Y. A. Deshmukh

Bacopa monniera protects rat heart against ischaemia–reperfusion injury: role of key apoptotic regulatory proteins and enzymes

Objectives  Rat isolated hearts were perfused in a Langendorff model to study the cardioprotective effects of Bacopa monniera, a medicinal herb used in the Indian system of medicine, on cardiomyocyte apoptosis and antioxidant status following ischaemia–reperfusion (I‐R) injury.

Prescribing pattern and efficacy of anti-diabetic drugs in maintaining optimal glycemic levels in diabetic patients

Context: Despite the availability of efficacious anti-diabetic drugs, which act by different mechanisms to reduce the blood-glucose, the majority of people with diabetes on anti-diabetic drug therapy, have poor glycemic control and diabetic vascular complications. Aim and Objectives: The aim was to study the prescribing pattern and efficacy of anti-diabetic drugs in maintaining optimal glycemic levels in diabetic patients attending tertiary care teaching hospital in Navi Mumbai. Materials and Methods: A prospective, cross-sectional, observational survey was carried out in 100 patients of diabetes mellitus attending diabetes outpatient/medicine outpatient departments, to assess their prescribing pattern of anti-diabetic drugs, and their blood-glucose level was measured by Accu-Chek Active glucometer to determine their glycemic control. Results: Average number of anti-diabetic drugs per prescription was 1.4. Sulfonylureas were the most commonly prescribed class, but metformin (biguanide) was the commonest prescribed individual drug among oral hypoglycemic agents (OHA). Fixed dose combination of biguanide and sulfonylurea was prescribed commonly. Monotherapy dominated over polytherapy and there was a higher percentage of use of insulin in Type 2 diabetics. Only 41% of patients on anti-diabetic therapy had optimal glycemic control. The association between anti-diabetic therapy along with lifestyle modification and glycemic control was statistically significant (P = 0.0011). Conclusions: OHAs still dominate the prescribing pattern, but there was a shifting trend toward the use of insulin preparations in the management of Type 2 diabetes mellitus. In achieving optimal glycemic control, the efficacy of the anti-diabetic drugs was only 41%; therefore intensification of current drug treatment as well as planning multiple drug interventions with lifestyle modification is necessary.

Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats

Background. The incidence of metabolic syndrome co-existing with diabetes mellitus is on the rise globally. Objective. The present study was designed to develop a unique animal model that will mimic the pathological features seen in individuals with diabetes and metabolic syndrome, suitable for pharmacological screening of drugs. Materials and Methods. A combination of High-Fat Diet (HFD) and low dose of streptozotocin (STZ) at 30, 35, and 40 mg/kg was used to induce metabolic syndrome in the setting of diabetes mellitus in Wistar rats. Results. The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for the study to induce diabetes mellitus. Various components of metabolic syndrome such as dyslipidemia {(increased triglyceride, total cholesterol, LDL cholesterol, and decreased HDL cholesterol)}, diabetes mellitus (blood glucose, HbA1c, serum insulin, and C-peptide), and hypertension {systolic blood pressure} were mimicked in the developed model of metabolic syndrome co-existing with diabetes mellitus. In addition to significant cardiac injury, atherogenic index, inflammation (hs-CRP), decline in hepatic and renal function were observed in the HF-DC group when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis, and inflammation in heart, pancreas, liver, and kidney of HF-DC group as compared to NC. Conclusion. The present study has developed a unique rodent model of metabolic syndrome, with diabetes as an essential component.

Drug Utilization Study in Ophthalmology Outpatients at a Tertiary Care Teaching Hospital

In view of the advancement in drug development and availability of new ocular therapeutics in the discipline of ophthalmology, we attempted to study the drug utilization and describe the prescribing practices of ophthalmologists in a tertiary care teaching hospital. Method. A prospective, cross-sectional, observational study was conducted on patients attending Outpatient Department of Ophthalmology for curative complaints. Prescriptions of 600 patients treated were analyzed by the WHO prescribing indicators and additional indices. Results. Analysis showed that the average number of drugs per prescription was 1.49. Percentage of drugs prescribed by generic name was 2.35%. Percentage of encounters with antibiotics was 44.83%. Percentage of drugs prescribed from National Essential drug list (NEDL)/National Formulary of India (NFI) was 19.48%. Patients knowledge of correct dosage was 93.83%. Antimicrobial agents were the most commonly prescribed drugs followed by antiallergy drugs and ocular lubricants. Fluoroquinolones accounted for 60% of the total antimicrobial drugs, of which gatifloxacin was the most frequently prescribed fluoroquinolone. Conclusion. The study indicated an awareness of polypharmacy, but showed ample scope for improvement in encouraging the ophthalmologists to prescribe by generic name and selection of essential drugs from NEDL/NFI.

Myocardial Salvaging Effects of Berberine in Experimental Diabetes Co-Existing with Myocardial Infarction

INTRODUCTION Berberine, an isoquinoline alkaloid isolated from the Berberis aristata, has been shown to display a wide array of pharmacological activities (hypoglycaemic and hypolipidemic). AIM The present study was designed to investigate whether these pharmacological properties translate into the cardioprotective effects of Berberine in the setting of diabetes mellitus. MATERIALS AND METHODS Necessary approval from the Institutional Animal Ethics Committee was taken for the study. Experimental diabetes was produced with single dose of Streptozotocin (STZ): 45mg/kg ip and myocardial infarction was induced by administering Isoproterenol (ISP): 85mg/kg, sc to rats on 35(th) & 36(th) day. After the confirmation of diabetes on 7(th) day (>200mg/dl), Berberine (100 mg/kg) was administered orally to experimental rats from day 8 and continued for 30 days thereafter. Various anti-diabetic (Glucose, HbA1c), cardioprotective (CPK-MB), metabolic (lipid profile), safety {liver function (SGPT, kidney function (Creatinine)} and histopathological indices of injury were evaluated in Healthy Control, Diabetic Control and Berberine treated groups. RESULTS Administration of STZ-ISP resulted in a significant decrease in body weight (p<0.001), diabetic changes (increase in blood glucose, HbA1c), cardiac injury (leakage of myocardial CPK-MB), altered lipid profile, SGPT, creatinine levels (p<0.001) in the diabetic control group rats as compared to healthy control. Berberine treatment demonstrated significant antidiabetic as well as myocardial salvaging effects as indicated by restoration of blood glucose, HbA1c and CPK-MB levels (p<0.001) compared to diabetic control group. In addition, Berberine favourably modulated the lipid parameters (total cholesterol, triglycerides, HDL, LDL). Subsequent to ISP challenge, histopathological assessment of heart, pancreas and biochemical indices of injury confirmed the cardioprotective effects of Berberine in setting of diabetes. In addition, Berberine was found to be safe to the liver and kidney. CONCLUSION Berberine treatment produced myocardial salvaging effects in the setting of diabetes challenged with ISP induced myocardial necrosis. Cardioprotection may be attributed to anti-diabetic and hypolipidemic activities.

Medicinal Herbs can Play Significant Role in Attenuation of Ischemia and Reperfusion Injury

Nature has been a source of medicinal treatments for thousands of years and plant-derived products continue to play an essential role in the primary health care of about 80-85% of the world’s population. Medicinal herbs are widely used in Ayurveda, the Indian System of Medicine and have been observed to possess numerous activities with regard to cardiovascular system viz. antiplatelet, hypolipidemic, anti-inflammatory, hypoglycemic and hypotensive actions. Hence, these herbal extracts traditionally used have been evaluated scientifically in the present study with an aim to define the role of these agents in limiting the deleterious effects of myocardial ischemia and reperfusion (IR) injury by providing scientific data to validate their use as prophylactic approaches or as an adjunct to standard treatment (synthetic compounds employed in conventional treatment protocols) of ischemic heart disease. The efficacy of Withania somnifera (Ws), Curcuma longa (Cl) and Ocimum sanctum (Os), and herbal combination (HCB) including {Ws (50 mg/kg) + Cl (100 mg/kg) + Os (75 mg/kg} to limit injury in the setting of myocardial ischemia and reperfusion was explored in the present study. An open chest left anterior descending coronary artery (LAD) occlusion and reperfusion induced myocardial injury was used as the experimental model. Wistar albino rats were divided into ten groups and orally fed saline once daily (sham, control IR) or medicinal herbs (Ws/Cl/Os/HCB; Ws-IR, Cl-IR/Os-IR/HCB-IR) respectively for 1 month. On the 31st day in the rats of the Control IR and Ws-IR, Cl-IR/Os-IR/HCB-IR groups, LAD was occluded for 45 min, and reperfused for 1 h. Hemodynamic parameters were recorded at preset points and subsequently sacrificed for biochemical, immunohistochemical and pathological studies. In the control IR group, significant ventricular dysfunction, cardiac necrosis, apoptosis; decline in antioxidant status and elevation in lipid peroxidation was observed. Chronic oral treatment with HCB per se for 1 month resulted in significant enhancement of the myocardial endogenous antioxidant enzymes. Pretreatment with Ws, Cl and the herbal combination exerted significant cardioprotective effects in the experimental model of myocardial injury. The most remarkable observation of the present study was that cardioprotective effect exerted by HCB treatment was found to be superior to that shown by singular treatment with individual herbal extracts. The combination of herbal extracts was found to significantly ameliorate the ischemia and reperfusion cardiomyocyte apoptosis, cardiac dysfunction, compromised antioxidant status and histopathologic alterations as compared to control IR group. Cardioprotection by HCB treatment may be attributed to its favorable hemodynamic effects, myocardial adaptogenic properties, and significant antioxidant and antiapoptotic properties. Furthermore, HCB decreased the severity of pathological changes and significantly preserved the myocardial creatinine phosphokinase confirming its myocardial salvaging effects. Results clearly demonstrated the therapeutic potential of the herbal drugs in the treatment of myocardial ischemia and reperfusion injury. If the beneficial effects can be established in-patients, these findings may represent a novel adjunctive therapy of ischemic heart disease and Myocardial Infarction.

Drug Utilization studies in Glaucoma patients at MGM medical College and Hospital

The present study evaluated the pattern of drug usage for glaucoma. A Proforma was designed specifically for the study factoring patients’ demographical profile, prescription regimen. A total of 100 prescriptions of patients suffering from glaucoma were analyzed. Maximum cases (36%) belonged of age group 40 to 50 years with a gender ratio (Male/female) of 2.3. All the patients were diagnosed as suffering from primary open angle glaucoma out of which 82% had bilateral glaucoma. The average number of drugs per prescription was 1.23. The total no. of drug prescribed was 123 and 18% of prescriptions showed polypharmacy practice. Most commonly prescribed drug was Timolol (41%), followed by Brimonidine 16.26%. Bimatoprost (12.19%), Dorzolamide (11.38%), Latanaprost (5.69%). Fixed dose combination (Latanoprost+Timolol) was encountered in 14% of the glaucoma patient’s prescription, who had high intraocular pressure. Prescription of drugs by brand names instead of the recommended generic names is a matter of concern. Drug Utilization studies in Glaucoma patients at MGM medical College and Hospital

Cost Variation Study of Antidiabetics: Indian Scenario

The Indian pharmaceutical industry has become a cornucopia of medicines with wide variation in prices for the same medicine marketed under different brand names. Methods: CIMS (current index of medical stores) Apr-June 2013 & IDR (Indian drug review) issue3 2013 & MIMS (Monthly Index of Medical Specialities) Feb. 2013 were reviewed for the prices of drugs used in the management of diabetes mellitus and the percentage variation in price were calculated. Results: In Single drug therapy of oral antidiabetics maximum % price variation is 830. In combination therapies maximum % price variation is 475. In Insulin preparations maximum % price variation is 1881.24. Conclusion: The average percentage price variation of different brands of the same drug is very wide and hence the physician must keep this in mind while prescribing, considering the financial background of the patient. This is necessary since the drug treatment may extend for a long time; usually lifelong.

Tribulus teresstris modulates heat shock protein and key anti-apoptotic proteins in the Langendorff model of myocardial ischemia and reperfusion injury

The cardioprotective effects of Tribulus teresstris (Tt), a medicinal herb, used in Indian system of medicine was evaluated in the Langendorff model of myocardial ischemia and reperfusion (I-R) injury. Tt (1, 2.5, 5, 10 mg/kg) was orally fed to healthy experimental rats once a day for 21 days followed by global ischemia and reperfusion injury. Biochemical parameters: lipid peroxidation product thiobarbituric acid reactive substances (TBARS), endogenous antioxidant: glutathione, antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GSHPx)) and myocardial enzyme creatine phosphokinase (CPK) were evaluated. To correlate the biochemical derangement and altered cardiac performance during I-R, changes in the hemodynamic variables heart rate (HR) and coronary perfusion pressure (CPP) was measured. Myocardial apoptotic was quantified using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression of anti-apoptotic protein Bcl-2, pro-apoptotic protein Bax, enzyme: Caspase 3 and heat shock protein (HSP) in cardiac myocytes was detected by immunohistochemistry. As compared with sham group, the CPP, TBARS levels, myocardial apoptosis, expression of Caspase 3, Bax, heat shock protein (HSP 72) proteins were increased significantly in I-R control group. Tt pre-treatment significantly restored the antioxidant network of the myocardium, reduced myocardial apoptosis, Bax, HSP 72 protein expression. These beneficial effects also translated into favourable hemodynamic effects. Histopathological studies and myocardial CPK content further confirmed the cardioprotective effects of Tt (2.5 mg/kg) in the experimental model of I-R injury.

Natural dipeptidyl peptidase-IV inhibitor mangiferin mitigates diabetes- and metabolic syndrome-induced changes in experimental rats

Background Mangiferin (MNG) is known to possess antidiabetic and antioxidant activity. However, there is no experimental evidence presently available in the literature with regard to its ameliorating effects on diabetes mellitus coexisting with metabolic syndrome. Objective The present study was designed to evaluate the protective effects of MNG on various components of metabolic syndrome with diabetes as an essential component. Material and methods Adult Wistar rats were fed high-fat diets for 10 weeks and challenged with streptozotocin (40 mg/kg) at week three (high-fat diabetic control group). After the confirmation of metabolic syndrome in the setting of diabetes, MNG 40 mg/kg was orally fed to these rats from the fourth to tenth week. Results The treatment with MNG showed beneficial effects on various components of metabolic syndrome, such as reduced dyslipidemia (decreased triglyceride, total cholesterol, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol) and diabetes mellitus (reduced blood glucose and glycosylated hemoglobin). In addition, an increase in serum insulin, C-peptide, and homeostasis model assessment-β and a reduction in homeostasis model assessment of insulin resistance-IR were observed in MNG-treated group compared with high-fat diabetic control group. MNG was also found to be cardioprotective (reduction in creatine phosphokinase-MB levels, atherogenic index, high-sensitivity C-reactive protein). Reduction in serum dipeptidyl peptidase–IV levels in the MNG-treated group correlated with improvement in insulin resistance and enhanced β-cell function. Conclusion The present study has demonstrated antidiabetic, hypolipidemic, and cardioprotective effects of MNG in the setting of diabetes with metabolic syndrome. Thus, MNG has the potential to be developed as a natural alternative to synthetic dipeptidyl peptidase-IV inhibitors beneficial in this comorbid condition.