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Biomedical subjects

A K Jain

Publications and source records attributed to A K Jain.

At least 19 recordsLinked to original sources

Photosensitizing efficiency of two regioisomers of the benzoporphyrin derivative monoacid ring A (BPD-MA).

Benzoporphyrin derivative, monoacid ring A (BPD-MA), currently in clinical trials as a photosensitizer for photodynamic therapy for cancer, consists of two regioisomers (A1 and A2) present in equal proportions. The contribution of the regioisomers to the overall photosensitizing potency of BPD-MA was tested in vitro and in vivo. The in vitro photosensitizing potencies of BPD-MA-A1 and -A2 were tested in a standard cytotoxicity assay using M1 (rhabdomyosarcoma of DBA/2 mice) tumor cells and were found to be equivalent. The in vivo photosensitizing efficacies of the regioisomers were tested in the M1 tumor model in DBA/2 mice and were also found to be equivalent. Biodistribution of the regioisomers in mouse plasma, tumor and liver was studied in M1 tumor-bearing DBA/2 mice at 15 min and 3 hr post intravenous injection of [14C]BPD-MA-A1/A2 at 4 mg/kg body weight. Plasma and extracts from tumor and liver were analysed by HPLC and tested for radioactivity. The two regioisomers were eliminated from plasma and liver at different rates, which resulted in A1:A2 ratios of 1:0.28 in plasma and 1:0.75 in liver at 3 hr post injection. The differential elimination was not observed to any significant degree in the tumor, where even at 3 hr post injection the A1:A2 ratio was 1:1.15. Therefore, we concluded that in tumor tissue, at 3 hr post injection, the time at which laser photodynamic therapy is carried out, both regioisomers were present in about equal proportions. Further, both regioisomers were fully active as determined by an in vitro cytotoxicity assay following extraction.

Animals

Commonly used Indian abortifacient plants with special reference to their teratologic effects in rats.

A survey programme was organised in Lucknow and Farrukhabad, two towns of Uttar Pradesh, from March 1987 to July 1987. During the survey, the common folk medicine plants used by women were recorded and Ayurvedic and Unani drug encyclopedias were consulted for the antireproductive potential of these plants. Aqueous or 90% ethanol extracts of the plants of interest were studied in rats orally dosed for 10 days after insemination with special reference to effects on foetal development. Leaf extracts of Moringa oleifera and Adhatoda vasica were 100% abortive at doses equivalent to 175 mg/kg of starting dry material. Only the flowers of Acacia arabica and Hibiscus rosa-sinensis appeared to lack teratologic potential at the doses tested.

Abnormalities, Drug-Induced

A study of nerve conduction velocity in patients on diphenylhydantoin therapy.

Peripheral nerve conduction studies were performed in 30 epileptics, treated with DPH and results were compared with age and sex matched controls. There was significant reduction in the amplitude of sensory nerve action potential of median (26.65 +/- 14.71 mu v) and superficial radial nerve (25.65 +/- 10.08 mu v) (p < 0.001) in DPH treated group as compared to controls, (median nerve 42.64 +/- 15.93 uv and superficial radial nerve 40.72 +/- 24.74 mu v). The results suggest that DPH causes a subclinical distal axonal neuropathy in therapeutic dosage.

Action Potentials

Endoscopic sphincterotomy: preliminary experience at a university hospital.

Endoscopic sphincterotomy (ES) was attempted in 38 patients with biliary calculi. There were 21 patients (55.3%) with common bile duct (CBD) stones following cholecystectomy, 14 patients (36.8%) with intact gall bladder and 3 patients with retained CBD stones along with T tube in the early post-operative period. Endoscopic sphincterotomy was possible in all but one patient and duct clearance was attained in 34 (89.4%) patients. Spontaneous clearance of calculi occurred in 31 (81.6%) patients while 3 patients required instrumental extraction. Four patients failed to clear stones and required surgical intervention. Complications occurred in 4 (10.5%) patients--haemorrhage in two, pancreatitis and cholangitis in one each. One patient died of bleeding on the 4th day following ES while hemostasis was achieved in other after two units of blood. Other complications were managed conservatively without any mortality. Endoscopic sphincterotomy appears to be a simple, effective and safe therapeutic modality for the management of biliary calculi.

Adolescent

Acute lymphoblastic leukaemia presenting as breast mass.

A 14 year old girl presented with bilateral symmetrical involvement of the breast with acute lymphoblastic leukaemia (ALL). Treatment with combined therapy of adriamycin, vincristine and prednisolone produced a remission in the leukaemia with complete resolution of the breast mass.

Adolescent

Antipyretic activity of tebufelone (NE-11740) in man.

Tebufelone (formerly NE-11740) is a member of the new class of di-tert-butyl-phenol anti-inflammatory agents. It has previously been reported that this new agent has potent analgesic, antipyretic, and anti-inflammatory effects using in vitro, in vivo, and ex vivo experimental models. A randomized, active- and placebo- controlled double-blinded study in 120 healthy males, 20 to 55 years old, was conducted to clinically assess tebufelone's antipyretic activity. Subjects received a single peroral dose of placebo, 650 mg aspirin (ASA), or tebufelone at doses of 25, 50, 100, or 200 mg. Thirty minutes later, E. coli endotoxin (2 ng/kg) was administered intravenously. Oral temperatures were recorded at 15 minute intervals from 30 minutes post dosing to 8 hours post endotoxin administration. Areas under the temperature curves (AUCs), adjusted for baseline, were significantly lower than placebo for ASA and all but the 25 mg tebufelone groups. An AUC dose-response equation estimates 60 mg tebufelone as equivalent to 650 mg ASA, with 50 mg tebufelone not significantly greater than 650 mg ASA. Side effects, attributable to the endotoxin, included mild flu-like symptoms and were worse in the placebo group and the non-efficacious 25 mg tebufelone group. Doses of 100 and 200 mg tebufelone had onset characteristics indistinguishable from 650 mg ASA, whereas 50 mg tebufelone showed significantly slower onset while suppressing temperature for a longer period than ASA. These results provide an important early demonstration of tebufelone's biological activity in man.

Adult

Ultrasound detection of tuberculomas of the spleen.

A case of multiple tuberculomas of the spleen, detected as hypoechoic masses on ultrasound and subsequently proved at operation and histopathology, is presented. This was the only manifestation of the disease.

Adult

Photosensitising potency of structural analogues of benzoporphyrin derivative (BPD) in a mouse tumour model.

The in vivo characteristics of four analogues of benzoporphyrin derivative (BPD) have been investigated. Biodistribution data obtained in DBA/2J mice with BPD-MA (monoacid ring A analogue) which had been tritiated or internally labelled with 14C showed that both labelled materials acted in an essentially identical manner during the period of study. Biodistribution and clearance studies showed that relative distribution in a variety of mouse tissues was similar for all BPD analogues. M1 tumour cells (rhabdomyosarcoma in DBA/2J mice) taken from tumours excised from animals treated 3 h earlier with BPD, and tested in vitro for photosensitivity provided evidence that significant levels of photosensitiser detected in tumour was both active and associated with tumour cells. The monoacid forms of BPD were found to be much more photodynamically active in this test than were the diacid analogues. The ability of the analogues to ablate tumours in mice by photodynamic therapy was also tested. Again, BPD-MA and BPD-MB proved to be measurably better than the diacid analogues. These findings are discussed in reference to structural and physical differences between the analogues.

Animals

In-vitro interaction of a novel immunosuppressant, FK 506, and antacids.

The effect of selected antacids on the amount of FK 506 in solution in simulated gastric juice has been studied. FK 506 (2.5 mg) was incubated in 100 mL simulated gastric fluid (SGF) with the equivalent of 500 mg of various antacids. The addition of Mylanta and Tums resulted in 14 and 30% loss of FK 506, respectively, in 24 h; 98% loss was observed in 12 h in the presence of Mag-Ox; 100% loss was observed in the presence of magnesium oxide powder in 2 h. The loss of FK 506 from these solutions appears to be due to a pH mediated degradation of FK 506. The addition of aluminium hydroxide gel USP (Roxane) to the FK 506 solution resulted in a 35% loss within 2 min but no further loss was noted for 24 h, indicative of adsorption of FK 506. These results suggest that until additional in-vivo studies are carried out, it is prudent not to dose FK 506 and antacids at the same time to avoid potential interactions.

Antacids

Frequency of sister chromatid exchange and chromosomal aberrations in asbestos cement workers.

Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. It was shown previously that asbestos samples collected from a local asbestos factory enhanced sister chromatid exchanges (SCEs) and chromosomal aberrations in vitro using human lymphocytes. In the present study, 22 workers from the same factory and 12 controls were further investigated. Controls were matched for age, sex, and socioeconomic state. The peripheral blood lymphocytes were cultured and harvested at 48 hours for studies of chromosomal aberrations and at 72 hours for SCE frequency determinations. Asbestos workers had a raised mean SCE rate and increased numbers of chromosomal aberrations compared with a control population. Most of the chromosomal aberrations were chromatid gap and break types.

Adult