk to the CPVE. CPV-2 can persist in the environment for more than a year, enabling susceptible dogs to pick up infection from CVP-2 contaminated feces, vomitus, or fomites. Although the feco-oral route is considered as primary path of disease transmission, infection through the oro-nasal route is also common in naive or under-immunized dogs due to ingestion of viruses shed in the vomitus or feces of CPV-2-infected animals [38]. However, direct contact or environmental contamination may also play a role [39]. Breed predisposition and seasonal prevalence of the disease are subject to considerable variations in wide geographical areas [40, 41].
Doberman, Rottweiler, and German shepherd (GS) dogs have been reported to be more susceptible to CPVE than other breeds [42]. Due to inherited immunodeficiency, the exotic breeds, German Sphered and Doberman, are more susceptible than the other breeds [43]. German shepherd has the highest CPV infection rate (70%) followed by the Doberman (55%) [44]. A cytokine bioassay revealed that the magnitude of TNF-α production by peripheral blood monocytes was greatest in dogs with a breed-related risk for CPVE. When compared to mixed breeds, highly susceptible breeds such as Rottweiler and Doberman Pinscher produce more TNF-α in response to LPS stimulation [45]. Increased TNF activity is predictive of mortality in naturally occurring CPVE infection in veterinary medicine [46]. Therefore, it has been hypothesized that dogs with a breed-related risk of developing CPVE, a disease associated with sepsis, would have a greater pro-inflammatory cytokine response to endotoxin [45].
The incubation period of CPV-2 infection ranges from 4 to 14 days. The infected dogs start to shed virus few days prior to the visible clinical signs and shedding of virus gradually declines 3–4 weeks postexposure [47]. Following entry into the body, the CPV-2 rapidly multiply in oropharyngeal lymph node, thymus and mesenteric lymph node, resulting in viremia within one week of exposure. After that, the virus attacks rapidly multiplying cells of crypts of intestine, epithelium of the tongue, oral cavity, bone marrow, and cardiac myocytes, besides lung, spleen, liver, and kidneys [48]. The key pathogenic event in CPV-2 infection is the virus-induced destruction of enterocyte, leading to mucosal barrier disruption, and villous atrophy. This causes profuse vomiting and hemorrhagic diarrhea, nutrient malabsorption, dehydration/hypovolemia, metabolic acidosis and/or alkalosis. The disruption of mucosal barrier allows bacterial translocation from intestinal compartment to systemic circulation, resulting in septicemia, endotoxemia, systemic inflammatory response syndrome as well as hypercoagulability [49]. The CPV-2 infection in the thymus and bone marrow precursor cells results in loss of thymic cortex and profound leucopenia, respectively [48]. Death may occur due to multi-organ failure when the affected dogs remain unattended [40, 49]. Previously, myocarditis was thought to be the acute cause of death in young puppies however, this form nowadays occurs rarely because of widespread CPV vaccination of dogs. The concurrent infections with parasitic, virus, or bacterial intestinal pathogens or stressors may aggravate the disease [50, 51, 52].
The degree of clinical manifestations may vary with age, breed, and immune status, duration of illness and virulence of virus. The clinical signs of dogs with CPV infection are nonspecific in nature and resembles to gastritis and enteritis. The most notable clinical signs of CPVE are lethargy, depression, weakness, lack of appetence, bouts of vomiting, and diarrhea. The diarrhea is characterized by foul-smell and mucoid to purely hemorrhagic because slugging of intestinal mucosa and bleeding. The excessive loss of fluid during vomiting and diarrhea causes marked dehydration that results in development of hypovolemic shock. Occasionally, intussusception occurs due to intestinal dysmotility. Neurologic signs in puppies with CPVE may result from hypoxia secondary to myocarditis, hypoglycemia, or intracranial thrombosis or hemorrhages [52]. The bacterial translocation from intestine to systemic circulation can cause fever, systemic inflammatory response syndrome and septic shock with hypotension and organ failure [40, 48]. Apart from diarrhea, respiratory distress, pulmonary congestion and edema, alveolar and bronchiolar hemorrhage and convulsions are also occasionally manifested due to hypovolemia, endotoxic and septicemic shock [8, 53]. The malabsorbtion of nutrients and inadequate storage of glycogen in muscle and liver result in hypoglycemic encephalopathy which leads to seizures. On hospital admission, the prognosis is poor in CPVE dogs with intussusception, systemic inflammatory response syndrome and severe leucopenia.
Virus isolation is considered as a gold standard for any viral disease diagnosis. In case of CPV-2 different cell lines like CRFK (Crandell Rees feline kidney), MDCK (Madin-Darby canine kidney) and A-72 are used for the isolation and propagation of the virus. The adapted virus causes distinct cytopathic effect in infected cell lines as cell rounding, aggregation, and necrosis of the affected cells. This requires the presence of special laboratory and is laborious [54].
It is an expensive technique for the detection of the virions by negative staining in the stool samples or culture isolated virus. Immunoelectron microscopy can also be done by using CPV-specific antibodies. The need of expensive electron microscope makes it out of reach for regular usage [55].
The property of the CPV to cause agglutination of the pig, cat or rhesus monkey red blood cells at 4°C is used for detection of the CPV. The reciprocal of the maximum dilution of virus exhibiting ample agglutination of erythrocytes (mat formation) is designated as HA titer. The HA titer of more than 1:32 is usually considered as specific for CPV-2 [56].
The use of electric current allows the rapid movement of antigen and antibody towards each other resulting into the formation of precipitation line quicker than simple diffusion reaction. This technique is not commonly used but have been utilized for the prevalence of CPV infection in clinically suspected dogs [57].
In this test, an antibody tagged with fluorescent dye is employed for detection of specific CPV antigen. Mostly it is used as direct FAT for the diagnosis of CPVE but is not used routinely for diagnostic purpose [58].
This is a commonly used test utilizing antigen–antibody interactions employing specific antigen or antibody and is mostly useful under the field conditions. Here, the property of agglutination of polystyrene beads coated with either specific antigen or antibody on their surface is used with anti-CPV monoclonal and polyclonal antibody to detect CPV-2 in the stool samples. Earlier it has been used for both qualitative and quantitative evaluation of CPV in suspected dog feces. Also, a recombinant VP2 protein-based LAT for determination of immune status in dogs against CPV-2. Besides LAT, a slide agglutination inhibition test has been used to detect the presence of CPV-specific antibodies by utilizing the agglutination property of CPV-2 [59].
This method is developed for the detection of CPV-2. SIT is an antibody typing system based on the ability of viral antibodies to bind with the virus and prevents the virus from binding to RBC. SAT is used for antigen detection by serially diluting the clinical sample and then incubating it with a fixed amount of RBC containing virus surface receptors. The virus particles in the sample bind to the RBC and form a lattice that can be seen visually [60].
It is an enzyme-based immunoassay involving antigen–antibody interactions to screen a large number of samples at a time. Recombinant VP2 protein-based indirect ELISAs has been developed to detect and quantify antibodies against CPV-2. Novel polyclonal antibody-based antigen capture ELISA using rabbit anti-CPV hyperimmune sera as capture antibody and guinea pig anti-CPV hyperimmune sera as detector antibody has been also developed. IgY-based ELISA comprising of the chicken egg yolk-derived has been developed for the detection of both antigen and antibodies. Different commercial ELISA kits are currently available for CPV-2 antigen and antibody detection [61].
IC assays or Lateral flow assays are strip-based devices utilized for the detection of a target analyte in test samples. Colloidal gold nanoparticles are commonly used in synthesis of the probe (conjugate) in majority of these strip-based points of care assays. Different components used are the sample pad, conjugate pad, nitrocellulose membrane, absorbent pad and a plastic cassette. These tests are now used routinely for the parvovirus diagnosis in affected dogs. A number of lateral flow assay-based commercial kits are available for rapid detection of both CPV-2 antigen in feces and antibodies in serum, which are also available in the market. These are helpful in the field and gives rapid results within 10–15 mins. Recombinant VP2 protein based immunochromatography tests has also been developed based on the rapid detection of CPV-2 [62].
It is an immunological test which uses charging of test antigen on to a nitrocellulose or PVDF membrane followed by detection using specific antibody against the antigen and an enzyme labeled secondary antibody which forms a color on addition of an insoluble substrate. It is helpful as on the spot assay for CPV diagnoses. It has been developed for detection of CPV-2 using hyperimmune sera raised against the whole virus/recombinant VP2 protein. Commercial dot ELISA kits are also available for evaluating IgM response against CPV-2 after vaccination or infection [63].
PCR is a molecular diagnostic assay which is used for the detection of viral nucleic acid and is relatively more sensitive than other conventional tests. Diverse antigenic types of the CPV can be distinguished by employing strain-specific primer or nested PCR or restriction enzyme analysis of the PCR. Also strain differentiation may be carried out with the help of oligonucleotide sequencing of the amplified gene [64].
This has also been reported for the detection of CPV nucleic acid. Here hybridization with CPV-specific biotin or radiolabelled probe is carried out onto the CPV nucleic acid charged nitrocellulose paper or nylon membrane from suspected samples and then formation of color and band in the radiograph indicates the presence of the virus [65].
It uses an isotopic-labeled probe for both the detection and tracking of CPV nucleic acid in affected morbid tissue specimens thus,using more incubation time for development of the positive reaction [66].
This technique can be employed to quantitate CPV-2 in samples using either TaqMan probe technology or SYBR Green method. It is used for strain differentiation of concurrent infection using Multiplex Real-time PCR; and also, to differentiate vaccine strain from wild CPV strains. Different multiplex assays real-time PCR has been validated for the presence of CPV, FPV and PPV [67].
It is used for the detection and typing of the known point mutations/single nucleotide polymorphism based on variable size of PCR-amplified products specific to a particular allele. In this PCR basically 2 pairs of primers are used (2 inner and 2 outer specific primers matching to individual allele type) in a single PCR tube and there are no post-PCR protocols used as restriction enzyme digestion (PCR-RFLP) and sequencing therefore they provide an economical confirmation. ARMS-PCR is a well-known technique frequently employed for phenotypic association and single nucleotide polymorphism (SNP) studies. This has been used for CPV detection and its antigenic typing [54].
It contains a stable electrically neutral peptide backbone and the PNA-DNA hybridization assay are relatively more sensitive and specific than TaqMan-based real-time PCR for CPV differentiation [68].
The assay is a sensitive and rapid technique used for amplification of DNA and thereby pathogen detection in an hour by using the DNA polymerase by autocycling strand displacement action by boiling at persistent temperature (60–65°C) in water bath. Usually, 2 sets of primers bind to 4 to 6 different regions of target viral DNA. LAMP has field application as there is no need for any thermocycler to carry out the target gene amplification. The amplification of VP2 gene of CPV-2 by LAMP assay has been developed. LAMP assay along with lateral flow dipstick (LFD) and LAMP-ELISA are also used for CPV DNA detection [69].
It is a convection-based method using a hydrolysis probe for detection of CPV-2 and its antigenic variants. The reaction mixture is sequentially allowed to pass in an automatic manner through variable temperature zones in a capillary tube which undergoes thermocyclic phase to amplify the DNA and the probe hydrolysis produces optical output providing the result within an hour [70].
This technique makes use of both conventional PCR and isothermal amplification as in LAMP and is completed within one and a half hour. Here mostly an exogenous sequence from an unrelated species or of botanical origin is incorporated at the 5′ end into the primer sequences used in PSR if a human or veterinary pathogen is targeted. PSR has been successfully used to detect all CPV antigenic variants with ten-fold higher sensitivity than traditional PCR [71].
It is a probe-based assay that uses melting curve analysis to detect and differentiate between CPV-2 variants. This assay consists of 2 TaqMan probes namely FAM labeled and HEX labeled. The FAM-labeled probe sequence is perfectly complementary to CPV-2a, with a 1 bp mismatch to CPV-2b and a 2 bp mismatch to CPV-2c. The HEX-labeled probe has complete complementarity with the original CPV-2 and a 1-bp mismatch with the other variants. This method is also capable of detecting samples containing more than one variant without sequencing [72].
Aptamers emerged as a good alternative to antibodies as affinity reagents. Recently, ssDNA aptamers that specifically bind with the recombinant VP2 (rVP2) protein of CPV-2 with affinity in the nanomolar range have been reported. The ssDNA aptamers specific to CPV-2 (rVP-2) were selected by the Systematic evolution of ligands through exponential enrichment (SELEX) method and their target binding was assessed by dot blot and enzyme-linked oligonucleotide assay (ELONA). Aptamers with high binding affinity and specificity against rVP-2 could be employed in diagnostics for rapid detection of CPV-2 [73].
It is primarily used for most viral genome identification and confirmation. Thus, considered as a gold standard for the antigenic typing of CPV variants. The amplified PCR product is either directly sequenced or cloned which is sequenced in a sequencer utilizing apt primers. The sequence data is analyzed using the appropriate bioinformatics database. Either nucleotide or amino acid sequence data or even both could be employed to recognize the evolutionary analysis of CPV-2 isolates from different geographical sites [74].
It is an analytical device which detects the DNA/RNA/protein/enzymes and alters it to the detectable electrical signals. A biosensor for CPV detection has been established by means of quartz crystal microbalance biosensor and ProLinker B [75]. Summary of different types of diagnostic assays are listed in the Table 1.
Diagnosis | Specimen | Diagnostic assay used | Feature | Remarks |
---|---|---|---|---|
CPV antigen | Feces or rectal swab | ELISA | High specificity Low sensitivity | Feces or rectal swab |
Haemagglutination assay | Low-cost and rapid. | Sensitivity and specificity vary | ||
Tissues or morbid samples | Necropsy specimens | Histopathology | Different histopathological techniques and IHC may be used. | Differential diagnosis with other enteric infections |
Viral DNA | Feces or rectal swab or any tissue | Polymerase chain reaction (PCR);qPCR | Efficient in diagnosing even minute amount of viral genome, can be quantified; Antigenic typing | Sensitivity and specificity vary. Vaccine virus shedding occurs upto weeks after immunization leading to false positives results. Inhibitory components may lead to false negative results. |
Virus | Feces or rectal swab or any tissue | Virus isolation | Confirmatory diagnosis | Requires special facility |
Virus particles | Feces or rectal swab or any tissue | Electron microscopy | Confirmatory diagnosis | Requires special facility, expensive |
Summary of the different types of diagnostic assays for CPVE diagnosis.
Commercially available kits are mostly based on antigen–antibody reactions, such as ELISA, dot ELISA, and immunochromatographic strip-based assays (Table 2).
Sl. No. | Test | Company | Principle | Reference |
---|---|---|---|---|
1 | SNAP parvo antigen test | IDEXX, United States | ELISA | [76] |
2. | Rapid Immunochromatographic (IC) strip test | ADDBIO, Korea | Immunochromatography test | [43, 77, 78] |
3. | Witness Parvo Test Kit | Zoetis, United states | Rapid Immuno Migration (RIM™) technology. | [79] |
4. | Fassisi® Parvo | Fassisi, Gottingen, Germany | Lateral flow immunoassays | [80] |
5. | FASTest parvo card | Vet lab, UK | Lateral flow immunoassays | [55] |
6. | 4 CPV Antigen Rapid Test Kit | Ubio Biotechnology systems Pvt. Ltd., India | Lateral flow immunoassays | [79] |
7. | Anigen Rapid CPV Ag Test Kit® | Bionote, Dongtan, South Korea | Lateral flow immunoassays | [80] |
8. | ImmunoRun CPV antigen detection kit | Biogal- Galed labs, Israel | Immunochromatographic assay | [79] |
9. | Primagnost® Parvo H + K | Dechra, Aulendorf, Germany | Lateral flow immunoassays | [80] |
10. | Canine Parvovirus & Distemper IgMAntibody Test Kit | Biogal Galed Laboratories Acs Ltd., Israel | Immunocomb | [79] |
11. | Vetexpert Rapid Test CPV Ag® | Vetexpert, Vienna, Austria | Lateral flow immunoassays | [80] |
List of commericially available kits for CPV-2 detection.
In absence of effective and appropriate antiviral drugs, the most universal therapeutic regimen for CPVE is supportive and symptomatic care until vomiting and diarrhea have resolved. Because of long-term illness of CPVE infected dogs, the challenges faced by the pet owners are cost of treatment and hospitalization. In private practice settings, the treatment cost may be huge, indicating that financial constraints may be a factor in disease-related euthanasia [81]. Therefore, fatality of CPVE is documented more in socioeconomically underprivileged areas, where level of education and financial opportunity for care and vaccination are not adequate [82]. Although the survival rate of CPVE in hospitalized and outpatient dogs is debatable, a recent prospective, randomized trial found no significant differences in survival (90% vs. 80%, P = 0.66) or duration of hospitalization (4.6d vs. 3.8d, P = 0.20) between inpatient and outpatient dogs [83]. However, given the possible risks of long-term hypoglycemia and leukopenia, aspiration pneumonia, edema, and intussusception in CPVE dogs, hospitalization appears to be the better option over outpatient treatment [84].
The principal components of supportive and symptomatic therapy include 1) fluid therapy and oncotic support, 2) antibiotics, 3) antiemetics, and 4) nutritional support. A wide range of other treatment measures including, though not limited to, antiviral treatments and pain management have been assessed in the past or are currently under investigation regarding their potential utility in CPVE.
The development of severe hypovolemia is the first impact of pathophysiology in dogs with CPVE, hence re-establishment of the circulating volume is the utmost need [85]. The hypokalemia, hypochloremic metabolic alkalosis, hypoglycemia, hypoproteinemia and loss of oncotic pressure in circulation are the major fluid and electrolyte abnormalities during episode of diarrhea and vomition in acute CPVE [86]. The most aggressive therapies consisting of administration of intravenous (IV) fluids to restore intravascular fluid volume status, replenish interstitial fluid losses, maintenance of hydration and oncotic support. A balanced isotonic crystalloid solution (eg, Lactated Ringers) should be used for initial restoration of intravascular volume and rehydration, with a rate titrated to improve perfusion parameters such as capillary refill time, mucosal color, pulse character, and mean arterial pressure or lactate concentrations. Apart from fluid administration, potassium need to be supplemented in hypokalemic patients whereas, 25% dextrose at the dose rate of 1-2 mL/Kg body weight followed by addition of 2.5–5% dextrose in the crystalloid fluids will be required for hypoglycemic patients with blood glucose level < 60 mg/dL. Initially, the fluid is administered at the dose rate of 80–90 mL/kg with a boluses of 15–20 mL/kg over 15–20 minutes to counter the hypovolemic shock and, to improve the fluid perfusion. After that, the maintenance dose for daily fluid depends on the body weight (kg) and percent of dehydration. The volume (L) required to correct the daily fluid loss is calculated as body weight (Kg) × % dehydration. Generally, 40–60 mL fluid for each kg body weight is considered as ideal maintenance dose. Since fluid absorption through subcutaneous route is impaired in hypovolemic patients, intravenous access is considered as choice of fluid treatment. However, intraosseous or jugular catheter are considered as appropriate option in severe hypovolemic or interstitially dehydrated patients [87].
In CPVE, protein loosing enteropathy attributes to pronounced hypoalbuminemia (<2 g/dL) and/or hypoproteinemia (<4 g/dL) resulting in peripheral edema, pleural or abdominal effusions [88]. In that case, provision of oncotic support in the form of either natural or synthetic colloids are very important to minimize the morbidity and mortality of patients [89]. For correction of hypoalbuminemia, fresh plasma (20 mL/kg) or fresh-frozen plasma (6.6–11 mL/kg IV or 3 doses administered intraperitoneally 12 hours apart) and canine-specific albumin concentrate are used [90]. The concentrated human albumin products can also be used but the risk of immune reaction is the major limitation. If further oncotic support is required, hydroxyethyl starch (20–30 mL/kg/d) can be given, depending on clinician choice [6]. Sometimes, administrations of whole blood (20 mL/kg, within 4 hours) or packed RBCs are needed in severe anemic dogs with CPVE.
Apart from fluid and electrolyte imbalance, emesis is another clinical manifestation in CPVE. So, antiemetic treatment is warranted in CPVE otherwise persistent vomition may enhance the duration of hospital stay and further aggravates the condition of patient. The clinical efficacy of number of antiemetics in CPVE had been investigated with varying degree of results. The earlier studies showed that metoclopramide, a dopaminergic antagonist, was found to be effective in reducing episode of vomition by exerting a prokinetic effect in the upper intestinal tract and blocking the chemoreceptor trigger zone when administered as a bolus or as a constant-rate infusion in dogs. The ondasetron or dolasetron, the serotonin receptor antagonists, are also found effective in reducing the number of vomiting events [85]. Recently, a substantial antiemetic effect of maropitant, an antagonist of neurokinin1 receptors, by stimulation of either central or peripheral emetic pathways has been reported in dogs however, the efficacy of maropitant in CPVE has yet to be thoroughly investigated [91]. The administration of maropitant once daily, singly or in combination with metoclopramide, is very effective in reducing vomition in CPVE [5].
Translocation of bacteria from intestinal compartment to systemic circulation is very common in CPVE because of villous collapse and disruption of the mucosal barrier. The translocation with concurrent marked neutropenia leads to a high risk of septicemia and endotoxemia. Additionally, hypotension from fluid loss and sepsis make dogs with CPVE at high risk of developing acute kidney injury. Therefore, parenteral administration of broad-spectrum bactericidal antibiotics is necessary in dogs with CPVE. Ampicillin and cefoxitin as single-agent treatments or in combination with enrofloxacin are the choice antimicrobials against Gram-positive and negative bacteria [85]. Aminoglycosides may also be considered in well-hydrated animals otherwise it may be avoided due to its inherent risk of nephrotoxicity. Puppies with CPVE often have comorbidities, including gastrointestinal parasitism. Hence, antiparasite therapy should be initiated once the puppy can tolerate oral therapies [6].
Restoration of early mucosal integrity and prevention of bacterial translocation from gut compartment to systemic circulation are very important for faster recovery of dogs with CPVE. Enteral feeding is reported to improve the mucosal integrity and faster repair, resulting in lower possibilities for bacterial translocation [8]. In earlier study, it was demonstrated that early enteral nutrition via nasoesophageal catheter starting 12 hours post-admission led to clinical improvement, significant weight gain, and improved gut barrier function was more early as compared to withholding of the traditional food until cessation of vomiting for 12 hours [92].
Severe vomition, enteritis, and or concurrent intussusception in CPVE are the possible reasons for abdominal pain. Hence, analgesic treatment to reduce visceral pain is one the important aspect in therapeutic management in CPVE. Partial mu-agonists such as buprenorphine (0.01–0.02 mg/kg IV every 8 hours) or an agonist–antagonist such as butorphanol (0.1–0.2 mg/kg/h) are the preferred analgesics over the pure mu agonists as opioid analgesics can promote ileus and vomiting. The α-2 agonists that promote extreme vasoconstriction and limit gastrointestinal perfusion, and non-steroidal anti-inflammatory drugs that impair gastrointestinal and renal perfusion, both are not indicated [93].
Like other viral infections, prophylaxis is the cornerstone for prevention of CPV in dogs. Although, an adequate number of killed and live CPV vaccines are marketed by pharmaceuticals but vaccines sometimes fail to protect completely due to poorly responding breeds (Rottweilers and Doberman pinschers), variation in genetic makeup of field and vaccine viruses, interference by presence of maternal antibodies and adjunct factors [94]. Therefore, development of some suitable antiviral drugs is utmost important for effective management of the CPVE in its acute illness stage. Till now, only few antiviral drugs have been evaluated for its clinical efficacy against CPVE. In an earlier placebo-control study, the therapeutic efficacy of Oseltamivir, a neuraminidase inhibitor, in CPVE had been evaluated and noted that Oseltamivir did not produce any additional benefit in terms of reduction of mortality or duration of hospitalization except some improvements in body weight and hemogram in dogs with CPV-illness [95]. In another study on naturally infected dogs, a promising anti-CPV activity of recombinant feline interferon-ω (rFeIFN-ω) has been recorded as compared to placebo-group. The intravenous administration of rFeIFN-ω at the dose rate of 2.5 mU/kg daily for consecutive three days remarkably reduced the clinical symptoms and mortality [96, 97]. Although the drug is currently available for use in Europe and Australia, the high price and frequent non-availability are major limitations. Recently, another antivital drug, Acyclovir, guanine analogue commonly used to treat herpes simplex virus infection, have been shown to improve the disease conditions [98]. Further, an
Passive immunization with specific antibodies against enteric viral infections in animals confers significant protection, reduces diarrhea and virus shedding and increase survival rates [101]. Thus, the of immunotherapeutics in viral infections is promising treatment approach because of lower adverse effects as well as no chance of any resistance as in antiviral drugs. The passive immunization by means of oral or intravenous administration of IgY specific for CPV-2 shows the protective effect in dogs challenged with the virus [102]. The reduction of clinical scores, duration of symptoms and mortality and improvement of body weight gain has been reported by anti-CPV-2 IgY therapy in experimentally produced CPVE [103]. Recent study reported that chicken IgY- single chain fragment variables (scFv) generated against the virus capsid protein could be a promising therapeutic target against CPV [104, 105]. Aside from IgY, the neutralization of CPV by anti-feline panleukopenia virus antibodies is also reported from an
The key physiopathological alterations of CPVE are destruction of intestinal crypts, neutropenia, secondary bacterial translocation, immunosuppression due to thymus atrophy, sepsis and systemic inflammatory response syndrome in puppies [6, 109]. Therefore, immunomodulators could be an option to enhance therapeutic efficacy of supportive treatment. A recent study demonstrated that subcutaneous administration of human dialyzable leukocyte extract-h (hDLE) along with supportive therapy in puppies with CPVE significantly increased the leukogram and reduced the clinical score, duration of hospitalization, mortality as compared to supportive therapy alone [110].
Leukopenia is one of the most important prognostic indicators of mortality in dogs with CPVE. Hence, stimulation of bone marrow and improvement of leukogram in peripheral circulation are considered as strategic approaches to reduce the CPVE associated mortality. Enhancement of endogenous canine G-CSF (cG-CSF) concentrations by exogenous administration of human G-CSF (hGCSF) and cG-CSF is reported to stimulate bone marrow, resulting in improvement of neutrophil counts in puppies with CPV infection [111]. However, the use of hG-CSF and cG-CSF may not necessarily improve survival [112, 113].
The interferon (IFN)-ω, a type I IFN (similar to IFN-α), is known for its antiviral, anti-proliferation, and antitumor activities. A notable therapeutic effect of rIFN-ω on CPV-infected dogs is reported [114]. Additionally, the promising therapeutic potential of other type I (IFN-α, IFN-β, IFN-ε, and IFN-κ) and III (IFN-λ) IFNs in CPVE has also been reported [115].
Recently, anti-CPV activity of the serum derived transfer factors (TFs), low molecular weight (<5000 daltons) biological response modifiers has been documented. It imparts therapeutic benefit in CPVE by altering the cytokine response of the host [116].
Probiotics, primarily comprised of live microorganisms in fermented foods, protect gut from acute diarrhea through adherence and colonization on gut mucosa [117]. Therapeutic efficacy of probiotics has been verified in dogs with CPV associated illnesses [118]. In an earlier study, oral administration of probiotic preparations as an adjunct therapy to young dogs with CPVE has shown faster resolution of clinical signs, improved leukogram and decreased mortality as compared to supportive treatment alone [119]; whereas, no benefit with respect to length of hospital stay or case fatality was recorded in other study [120].
The disturbance in oxidant/antioxidant equilibrium is evident in CPV-gastroenteritis and oxidative stress is believed to link with pathogenesis of CPVE [121]. Hence, addition of antioxidants in supportive therapy has emerged as a promising therapeutic option to improve the response of treatment in viral diseases. Treatment with
An interest in natural products including herbs, plants and their extracts/metabolites as antiviral drug candidates has increased in the last few decades especially due to rising emergence of antimicrobial resistance globally and potential side-effects of many antimicrobials [123]. Very recently, anti-parvoviral activity of propolis, a traditional Chinese medicine, prepared from honeybee hives has been documented [124]. The
Alteration in the gut microbiome is reported in enteric viral diseases including CPVE and other gastrointestinal diseases in dogs [125]. The disruption of gut microbiota leads to impediment in the enterocyte nutrition, immune regulation, protective barrier function, and gastrointestinal motility [126]. Therefore, restoration or re-establishment of the microbiota could have a good interest therapeutically. Recently, a randomized clinical trial showed that administration of fecal microbiota (10 g feces diluted in 10 mL of sterile 0.9% saline) obtained from healthy donor rectally at 6–12 hours post-admission caused faster resolution of diarrhea, shortened the duration of hospitalization and reduced the mortality in young dogs with CPVE when compared with standard therapy alone [126].
A modified live virus (MLV) and an inactivated vaccine are the two types of CPV-2 vaccines currently available [94]. Administration of the vaccine should start at 6 to 8 weeks of age and then every 2–4 weeks until 16 weeks of age or older. For dogs that are 16 weeks or older, 2 doses of vaccination are recommended with an interval of 2–4 weeks [127]. A recombinant vaccine based on virus-like particles (VLPs) is being developed, which has the advantage of becoming highly immunogenic and safe [128]. Peptide vaccines containing major antigen neutralizing region N terminal of VP2 are also under developmental stage [129]. A single-dose vaccination of Vaccinia virus encoding CPV2-VP2 elicited substantial antibody responses and provided comparable protection for dogs with attenuated CPV2 vaccine. This vaccine could be used as a promising vaccine candidate to prevent CPV-2 infection in dogs [130].
CPV-2 is one of the most significant viral enteropathogens of canines causing high morbidity and mortality and manifested by vomition and severe acute haemorhagic gastroenteritis. Prompt symptomatic therapy will increase survivability of infected puppies but vaccination is best way to prevent the disease in dogs. Despite the pups are protected through vaccination from the pregnant bitch, it is more vulunerable to CPV-2 infection as maternal antibody titers started declining. Despite the availability of high sensitive and specific diagnostic approaches and the effective prophylactics such as modified live virus and inactivated vaccines, a large number of outbreaks are still reported in wide geographical areas across the globe in both vaccinated and unvaccinated dogs. The future studies should be taken up towards vaccination failures, occurrence of CPV-2 in different canine species and the emergence of antigenic variants of the CPV-2 involved in the outbreaks.
All the authors acknowledge and thank to their Institute.
The authors declare no conflict of interest.
This compilation is a book chapter written by its authors and required no substantial funding to be stated.
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',metaTitle:"Terms and Conditions",metaDescription:"These terms and conditions outline the rules and regulations for the use of IntechOpen Website at https://intechopen.com and all its subdomains owned by Intech Limited located at 7th floor, 10 Lower Thames Street, London, EC3R 6AF, UK.",metaKeywords:null,canonicalURL:"/page/terms-and-conditions",contentRaw:'[{"type":"htmlEditorComponent","content":"By accessing the website at www.intechopen.com you are agreeing to be bound by these Terms of Service, all applicable laws and regulations, and agree that you are responsible for compliance with any applicable local laws. Use and/or access to this site is based on full agreement and compliance of these Terms. All materials contained on this website are protected by applicable copyright and trademark laws.
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\n\nThe following terminology applies to these Terms and Conditions, Privacy Statement, Disclaimer Notice, and any or all Agreements:
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\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. 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. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. from Integral University, Lucknow, India, with his work titled ‘Development and evaluation of silymarin nanoformulation for hepatic carcinoma’. Currently, he is an Assistant Professor of Pharmaceutics, at the Faculty of Pharmacy, Integral University. He has been teaching PharmD, BPharm, and MPharm students and conducting research in the novel drug delivery domain. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than twenty-four original journal articles, two edited books, four book chapters, and several scientific articles to his credit. He is a member of the American Association for Cancer Research, the International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. 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International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. 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Dr. Şentürk currently works as an professor of Biochemistry in the Department of Basic Pharmacy Sciences, Faculty of Pharmacy, Ağri Ibrahim Cecen University, Turkey. \nDr. Şentürk published over 120 scientific papers, reviews, and book chapters and presented several conferences to scientists. \nHis research interests span enzyme inhibitor or activator, protein expression, purification and characterization, drug design and synthesis, toxicology, and pharmacology. \nHis research work has focused on neurodegenerative diseases and cancer treatment. 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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,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",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,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,series:{id:"11",title:"Biochemistry"}}},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:318,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/183180",hash:"",query:{},params:{id:"183180"},fullPath:"/profiles/183180",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()