Studies on capsaicin inhibition of chemically induced lipid peroxidation in the lung and liver tissues of rat

Previous work from this laboratory has already indicated that capsaicin, stabilizes the rat lung membrane lipid system on long-term treatment. This stabilization of the membrane is further supported by our present findings that capsaicin pretreatment causes significant inhibition of various chemically induced lipid peroxidative changes at both cellular and subcellular levels. Both in vivo and in vitro studies, using whole lung and liver tissue slices and mitochondrial and microsomal fractions, have shown that capsaicin pretreatment inhibits peroxidative changes at both cellular and subcellular levels. Both in vivo and in vitro studies, using whole lung and liver tissue slices and mitochondrial and microsomal fractions, have shown that capsaicin pretreatment inhibits peroxidative changes induced by different chemical irritants such as chloroform, dichloromethane, carbon tetrachloride as well as ferrous sulphate.     

Perinatal lung development following maternal exposure to methylmercuric chloride

Mercury ingested from dietary sources has potent neurotoxic and teratogenic effects. Initial studies have shown that mercury may also affect fetal lung development. Since these pulmonary effects may play a role in subsequent neonatal morbidity and mortality due to compromising of the development of the lung, mercury effects in fetal and neonatal lung were investigated. Methylmercuric chloride (MMC), 1,000 ppm (15 mg/kg of body weight), was administered via an intragastric tube to timed-pregnant Swiss/Webster mice on day 9 of gestation. Lungs from fetuses on gestational day 18 and from neonates on days 1, 5, or 10 after birth were studied. Significant changes in MMC-exposed lungs compared to controls occurred at postnatal day 1. At this time, lung weight per gram body weight increased, phospholipid content per gram of lung or per microgram of DNA decreased, while DNA per gram of lung increased. Methylmercury appears to have delayed lung maturation. Cuboidal epithelial cells in alveolar tubules contained conspicuous glycogen deposits, and differentiation of alveolar type II cells was adversely affected. These results suggest that prenatal exposure to methylmercury may be detrimental to lung development, specifically to the initiation of surfactant synthesis, by delaying the normal pattern of maturation of the alveolar type II cells within the lungs. Pediatr Pulmonol. 1994; 17:11–21 . © 1994 Wiley-Liss. Inc.     

Congenital thrombophilia among patients with venous thromboembolism.

During a 3-year period we studied 393 adult patients (382 of whom were unrelated) with a history of acute venous thromboembolism. A congenital deficiency state known to predispose to thrombosis was found in 27.2%. Of these, most were due to deficiencies of protein C (9.2%), protein S (7.6%), antithrombin III (5%) or to increased plasma PAI-1 concentration (3.1%) which, in the absence of any known factor that predisposes towards thrombosis, results in a diminished fibrinolytic activity. There was a characteristic pattern between the age of onset (mean 34 years) of thrombosis and individual protein deficiency. Thrombosis appeared spontaneously in 73% of cases with recurrence in 80%. In contrast, in the remaining unrelated patients, 138 (35.1%) in whom venous thromboembolism was secondary and occurred at a mean age of 43 years, and in the other 140 (35.6%) who suffered thromboembolism spontaneously at a later age (mean age 55), there was no permanent protein deficiency state or alteration in fibrinolytic activity and thrombosis recurrence was lower (53.6% and 20.7% respectively). Of the 393 patients, deep vein thrombosis was the most common manifestation; however, in congenital thrombophilia, thrombosis of visceral vessels and Raynaud's syndrome (6%) were also detected.     

Pharmacokinetic evaluation of conventional and controlled release dosage form of propranolol

A comparative pharmacokinetic study of a new controlled release multiple unit propranolol formulation and a conventional propranolol tablet was carried out in twelve healthy human volunteers in a randomized balanced crossover design. Under a single dosage regimen, subjects were administered either a single capsule containing controlled release propranolol equivalent to 160 mg of the drug or 80 mg of conventional propranolol tablet, twelve hourly. Peak plasma propranolol concentrations were low which occurred later after controlled release administration than after the administration of the conventional tablet. Analysis of the area under the plasma concentration-time curve (AUC) for the two formulations indicate no significant difference of bioavailability despite a prolonged absorption time and maintenance of effective plasma concentration for the controlled release preparation.     

Biotype traits and antibiotic susceptibility of Vibrio cholerae serogroup O1 before, during and after the emergence of the O139 serogroup.

Sixty-nine strains of Vibrio cholerae O1 isolated at different times were analysed to investigate if there were any differences among the O1 strains isolated before, during and after the advent of the O139 serogroup. Of the 69 O1 strains examined, 68 belonged to the Ogawa serotype while one belonged to the Inaba serotype. With the exception of one strain all other strains of V. cholerae O1 belonged to the eltor biotype. A single O1 strain isolated before the emergence of the O139 serogroup could not be classified as either eltor or classical biotype because it was resistant to both classical and eltor specific bacteriophages. Marked variations in the susceptibility to antibiotics of V. cholerae O1 isolated during the different periods were observed. In addition, strains of V. cholerae isolated after the epidemic of serogroup O139 in Calcutta showed an expanding R-type with resistance to a variety of drugs as compared to the O1 strains isolated before the advent of the O139 serogroup. From this study, it is clear that there is a substantial mobility in genetic elements of V. cholerae O1 which necessitates a continuous monitoring to keep abreast of the changing traits of the etiologic agent of cholera.     

Reduction of glutathione is associated with growth restriction and enlargement of bovine pulmonary artery endothelial cells produced by transforming growth factor-beta 1.

In addition to inhibiting proliferation and causing enlargement of bovine pulmonary artery endothelial cells in culture, porcine platelet transforming growth factor-beta 1 (TGF-beta 1) (2 ng/ml) lowered glutathione (GSH) of these cells by 48% after 96 h in culture when GSH levels were normalized for cell counts. This lowering of cellular GSH was more marked when corrections were made for approximated cell volume. TGF-beta 1 produced only moderate inhibition of pulmonary artery smooth muscle cell proliferation and did not significantly reduce the GSH content of these cells, even at concentrations as high as 8 ng/ml. Elevation of GSH of endothelial cells above control levels by 0.05 mM diethylmaleate or 1 mM cystine prevented the inhibition of cellular proliferation produced by TGF-beta 1. Lowering cellular GSH levels by approximately 85% for 24 to 72 h with 0.01 mM buthionine sulfoximine (BSO) in the absence of TGF-beta 1 had no effect on proliferation or size of the endothelial cells. However, 0.01 mM BSO potentiated the inhibitory effect of TGF-beta 1 on endothelial cell proliferation and in combination with TGF-beta 1 caused cellular detachment at low endothelial cell densities. Thus, although TGF-beta 1 lowers the level of endothelial cellular GSH, this in itself does not appear to account for the inhibition of proliferation and enlargement of these cells produced by TGF-beta 1. Rather, the combination of another unidentified action of TGF-beta 1 in the presence of reduced cellular GSH likely accounts for these effects.     

Immunomodulation during prolonged treatment with combined interleukin-2 and interferon-alpha in patients with advanced malignancy.

Treatment with combined IL-2 and alpha-IFN has resulted in synergistic antitumour efficacy in animal studies. The mechanisms responsible for this synergy remain unclear. In this study, several immune parameters which might be involved in mediating antitumour activity have been monitored serially in 15 patients with advanced malignant melanoma or renal cell cancer during treatment with concurrent IL-2 and alpha-IFN. Both drugs were given subcutaneously in low to moderate (outpatient) dosages but for a prolonged duration. This treatment resulted in remarkable immunomodulation. In vivo induction of cytotoxicity against K562 and Daudi target cells was consistently seen, and percentages of peripheral blood cells expressing CD 25 (IL-2 receptor) and CD 56 (Leu-19) increased. In vitro proliferation of lymphocytes in response to IL-2 was enhanced during the treatment periods, whereas spontaneous proliferation was inhibited. Moreover, correlations between immune parameters and subsequent clinical responses were present in the early phase of the study. Cytotoxicity levels generated in vivo as well as the percentage of CD 56+ lymphocytes were higher in patients who responded to treatment than in non-responders. In contrast, responders had lower levels of CD 25+ cells. These findings indicate that it might be possible to select patients who are likely to benefit from prolonged immunotherapy.     

Pancreatic pseudocysts: treated with dual drainage.

Four patients with retrogastric pancreatic pseudocysts were successfully treated by the combined placement of a transgastric external drain and a cystogastric stent. We describe the advantages of using external transgastric drainage along with the cystogastric stent.     

Epidemiological study of the victims of vehicular accidents in Delhi.

The mortality and morbidity connected with road traffic accidents are increasing at an alarming rate throughout the world as a direct result of the rapid industrialization and increase of fast moving vehicles combined with lack of traffic sense of road users of this country. Epidemiological aspects manifested in vehicular accidents in New Delhi during the year 1983-84 are illustrated here.