Uric acid and diabetes mellitus: an update.

The relationship between diabetes mellitus (DM) and high serum uric acid is complex and controversial. Many epidemiological studies have reported a positive association, whereas others have reported an inverse association or none. In the pathogenesis of DM it is the intracellular urate that is more important than the extracellular and dissociation between the two is possible. Evidence suggests that high serum uric acid induces insulin resistance and beta cell failure in animal models. Reduction of intracellular uric acid can be achieved by dietary measures such as reducing fructose and salt intake, and uric acid-lowering drugs. We suggest that in the Western diet, these elements play a crucial role in pathogenesis of DM. To determine the precise and exact interrelationship between intracellular and extracellular uric acid, well-designed studies are required. Besides this, clinical trials are needed to determine whether intracellular and extracellular urate reduction will provide benefit in prevention and treatment of DM and complications associated with it.

Prevalence of Hypouricemia and Hyperuricemia and Looking Beyond Serum Uric Acid in Patients with Newly Onset Type 2 Diabetes Mellitus in Eastern Part of Uttar Pradesh: A Cross-sectional Study.

INTRODUCTION: The prevalence of hyperuricemia (HU) and hypouricemia (Hypo-U) is highly variable in different parts of India and there is a lack of data from the Eastern part of Uttar Pradesh. We designed this study in order to know the exact prevalence of HU and Hypo-U. MATERIALS AND METHODS: This is a cross-sectional study conducted in Varanasi. Data were collected from newly onset diabetic patients over a period of 1 year. RESULTS: Among the 312 diabetic patients, 12.5 and 19.23% were found to have HU and Hypo-U, respectively. Hypouricemic diabetic patients are phenotypically different. They are characterized by the female sex, higher glycated hemoglobin A1c (GlyHbA1c), higher estimated glomerular filtration rate (eGFR), lower body mass index (BMI), and less insulin resistance. CONCLUSION: The prevalence of HU and Hypo-U is high in newly-onset diabetic patients. Hypouricemic diabetic patients are phenotypically different. Hence routine screening of uric acid is essential for proper diagnosis and appropriate treatment of hypouricemic diabetic patients.

Molecular epidemiology of Orientia tsutsugamushi from outbreak regions, Madhya Pradesh, central India.

Scrub typhus is a seriously neglected life threatening disease in Asia and the islands of the Pacific and Indian oceans. The causative agent is Orientia tsutsugamushi, an obligate intra-cytosolic bacterium transmitted to vertebrate animals such as human or rodent by larval trombiculid mites (chiggers). Here, we conducted an outbreak investigation in Madhya Pradesh state in central India after sudden upsurge in scrub typhus cases and mortality in humans. Sixty-five live traps were placed for capturing the rodents. The captured rodent species were identified and the samples were subjected to nested PCR targeting 56kDa TSA gene. Analysis revealed for the first-time predominant circulation of Karp genotype in this region. The vector species involved in transmission is Leptotrobidium deliense. In conclusion, we reported the circulation of Karp strain in outbreak regions of Madhya Pradesh and suggest that public health monitoring and surveillance needs to be improved. Studies on antigenic diversity, association of strains with clinical spectrum and pathogenicity in the local setup will be essential for development of region-specific diagnostics and vaccines.

Gerontolizing Nephrology: Spectrum of Histopathological Findings of Kidney Biopsy in the Elderly.

INTRODUCTION: The spectrum of renal disorder in the elderly differs from the younger population. There is a paucity of literature regarding kidney biopsy in elderly. This study aims to highlight the clinical profile and histopathological spectrum of the elderly patient undergoing a renal biopsy. MATERIALS AND METHODS: This retrospective study included all patients (age ≥60 years) undergoing native renal biopsies from January 2012 to December 2017. The clinical profile, laboratory parameters, and renal biopsy findings of these patients were recorded from the case files. RESULTS: Out of 1656 renal biopsies performed during the study period, 230 (13.9%%) performed on the elderly were included. Mean age was 64.02 ± 7.87 years (Range: 60-87 years), and males were predominant (70.4%). The commonest indication for biopsy was nephrotic syndrome (NS) (49.6%) followed by Rapidly progressive renal failure (RPRF) (20.9%) and Acute Kidney Injury (AKI) (15.7%). The most frequent histological diagnosis was membranous nephropathy (15.2%) followed by amyloidosis (13.9%) and Focal Segmental Glomerulosclerosis (FSGS) (13.0%). The commonest cause of NS was MGN (29.8%) followed by FSGS (24.6%) and amyloidosis (22.8%). The commonest cause of nephritic syndrome was Diffuse Proliferative Glomerulonephritis (29.4%) and Membranoproliferative Glomerulonephritis (29.4%). Hypertensive nephrosclerosis (40.0%) and diabetic nephropathy (26.7%)) were the commonest histological diagnosis in the patients who underwent renal biopsy for clinical Chronic kidney disease. Crescentic GN (35.4%) and Myeloma cast nephropathy 14.6%) were the commonest cause of RPRF while Acute Tubular Necrosis (41.7%) was the commonest cause of AKI. None of the patients had major complications. CONCLUSION: Renal biopsy is safe in the elderly and provides a wealth of information with regards to the diagnosis and prognosis of renal disorder.

Suboptimal glycemic control among subjects with diabetes mellitus in India: a subset analysis of cross-sectional wave-7 (2016) data from the International Diabetes Management Practices Study (IDMPS).

OBJECTIVE: To assess the real-world management practices of subjects with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM) in India. METHODS: This cross-sectional study was conducted between 7 March 2016 and 15 May 2016 in India as part of the seventh wave (2016) of the International Diabetes Management Practices Study (IDMPS). Adult subjects with T1DM or T2DM visiting physicians during a 2-week recruitment period were included. RESULTS: A total of 55 physicians included 539 subjects who met eligibility criteria. Of 495 subjects with T2DM, 303 were treated with oral glucose lowering drugs (OGLDs) only, 158 were treated with OGLD + insulin, and 27 received insulin only. Among 44 subjects with T1DM receiving insulin, 13 (29.5%) were also treated with OGLD therapy. The most commonly used insulin regimens were basal alone (69/184; 37.5%) and premixed alone (63/184; 34.2%) in subjects with T2DM, and basal + prandial insulin (24/44; 54.5%) in subjects with T1DM. Proportions of subjects achieving glycemic targets were low [glycated haemoglobin (HbA1c) <7%: T1DM = 7.3% (3/44), T2DM = 25.2% (106/495); as targeted by the treating physician: T1DM = 31.8% (14/44), T2DM = 32.1% (59/185); global target: T1DM = 4.8% (2/42) and T2DM = 1.7% (8/482)]. In subjects with T2DM, HbA1c <7% was noted in 11/22 subjects receiving insulin only and 76/260 receiving only OGLDs. Lack of experience in self-managing insulin dosing, poor diabetes education and failure to titrate insulin dosages were the main reasons for non-achievement of glycemic targets. CONCLUSION: Timely insulinization, education and empowerment of people with diabetes may help improve glycemic control in India.

Sofosbuvir-Velpatasvir Fixed Drug Combination for the Treatment of Chronic Hepatitis C Infection in Patients With End-Stage Renal Disease and Kidney Transplantation.

INTRODUCTION: India is witnessing high hepatitis C virus (HCV) infection burden in patients of chronic kidney disease. Due to unavailability of costly Kidney Disease Improving Global Outcomes-recommended directly acting antiviral drugs, a widely available pan-genotypic combination of Sofosbuvir and Velpatasvir can become an economical option. Data regarding treatment experience of sofosbuvir-velpatasvir combination in chronic kidney disease is scarce. No data from India have been published in patients on renal replacement therapies till now. METHODS: This retrospective analysis included all patients of end-stage renal disease on maintenance hemodialysis with treatment-naïve chronic HCV infection treated with sofosbuvir (400 mg) and velpatasvir (100 mg) fixed-dose combination. Pretreatment routine investigations were performed, which included HCV viral load, genotype, fibro scan, endoscopy for esophageal varices, and portal vein Doppler. The patients were followed up with HCV viral load to declare sustained virologic response. RESULT: patients were included with a mean age of 39.8 ± 10.8 years, and 77.4% were male. Genotype 1 was found to be most prevalent (67.7%), with a median viral load of 106copies/ml. Six (19.3%) patients had hepatitis B virus co-infection. Three (9.7%) patients had cirrhosis. Sustained virologic response (SVR12) was achieved in 30 (96.8%) patients, and one (3.2%) patient had relapse. Furthermore, 14 (45.2%) patients underwent renal transplantation, and none of them had relapsed. Dyspepsia (9.7%) was the most common side effect observed with no major adverse effect. CONCLUSION: Our study showed excellent efficacy with the safety profile of this drug combination in end-stage renal disease patients. However, larger prospective studies and multicenter randomized controlled trials are needed for further confirmation.

N-Mannich Bases of Aromatic Heterocyclic Amides: Synthesis via Copper-Catalyzed Aerobic Cross-Dehydrogenative Coupling under Ambient Conditions.

An efficient and facile method to synthesize N-Mannich bases has been developed using an inexpensive copper(I) bromide/air catalyst system at ambient temperature. A cross-dehydrogenative coupling of N,N-dimethylarylamines occurs efficiently with aromatic heterocyclic amides (oxindoles, isatins), cyclic amides (lactams), simple amides (benzamide), as well as imides (succinimide, phthalimide) to furnish the corresponding amidated/imidated derivatives in good to excellent yields. Preliminary mechanistic and isotope-labeling studies suggest the reaction follows a radical pathway and involves an iminium ion intermediate.

Quinapyramine sulfate-loaded sodium alginate nanoparticles show enhanced trypanocidal activity.

AIM: To reduce the dose, toxic effects and to ensure sustained release of quinapyramine sulfate (QS), a highly effective drug against Trypanosoma evansi. MATERIALS & METHODS: QS-loaded sodium alginate nanoparticles (QS-NPs) were formed by emulsion-crosslinking technology using dioctyl-sodium-sulfosuccinate and sodium alginate. The formulation was characterized for size, stability, morphology and functional groups by a zetasizer, scanning electron microscopy, atomic force microscopy, transmission electron microscopy and Fourier transform infrared spectroscopy. In vitro safety and toxicity studies were performed by metabolic assay in Vero cell lines, and in vivo efficacy was evaluated in mice. RESULTS: QS-NPs were <60 nm with 96.48% entrapment efficiency and 3.70% drug loading. The formulation showed an initial burst effect followed by slow drug release in accordance with quasi-Fickian Higuchi diffusion mechanism. QS-NPs were much less toxic and able to clear the parasite at a much lower concentration than QS. CONCLUSION: The QS-NPs synthesized are safe, less toxic and highly effective compared with QS.