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Biomedical subjects

S K Puri

Publications and source records attributed to S K Puri.

138 records · Page 8Linked to original sources

Plasmodium yoelii: activity of azithromycin in combination with pyrimethamine or sulfadoxine against blood and sporozoite induced infections in Swiss mice.

The efficacy of pyrimethamine or sulfadoxine administered in combination with azithromycin was examined in a rodent malaria model. Outbred Swiss mice infected with blood stage parasites were treated from day 0 to day 3 and efficacy of different regimens was monitored in terms of the curative response and the delay time to reach 2% parasitaemia (2% DT). Administration of azithromycin alone at 60 mg/kg/day produced curative response while lower doses showed marginally delayed 2% DT. A marked potentiation in activities of pyrimethamine (100-fold) or sulfadoxine (10-fold) was observed when administered at non-curative doses of 0.1 mg/kg/day in combination with azithromycin (30 mg/kg/day) against blood stage parasites. A combination of 10 mg/kg/day azithromycin with 0.3 mg/kg/day sulfadoxine was also curative. Likewise in the causal prophylactic test, a combination regimen comprising 1/16th and 1/3rd the individual curative doses of pyrimethamine and azithromycin, respectively, prevented the development of patent infection after Plasmodium yoelii sporozoite challenge. Our results suggest that a combination of azithromycin with the second line treatment regimen of fansidar may enhance the therapeutic efficacy of the latter and also provide better prophylaxis against Plasmodium falciparum malaria.

Animals↗

Effect of anti-relapse antimalarial compound CDRI 80/53 and primaquine on hepatic mixed function oxidase system of rhesus monkey.

A potential anti-relapse antimalarial compound CDRI 80/53 [N1-(3-acetyl-4-5-dihydro-2-furanyl)-N4-(6-methoxy-8-quinolinyl)1,4- pentanediamine] at 7.5 mg/kg body weight and primaquine at 6.0 mg/kg body weight did not cause any significant change in the status of hepatic microsomal mixed function oxidase system of rhesus monkeys, when given orally for 7 days. Further, the extension of the treatment at the same dossier up to 21 days resulted in impairment of the different indices of the MFO system. The compound CDRI 80/53 inhibited cytochrome P-450, aminopyrine-N-demethylase, aniline and benzo(a)pyrene hydroxylases, cytochrome b5 and haem levels by 17, 11, 58, 0, 36 and 35% whereas the inhibition caused by primaquine was 34, 40, 72, 54, 39 and 38% respectively, establishing that the cytochrome P-450 dependent mono-oxygenase system of monkey liver was comparatively less suppressed by compound CDRI 80/53. The cessation of the compound/drug treatment resulted in almost complete reversal of all the MFO activities to normal in a period of about 6 weeks.

Aminoquinolines↗

NADP-specific isocitrate dehydrogenase from the simian malaria parasite Plasmodium knowlesi: partial purification and characterization.

Cell-free schizonts of Plasmodium knowlesi, a simian malaria parasite, possess significant isocitrate dehydrogenase (IDH) activity, about 90% of which is contributed by the NADP-specific enzyme that is localized in the cytosolic fraction. The enzyme has been partially purified by affinity chromatography using Blue sepharose CL-6B. Although unstable in nature, it is stabilized by citrate and glycerol. Kinetic studies with DL-isocitrate and NADP yielded hyperbolic curves with Michaelis constants of 0.210 and 0.038 mM, respectively. Manganous or magnesium ions are essential for activity. The enzyme is thermosensitive, shows maximum activity at pH 8.0, and has a molecular mass of about 48.5 kDa. It is strongly inhibited by thiol-blocking agents but protected against them by thiol-providing agents. Cupric and argentic ions also have a marked inhibitory effect on its activity. The enzyme is significantly inhibited by chloroquine and oxytetracycline in vitro, but to a lesser degree by tetracycline.

Animals↗

Reduced single-dose clearance of clobazam in elderly men predicts increased multiple-dose accumulation.

The rate and extent of accumulation of clobazam and its major metabolite, desmethylclobazam, during multiple dosage with clobazam were evaluated in 4 similarly sized groups of young male, young female, elderly male, and elderly female volunteers. Subjects received single 10mg doses of clobazam daily for 22 consecutive days. Plasma levels were measured during and after the period of dosage. Compared with the young male subjects, elderly males had slower rates of clobazam accumulation and washout, higher steady-state plasma levels, and lower steady-state clearance. Accumulation of desmethylclobazam also was slower and more extensive in the elderly male group. Among females, however, age-related kinetic differences did not approach significance. Among all subjects, pharmacokinetic variables for clobazam determined in a previous single-dose study were highly consistent with the multiple-dose pharmacokinetic profile. Single-dose vs post-multiple dosage half-life, single-dose vs steady-state clearance, observed vs predicted accumulation ratios, and observed vs predicted steady-state plasma concentrations were all highly correlated, with regression line slopes close to unity. Thus, reduced single-dose clearance of clobazam in elderly men leads to slower and more extensive accumulation during multiple dosage. The single-dose pharmacokinetic profile of clobazam is highly predictive of drug behaviour during repeated dosage, suggesting that clobazam kinetics are dose- and concentration-independent within the range studied, and that self-induction or inhibition of clearance is not evident during 3 weeks of dosage.

Adult↗

Ultrasonographic evaluation of common duct diameter in pre and post cholecystectomy patients.

Thirty four patients with gall bladder disease and normal common duct were investigated prospectively by ultrasonography just before cholecystectomy and at periodic intervals of 1 months, 2 months, 3 months and once in 4-6 months after cholecystectomy. The pre and post cholecystectomy common duct diameters were measured at each visit and compared with each other to determine the statistical significance. No significant change (p > 0.05) occurred in common duct diameter following cholecystectomy.

Adolescent↗

Percutaneous catheter drainage in pancreatic pseudocysts.

Percutaneous catheter drainage (PCD) was performed in 12 pancreatic pseudocysts in 11 patients. The procedure was performed under realtime ultrasound guidance adopting a direct transperitoneal approach in all cases. Complete cure was achieved in 9 (75%) of the Pseudocysts drained. Success rate was higher in pseudocysts not communicating with the main pancreatic duct (MPD), 7 of 8 (87.5%) as compared to those with ductal communication, 2 of 4 (50%). The mean duration of catheter drainage was 14.2 days in the first group while it was significantly longer, (42.5 days) in the latter group. No death or major complication related to the procedure was encountered in the study. A single pseudocyst got infected after catheter insertion but it was treated successfully with antibiotics. The follow up period was 3-18 months with a mean of 6.8 months. PCD failed in 2 pseudocysts communicating with MPD and associated strictures in the MPD. In one case having no communication with MPD the procedure failed because the cyst had thick debris which could not be drained properly. PCD may be a safe and effective therapy in the management of pseudocysts with best results in those not communicating with the MPD. Communicating pseudocysts, also having strictures in MPD, should not be subjected to PCD.

Adult↗

AIDS cholangiopathy.

A 45-year-old man presented with diarrhea and profound weight loss over one year. His serum alkaline phosphatase was raised and ultrasonography showed dilated intrahepatic biliary ducts and upper part of common bile duct (CBD). ERCP showed papillary stenosis, dilated CBD, stricture at the confluence and saccular dilatation of the left intrahepatic biliary ducts. He was found HIV-positive. Duodenal biopsy, rectal biopsy and stool examination could not identify any opportunistic organism.

Acquired Immunodeficiency Syndrome↗