Ashish Kumar Sharma

Triple verses glimepiride plus metformin therapy on cardiovascular risk biomarkers and diabetic cardiomyopathy in insulin resistance type 2 diabetes mellitus rats

IRtype2DM patients are often treated with a combination of antidiabetic agents. Drugs with different complementary mechanisms of action frequently used in daily clinical practice but glycemic control with monotherapeutic attempts fail in the long run. To date, biomarkers for cardiovascular risk and insulin sensitivity with combination of triple oral hypoglycemic therapies are not fully revelled in view of additional cardiovascular risk reduction. In the present study, IRtype2DM induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rat model. IRtype2DM rats were selected by determining FPI [>60 pmol/l]; HOMA-IR & Hyperinsulinemic euglycemic clamp technique at 6 weeks and then treated for 8 weeks with (i) Metformin (120 mg/kg, o.d.)+Glimepiride (1mg/kg, o.d.), (ii) Metformin (265 mg/kg, o.d.)+Rosiglitazone (1mg/kg, o.d.)+Glimepiride (0.7 mg/kg, o.d.). At the end cardiovascular risk parameters evaluated by ELISA kits and insulin sensitivity were determined by HOMA-IR. In conclusion, triple oral hypoglycemic therapy improves glycemic control, insulin sensitivity, retards diabetic cardiomyopathy and does not increased body weight; decrease more detrimental inflammatory markers, increase interleukin-10 and adiponectin in neonatal streptozotocin-induced IRtype2DM Wistar Albino Rats. Triple therapy showed a synergistic effect and was promising in insulin resistance, better in additional cardiovascular risk reduction and those nonresponders to metformin add on glimepiride therapy.

Sitagliptin, sitagliptin and metformin, or sitagliptin and amitriptyline attenuate streptozotocin-nicotinamide induced diabetic neuropathy in rats

Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neuropathy, and thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced with nicotinamide-streptozotocin. Drug treatment was initiated on the d 15, with the combination regimen of metformin, pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to significantly improved glycemic control, increased grip strength and paw jumping response on d 21, 28 and 35 (P < 0.001). Significant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21, 28 and 35 (P < 0.001). Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells, while administration of metformin and sitagliptin showed tissue regeneration and no body weight gain. In conclusion, treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain, but causes an increase in grip strength and pain sensitivity, exhibits neural protection, and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes.

Dual therapy of vildagliptin and telmisartan on diabetic nephropathy in experimentally induced type 2 diabetes mellitus rats

Introduction: The objective of this article is to investigate the combination of telmisartan with vildagliptin therapy versus monotherapy of vildagliptin and telmisartan on diabetic nephropathy in type 2 diabetes mellitus rats. Materials and methods: In adult rats streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg) were injected intraperitoneally to produce diabetic nephropathy. Rats of either sex allotted to the following groups: (i) triple therapy: metformin (120 mg/kg, o.d.) + pioglitazone (1.25 mg/kg, o.d.) + glimepiride (0.7 mg/kg, o.d.); (ii) dual therapy: vildagliptin (8.76 mg/kg, o.d.) + telmisartan (6.48 mg/kg, o.d.); (iii) vildagliptin (8.76 mg/kg, o.d.); and (iv) telmisartan (6.48 mg/kg, o.d.); therapy was carried out for 35 days orally. Weekly at days 7, 14, 21, 28 and 35, blood pressure, blood glucose level, body weight, blood serum creatinine level, protein albumin level in urine, and blood urea nitrogen (BUN) were estimated. Renal structural changes were observed. Results: Blood pressure, blood glucose level, blood serum creatinine level, protein albumin level in urine, BUN and renal deterioration increased significantly in diabetic rats compared with normal control rats. The vildagliptin + telmisartan treatment group showed no weight gain and controlled blood pressure, renovascular structural and biochemical parameters in diabetic neuropathy rats. Conclusions: The addition of telmisartan to vildagliptin demonstrated the best control over blood pressure, glycemia and diabetic nephropathy markers, renal structural changes and improvement of renal function as opposed to monotherapy with either drug, possibly because of the dual inhibitory effect on the renin–angiotensin system.

Involvement of adenosine and standardization of aqueous extract of garlic (Allium sativum Linn.) on cardioprotective and cardiodepressant properties in ischemic preconditioning and myocardial ischemia-reperfusion induced cardiac injury

The present study investigated the effect of garlic (Allium sativum Linn.) aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic preconditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the 0.05% dose was found to be the most effective. Higher doses (more than 0.05%) were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline (1,000 µmol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide.

Neurobrucellosis: A Case Report from Himachal Pradesh, India, and Review of the Literature

Human brucellosis is a multisystem disease that commonly presents as a febrile illness along with variable spectrum of clinical manifestations. Neurological complications include encephalitis, meningoencephalitis, radiculitis, myelitis, peripheral and cranial neuropathies, subarachnoid hemorrhage, and psychiatric manifestations. We report a case diagnosed as neurobrucellosis who presented with fever and bilateral upper motor neuron symptoms and signs along with bilateral sensorineural deafness. Diagnosis was confirmed by Rose Bengal Test (RBT) and standard tube agglutination test (SAT).

Design, development and permeation studies of nebivolol hydrochloride from novel matrix type transdermal patches

Background : Nebivolol hydrochloride is a third generation β-blocker with highly selective β1 -receptor antagonist with antihypertensive properties having plasma half life of 10 h and 12% oral bioavailability. The aim of the present investigation was to form matrix type transdermal patches containing Nebivolol hydrochloride to avoid its extensive hepatic first pass metabolism, lesser side effect and increase bioavailability of drug. Materials and Methods: Matrix type transdermal patches containing Nebivolol hydrochloride were prepared using EudragitRS100, HPMC K100M (2:8) polymers by solvent evaporation technique. Aluminum foil was used as a backing membrane. Polyethylene glycol (PEG) 400 was used as plasticizer and Dimethyl sulfoxide (DMSO) was used as a penetration enhancer. Drug polymer interactions determined by FTIR and standard calibration curve of Nebivolol hydrochloride were determined by using UV estimation. Result : The systems were evaluated physicochemical parameters and drug present in the patches was determined by scanning electron microscopy. All prepared formulations indicated good physical stability. In vitro drug permeation studies of formulations were performed by using Franz diffusion cells using abdomen skin of Wistar albino rat. Result showed best in vitro skin permeation through rat skin as compared to all other formulations prepared with hydrophilic polymer containing permeation enhancer. Conclusions: It was observed that the formulation containing HPMC: EudragitRS100 (8:2) showed ideal higuchi release kinetics. On the basis of in vitro drug release through skin permeation performance, Formulation F1 was found to be better than other formulations and it was selected as the optimized formulation.

Cardioprotective activity of alcoholic extract of Tinospora cordifolia (Willd.) Miers in calcium chloride-induced cardiac arrhythmia in rats.

The present study investigated the antiarrhythmic activity of alcoholic extract of Tinospora cordifolia (T. cordifolia) in CaCl2 induced arrhythmia. CaCl2 (25 mg/kg) was administered by intravenous infusion (iv) to produce arrhythmia in rats. The animals were then treated with T. cordifolia extract (150, 250, and 450 mg/kg) and verapamil (5 mg/kg,iv). Lead II electrocardiogram was monitored. Plasma calcium, sodium and potassium levels were measured. In CaCl2 induced arrhythmia, heart rate was decreased by 41.10%, T. cordifolia at 150, 300, and 450 mg/kg decreased the heart rate by 26.30%, 29.16%, and 38.29%, respectively, and verapamil reduced the heart rate by 9.70% compared to the normal group. The PQRST waves were normalized and atrial and ventricular fibrillation was controlled in rats treated with verapamil and T. cordifolia. CaCl2 increased calcium and sodium levels and decreased potassium levels in blood. T. cordifolia dose-dependently decreased calcium and sodium levels and increased potassium levels. Hence, T. cordifolia can be used in antiarrhythmic clinical settings and beneficial in atrial and ventricular fibrillation and flutter and may be indicated in ventricular tachyarrhythmia.

Advanced age and higher national institutes of health stroke scale score as predictors of poor outcome in ischemic stroke patients treated with alteplase: A study from a tertiary care centre in rural North-west India

Introduction: Thrombolytic therapy in acute ischemic stroke has been approved for treatment of acute stroke for past two decades. However, identification of predictors of poor outcome after the intravenous (IV) alteplase therapy in acute stroke patients is a matter of research. The present study was conducted with the aim of identifying poor prognostic factors in patients of acute ischemic stroke patients. Methods: The data of 31 acute stroke patients treated with alteplase were gathered to identify the factors that were independent predictors of the poor outcome. Outcome was dichotomized using modified Rankin scale (mRS) score and National Institutes of Health Stroke Scale (NIHSS) score at 3 months after treatment into good outcome mRS – 0–2 and poor outcome mRS – 3–6. Predictors of poor outcome were analyzed. Results: Good outcome (mRS – score 0–2) was seen in 15 (48.4%) patients with median age of (60) and poor outcome (mRS – score 3–6) was seen in 16 (51.6%) patients median age of 75 years, which was statistically significant with the P = 0.002. The presence of risk factors such as hypertension, diabetes, dyslipidemia, smoking, alcohol intake, history of stroke, coronary artery disease, and rheumatic heart disease among the two groups did not seem influence outcome. The severity of stroke as assessed by NIHSS score at the time of presentation was significantly higher among the patients with poor outcome, with P = 0.01. Conclusion: Advance age and higher NIHSS score at the time of onset of stroke and are the independent predictors of the poor outcome after thrombolysis with IV alteplase treatment in acute ischemic stroke patients.

Synthesis and Evaluating Anti-Inflammatory, Antibacterial activity of substituted benzylidene Thiazolidinediones

This compound we synthesize by a Knoevenagel condensation of 4-aminobenzaldehyde with compound (I) in presence of sodium acetate, but this compound do not comply with the primary aromatic amine test like nitrous acid test and carbylamine test as well as H1 NMR spectra, in this reaction the amine group of benzaldehyde was further reacted another molecules of aldehydes. We modified the process and synthesized compound (Ia), the nitro group of compound Ia was converted in amino group by reduction.

Postpartum pituitary apoplexy with isolated oculomotor nerve palsy: A rare medical emergency

Pituitary apoplexy is a clinical syndrome characterized by sudden onset headache, visual deficits, ophthalmoplegia, altered mental status, and hormonal dysfunction due to an expanding mass within the sella turcica resulting from hemorrhage or infarction of pituitary gland. We report a case of pituitary apoplexy that developed in postpartum period following postpartum hemorrhage and presented with isolated third cranial nerve palsy.