Wahid Ali

Effect of high-dose zinc supplementation with oral hypoglycemic agents on glycemic control and inflammation in type-2 diabetic nephropathy patients.

Objective: The study aims to evaluate the effect of zinc sulfate on markers of glycemic control, lipid profile and inflammation in type-2 diabetes with microalbuminuria patients. Materials and Methods: Type-2 diabetes with microalbuminuria patients on oral hypoglycemic agents (OHA) and angiotensin converting enzyme (ACE) inhibitors were selected and divided into 2 groups: One group (n = 27) continued with OHA alone, second group (n = 27) was on OHA and in addition 50 mg elemental zinc as zinc sulphate supplementation for 12 weeks. Fasting, post-prandial blood glucose, glycosylated hemoglobin, lipid profiles, inflammatory marker hs-CRP and urine microalbumin were measured. Results: There were no significant differences in biochemical status among groups at baseline. After receiving zinc, the mean fasting blood glucose (FBS), post-prandial blood glucose (PPBS) and glycosylated hemoglobin (HbA1c) were decreased significantly (P = 0.0001). Significant decrease was observed in TG (P = 0.002) and VLDL-cholesterol (P = 0.002), whereas there was no significant decrease in TC and LDL-cholesterol. The high-density lipoprotein (HDL) cholesterol was significantly (P = 0.0001) increased from baseline. Zinc supplementation had significant effects in decreasing serum hs-CRP from 10.51 ± 1.68 mg/L to 7.75 ± 1.56 mg/L (P = 0.0001) and microalbumin level from 146.87 ± 30.83 mg/day to 80.70 ± 33.99 mg/day (P = 0.0001). There were no significant changes in the levels of all these parameters in OHA group. Conclusion: Our results conclude that supplementation of zinc improved the effectiveness of OHA and may be beneficial in decreasing blood glucose, TG, urinary albumin excretion and inflammation in diabetic nephropathy patients and thus reducing the risk of complications.

Epidemiology and mortality of burns in the Lucknow Region, India-A 5 year study

Nearly 95% of global burn deaths and disabilities are estimated to occur in low and middle income countries of the world. Burns are extremely common and are a major public health problem in a developing country like India. The purpose of this study was to record and evaluate the causes and the magnitude of the fatal burns retrospectively. An analysis of autopsy records revealed 2225 (10.7%) cases of burns among the total autopsies done over 5 years period (1st January 2008-27th November 2012) in the mortuary of Forensic Medicine & Toxicology, K.G.M.U., Lucknow. The majority of deaths (88.8%) occurred between 10 and 49 years of age group with a preponderance of females (87.5%). The flame burns were seen in 60.1% of the victims. The majority of burn incidents were suicidal (38.6%) in nature followed by accidental (37.3%) and homicidal (24.1%) deaths. The percentages of burns with a total body surface area (TBSA) over 50% were observed in most of the cases (82.5%). In most of the cases deaths occurred within a week (82%) and most of the victims died from septicaemia and pneumonia (43.7%) followed by neurogenic shock (28.5%). The results of this study provide the necessary information to implement programmes for health education relating to prevention of burns focusing on the domestic setting.

Lipoprotein (a) levels in relation to severity of coronary artery disease in north Indian patients

Background: Lipoprotein (a) [Lp (a)] is an established risk marker of coronary artery disease which is independent from other risk factors. Objective: The aim was to address the association between Lp (a) and CAD risk in North Indians. To evaluate whether high levels of lipoprotein (a) [Lp (a)] is a predictor of risk and is related to the severity of CAD. Materials and Methods: This was a cross-sectional study done on 360 patients presenting with chest pain. Coronary angiography revealed CAD in 270 patients and 90 patients without CAD. Lipoprotein (a) level, lipid profile, fasting blood glucose, anthropometric and clinical parameters were analyzed. Results: Lipoprotein (a) 21.0 mg/dL is associated with the presence of coronary lesions (P = 0.0001). A highly significant difference in Lp (a) levels was observed between normal coronaries vs. single-vessel disease, double-and triple-vessel disease ( P < 0.0001). Body mass index (BMI) was significantly raised in CAD group compared to normal coronary. Conclusion: Multivariate analysis found that Lp (a) was considered an independent predictor for severity of CAD and Lp (a) levels 21.0 mg/dL are associated with severe patterns of coronary atherosclerosis.

L-Plastin S-glutathionylation promotes reduced binding to β-actin and affects neutrophil functions

Posttranslational modifications (PTMs) of cytoskeleton proteins due to oxidative stress associated with several pathological conditions often lead to alterations in cell function. The current study evaluates the effect of nitric oxide (DETA-NO)-induced oxidative stress-related S-glutathionylation of cytoskeleton proteins in human PMNs. By using in vitro and genetic approaches, we showed that S-glutathionylation of L-plastin (LPL) and β-actin promotes reduced chemotaxis, polarization, bactericidal activity, and phagocytosis. We identified Cys-206, Cys-283, and Cys-460as S-thiolated residues in the β-actin-binding domain of LPL, where cys-460 had the maximum score. Site-directed mutagenesis of LPL Cys-460 further confirmed the role in the redox regulation of LPL. S-Thiolation diminished binding as well as the bundling activity of LPL. The presence of S-thiolated LPL was detected in neutrophils from both diabetic patients and db/db mice with impaired PMN functions. Thus, enhanced nitroxidative stress may results in LPL S-glutathionylation leading to impaired chemotaxis, polarization, and bactericidal activity of human PMNs, providing a mechanistic basis for their impaired functions in diabetes mellitus.

Temperature-Dependent Postmortem Changes in Human Cardiac Troponin-T (cTnT): An Approach in Estimation of Time Since Death.

Estimation of time of death is an indispensible requirement of every medico‐legal autopsy, but unfortunately, there is not a single method by which it could be determined accurately. This study focused on the temperature‐dependent postmortem degradation of cardiac troponin‐T and its association with postmortem interval (PMI) in human. The analysis involved extraction of the protein, separation by denaturing gel electrophoresis (SDS‐PAGE), and visualization by Western blot using cTnT‐specific monoclonal antibodies. The area of the bands within a lane was quantified by scanning and digitizing the image using Gel Doc (Universal Hood). The results indicate a characteristic banding pattern among human cadavers (n = 6) and a pseudo‐linear relationship between percentage of cTnT degradation and the log of the time since death (r > 0.95), which can be used to estimate the postmortem interval. The data presented demonstrate that this technique can provide an extended time range during which PMI can be more accurately estimated.

Intentional and non-intentional burn related deaths: a comparative study of socio-demographic profile

This is a retrospective study of 1689 consecutive admissions of burn deaths to the mortuary over a period of 5 years. The socio-demographic data was collected using special Performa and interviewing the family members, relatives, neighbours and from police reports. Depending on the presence or absence of intentional intent, cases were divided into two groups and compared with regard to their socio-demographic profile. Both groups did not differ significantly with regard to age, sex and educational status. The cases with intentional deaths came from nuclear family, unmarried, student, low socio-economic status, had more stressful life events and suffered larger burns injuries compared with those who experienced non-intentional deaths. The majority of the cases were below the age of 35, unemployed and females outnumbered males in both the groups.

Factors affecting response to medical management in patients of filarial chyluria: A prospective study

Introduction: Filarial chyluria is a common problem in filarial endemic countries. Its management begins with medical therapy but some patients progress to require surgery. The present study aimed to determine factors affecting response to medical management in patients of filarial chyluria. Materials and Methods: This prospective study conducted between August 2008 and November 2012, included conservatively managed patients of chyluria. Demographic profile, clinical presentation, treatment history and urinary triglycerides (TGs) and cholesterol levels at baseline were compared between the responders and non-responders. Apart from the clinical grade of chyluria, hematuria was evaluated as an independent risk factor. Results: Out of the 222 patients (mean age, 37.99 ± 13.29 years, 129 males), 31 patients failed to respond while 35 had a recurrence after initial response; the overall success rate being 70.3% at a mean follow-up of 25 months. No difference was observed in demographics, clinical presentation, presence of hematuria, disease duration and mean urinary TGs loss between responders and non-responders. On multivariate analysis, patients with treatment failure were found to have a higher-grade disease (14.3% Grade-I, 36.6% Grades-II and 60% Grade-III), higher number of pretreatment courses (1.59 ± 1.08 vs. 1.02 ± 0.79) and heavier cholesterol (26.54 ± 23.46 vs. 8.81 ± 8.55 mg/dl) loss at baseline compared with responders (P < 0.05). Conclusion: Conservative management has a success rate in excess of 70%, not affected by the disease chronicity, previous episodes and recurrent nature. However, higher-grade disease, extensive pre-treatment with drugs and higher urinary cholesterol loss at baseline are the predictors of poor response. Hematuria is not an independent poor risk factor for conservative management.

A Study of Unnatural Female Death Profile in Lucknow, India

AbstractEpidemiological and medicolegal, including forensic pathological, aspects of 456 cases of unnatural deaths of females aged 16 to 30 years were studied in Lucknow during the period of 1 year (May 2, 2011 to May 1, 2012). These constituted 62.5% of the total unnatural deaths autopsied from all ages in females. Most of the victims were young Hindu housewives killed or who died within 7 years of marriage. The most common cause was vehicular accidents followed by poisons and burns. The homicidal, suicidal, and accidental deaths were 87, 129, and 240, respectively. The common motives and circumstances were mental stress due to various reasons, family quarrel, maladjustment in married life, and cruelty by the in-laws. Level of education, joint family structure, unemployment, dependence of the woman on the in-laws, infidelity, large families, and failure in love in unmarried girls were other contributing factors affecting the incidence. The study suggests different measures to check unnatural female deaths to improve the situation.

Leptin augments protective immune responses in murine macrophages and enhances potential of miltefosine against experimental visceral leishmaniasis.

Adverse side effects and drug resistance issues are the two most important drawbacks which influence the widespread use of existing antileishmanial drugs. Use of immune stimulating agent with standard antileishmanial might be helpful to minimize the toxic effect of drug, shorten the dose regimen and delay the emergence of resistance. In the present study, we explored the in vitro immunomodulatory potential of an immunomodulator, leptin with lower concentration of standard drug, miltefosine. The level of Th1/Th2 cytokines, production of nitric oxide and reactive oxygen species and phagocytic activity was assessed by ELISA, Griess reaction and flow cytometric analysis, respectively. Leptin at a concentration of 15μg/mL showed heightened level of Th1 cytokines and nitric oxide generation from murine macrophages (J-774A.1 cells). Leptin (15μg/mL) also reduces the effective concentration of miltefosine by 2-folds from 7.5μM to 3.7μM. When given in conjunction with lower concentration of miltefosine (4μM), leptin (15μg/mL) significantly (***p<0.001) elevated the level of IL-12 (7.7 fold), TNF-α (8.1 fold) and nitric oxide (6.6 fold) along with markedly (***p<0.001) suppressed level of IL-10 and TGF-β when compared with untreated infected macrophages. Leptin plus miltefosine also induces the phagocytic ability (**p<0.01) of macrophages in comparison to leptin alone and miltefosine alone treated groups. These finding illustrate that leptin activates host macrophages to generate protective immune response for the successful elimination of Leishmania parasite at lower concentration of miltefosine and has potential for further exploration in experimental animal model of visceral leishmaniasis (VL).

Serum zinc levels and its association with vitamin A levels among tuberculosis patients

Introduction: One-third of the total human population is infected with the Mycobacterium tuberculosis. This bacterium causes illness in up to 9 million people annually and is responsible for three deaths every minute world-wide. Objective: To determine the association of serum zinc level with vitamin A level in active pulmonary tuberculosis (TB) cases. Materials and Methods: It was a cross-sectional study of 208 active pulmonary TB patients aged 18-55 years. Blood samples were obtained from these patients to determine the serum zinc and serum retinol levels. Results: The mean age of the patients was 30.56 (±11.38) years ranging from 18 years to 55 years. More than half (54.3%) of the patients were males and 63% were married. Body mass index of the patients was 18.40 ± 3.10. The serum zinc and vitamin A levels among the patients were 9.60 (±0.86) μmol/l and 0.77 (±0.22) μmol/l respectively. However, haemoglobin, white blood cell, erythrocyte sedimentation rate, and serum albumin were 10.02 (±1.33) g/dl, 10076.01 (±1822.67) cell/mm3, 14.50 (±2.95) mm/h and 3.40 (±0.32) g/dl respectively. There was a strong correlation between serum zinc and vitamin A levels (r = 0.86, P < 0.01). Vitamin A levels were not significantly different among the different age groups; however, this was significantly (P = 0.001) higher in male (0.82 ± 0.23, 95% confidence interval [CI] =0.77-0.86) patients as compared to females (0.71 ± 0.20, 95% CI = 0.67-0.75). Conclusion: Zinc deficiency may indirectly influence the metabolism of Vitamin A via reduction of the levels of circulating proteins.