Polysaccharide and monosaccharide guided liver delivery of Sorafenib Tosylate - A nano-strategic approach and comparative assessment of hepatospecificity.

Hepatospecific delivery by ligand based receptor targeting is an established strategy to augment therapy associated with liver diseases and disorders. Previously, we have investigated the effect of ligand headgroup on cellular uptake mediated by the asialoglycoprotein receptor by in silico and in vitro approach. In this paper, we report the design of agarose based liposomes for delivery to liver cancer cells and provide a proof of concept of the targeting efficiency against galactose liposomes using an in vivo approach. Sorafenib Tosylate loaded targeting liposomes were developed and optimized using factorial design. Comparative evaluation including cell cytotoxicity, pharmacokinetics and biodistribution and hepatospecific uptake was performed for both the liposomal systems. The formulations possessed a particle size of 150 - 180 nm and a zeta potential of 30 - 60 mV depending on the amount of ligand and drug loading, with more than 90% entrapment efficiency. A two-fold increase in cytotoxicity was observed with agarose-based liposomes as compared to galactose based liposomes. In vivo PK evaluation indicated a reduction in half life of drug when loaded in agarose ligand loaded system, probably due to greater uptake in the liver as evidenced in biodistribution study. Intrahepatic disposition revealed a higher PC/NPC uptake ratio with the targeted systems as compared to conventional liposomes, although the agarose-based system resulted in highest uptake ratio. A biocompatible platform for specific delivery of drugs to hepatocytes was established validating a rational approach to design liver targeting systems.

A mysterious journey of a cardiac pacemaker.

A permanent bipolar cardiac pacemaker was inserted in the abdomen of a child with Down's syndrome, due to complete heart block following repair of atrioventricular septal defect. This report describes an unusual and unreported complication of the pacemaker getting extruded through the rectum without dysfunction. Implications for early diagnosis and appropriate management and steps to prevent such episodes in future are discussed.

O-Galloyl-C-glycosylflavones from Pelargonium reniforme.

The unique series of C-2''-acylated C-glycosylflavones is extended by the discovery of the C-8-glucosyl derivatives 2''-O-galloylvitexin and 2''-O-galloylorientin and their C-6 analogues 2''-O-galloylisovitexin and 2''-O-galloylisoorientin, representing the first described O-galloyl-C-glycosylflavones. They are accompanied in the aerial parts of Pelargonium reniforme by the known non-galloylated parent analogues vitexin, orientin, isovitexin and isoorientin, as well as several known flavonoid-O-glycosides. The structures of these compounds were established from spectroscopic studies. Differentiation between C-glycosylation at C-6 and C-8 is discussed on the basis of the effects of dynamic rotational isomerism.

A cross-cultural study of the subjective well-being of married elderly persons in the United States and India.

Systematically comparable data on married elders from the United States (n = 567; ages 60+) and Madras, India (n = 207; ages 55+) and simultaneous factor analyses (LISREL) were used to test the cross-cultural metric and structural invariance of a model of the influence of emotional social support from role relationships (adult children, spouse, and friends and relatives) on subjective well-being, based on social support and interactional role theories. Except for cross-cultural differences in measurement error variances, the model showed a high degree of invariance across the two samples. Americans and Indians were unexpectedly similar in terms of the influence of emotional social support from role relationships on their subjective well-being. The discussion explores why cross-culturally similar relationships exist between emotional support and subjective well-being for married elders in two such apparently different societies.

Potential of diet therapy on murine AIDS.

Recently, a murine retrovirus (LpBM5 MuLV), which induces immunodeficiency syndrome in mice, termed MAIDS, has been found to have several features similar to those seen in human acquired immunodeficiency syndrome (AIDS). The present study was undertaken to compare the effects of 40% energy restriction (R) and/or ad libitum (AL) diets with vegetable [corn oil, (CO) (n-6)] or marine oil [menhaden fish oil (FO), (n-3)] as a source of dietary fats on the immune function and survival rate of C57BL/6 mice injected with the LpBM5 MuLV virus. Weanling mice were fed, throughout the study, either a 5% CO-, 5% CO(R)-, 20% CO- or 20% FO-based diet and 8 wk later the mice were injected with the LpBM5 MuLV (5 x 10(5) plaque-forming units). The results revealed a significantly prolonged postinjected survival rate in the mice fed 20% FO and 5% CO(R) diets [5% CO = 131 +/- 7 d; 5% CO(R) = 161 +/- 13 d; 20% CO = 125 +/- 6 d; 20% FO = 164 +/- 14 d]. Immunological studies conducted 4 wk after injection revealed decline in both interleukin-2 production and proliferative response to mitogens in spleen cells of mice in all four dietary groups. However, this decline was less apparent in mice fed 5% CO(R) and 20% FO diets.(ABSTRACT TRUNCATED AT 250 WORDS)