Comparative Evaluation of Angiotensin-Converting Enzyme Inhibitors for their Beneficial Effects in Patients with Ischemic LV Systolic Dysfunction and Undergoing Coronary-Artery Bypass Surgery.

We compared three angiotensin-converting enzyme (ACE) inhibitors, captopril, perindopril, and ramipril, in the presented prospective study for their effectiveness in patients having left ventricular (LV) systolic dysfunction and undergoing coronaryartery bypass grafting (CABG). We enrolled 27 patients in captopril, 43 patients in perindopril, and 70 patients in ramipril group. There was about 25%–36% rise in LVEF after 3 and 6 months of ACE inhibitor administration in all three groups. The reduction in LV diameters did not differ significantly amongst the three groups. There was a significant decrease (p < 0.05) in LV end-diastolic diameter from baseline levels in captopril and perindopril groups after 3 months that got increased after 6 months but remained below pretreatment levels in both the groups. In ramipril group, there was no much change in this parameter from baseline levels at 3 and 6 months of treatment. After 6 months of treatment, the percent reduction in LV end-systolic diameter was also sustained in perindopril-treated patients. The percent reduction was greater in the perindopril group (3 and 6 months: 7.39 ± 5.94 and 7.73 ± 3.43, respectively) as compared to that observed in captopril group (3 and 6 months: 5.67 ± 1.05 and 2.52 ± 3.11, respectively) and ramipril group (3 and 6 months: 7.30 ± 2.75 and 4.93 ± 3.22, respectively). Mitral-valve regurgitation was greatly reduced in the captopril group at 3 as well 6 months of ACE inhibitor administration. However, the percent reduction from baseline levels was not statistically significant amongst the three groups. The percent improvement in functional status was significantly greater in the ramipril treatment group (36.46 ± 3.14) after 6 months of treatment as compared to that of captopril (6.67 ± 10.64) and perindopril (4.17 ± 2.73) group. In conclusion, our data show equal beneficial effects with all three ACE inhibitors under investigation in CABG patients with LV systolic dysfunction, with marginal superiority for perindopril.

Hepatoprotective activity of Hemidesmus indicus R. br. in rats.

Treatment of rats with paracetamol and CCl4 produced a significant increase in the levels of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total and direct bilirubin. Rats pretreated with methanolic extract of roots of H. indicus (100-500 mg/kg body weight, po) exhibited rise in the levels of these enzymes but it was significantly less as compared to those treated with paracetamol or CCl4 alone. The results of methanolic extract of H. indicus were comparable with the standard hepatoprotective agent silymarin (100 mg/kg). Maximum hepatoprotective effect was found to be at the dose of 250 mg/kg body weight in case of CCl4 induced hepatic damage while 500 mg/kg body weight in case of paracetamol induced hepatic damage. The results suggest that methanolic extract of H. indicus roots possesses a potential antihepatotoxic activity.

Spotted dermopathy in a diabetic patient due to insulin allergy.

A rare case of diabetic patient who developed multiple cutaneous hyperpigmented spots following bovine isophane (NPH) insulin injection is described here.

Superiority of dat over elisa as a diagnostic and seroepidemiological tool for the diagnosis of Indian kala-azar.

The aim of this study was to evaluate two methods for the diagnosis of Kala-azar. The sera of 160 individuals were evaluated by ELISA using soluble antigen and direct agglutination test (DAT) for Kala-azar. These were categorized as 100 cases of clinically and parasitologically confirmed Kala-azar and 60 controls. The controls included clinically suspected but parasitologically not confirmed Kala-azar patients (10), endemic normals (15), non-endemic normals (19), typhoid fever (10) and malaria (15). The positivity rate amongst the clinically and parasitologically confirmed Kala-azar patients by ELISA and DAT were 93% and 98% respectively. Out of 10 clinically suspected Kala-azar cases three showed positive reaction in ELISA and two in DAT. Of the endemic normals, one case was found positive by both the tests whereas ELISA was found positive in one additional case. DAT did not show any cross reactivity with malaria while ELISA was found positive in one case. Both endemic normals and typhoid fever cases showed no reaction by both tests. ELISA showed a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 93%, 90%, 93% and 90% respectively while for DAT these values were 98%, 95%, 98 and 95% respectively. The diagnostic accuracy for ELISA and DAT was found to be 91.9% and 96.9%, respectively. The present study shows that DAT is a simple, sensitive, specific and cost effective test with high PPV and NPV along with approximately 97% diagnostic accuracy and is comparable to ELISA. It may be applied for the routine diagnosis as well as seroepidemiological study of Kala-azar.

Asparagus racemosus--an update.

Asparagus racemosus (Shatavari) is recommended in Ayurvedic texts for prevention and treatment of gastric ulcers, dyspepsia and as a galactogogue. A. racemosus has also been used successfully by some Ayurvedic practitioners for nervous disorders, inflammation, liver diseases and certain infectious diseases. However, no scientific proof justifying aforementioned uses of root extract of A. racemosus is available so far. Recently few reports are available demonstrating beneficial effects of alcoholic and water extracts of the root of A. racemosus in some clinical conditions and experimentally induced diseases, e.g. galactogogue effect, antihepatotoxic and immunomodulatory activities. The present article includes the detailed exploration of pharmacological properties of the root extract of A. racemosus reported so far.

Myopathy secondary to simvastatin in a type 2 diabetic patient.

The most important but rare adverse effect of simvastatin is myopathy. In megatrials with simvastatin, the overall incidence of myopathy is 0.025%. We present a case of myopathy presenting as proximal muscle weakness in both upper limbs secondary to simvastatin which reversed spontaneously after cessation of the drug.

Effect of chronic treatment with losartan on streptozotocin induced diabetic rats.

Treatment of rats with streptozotocin (STZ, 45mg/kg, i.v.,single dose) produced cardinal symptoms of diabetes mellitus including hyperglycemia, hypoinsulinemia and increase in blood pressure. Treatment with losartan--an angiotensin (AT1) receptor antagonist, 2 mg/kg, po for 6 weeks decreased the blood glucose levels by 16.5%. There was 190% increase in AUCglucose and 59.4% decrease in AUCinsulin in STZ-diabetic rats as compared to control rats. Treatment with losartan caused slight decrease in AUCglucose and slight increase in AUCinsulin. There was no significant difference in insulin sensitivity (K(ITT)) index of STZ-diabetic group as compared to control. Losartan treatment failed to alter these levels significantly. Serum cholesterol and creatinine levels were found to be increased significantly in STZ-diabetic rats. Treatment with losartan significantly prevented the rise in cholesterol and creatinine levels by 20.1 and 81% respectively. The results suggest that losartan produces some beneficial effects in STZ-diabetic rats.

Blackwater fever treated with artemether.

Blackwater fever is a rare manifestation of falciparum malaria characterized by sudden intravascular hemolysis followed by fever and hemoglobinuria. We present a case of blackwater fever, having occurred after administration of quinine, which was treated successfully with artemether.

Coronary risk and dyslipidemia in type 2 diabetic patients.

OBJECTIVES: A prospective study was carried out to find out the percentage of dyslipidemia in type 2 diabetics, to study the pattern of dyslipidemia, categorize the levels of LDL, HDL and triglycerides into higher, borderline and lower risk of developing coronary heart disease in type 2 diabetics and to compare the lipid profile with non-diabetics. MATERIAL AND METHODS: Five hundred patients of type 2 diabetes mellitus and 150 age, sex and BMI matched non-diabetic healthy individuals were studied. The labelling of dyslipidemia and the categorization of risk for developing coronary heart disease (CHD) was done according to the guidelines of American Diabetes Association (ADA, 1998). RESULTS: Dyslpidemia was present in 89% of diabetic patients with LDL hyperlipoproteinemia (LDL > 100 mg%) in 76%, HDL dyslipidemia (HDL < 35 mg%) in 58%, hypertriglyceridemia (TG > 200 mg%) in 22% patients. On analysing CHD risk based on lipid profile, it was revealed that in LDL moiety 48% fell in higher risk of CHD (LDL > 130 mg%), 28% in borderline risk (LDL 100-130 mg%) and 24% (LDL < 100 mg%) in lower risk. For HDL 18.5% fell in higher risk (HDL < 35 mg%) and TG only 0.5% fell in higher risk (TG > 400 mg%). The lipid profile was significantly altered in diabetic patients as compared to non diabetics. CONCLUSIONS: The major concern which our study highlights is the high percentage of LDL dyslipidemia majority of whom fell in higher risk of developing CHD. Triglyceride and HDL levels were of lesser significance when newer ADA (1998) criteria for dyslipidemia were applied.

Toxic epidermal necrolysis secondary to carbamazepine in a patient with human immunodeficiency virus infection.

Toxic epidermal necrolysis (TEN) is a rare but very serious dermatologic disorder and is seen more commonly in human immunodeficiency virus (HIV) infected patients. We present a case of TEN in HIV infected person secondary to carbamazepine who responded favourably to corticosteroids.

Effect of chronic treatment with Bis(maltolato)oxovanadium (IV) in rat model of non-insulin-dependent-diabetes.

Effect of chronic treatment with Bis(maltolato)oxovanadium (IV) (BMOV) was studied in streptozotocin (STZ)-induced neonatal non-insulin-dependent-diabetic (NIDDM) rats. Intraperitoneal injection of STZ (90 mg kg(-1)) in Wistar rat pups (day 2 old) produced mild hyperglycemia, impaired glucose tolerance and insulin resistance at the age of 3 months. Treatment with BMOV (0.23 mM kg(-1)) in drinking water for 6 weeks produced a significant decrease in elevated serum glucose levels without any significant change in serum insulin levels in diabetic rats. BMOV treatment significantly decreased integrated area under the glucose curve without any significant change in integrated area under the insulin curve indicating improved glucose tolerance. Treatment also significantly increased K(ITT) value of diabetic rats indicating increased insulin sensitivity. BMOV treatment significantly reduced hypercholesterolemia in diabetic rats. Treatment also significantly decreased serum triglyceride levels in both diabetic and non-diabetic rats. The data suggest that chronic BMOV treatment improves glucose and lipid homeostasis. These effects appear to be due to the insulin sensitizing action of vanadium.

Lipid-lowering effect of simvastatin in patients of type 2 diabetes mellitus.

BACKGROUND: Dyslipidemia is an important factor in causation of macrovascular disease in type 2 diabetics. The role of simvastatin in the management of dyslipidemia in patients with type 2 diabetes mellitus is not very well elucidated, particularly in the context of the recent American Diabetes Association criteria 2001. The American Diabetes Association suggests that aggressive therapy of diabetic dyslipidemia will reduce the risk of coronary heart disease in diabetics and that optimal levels are serum low-density lipoprotein cholesterol <2.60 mmol/L (< 100 mg/dl), high-density lipoprotein cholesterol >1.1 5 mmol/L (>45 mg/dl) and triglycerides <2.30 mmol/L, (<200 mg/dl).This study was planned to compare the effect of simvastatin together with behavioral modification and behavioral modification alone, in age, sex and body mass index matched patients with type 2 diabetes mellitus with dyslipidemia, in reaching the target levels of various lipids as suggested by the American Diabetes Association criteria 2001. METHODS AND RESULTS: An open-label, prospective study was conducted on 80 patients with type 2 diabetes mellitus, who had fair to moderate glycemic control with a total glycated hemoglobin < 10%. The patients in the control group (n=40) were treated with only behavioral modifications like calorie control and daily walking for 30 minutes, and no lipid-lowering agent was given. The lipid profile was re-evaluated after 6 and 12 weeks. The patients in the test group (n=40) were advised behavioral modification and given simvastatin. The starting dose was 10 mg at bed time. After 6 weeks of simvastatin therapy, a lipid profile was done. If the goal of low-density lipoprotein cholesterol < 100 mg/dl and/or triglycerides <200 mg/dl and/or high-density lipoprotein cholesterol >45 mg/dl was not achieved, the dose of simvastatin was increased to 20 mg at bedtime for another 6 weeks. It was observed that low-density lipoprotein dyslipidemia was most prevalent. In the control group, a favorable alteration in lipid levels was brought about but none was statistically significant and the American Diabetes Association goals were not achieved in any of the patients. In the test group, there was a significant and favorable alteration in all lipid moieties, and the target levels were achieved in 80% of patients after 12 weeks. There was no significant alteration in glycemic control and liver functions. Myopathy and epigastric pain were seen in 1 patient in each group. CONCLUSIONS: In our study, behavioral modification alone did not achieve the target levels of various lipids in diabetic dyslipidemia as per the American Diabetes Association guidelines. Hence, pharmacological therapy with statins should be resorted to in patients with type 2 diabetes mellitus who carry a high risk of coronary heart disease. Simvastatin is a safe and efficacious lipid-lowering drug.

An overview of pathophysiology and treatment of insulin resistance.

Insulin resistance has emerged out as a concept linking diabetes mellitus and hypertension. Clinically it is characterized by hyperinsulinemia, hypertension, central obesity, abnormal lipid profile and cardiovascular complications. Insulin resistance is often associated with presence of anti-insulin antibodies and absent or dysfunctional insulin receptors. At molecular level insulin resistance appears to occur at the level of G-protein, kinase activation, glucose carriers (GLUT) and gene expression. Although with advent or research, the molecular mechanisms of insulin resistance are becoming more clear and there is development of new therapeutic agents like insulin sensitizers (thizolidinediones), in clinical practice, as of today, a patient with insulin resistance is looked upon as hypertensive or having diabetes mellitus. Accordingly he is taking either antihypertensives or antidiabetic drugs or both. It is thus essential to look into effects of these agents on insulin sensitivity. In recent years some scattered studies have been conducted to evaluate the effect of various antihypertensives and antidiabetics on insulin sensitivity. An antihypertensive or antidiabetic drug should directly benefit the cardiovascular risk profile of these patients. Although various newer approaches are explored to have a therapeutic benefit in insulin resistance, it is still a long way in the research, when a suitable pharmacological agent with least untoward effects will be available for the treatment of insulin residence.

Serum insulin assay: an important therapeutic tool in management of freshly diagnosed type 2 diabetes mellitus.

OBJECTIVES: The study was performed to see that, whether metabolic control and response to treatment in freshly diagnosed patients of type 2 diabetes mellitus is affected by primary pathology (hyperinsulinemia/inappropriate insulin secretion). METHODS: One hundred and eight freshly diagnosed patients of type 2 diabetes mellitus with age range from 30-65 years were followed for a period of three months. The blood glucose, serum triglyceride, and serum insulin levels were determined in each patient. Patients were found to have either higher or normal to low serum insulin values at fasting, and accordingly patients were distributed into two groups; group one (normal to low initial fasting serum insulin level i.e. < or = 30 microU/ml) and group two (high fasting serum insulin level i.e. > or = 30 microU/ml). Each group was further divided into two subgroups A and B. Subgroup A was treated with glipizide and B with metformin. RESULTS: Diabetic patients who had fasting hyperinsulinemia (n = 53, 100%) had blood pressure > or = 140/90 at the time of presentation. Patients who had fasting serum insulin within normal range only 30% (n = 17) had hypertension. Patients of group one had good recovery from hyperglycemia and reduction in triglyceride values when treated with sulphonylurea (subgroup A) as compared to patients treated with biguanide (subgroup B). On the contrary patients of group two showed poor glycemic control, increase in blood pressure and rise in serum triglyceride titre when treated with sulphonylurea (subgroup A) while in the same group biguanide effectively produced euglycemia with normalization of blood pressure and decrease in triglyceride levels (subgroup B). CONCLUSION: Assessment of initial serum insulin levels is helpful guide to decide about the type of oral hypoglycemic agent to be used in freshly diagnosed patients to type 2 diabetes mellitus.