Study of Prevalence and Stages of diabetic nephropathy in a rural tertiary care centre - Southern India (2011-12)

Type 2 diabetes mellitus (T2DM) is an alarming health care concern the world over affecting more-than 220 million people worldwide according to World Health Organization. Kidney disease in diabetic patients is clinically characterized by increasing rates of urinary albumin excretion (UAE), starting from normoalbuminuria, which progresses to microalbuminuria, macroalbuminuria and eventually to End-Stage Renal Disease. Diabetic nephropathy has been categorized into stages based on the values of urinary albumin excretion and estimated glomerular filtration (eGFR). There is accumulating evidence suggesting that the risk for developing diabetes nephropathy and cardiovascular disease starts when UAE values are still within normoalbuminic range. Objective: To study the prevalence and stages of nephropathy in T2DM patients and to compare albumin levels with glycemic control in rural population. Methodology: Cross-sectional study was carried out from January 2011 to April 2012 among diabetic patients attending General Medicine department in RL Jalappa Hospital. Random blood sample and spot urine sample was collected for analysis and the data was collected in a predesigned, pretested semi-structured questionnaire. Results: The prevalence of diabetic nephropathy in our study was 37.02%. The prevalence microalbuminuria was 30.79% in males and 24.46% in females. The prevalence of overt nephropathy was 9.27% in males and 6.73% in females. Around 62.97% were in microalbuminuric range. 75.76% of the patients had poor glycemic control, but among patients with poor glycemic control 79.78% had overt nephropathy and 86.80% had microalbuminuria. Among patients with good glycemic control 20.28% had overt nephropathy and 13.19% had microalbuminuria. Conclusion: Microalbuminuria was earliest sign in Diabetic Nephropathy (DN). Progression of DN can be prevented on early detection. Poor glycemic control and duration of diabetes was associated with increase in UAE level and progression of Chronic Kidney Disease. Screening for DN at the time of diagnosis in T2DM and measures to reduce albuminuria at earliest could prevent further progression of DN in patients with T2D

LUCIFERASE REPORTER MYCOBACTERIOPHAGES FOR EVALUATING NORBORNENE-BASED ANTITUBERCULOSIS DRUG SUSCEPTIBILITY TESTING ON MYCOBACTERIUM TUBERCULOSIS

  Objective: In 2015, 9.6 million people around the world became sick with tuberculosis (TB) disease and 1.5 million TB-related deaths worldwide. Recent increasing incidence of multidrug-resistant (MDR; resistance to at least rifampicin (RIF) and isoniazid [INH]) and extensively drug-resistant (MDR resistance plus resistance to a fluoroquinolone and an aminoglycoside) makes TB a serious concern. Lot of research is needed to deal with this infectious disease for a better alternative in treatment or modification of these older TB drugs. The present study aimed at evaluating antimycobacterial activity of norbornene (NOR) derived INH copolymer with poly ethylene glycol (NOR- polyethylene glycol [PEG]-INH) a novel nanocarrier along with the anti-TB drug using luciferase reporter phages (LRPs).Methods: NOR derived INH accounts for 74% of INH, 24% of NOR, and 2% of PEG. H37Rv control strain, a sensitive, and a resistant strain of Mycobacterium TB (MTB) used in this study. The in vitro activity of the drug was evaluated using absolute concentration method. The resistant strain was evaluated using LRP assay to observe the minimum inhibitory concentration of the drug.Results: Reduction in light units was observed for the resistant strain exposed to plain INH and NOR-PEG-INH separately. 24% of reduction was observed in strains exposed to plain INH whereas 37% of reduction was observed in strains exposed to NOR-PEG-INH.Conclusion: NOR-based INH had better antimycobacterial activity compared to plain INH and RIF. Antimycobacterial activity of INH and RIF increases even with very low dosage with NOR conjugate

Does time of surgery influence the rate of false-negative appendectomies?:A retrospective observational study of 274 patients

Background Multiple disciplines have described an “after-hours effect” relating to worsened mortality and morbidity outside regular working hours. This retrospective observational study aimed to evaluate whether diagnostic accuracy of a common surgical condition worsened after regular hours. Methods Electronic operative records for all non-infant patients (age > 4 years) operated on at a single centre for presumed acute appendicitis were retrospectively reviewed over a 56-month period (06/17/2012–02/01/2017). The primary outcome measure of unknown diagnosis was compared between those performed in regular hours (08:00–17:00) or off hours (17:01–07:59). Pre-clinical biochemistry and pre-morbid status were recorded to determine case heterogeneity between the two groups, along with secondary outcomes of length of stay and complication rate. Results Out of 289 procedures, 274 cases were deemed eligible for inclusion. Of the 133 performed in regular hours, 79% were appendicitis, compared to 74% of the 141 procedures performed off hours. The percentage of patients with an unknown diagnosis was 6% in regular hours compared to 15% off hours (RR 2.48; 95% CI 1.14–5.39). This was accompanied by increased numbers of registrars (residents in training) leading procedures off hours (37% compared to 24% in regular hours). Pre-morbid status, biochemistry, length of stay and post-operative complication rate showed no significant difference. Conclusions This retrospective study suggests that the rate of unknown diagnoses for acute appendicitis increases overnight, potentially reflecting increased numbers of unnecessary procedures being performed off hours due to poorer diagnostic accuracy. Reduced levels of staffing, availability of diagnostic modalities and changes to workforce training may explain this, but further prospective work is required. Potential solutions may include protocolizing the management of common acute surgical conditions and making more use of non-resident on call senior colleagues

Rising burden of Hepatitis C Virus in hemodialysis patients

<p>Abstract</p> <p>Aim</p> <p>High prevalence of Hepatitis C virus (HCV) has been reported among the dialysis patients throughout the world. No serious efforts were taken to investigate HCV in patients undergoing hemodialysis (HD) treatment who are at great increased risk to HCV. HCV genotypes are important in the study of epidemiology, pathogenesis and reaction to antiviral therapy. This study was performed to investigate the prevalence of active HCV infection, HCV genotypes and to assess risk factors associated with HCV genotype infection in HD patients of Khyber Pakhtunkhwa as well as comparing this prevalence data with past studies in Pakistan.</p> <p>Methods</p> <p>Polymerase chain reaction was performed for HCV RNA detection and genotyping in 384 HD patients. The data obtained was compared with available past studies from Pakistan.</p> <p>Results</p> <p>Anti HCV antibodies were observed in 112 (29.2%), of whom 90 (80.4%) were HCV RNA positive. In rest of the anti HCV negative patients, HCV RNA was detected in 16 (5.9%) patients. The dominant HCV genotypes in HCV infected HD patients were found to be 3a (n = 36), 3b (n = 20), 1a (n = 16), 2a (n = 10), 2b (n = 2), 1b (n = 4), 4a (n = 2), untypeable (n = 10) and mixed (n = 12) genotype.</p> <p>Conclusion</p> <p>This study suggesting that i) the prevalence of HCV does not differentiate between past and present infection and continued to be elevated ii) HD patients may be a risk for HCV due to the involvement of multiple routes of infections especially poor blood screening of transfused blood and low standard of dialysis procedures in Pakistan and iii) need to apply infection control practice.</p

Dielectric disorder in two-dimensional materials

Understanding and controlling disorder is key to nanotechnology and materials science. Traditionally, disorder is attributed to local fluctuations of inherent material properties such as chemical and structural composition, doping or strain. Here, we present a fundamentally new source of disorder in nanoscale systems that is based entirely on the local changes of the Coulomb interaction due to fluctuations of the external dielectric environment. Using two-dimensional semiconductors as prototypes, we experimentally monitor dielectric disorder by probing the statistics and correlations of the exciton resonances, and theoretically analyse the influence of external screening and phonon scattering. Even moderate fluctuations of the dielectric environment are shown to induce large variations of the bandgap and exciton binding energies up to the 100 meV range, often making it a dominant source of inhomogeneities. As a consequence, dielectric disorder has strong implications for both the optical and transport properties of nanoscale materials and their heterostructures

Anti-apoptotic effect of HCV core gene of genotype 3a in Huh-7 cell line

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) Core protein regulates multiple signaling pathways and alters cellular genes expression responsible for HCV induced pathogenesis leading to hepatocellular carcinoma (HCC). Prevalence of HCV genotype 3a associated HCC is higher in Pakistan as compare to the rest of world; however the molecular mechanism behind this is still unclear. This study has been designed to evaluate the effect of HCV core 3a on apoptosis and cell proliferation which are involved in HCC</p> <p>Methodology</p> <p>We examined the in vitro effect of HCV Core protein of genotype 3a and 1a on cellular genes involved in apoptosis by Real time PCR in liver cell line (Huh-7). We analyzed the effect of HCV core of genotype 1a and 3a on cell proliferation by MTT assay and on phosphrylation of Akt by western blotting in Huh-7 cells.</p> <p>Results</p> <p>The HCV 3a Core down regulates the gene expression of Caspases (3, 8, 9 and 10), Cyto C and p53 which are involved in apoptosis. Moreover, HCV 3a Core gene showed stronger effect in regulating protein level of p-Akt as compared to HCV 1a Core accompanied by enhanced cell proliferation in Huh-7 cell line.</p> <p>Conclusion</p> <p>From the current study it has been concluded that reduced expression of cellular genes involved in apoptosis, increased p-Akt (cell survival gene) and enhanced cell proliferation in response to HCV 3a core confirms anti apoptotic effect of HCV 3a Core gene in Huh-7 that may lead to HCC.</p

Inhibition of HCV 3a genotype entry through Host CD81 and HCV E2 antibodies

<p>Abstract</p> <p>Background</p> <p>HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage hepatocellular carcinoma and death. HCV glycoproteins play an important role in HCV entry by binding with CD81 receptors. Hence inhibition of virus at entry step is an important target to identify antiviral drugs against HCV.</p> <p>Methods and result</p> <p>The present study elaborated the role of CD81 and HCV glycoprotein E2 in HCV entry using retroviral pseudo-particles of 3a local genotype. Our results demonstrated that HCV specific antibody E2 and host antibody CD81 showed dose- dependent inhibition of HCV entry. HCV E2 antibody showed 50% reduction at a concentration of 1.5 ± 1 μg while CD81 exhibited 50% reduction at a concentration of 0.8 ± 1 μg. In addition, data obtained with HCVpp were also confirmed with the infection of whole virus of HCV genotype 3a in liver cells.</p> <p>Conclusion</p> <p>Our data suggest that HCV specific E2 and host CD81 antibodies reduce HCVpp entry and full length viral particle and combination of host and HCV specific antibodies showed synergistic effect in reducing the viral titer.</p

siRNAs: Potential therapeutic agents against Hepatitis C Virus

Hepatitis C virus is a major cause of chronic liver diseases which can lead to permanent liver damage, hepatocellular carcinoma and death. The presently available treatment with interferon plus ribavirin, has limited benefits due to adverse side effects such as anemia, depression and "flu-like" symptoms. Needless to mention, the effectiveness of interferon therapy is predominantly, if not exclusively, limited to virus type 3a and 3b whereas in Europe and North America the majority of viral type is 1a and 2a. Due to the limited efficiency of current therapy, RNA interference (RNAi) a novel regulatory and powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process represents an alternative option. Several reports have indicated the efficiency and specificity of synthetic and vector based siRNAs inhibiting HCV replication. In the present review, we focused that combination of siRNAs against virus and host genes will be a better option to treat HC

Site-Directed Mutations and the Polymorphic Variant Ala160Thr in the Human Thromboxane Receptor Uncover a Structural Role for Transmembrane Helix 4

The human thromboxane A2 receptor (TP), belongs to the prostanoid subfamily of Class A GPCRs and mediates vasoconstriction and promotes thrombosis on binding to thromboxane (TXA2). In Class A GPCRs, transmembrane (TM) helix 4 appears to be a hot spot for non-synonymous single nucleotide polymorphic (nsSNP) variants. Interestingly, A160T is a novel nsSNP variant with unknown structure and function. Additionally, within this helix in TP, Ala1604.53 is highly conserved as is Gly1644.57. Here we target Ala1604.53 and Gly1644.57 in the TP for detailed structure-function analysis. Amino acid replacements with smaller residues, A160S and G164A mutants, were tolerated, while bulkier beta-branched replacements, A160T and A160V showed a significant decrease in receptor expression (Bmax). The nsSNP variant A160T displayed significant agonist-independent activity (constitutive activity). Guided by molecular modeling, a series of compensatory mutations were made on TM3, in order to accommodate the bulkier replacements on TM4. The A160V/F115A double mutant showed a moderate increase in expression level compared to either A160V or F115A single mutants. Thermal activity assays showed decrease in receptor stability in the order, wild type>A160S>A160V>A160T>G164A, with G164A being the least stable. Our study reveals that Ala1604.53 and Gly1644.57 in the TP play critical structural roles in packing of TM3 and TM4 helices. Naturally occurring mutations in conjunction with site-directed replacements can serve as powerful tools in assessing the importance of regional helix-helix interactions