scholarly journals Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation

Author(s):  
Jefferson Antonio Buendía ◽  
Esteban Halac ◽  
Andrea Bosaleh ◽  
María Teresa Garcia de Davila ◽  
Oscar Invertasa ◽  
...  

The body of evidence available in paediatrics population is limited for making clinical decisions regarding pharmacotherapy optimization of tacrolimus. The objective of this study was to estimate the frequency of CYP3A5 genetic polymorphisms and their relationship with tacrolimus requirements in paediatric population. This was a longitudinal cohort study, with two-year follow-up of 77 patients under 18 who had liver transplant over the period 2009-2012 at the Paediatric Hospital J. P Garrahan. Tacrolimus levels from day 5 to 2-year post-transplant were obtained from hospital records of routine therapeutic drug monitoring. The genotyping of CYP3A5 (CYP3A5*1/*3 or *3/*3) were performed in liver biopsies of both the donor and the recipient. Recipients frequency of CYP3A5 *1 expression was 37.1% and 32.2% for Donors. Patient who received an organ expresser showed lower Co/dose especially after 90 days post-surgery. The role of each polymorphism is different according to days after transplantation proceeds and it must be taken into account to optimize the benefits of TAC therapy during the post-transplant induction and maintenance phase.

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 898 ◽  
Author(s):  
Jefferson Antonio Buendía ◽  
Esteban Halac ◽  
Andrea Bosaleh ◽  
María T. Garcia de Davila ◽  
Oscar Imvertasa ◽  
...  

The evidence available in the pediatric population is limited for making clinical decisions regarding the optimization of tacrolimus (TAC) in pharmacotherapy. The objective of this study was to estimate the frequency of CYP3A5 genetic polymorphisms and their relationship with tacrolimus requirements in the pediatric population. This was a longitudinal cohort study with a two-year follow-up of 77 patients under 18 years old who underwent a liver transplant during the period 2009–2012 at the J.P. Garrahan Pediatric Hospital. Tacrolimus levels from day five up to two years after the transplant were obtained from hospital records of routine therapeutic drug monitoring. The genotyping of CYP3A5 (CYP3A5*1/*3 or *3/*3) was performed in liver biopsies from both the donor and the recipient. The frequency of CYP3A5*1 expression for recipients was 37.1% and 32.2% for donors. Patients who received an expresser organ showed lower Co/dose, especially following 90 days after the surgery. The role of each polymorphism is different according to the number of days after the transplant, and it must be taken into account to optimize the benefits of TAC therapy during the post-transplant induction and maintenance phases.


2021 ◽  
Vol 16 (4) ◽  
pp. 25-34
Author(s):  
Svetlana Ssablina ◽  
Tat'yana Elovicova ◽  
Sergey Griroriev ◽  
Oksana Khromtsova ◽  
Alla Zakroeva ◽  
...  

Subject. The role of vitamin D in maintaining oral health. Objectives. To review literature on the role of vitamin D in maintaining oral health. Methodology. This literature review is based on analysis of published research reports on effects of vitamin D on oral health. Using key words, research studies published in the past five years with the most comprehensive explanations of the role of vitamin D and its metabolites in the body are selected on such e-resources as PubMed, Medline, Cochrane, Elibrary, Cyberleninka. The data on secosteroid epidemiology, synthesis, metabolism, physiological effects, local effects on immune function and specific symptoms in various somatic disorders are systemized. Conclusion. Epidemiological and genetic studies confirm biological effects of vitamin D active metabolites involved in synthesis of proteins required to form oral mucosal stability and prevent pathogen penetration into subjacent tissues. The most significant is involvement of vitamin D in synthesis of antibacterial monocyte and macrophage-directed peptides ensuring reduction of risks of alveolar resorption and subsequent tooth loss. Modern concepts in this secosteroid refer to the new evidence showing availability of vitamin D activating ferment in tissues which supports intracellular or paracrine function of vitamin D out of the skeleton. The personified approach for vitamin D application as a therapeutic drug for treatment of periodontium inflammations and oral mucosa with preliminary testing of levels in blood serum will allow to develop effective approaches to maintaining people’s oral health.


2016 ◽  
Vol 144 (13) ◽  
pp. 2773-2779 ◽  
Author(s):  
A. S. GASTAÑADUY ◽  
J. ZABALETA ◽  
L. LI ◽  
R. E. BÉGUÉ

SUMMARYGastroenteritis remains an important cause of morbidity and mortality worldwide. With the introduction of vaccines against rotavirus, interest has shifted to understanding the epidemiology of norovirus (NoV). While the importance of NoV in gastroenteritis outbreaks is well established, its role in sporadic gastroenteritis is less known. To better define the role of NoV as a cause of sporadic gastroenteritis we investigated its prevalence in the patients seen in our paediatric hospital with special emphasis on its seasonal and age distribution. Over a 12-month period discarded stool specimens submitted to our paediatric hospital for testing of an infectious aetiology were retrieved and additionally tested for NoV by real-time reverse transcriptase–polymerase chain reaction; demographical and clinical information were also obtained. Overall, NoV was the single most commonly identified pathogen and found in 68/892 (7·6%) total specimens or 68/258 (26%) of pathogen-positive specimens. The highest rates of NoV were detected in children aged 6 months to 4 years (50/332, 15·1%) and presenting between October and January (46/314, 14·7%). NoV has become the main cause of gastroenteritis in our paediatric population.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


1990 ◽  
Vol 29 (04) ◽  
pp. 282-288 ◽  
Author(s):  
A. van Oosterom

AbstractThis paper introduces some levels at which the computer has been incorporated in the research into the basis of electrocardiography. The emphasis lies on the modeling of the heart as an electrical current generator and of the properties of the body as a volume conductor, both playing a major role in the shaping of the electrocardiographic waveforms recorded at the body surface. It is claimed that the Forward-Problem of electrocardiography is no longer a problem. Several source models of cardiac electrical activity are considered, one of which can be directly interpreted in terms of the underlying electrophysiology (the depolarization sequence of the ventricles). The importance of using tailored rather than textbook geometry in inverse procedures is stressed.


2020 ◽  
Vol 99 (4) ◽  
pp. 379-383
Author(s):  
Vasily N. Afonyushkin ◽  
N. A. Donchenko ◽  
Ju. N. Kozlova ◽  
N. A. Davidova ◽  
V. Yu. Koptev ◽  
...  

Pseudomonas aeruginosa is a widely represented species of bacteria possessing of a pathogenic potential. This infectious agent is causing wound infections, fibrotic cystitis, fibrosing pneumonia, bacterial sepsis, etc. The microorganism is highly resistant to antiseptics, disinfectants, immune system responses of the body. The responses of a quorum sense of this kind of bacteria ensure the inclusion of many pathogenicity factors. The analysis of the scientific literature made it possible to formulate four questions concerning the role of biofilms for the adaptation of P. aeruginosa to adverse environmental factors: Is another person appears to be predominantly of a source an etiological agent or the source of P. aeruginosa infection in the environment? Does the formation of biofilms influence on the antibiotic resistance? How the antagonistic activity of microorganisms is realized in biofilm form? What is the main function of biofilms in the functioning of bacteria? A hypothesis has been put forward the effect of biofilms on the increase of antibiotic resistance of bacteria and, in particular, P. aeruginosa to be secondary in charcter. It is more likely a biofilmboth to fulfill the function of storing nutrients and provide topical competition in the face of food scarcity. In connection with the incompatibility of the molecular radii of most antibiotics and pores in biofilm, biofilm is doubtful to be capable of performing a barrier function for protecting against antibiotics. However, with respect to antibodies and immunocompetent cells, the barrier function is beyond doubt. The biofilm is more likely to fulfill the function of storing nutrients and providing topical competition in conditions of scarcity of food resources.


Somatechnics ◽  
2017 ◽  
Vol 7 (2) ◽  
pp. 288-303
Author(s):  
Michael Connors Jackman

This article investigates the ways in which the work of The Body Politic (TBP), the first major lesbian and gay newspaper in Canada, comes to be commemorated in queer publics and how it figures in the memories of those who were involved in producing the paper. In revisiting a critical point in the history of TBP from 1985 when controversy erupted over race and racism within the editorial collective, this discussion considers the role of memory in the reproduction of whiteness and in the rupture of standard narratives about the past. As the controversy continues to haunt contemporary queer activism in Canada, the productive work of memory must be considered an essential aspect of how, when and for what reasons the work of TBP comes to be commemorated. By revisiting the events of 1985 and by sifting through interviews with individuals who contributed to the work of TBP, this article complicates the narrative of TBP as a bluntly racist endeavour whilst questioning the white privilege and racially-charged demands that undergird its commemoration. The work of producing and preserving queer history is a vital means of challenging the intentional and strategic erasure of queer existence, but those who engage in such efforts must remain attentive to the unequal terrain of social relations within which remembering forms its objects.


2020 ◽  
Vol 32 (3) ◽  
pp. 138-144
Author(s):  
Brian A. Jacobs

In federal criminal cases, federal law requires that judges consider the sentences other courts have imposed in factually similar matters. Courts and parties, however, face significant challenges in finding applicable sentencing precedents because judges do not typically issue written sentencing opinions, and transcripts of sentencings are not readily available in advanced searchable databases. At the same time, particularly since the Supreme Court’s 2005 decision in United States v. Booker, sentencing precedent has come to play a significant role in federal sentencing proceedings. By way of example, this article discusses recent cases involving defendants with gambling addictions, and recent cases involving college admissions or testing fraud. The article explores the ways the parties in those cases have used sentencing precedent in their advocacy, as well as the ways the courts involved have used sentencing precedent to justify their decisions. Given the important role of sentencing precedent in federal criminal cases, the article finally looks at ways in which the body of sentencing law could be made more readily available to parties and courts alike.


2014 ◽  
Vol 31 (1) ◽  
pp. 91-124
Author(s):  
Michael Dorfman

In a series of works published over a period of twenty five years, C.W. Huntington, Jr. has developed a provocative and radical reading of Madhyamaka (particularly Early Indian Madhyamaka) inspired by ‘the insights of post- Wittgensteinian pragmatism and deconstruction’ (1993, 9). This article examines the body of Huntington’s work through the filter of his seminal 2007 publication, ‘The Nature of the M?dhyamika Trick’, a polemic aimed at a quartet of other recent commentators on Madhyamaka (Robinson, Hayes, Tillemans and Garfield) who attempt ‘to read N?g?rjuna through the lens of modern symbolic logic’ (2007, 103), a project which is the ‘end result of a long and complex scholastic enterprise … [which] can be traced backwards from contemporary academic discourse to fifteenth century Tibet, and from there into India’ (2007, 111) and which Huntington sees as distorting the Madhyamaka project which was not aimed at ‘command[ing] assent to a set of rationally grounded doctrines, tenets, or true conclusions’ (2007, 129). This article begins by explicating some disparate strands found in Huntington’s work, which I connect under a radicalized notion of ‘context’. These strands consist of a contextualist/pragmatic theory of truth (as opposed to a correspondence theory of truth), a contextualist epistemology (as opposed to one relying on foundationalist epistemic warrants), and a contextualist ontology where entities are viewed as necessarily relational (as opposed to possessing a context-independent essence.) I then use these linked theories to find fault with Huntington’s own readings of Candrak?rti and N?g?rjuna, arguing that Huntington misreads the semantic context of certain key terms (tarka, d???i, pak?a and pratijñ?) and fails to follow the implications of N?g?rjuna and Candrak?rti’s reliance on the role of the pram??as in constituting conventional reality. Thus, I find that Huntington’s imputation of a rejection of logic and rational argumentation to N?g?rjuna and Candrak?rti is unwarranted. Finally, I offer alternate readings of the four contemporary commentators selected by Huntington, using the conceptual apparatus developed earlier to dismiss Robinson’s and Hayes’s view of N?g?rjuna as a charlatan relying on logical fallacies, and to find common ground between Huntington’s project and the view of N?g?rjuna developed by Tillemans and Garfield as a thinker committed using reason to reach, through rational analysis, ‘the limits of thought.’


Author(s):  
Gandhi M. ◽  
Swaminathan S.

Ghrelin as human natural hormones is involved in fundamental regulatory process of eating and energy balance. It is a stomach derived hormone that acts as at the ghrelin receptor in multiple tissues throughout to the body. Its properties includes increasing appetite, decreasing systemic inflammation, decreasing vascular resistance ,increasing cardiac output, increasing glucose and IGF-1 levels, Hence it may play a significant role in Diabetes mellitus. Many studies have linked ghrelin to obesity and this paper is an attempt to bring out recent findings on the role of ghrelin in Diabetes Mellitus, particularly type2 Diabetes mellitus.


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