Clinical and biochemical parameters in relation to serum leptin levels in south indian children and adolescents.

Objective. To investigate the relationship between serum leptin and lipid profile in South Indian School children and adolescents, and to evaluate the role of serum leptin in obese, overweight and congenital heart diseased children and adolescents; in South Indian population and its correlation with anthropometric and biochemical parameters. Methods. The study included 185 school going children and adolescents. (52 obese, 49 overweight, 25 congenital heart disease children and adolescents, were compared with 59 normal controls, aged between 10-17 years). Anthropometric variables, lipid profile, fasting serum glucose were analyzed by autoanalyser and serum leptin by ELISA. Results. Serum leptin levels were significantly elevated in obese and overweight children than in control children (36.88±18.60ng/mL, 20.64±11.18ng/mL vs 7.97±2.79ng/mL; p value <0.001), and decreased in congenital heart diseased children than in control children (6.20±4.23 ng/mL vs 7.97±2.79ng/mL; p value <0.005). Conclusions. This study provides a good relationship between serum leptin levels and anthropometric and biochemical parameters, such as total cholesterol, triglycerides and LDL-cholesterol. We observed negative correlation between serum leptin and fasting glucose levels and HDL-cholesterol levels were found to be non-significant among the groups. Further studies with large sample size are needed to ascertain the relationship between serum leptin and lipid profile in different groups of children and adolescents.

Disposition of uric acid upon administration of ofloxacin alone and in combination with other anti-tuberculosis drugs.

Disposition of uric acid upon administration of ofloxacin (O) alone and in combination with other anti-tuberculosis drugs, rifampicin (R), isoniazid (H) and pyrazinamide (Z) was studied. Twelve male healthy volunteers were investigated on four different occasions with the four drugs alone or in combinations. A partially balanced incomplete block design was adopted and the subjects were randomly allocated to each group. Uric acid concentration in urine samples excreted over 0-8 hr, were determined after coding the samples. There was significant decrease in the group receiving Z when compared to other groups. Though there was a decrease in uric acid excretion in the group receiving O, it was not statistically significant. Rifampicin and H seem to increase the uric acid excretion. The incidence of arthralgia was mainly due to Z and not due to either O or other drugs in the treatment of pulmonary tuberculosis.

Standardization of the method for estimation of ethambutol in pharmaceutical preparations and biological fluid.

A simple column chromatographic method for determination of ethambutol (EMB) in pharmaceutical preparations containing EMB in combination with other anti-TB drugs is presented. The method involved extraction of EMB into an organic solvent, followed by basification and column chromatographic separation on Amberlite CG 50 (100-200 mesh) and elution with suitable eluants and estimation at a wavelength of 270 nm. The assay was linear from 25 to 400 microg/ml. The relative standard deviations of intra and inter day assays were lower than 5%. Ethambutol was recovered from human urine quantitatively and stable for a period of at least one week in urine stored at -20 degrees C.

Bioavailability of rifampicin following concomitant administration of ethambutol or isoniazid or pyrazinamide or a combination of the three drugs.

BACKGROUND & OBJECTIVES: Poor bioavailability of rifampicin (R) in combination with other anti-tuberculosis drugs such as isoniazid (H), pyrazinamide (Z), and ethambutol (E) is a subject of much concern for the last few decades. This could be due to an interaction between R and other drugs. An investigation was therefore undertaken to examine the bioavailability of R in the presence of H, Z and E or a combination of the three drugs. METHODS: The study included eight healthy volunteers, each being investigated on four occasions at weekly intervals once with R alone and with three of the four combinations on the three remaining occasions. A partially balanced incomplete block design was employed and the allocation of R or the drug combinations was random. Plasma concentrations of R at intervals up to 12 h were determined by microbiological assay using Staphylococcus aureus as the test organism. The proportion (%) dose of R as R plus desacetyl R (DR) in urine excreted over the periods 0-8 and 8-12 h was also determined. Bioavailability was expressed as an index (BI) of area under time concentration curve (AUC) calculated from the plasma concentrations or proportion of dose of R excreted as R plus DR in urine with the combinations to that with R alone. RESULTS: The bioavailability indices based on AUC were 0.96 with RE, 0.76 with RH, 1.08 with RZ and 0.65 with REHZ. The indices based on urine estimations (0-8 h) were similar, the values being 0.94, 0.84, 0.94 and 0.75, respectively. A second investigation revealed that the decrease of bioavailability of R with H was not due to the excipients present in H tablets. INTERPRETATION & CONCLUSION: Isoniazid alone or in combination with E and Z reduces the bioavailability of R. Urinary excretion data offer a simple and non invasive method for the assessment of bioavailability of R.

Effect of rifampicin & isoniazid on cytochrome P-450 in mycobacteria.

BACKGROUND & OBJECTIVES: Rifampicin and isoniazid are the most important first line drugs used in the treatment of tuberculosis. These drugs are also used in combination with other medications to treat co-infections. It, therefore, becomes important to study the effect of these drugs on the drug metabolizing system, namely, cytochrome P-450, not only in the host but also in the bacteria. We report the effect of rifampicin and isoniazid on the cytochrome P-450 activity in Mycobacterium smegmatis and M. tuberculosis H37Rv. METHODS: Subinhibitory concentrations of rifampicin and isoniazid were added to the organisms after they had attained the growth phase and cytochrome P-450 activity was estimated in the membranous fractions of the bacteria at different time points. RESULTS: Rifampicin was able to significantly enhance cytochrome P-450 in both M. smegmatis and M. tuberculosis H37Rv. Isoniazid was found to inhibit cytochrome P-450 in M. tuberculosis H37Rv, while there seemed to be no effect in M. smegmatis. INTERPRETATION & CONCLUSION: We report here the effect of rifampicin and isoniazid on mycobacterial cytochrome P-450. These findings are similar to those found in eukaryotic organisms. The role of mycobacterial cytochrome P-450 in the metabolism of drugs within the bacteria needs to be elucidated.