HYPERPHOSPHATEMIA IN END STAGE RENAL DISEASE: PREVALENCE AND PATIENTS CHARACTERISTICS OF MULTIETHNIC POPULATION OF UNITED ARAB EMIRATES

Objective: Hyperphosphatemia is significantly associated with increased mortality among end stage renal disease (ESRD) patients on hemodialysis. There is paucity of data on hyperphosphatemia in ESRD patients of the multiethnic population of United Arab Emirates (UAE). The study aimed to investigate the prevalence and characteristics of hyperphosphatemia in ESRD patients of the multiethnic population of UAE undergoing maintenance hemodialysis.Methods: Adults ESRD patients undergoing maintenance hemodialysis for more than six months at the study site were included. Demographic, clinical and biological data of the patients were collected. Patient characteristics were compared as per the serum phosphate level, between patients with or without hyperphosphatemia. Univariate and multivariate logistic regression analyses were carried out to identify the predictors of hyperphosphatemia.Results: Hyperphosphatemia was present in 73.8% of the study population, while 31.3% presented with high calcium-phosphate product. Univariate logistic analysis revealed that hyperphosphatemia was inversely correlated with age, hemoglobin, serum calcium, and hypertensive nephropathy as cause of renal disease, and positively correlated with female gender, expatriate status, body mass index (BMI), higher number of comorbidities, calcium-phosphate product and parathyroid hormone (PTH). Multivariate logistic regression model revealed that only age, BMI, hemoglobin and PTH independently correlated with hyperphosphatemia.Conclusion: We report a high prevalence of hyperphosphatemia in multiethnic study population undergoing maintenance hemodialysis at a secondary care hospital in UAE. In this study population, only age, BMI, hemoglobin and PTH were identified as independent predictors of hyperphosphatemia

Synthesis and pharmacological activities of some condensed 4-chloro-2,2-dialkyl chromene-3-carbaldehyde derivatives

Novi hidrazono- 5a,b, tiosemikarbazono- 6a-c i oksimo kromeni 7a-c sintetizirani su iz odgovarajućeg β-klorkarbaldehida 3 i hidrazina, aromatskog hidrazina, tiosemikarbazida ili hidroksilamin hidroklorida, dok su eterski derivati 8a-h pripremljeni iz pripadajućih aldoksima 7a-c. Novi spojevi ispitani su na protuupalno i ulcerogeno djelovanje, a njihovo djelovanje uspoređeno je s djelovanjem indometacina.Some new hydrazono- 5a,b, thiosemicarbazono- 6a-c, and oximo chromenes 7a-c were prepared via the reaction of the corresponding β-chlorocarbaldehyde 3 with hydrazine, aromatic hydrazine, thiosemicarbazide and hydroxylamine hydrochloride, respectively. In addition, ether derivatives 8a-h were prepared from the corresponding aldoximes 7a-c. The new products were tested for anti-inflammatory and ulcerogenic score activities compared to indomethacin

High prevalence of ACE DD genotype among north Indian end stage renal disease patients

BACKGROUND: The Renin-Angiotensin system (RAS) is a key regulator of both blood pressure and kidney functions and their interaction. In such a situation, genetic variability in the genes of different components of RAS is likely to contribute for its heterogeneous association in the renal disease patients. Angiotensin converting enzyme-1 (ACE-1) is an important component of RAS which determines the vasoactive peptide Angiotensin-II. METHODS: In the present study, we have investigated 127 ESRD patients and 150 normal healthy controls from north India to deduce the association between ACE gene polymorphism and ESRD. The inclusion criteria for patients included a constantly elevated serum creatinine level above normal range (ranging from 3.4 to 15.8) and further the patients were recommended for renal transplantation. A total of 150 normal healthy controls were also genotyped for ACE I/D polymorphism. The criterion of defining control sample as normal was totally based on the absence of any kidney disease determined from the serum creatinin level. Genotyping of ACE I/D were assayed by polymerase chain reaction (PCR) based DNA amplification using specific flanking primers Based on the method described elsewhere. RESULTS: The difference of DD and II genotypes was found highly significant among the two groups (p = 0.025; OR = 3.524; 95%CI = 1.54-8.07). The combined genotype DD v/s ID+II comparison validated that DD genotype is a high risk genotype for ESRD (p = 0.001; OR = 5.74; 95%CI limit = 3.4-8.5). However, no correlation was obtained for different biochemical parameters of lipid profile and renal function among DD and non DD genotype. Interestingly, ~87% of the DD ESRD patients were found hypertensive in comparison to the 65% patients of non DD genotype CONCLUSION: Based on these observations we conclude that ACE DD genotype implicate a strong possible role in the hypertensive state and in renal damage among north Indians. The study will help in predetermining the timing, type and doses of anti-hypertensive therapy for ESRD patients

P2X7R mutation disrupts the NLRP3-mediated Th program and predicts poor cardiac allograft outcomes

Purinergic receptor-7 (P2X7R) signaling controls Th17 and Th1 generation/differentiation, while NOD-like receptor P3 (NLRP3) acts as a Th2 transcriptional factor. Here, we demonstrated the existence of a P2X7R/NLRP3 pathway in T cells that is dysregulated by a P2X7R intracellular region loss-of-function mutation, leading to NLRP3 displacement and to excessive Th17 generation due to abrogation of the NLRP3-mediated Th2 program. This ultimately resulted in poor outcomes in cardiac-transplanted patients carrying the mutant allele, who showed abnormal Th17 generation. Transient NLRP3 silencing in nonmutant T cells or overexpression in mutant T cells normalized the Th profile. Interestingly, IL-17 blockade reduced Th17 skewing of human T cells in vitro and abrogated the severe allograft vasculopathy and abnormal Th17 generation observed in preclinical models in which P2X7R was genetically deleted. This P2X7R intracellular region mutation thus impaired the modulatory effects of P2X7R on NLRP3 expression and function in T cells and led to NLRP3 dysregulation and Th17 skewing, delineating a high-risk group of cardiac-transplanted patients who may benefit from personalized therapy

Immunotherapy for type 1 diabetes

Introduction: Although many approaches have been tested to overcome the insulin dependence caused by the pancreatic \u3b2-cells destruction observed in individuals affected by type 1 diabetes (T1D), medical research has largely failed to halt the onset or to reverse T1D. Methods: In this work, the state of the art of immunotherapy will be examined, and the most important achievement in the field will be critically discussed. Particularly, we will focus on the clinical aspect, thus avoiding the tedious preclinical work done in NOD mice, which has been so poorly translated to the bedside. Conclusions: Stem cell therapies achieved thus this far the most promising results, while immune ablation and standard immunosuppressants did not maintain the premises of preclinical results. The next step will be to generate a feasible and safe clinical approach in order to cure the thousands of patients affected by T1D

Discovery of Quinazoline-2,4(1H,3H)-Dione Derivatives as Potential Antibacterial Agent: Design, Synthesis, and Their Antibacterial Activity

In this paper, we report on the design and synthesis of a novel series of quinazoline-2,4(1H,3H)-dione derivatives as fluoroquinolone-like inhibitors of bacterial gyrase and DNA topoisomerase IV to identify and develop antimicrobial agents to prevent bacterial resistance problems. Their structures were confirmed using spectroscopic analyses (IR, NMR, and EI-MS). The novel quinazoline-2,4(1H,3H)-dione derivatives were evaluated for their antimicrobial activities against Gram-positive and Gram-negative bacterial strains using the Agar well diffusion method to study the antimicrobial activities and compared them with the standard drugs. Most compounds displayed moderate activity. Among the tested compounds, the most promising compounds 13 and 15 provided broad bioactive spectrum against Gram-positive and Gram-negative strains compared to the standard drugs

Harnessing the immunological properties of stem cells as a therapeutic option for diabetic nephropathy

Diabetic nephropathy is the leading and possibly the most devastating complication of diabetes, with a prevalence ranging from 25 to 40\ua0% in diabetic individuals, and as such represents an important challenge for public health worldwide. As a major cause of end-stage renal disease, diabetic nephropathy also accounts for a large proportion of deaths in diabetic individuals. To date, therapeutic options for overt diabetic nephropathy include medical interventions to reduce blood glucose levels and to control blood pressure and proteinuria. Recent evidence suggests a strong role for inflammation in the development and progression of diabetic nephropathy. Various immune cells, cytokines and chemokines have been implicated in the onset of diabetic nephropathy, while immune-related transcription factors and adhesion molecules have been correlated with the establishment of a renal proinflammatory microenvironment. Both inflammation and immune activation may promote severe distress in the kidney, with subsequent increased local fibrosis, ultimately leading to the development of end-stage renal disease. Stem cells are undifferentiated cells capable of regenerating virtually any organ or tissue and bearing important immunoregulatory and anti-inflammatory properties. Due to the aforementioned considerations, significant interest has been ignited with regard to the use of stem cells as novel therapeutics for diabetic nephropathy. Here, we will be examining in detail how anti-inflammatory properties of different populations of stem cells may offer novel therapy for the treatment of diabetic nephropathy

Co-transplantation of autologous MSCs delays islet allograft rejection and generates a local immunoprivileged site

Aims: Mesenchymal stem cells (MSCs) are multipotent cells with immunomodulatory properties. We tested the ability of MSCs to delay islet allograft rejection. Methods: Mesenchymal stem cells were generated in vitro from C57BL/6 and BALB/c mice bone marrow, and their immunomodulatory properties were tested in vitro. We then tested the effect of a local or systemic administration of heterologous and autologous MSCs on graft survival in a fully allogeneic model of islet transplantation (BALB/c islets into C57BL/6 mice). Results: In vitro, autologous, but not heterologous, MSCs abrogated immune cell proliferation in response to alloantigens and skewed the immune response toward a Th2 profile. A single dose of autologous MSCs co-transplanted under the kidney capsule with allogeneic islets delayed islet rejection, reduced graft infiltration, and induced long-term graft function in 30 % of recipients. Based on ex vivo analysis of recipient splenocytes, the use of autologous MSCs did not appear to have any systemic effect on the immune response toward graft alloantigens. The systemic injection of autologous MSCs or the local injection of heterologous MSCs failed to delay islet graft rejection. Conclusion: Autologous, but not heterologous, MSCs showed multiple immunoregulatory properties in vitro and delayed allograft rejection in vivo when co-transplanted with islets; however, they failed to prevent rejection when injected systemically. Autologous MSCs thus appear to produce a local immunoprivileged site, which promotes graft survival