A. K. Azad Chowdhury

Field tests for rational drug use in twelve developing countries

Increasing efforts are being made to improve drug-use practices and prescribing behaviour in developing countries. An essential tool for such work is an objective and standard method of assessment. We present here a set of drug-use indicators produced and tested in twelve developing countries. We describe practical applications, which include the use of indicators to increase awareness among prescribers in Malawi and Bangladesh, to identify priorities for action (eg, polypharmacy in Indonesia and Nigeria, overuse of injections in Uganda, Sudan, and Nigeria, and low percentage of patients who understood the dosage schedule in Malawi), and to quantify the impact of interventions in Yemen, Uganda, Sudan, and Zimbabwe.

Antibacterial activity of two limonoids from Swietenia mahagoni against multiple-drug-resistant (MDR) bacterial strains.

Solvent partitioning followed by column chromatography of the MeOH extract of the seeds of Swietenia mahagoni afforded two limonoids, swietenolide (1) and 2-hydroxy-3-O-tigloylswietenolide (2). The compounds were identified by spectroscopic means. The antibacterial activity of these compounds was assessed against eight multiple-drug-resistant bacterial strains (clinical isolates) by the conventional disc diffusion method. While both compounds were active against all test organisms, compound 2 displayed overall more potent activity than compound 1.

Antioxidants in detoxification of arsenic-induced oxidative injury in rabbits: preliminary results.

Abstract To assess the oxidative injuries caused by arsenic toxicity in rabbits and evaluate the detoxifying effects of exogenous antioxidants, we administered arsenic trioxide (3–5 mg/kg/day) in rabbits through a feeding tube for seven days. These rabbits were then treated with a recipe of vitamins, zinc, selenium (VZS) or a plant polyphenol or a placebo for the next seven days. Blood samples were collected from ear vein for spectrophotometric assay of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and nitrite/nitrate (NO x ; index of nitric oxide formation) before arsenic administration, seven days after arsenic administration, and seven days after antioxidant treatment. The total arsenic concentrations in hair and spot urine samples of rabbits before arsenic administration were 0.6 ± 0.21 µg/g and 34.0 ± 5.9 µg/L, respectively. Administration of arsenic trioxide significantly increased arsenic concentrations in hair and in urine to 2.8 ± 0.40 µg/g (p<0.001) and 7372 ± 1392.0 µg/L (p<0.001), respectively. Arsenic administration to rabbits significantly reduced GSH concentration (post-arsenic,17.5 ± 0.81 mg/dL vs. pre-arsenic, 32.0 ± 0.76 mg/dL, p<0.001), increased TBARS concentration (post-arsenic, 8 ± 1.1 µM vs. pre-arsenic, 5 ± 0.7 µM, p<0.05), and NO x concentration (post-arsenic, 465 ± 38.5 µM vs. pre-arsenic, 320 ± 24.7 µM, p<0.001) as compared to the pre-arsenic levels. There was a negative correlation between TBARS and GSH concentrations (r = −0.464, p<0.01) and between NO x and GSH concentrations (r = − 0.381, p<0.05) of intoxicated rabbits. The recovery of the depleted GSH was significantly greater in the polyphenols (77.0 ± 12.0%) or VZS (67.0 ± 17.0%) treatment groups compared with the placebo group (36.0 ± 7.0%). The decrease in NO x level of arsenic-treated rabbits was significantly greater in polyphenols treatment group than the placebo group (60.0 ± 9.0% vs. 17.0 ± 6.0%, p<0.001). These results indicate that arsenic induces toxicity in rabbits associated with an increase in lipid peroxidation. Arsenic toxicity increases nitric oxide production in the body. Exogenous antioxidants such as polyphenols and recipe of vitamins, zinc, and selenium are useful for arsenic detoxification.

Pachypodol, a flavonol from the leaves of Calycopteris floribunda, inhibits the growth of CaCo 2 colon cancer cell line in vitro.

Calycopteris floribunda Lam., commonly known as ‘goichia lata or goache lata’, is a large climbing woody shrub from Bangladesh, and well distributed in a number of other south‐east Asian countries. Traditionally, C. floribunda has been used in colic, as an antihelminthic, astringent and carminative, and for the treatment of diarrhoea, dysentery, jaundice and malaria in many countries including Bangladesh. Pachypodol (5,4′‐dihydroxy‐3,7,3′‐trimethoxyflavone) has been isolated from the leaves of C. floribunda by repeated column chromatography on silica gel, and the structure confirmed by spectroscopic means. While the general toxicity of pachypodol was determined by the brine shrimp lethality assay, the cytotoxic potential of this flavonoid has been evaluated by the Promegas CellTiter 96 Non‐Radioactive Cell Proliferation Assay using the CaCo‐2 colon cancer cell line (IC50 = 185.6 µM). A summary of the biological activities of pachypodol reported to date is also presented. Copyright

Therapeutic potential of the volatile oil of Nigella sativa seeds in monkey model with experimental shigellosis

The volatile oil of Nigella sativa seeds was prominent in in vitro anti‐shigella activity against eight multiple drug resistant strains of Shigella flexneri. The anti‐shigella activity against Shigella flexneri Y SH‐4 was observed in the sera of monkeys after 45–60 min of oral administration of the oil. It exhibited promising in vivo anti‐shigella activity against the same strain when tested in monkey models with experimental shigellosis, fully curing the infected monkeys within 3 days. The rectal swabs of the experimental groups became free of the challenge organism on day 3 of treatment with the volatile oil.

Effect of Aqueous Extracts of Black and Green Teas in Arsenic-induced Toxicity in Rabbits

Arsenic causes oxidative stress in the body. Its administration (3 mg/kg/day) for 14 days in rabbits resulted in a significant reduction of whole blood glutathione (GSH), and elevation of thiobarbituric acid reactive substances (TBARS) and the index of nitrite/nitrate (NOx) levels. These are the markers of oxidative stress. Both black tea (BT) and green tea (GT) (Camellia sinensis), when administered to the arsenic‐treated rabbits for 14 days, caused a significant elevation of the depleted GSH level to 53.12% and 57.47%, respectively. On the contrary, in the placebo group the level was 26.59%. The BT and GT reduced the elevated TBARS level to 43.27% and 62.28%, respectively, whereas the corresponding level in the placebo groups was 21.24%. The NOx levels were also reduced to 63.62%, 67.67% and 58.94% in BT, GT and the placebo groups, respectively. When arsenic and black tea were given concurrently to another group the results were even more pronounced. The polyphenol components of black and green tea were 27.69% and 29.71% of the dry weight of the total extracts, respectively. These results indicated that arsenic‐induced toxicities in rabbits were significantly reversed by the black and green tea polyphenols. The greater activity of green tea than that of black tea correlates with the slightly higher content of polyphenols in green tea. Copyright

Serum levels of gentamicin at peak and trough in neonates and infants

The peak and the trough levels of serum gentamicin were determined in 50 cases of neonates and infants by microbiological assay method. The peak levels in the neonates and the infants were 5.98±0.48 and 4.63±0.31 mcg/ml respectively. The trough levels in the corresponding group were 1.06±0.19 and 0.94±0.23 mcg/ml. The mean values of the peak and trough levels of the antibiotic were 5.57 and 1.02 mcg/ml respectively. It was observed that there was a significant lower peak concentration in the infants than in the neonates. A significantly higher peak concentration of gentamicin was observed in babies aged under 7 days than in those above 7 days. The route of administration (between I/M and I/V) did not seem to have any effect on the peak and trough levels of the antibiotics.

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.

Total Synthesis and Analgesic Activity of 6-Fluoroindan-1-acetic Acid and its 3-Oxo Derivative

6-Fluoro-3-oxo-indan-1-acetic acid (5) and 6-fluoroindan-1-acetic acid (6) were conveniently synthesised from 3-fluorobenzaldehyde in four and five steps, respectively. The structures of these new compounds and two other intermediates, 3-fluorobenzylidine-bis-acetoacetate (2) and 3-fluoro-beta-phenyl glutaric acid (3) were elucidated by spectroscopic means, notably, HRMS, 1D and 2D NMR. The analgesic activity of compounds 5 and 6 were assessed by the acetic acid induced writhing in Swiss albino mice.

Comparative in vitro-in vivo correlation analysis with pioglitazone tablets

Objective To assess the in vitro-in vivo correlation of immediate release formulation of pioglitazone 30 mg film coated tablet.