Biochemical alterations and liver toxicity analysis with pioglitazone in healthy subjects.

Pioglitazone, a member of the thiazolidinediones, is a potent, highly selective agonist for peroxisome proliferator-activated receptor gamma and is an excellent insulin sensitizer used in treating type 2 diabetes mellitus. The present study investigated the effect of pioglitazone on glucose, total cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol, total proteins, albumin (ALB), alanine transaminase (ALT), and aspartate transaminase (AST) levels in 20 healthy Bengali male volunteers in a randomized, placebo-controlled study. Blood samples were collected before and 0.5-24.0 hours after a single oral dose of a 30 mg pioglitazone tablet. Plasma pioglitazone level was determined using a validated method of reverse-phase binary high-performance liquid chromatography. Blood lipid profile and levels of glucose, ALT, and AST were estimated using enzyme assay kits, plasma protein level was estimated by the biuret method, and plasma ALB level was determined colorimetrically. No significant change in blood glucose, total proteins, total cholesterol, triglyceride, HDL, and LDL levels was observed over the 24-hour assessment period, indicating no plasma biochemical alterations. There were no significant differences between baseline and 24-hour values of ALB, ALT, and AST levels, indicating a lack of liver toxicity. Our results indicate that a single dose of 30 mg of pioglitazone has no hypoglycemic or hypolipidemic effect or liver toxicity within 24 hours of treatment among healthy Bengali males.

Familial aggregation of Vibrio cholerae-associated infection in Matlab, Bangladesh.

Vibrio cholerae is a major cause of diarrhoeal illness in endemic regions, such as Bangladesh. Understanding the factors that determine an individual's susceptibility to infection due to V. cholerae may lead to improved prevention and control strategies. Increasing evidence suggests that human genetic factors affect the severity of V. cholerae-associated infection. This study, therefore, sought to characterize the heritable component of susceptibility to infection due to V. cholerae using the Matlab Health and Demographic Surveillance System database of the International Centre for Diarrhoeal Disease Research, Bangladesh. In total, 144 pedigrees that included a cholera patient and 341 pedigrees without a cholera patient were evaluated during 1 January-31 December 1992. The odds of the sibling of a patient being admitted with cholera were 7.67 times the odds of the sibling of an unaffected individual being admitted with cholera [95% confidence interval (CI) 2.40-24.5, p < 0.001], after adjustment for gender, age, socioeconomic status, and hygiene practices. Although exposure to environmental reservoirs is essential in the epidemiology of cholera, household-specific factors, such as familial relatedness to an index case, may also be important determinants of risk of cholera. Further analysis of human genetic factors that contribute to susceptibility to cholera may be productive.

Determinants of reduction in maternal mortality in Matlab, Bangladesh: a 30-year cohort study.

BACKGROUND: Research on the effectiveness of strategies to reduce maternal mortality is scarce. We aimed to assess the contribution of intervention strategies, such as skilled attendance at birth, to the recorded reduction in maternal mortality in Matlab, Bangladesh. We examined and compared trends in maternal mortality in two adjacent areas over 30 years, by separate analyses of causes of death, underlying sociodemographic determinants, and areas and time periods in which interventions differed. METHODS: We analysed survey data that was routinely collected between 1976 and 2005 for about 200 000 inhabitants of Matlab, in Bangladesh, in adjacent areas served by either the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) or by the government. We used logistic regression to assess time trends in maternal mortality. We separately analysed deaths due to direct obstetric causes, abortion-related causes, and other causes. FINDINGS: Maternal mortality fell by 68% in the ICDDR,B service area and by 54% in the government service area over 30 years. Maternal mortality remained stable between 1976 and 1989 (crude annual OR 1.00 [0.98-1.01]) but decreased substantially after 1989 (OR 0.95 [0.93-0.97]). The speed of decline was faster after the skilled-attendance strategy was introduced in the ICDDR,B service area in 1990 (p=0.09). Abortion-related mortality fell sharply from 1990 onwards (OR 0.91 [0.86-0.95]). Educational differentials for mortality were substantial; the OR for more than 8 years of schooling compared with no schooling was 0.30 (0.21-0.44) for maternal mortality and 0.09 (0.02-0.37) for abortion mortality. INTERPRETATION: The fall in maternal mortality over 30 years occurred despite a low uptake of skilled attendance at birth. Part of the decline was due to a fall in abortion-related deaths and better access to emergency obstetric care; midwives might also have contributed by facilitating access to emergency care. Investment in midwives, emergency obstetric care, and safe pregnancy termination by manual vacuum aspiration have clearly been important. However, additional policies, such as those that bring about expansion of female education, better financial access for the poor, and poverty reduction, are essential to sustain the successes achieved to date.

Synthesis, Characterization and Comparison of Local Analgesic, Anti-Inflammatory, Anti-Ulcerogenic Activity of Copper and Zinc Complexes of Indomethacin.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) exert gastrointestinal upset by inhibiting mucosal cyclooxygenase (COX) activity and complexation technique with metals has been adopted to overcome this drawback. OBJECTIVE: The study aimed to overcome the gastrointestinal side effects associated with indomethacin treatment by synthesizing copper (Cu) and zinc (Zn) complexes of indomethacin along with assessing potential pharmacological effects of these complexes. METHOD: The characterization of synthesized complexes was done by FT-IR, XRD, UV-Vis, Atomic Absorption Spectroscopy (AAS) and Differential Scanning Calorimetry (DSC). Biological properties as local analgesic activity, anti-inflammatory activity and antiulcerogenic activity were evaluated following radiant heat tail flick, inhibition of rat hind paw edema and inhibition of NSAID induced gastroenteropathy method respectively. RESULTS: 0.3 ml of indomethacin-copper complex demonstrated prominent analgesia at 25 µg/ml dose and 0.3 ml of indomethacin-zinc complex, after 30, 60 and 90 minutes of oral administration, shown significant local analgesia at 25, 50 and 100 µg/ml dose. In antiinflammatory activity assay, indomethacin-copper exhibited significant inhibition at 20 mg/kg dose after 2nd, 3rd and 4th hour of administration whereas indomethacin-zinc illustrated significant inhibition at 10 mg/kg dose after 2nd, 3rd and 4th hour of administration. Anti-ulcerogenic activity study of the complexes exhibited no macroscopic damage to the stomach and intestine, except minor microscopic damage. CONCLUSION: In view of the results, the copper and zinc complexes of indomethacin may be used as better substitutes of the parent indomethacin owing to their minimal side effects with additional pharmacological effects.