Tissue Specific Effects of Chronic Sustained Hypoxia on Oxidative Stress: Role of Cilnidipine, a Dual L/N Type Calcium Channel Blocker.

Background: Blood flow, metabolic rate and oxygenrequirements of an organ guide the extent of oxidativestress experienced by any tissue in response to chronichypoxia. Currently cilnidipine is used in themanagement of hypertension and its antioxidant actionsare gaining wide interest. Aim and Objectives: Toevaluate the tissue specific effects of chronic sustainedhypoxia with regards to oxidative stress in the contextof cilnidipine. Material and Methods: Twenty fouradult male Wistar strain albino rats were randomlyassigned into four groups: group 1, control, normoxia(21% O ); group 2, chronic hypoxia (CH) (10% O ) for 2 221 days; group 3, normoxia + cilnidipine (Cil) for 21days; group 4, chronic hypoxia + cilnidipine (CH+Cil)for 21 days. Following 21 days of intervention bloodwas collected and animals were sacrificed and liver,lung and heart were collected. Serum MDA and MDAin tissue homogenate of liver, lung and heart wereestimated. Results: Our results demonstrate theelevated serum MDAlevels in chronic hypoxia exposedrats (group 2). We also observed increased MDAin liverfollowed by lung and least in the heart in chronichypoxia exposed rats (group 2). Treatment withcilnidipine reduced serum MDA and heart MDA levelsin cilnidipine treated chronic hypoxia exposed rats(group 4). However cilnidipine did not have anyinfluence on MDA levels in the liver and lung in samegroup of rats. Conclusion: The results demonstratetissue specific effects of chronic sustained hypoxia withthe highest oxidative stress observed in the liverfollowed by the lung. Although oxidative stress is alsoobserved in the heart it is the least in comparison to theliver and the lung. Cilnidipine, a dual L/N type calciumchannel blocker demonstrated beneficial antioxidantactions only in the heart supporting the cardioprotectiverole of cilnidipine

Evaluation of efficacy and safety of fixed dose combination of glimepiride 2 mg pluspioglitazone 15 mg plus metformin SR 500 mg in the management of patients with type-2 diabetes mellitus.

An estimated 25 million Indians currently have diabetes and the projections indicate Indians would be the largest group by the year 2025 AD. An open, phase III, multicentric study was conducted to determine the efficacy and tolerability of the triple drug combination glimepiride 2 mg plus pioglitazone hydrochloride 15 mg plus metformin SR 500 mg for 8 weeks in 101 Indian patients with type 2 diabetes mellitus. The study revealed that the triple drug combination could achieve the recommended goals, recommended by American Diabetic Association, for fasting blood glucose < or = 140 mg/dl and glycosylated haemoglobin (HbA1c) of < or = 8%. After 8 weeks, the mean fasting blood glucose (baseline 189.61) was reduced to 111.68 (41% reduction); the mean glycosylated haemoglobin (baseline 10.32) was significantly reduced to 7.54 (26% reduction). The triple drug combination significantly reduced the levels of triglyceride, low density lipoproteins and total cholesterol. These significant levels were achieved within 8 weeks and all patients tolerated the drug well with no reported case of serious adverse events including hypoglycaemia. There were also no reported drug interactions in the study. Since the decrease in HbA1c was continuous and throughout the study, a further decrease in the HbA1c levels would have been noted since the present trial was designed for a period of 8 weeks. Thus, the present study confirms the efficacy and safety of FDC of the triple drug combination in patients with type 2 diabetes.

Levofloxacin in enteric fever--a study.

Typhoid fever is an important cause of morbidity and mortality in patients especially in developing country. Therapy with conventional drugs is associated with increasing resistance, non-compliance to therapy and toxicity. Oral fluoroquinolones have been shown to be effective compared to parenteral broad-spectrum cephalosporins in the treatment of uncomplicated typhoid. However, there is no data available regarding the use of levofloxacin in the treatment of typhoid fever in spite of the susceptibility of Salmonella species to levofloxacin. The present study was undertaken to evaluate the efficacy, safety and tolerability of oral levofloxacin 750 mg once daily in the treatment of typhoid fever. Results indicated that levofloxacin 750 mg administered orally once daily was an effective, safe, well-tolerated and cost-effective option in the treatment of typhoid fever in adult Indian males and non-pregnant females.

A pilot study for evaluation of the efficacy and safety of telmisartan in reducing microalbuminuria in hypertensive patients with type 2 diabetes mellitus.

To evaluate efficacy and tolerability of telmisartan, an angiotensim II receptor blocker, in reducing microalbuminuria in adult Indian hypertensive patients with type 2 diabetes mellitus, a prospective, open-label, non-comparative, assessor-blind, multicentric, pilot study was conducted in 60 eligible hypertensive patients with type 2 diabetes mellitus and microalbuminuria after obtaining their informed consent. The study was approved by the respective institutional review boards. Each patient received telmisartan 40 mg initially once daily for first 4 weeks which was titrated upwards to 80 mg once daily for the next 8 weeks. Blood pressure was assessed at the end of every 2 weeks and urinary albumin excretion and creatinine clearance were measured at baseline and after 12 weeks of therapy. Safety outcome measures included monitoring of physical examination, laboratory parameters and monitoring treatment-emergent adverse events. Fifty-five patients completed the study while 5 cases were lost to follow-up. The mean age of the patients was 48.27 years. Of the total patients 63.6% were males and 46.4% were females. At baseline the mean urinary albumin excretion rate was 131.81 +/- 38.82 mg/minute. A statistically significant (p < 0.05) reduction (32.96%) in urinary albumin excretion rate occurred after 12 weeks of therapy (118.36 +/- 37.22). The mean pre-study systolic blood pressure was 165.05 +/- 15.24 mmHg which was significantly (p < 0.05) reduced to 123.72 +/- 5.88 mmHg at the end of 12 weeks. At baseline the mean diastolic blood pressure was 103.55 +/- 9.84 mmHg which was significantly (p < 0.05) reduced to 84.71 +/- 8.54 mmHg. The JNC-VII goal of blood pressure below 130/80 was achieved in 34 (61.8%)of the 55 patients at the end of 12 weeks. Both fasting and postprandial blood sugar levels were well-controlled at the end of the study. Telmisartan was well tolerated with only 9.09% of the patients reported mild and transient adverse events like fatigue, dizziness, nausea and diarrhoea. No abnormalities were detected in the laboratory parameters. The results of this pilot study indicate that telmisartan is effective, safe and well tolerated while reducing microalbuminuria in adult Indian hypertensive patients with type 2 diabetes mellitus.