A V Lal

Publications of A V Lal

• 1,25-dihydroxyvitamin D3 receptor is upregulated in aortic smooth muscle cells during hypervitaminosis D.

  Authors: S Rajasree, P R Umashankar, A V Lal, P Sankara Sarma, C C Kartha

  Life sciences. 04/2002; 70(15):1777-88.

  Several studies have demonstrated that excess of vitamin D3 is toxic particularly to vascular tissues. A notable pathological feature is arterial calcification. The nature of the toxic metabolite inSeveral studies have demonstrated that excess of vitamin D3 is toxic particularly to vascular tissues. A notable pathological feature is arterial calcification. The nature of the toxic metabolite in hypervitaminosis D and the pathogenesis of arterial calcification are not clearly understood. The present study was undertaken to explore whether arterial calcification is a sequel of increased calcium uptake by arterial smooth muscle mediated by up regulation of vitamin D receptor in the cells in response to elevated circulating levels of vitamin D3 in serum. The experimental study was performed in 20 New Zealand white female rabbits aged 6 months. Animals in the test group were injected 10,000 IU of cholecalciferol intramuscularly twice a week for one month. Six control animals were given intra-muscular injections of plain cottonseed oil. Animals were sacrificed and aortas were examined for pathological lesions, 1,25-dihyroxyvitamin D3 (1,25(OH)2 D3) receptor levels and 45Ca uptake in smooth muscle cells. Serum samples collected at intervals were assayed for levels of 25-OH-D3 and calcium. The results showed that in animals given injections of cholecalciferol, serum levels of 25-OH-D3 were elevated. In four of these animals calcification and aneurysmal changes were seen in the aorta. Histological lesions comprised of fragmentation of elastic fibers as well as extensive loss of elastic layers. 1,25(OH)2 D3 receptor levels were up regulated and 45Ca uptake enhanced in aortas of animals which were given excessive vitamin D3. The evidences gathered suggest that excess vitamin D is arteriotoxic and that the vitamin induces arterial calcification through up regulation of 1,25(OH)2D3 receptor and increased calcium uptake in smooth muscle cells of the arteries.

• Progesterone release from glutaraldehyde cross-linked casein microspheres: in vitro studies and in vivo response in rabbits.

  Authors: M S Latha, A V Lal, T V Kumary, R Sreekumar, A Jayakrishnan

  Contraception. 06/2000; 61(5):329-34.

  Microspheres of bovine milk protein casein loaded with progesterone were fabricated by glutaraldehyde cross-linking of an aqueous alkaline solution of the protein dispersed in a hexane andMicrospheres of bovine milk protein casein loaded with progesterone were fabricated by glutaraldehyde cross-linking of an aqueous alkaline solution of the protein dispersed in a hexane and dichloromethane non-aqueous dispersion medium with an aliphatic polyurethane as the stabilizer. Microspheres were characterized for their surface morphology and internal structure using scanning electron microscopy. In vitro release studies in phosphate buffer at 37 degrees C demonstrated that the rate of release of the steroid from the microsphere matrix was a function of cross-linking density, particle size, and drug payload. Microsphere formulations released 50% to 60% of the incorporated steroid in about 30 days and, thereafter, attained a steady state. In the presence of a protein-digesting enzyme such as protease, complete release of the steroid was observed in about 4 days in vitro into phosphate buffer. Intramuscular injection of progesterone-loaded microspheres into rabbits showed a plasma concentration of 1 to 2 ng/mL up to 5 months without any significant burst effect, whereas the powdered steroid administered in saline demonstrated a large burst effect peaking over 20 ng/mL, and the plasma concentration was not sustained beyond 4 days. Data obtained suggest that casein microspheres would be promising as a biodegradable drug carrier for sustained delivery of steroids.

• Pattern of cardiac fibrosis in rabbits periodically fed a magnesium-restricted diet and administered rare earth chloride through drinking water.

  Authors: C C Kartha, J T Eapen, C Radhakumary, V R Kutty, K Ramani, A V Lal

  Biological trace element research. 08/1998; 63(1):19-30.

  It has been postulated that causation of the tropical cardiomyopathy endomyocardial fibrosis (EMF) is linked to magnesium (Mg) deficiency and cardiac toxicity of the rare earth element cerium (Ce).It has been postulated that causation of the tropical cardiomyopathy endomyocardial fibrosis (EMF) is linked to magnesium (Mg) deficiency and cardiac toxicity of the rare earth element cerium (Ce). The aim of the present study was to define the myocardial lesions in rabbits that were fed on Mg-restricted diet (70-80 ppm) periodically and were provided drinking water contaminated with rare earth chloride (1 g/L). Forty New Zealand white rabbits were divided into four groups following a 2 x 2 factorial design. Two groups were periodically fed on Mg-restricted diet with one of them receiving water contaminated with rare earth chloride. The other two groups were continuously fed on Mg-sufficient diet (350-400 ppm) with one of them receiving water contaminated with rare earth chloride. All animals were sacrificed at the end of 6 mo. Cardiac tissues were subjected to histology, elemental analysis (calcium [Ca], Mg, and Ce) and estimation of collagen content and collagen phenotypes. Histological lesions were compared with those of EMF in humans and those of acute Mg deficiency in animals. The results suggest that in rabbits, recurrent episodes of Mg deficiency lead to myocardial fibrosis similar to the pattern observed in human EMF.

• Progesterone-loaded chitosan microspheres: a long acting biodegradable controlled delivery system.

  Authors: S R Jameela, T V Kumary, A V Lal, A Jayakrishnan

  Journal of controlled release : official journal of the Controlled Release Society. 04/1998; 52(1-2):17-24.

  Smooth, highly spherical, crosslinked chitosan microspheres in the size range of 45-300 microns loaded with progesterone were prepared by glutaraldehyde crosslinking of an aqueous acetic acidSmooth, highly spherical, crosslinked chitosan microspheres in the size range of 45-300 microns loaded with progesterone were prepared by glutaraldehyde crosslinking of an aqueous acetic acid dispersion of chitosan containing progesterone in a non-aqueous dispersion medium consisting of liquid paraffin and petroleum ether stabilized using sorbitan sesquioleate. In vitro release of the drug into phosphate buffer at 37 degrees C was determined as a function of crosslinking density of the microspheres and particle size. The extent of drug release had a remarkable dependence on the crosslinking density of the microspheres, the highly crosslinked spheres releasing only around 35% of the incorporated steroid in 40 days compared to 70% from spheres lightly crosslinked. Determination of the in vivo bioavailability of the steroid from microsphere formulation by intramuscular injection in rabbits showed that a plasma concentration of 1 to 2 ng/ml was maintained up to 5 months without a high 'burst effect'. Data obtained suggest that the crosslinked chitosan microspheres would be an interesting system for long term delivery of steroids.

• Prevention of calcification of tissue valves.

  Authors: J Chanda, S B Rao, M Mohanty, A V Lal, C V Muraleedharan, G S Bhuvaneshwar, M S Valiathan

  Artificial organs. 11/1994; 18(10):752-7.

  In this study an attempt was made to find an optimum method of chemical treatment to prevent the calcification of bioprosthetic heart valves. Bovine pericardium was washed in a 5% sodium chlorideIn this study an attempt was made to find an optimum method of chemical treatment to prevent the calcification of bioprosthetic heart valves. Bovine pericardium was washed in a 5% sodium chloride solution followed by trypsin (Tr) treatment and was kept in 0.1% glutaraldehyde (GA) with a gradual increase in concentration up to 0.25% GA and finally posttreated with a 4% chitosan (Ch) solution. Fresh, 0.2% GA, 0.625% GA, and sodium chloride-Tr-GA treated pericardial samples were taken for comparative study. Tensile testing showed comparable strength and elongation at the breaking point for all groups. The thermal shrinkage studies indicated merit of the proposed treatment (5% sodium chloride-trypsin-glutaraldehyde treated pericardia with chitosan and without chitosan posttreatment). Collagenase assay showed that all differently treated (GA) materials were equally resistant to collagenase. All samples were implanted subcutaneously in rats for 2, 4, 8, or 12 weeks for calcification study. Morphological and mineral analyses showed complete prevention of calcification in sodium chloride-trypsin-GA-chitosan treated pericardium (Ca was 1.1 +/- 0.27 mg/g, von Kossa 0) at the 12th week of implantation.

• Chronic arterial occlusion in a canine model: a novel technique.

  Authors: K Ravimandalam, V R Rao, S Kumar, S Joseph, A V Lal, M Mohanty

  AJR. American journal of roentgenology. 01/1991; 155(6):1348.

• Prevention of calcification of tissue valves

  Authors: J Chanda, S B Rao, M Mohanty, A V Lal, CV Muraleedharan, GS Bhuvaneshwar, MS Valiathan

  Artificial organs. 18(10):752-757.

• Progesterone-loaded chitosan microspheres: a long acting biodegradable controlled delivery system

  Authors: S.R Jameela, T.V. Kumary, A.V. Lal, A. Jayakrishnan

  Journal of Controlled Release.

  Smooth, highly spherical, crosslinked chitosan microspheres in the size range of 45–300 μm loaded with progesterone were prepared by glutaraldehyde crosslinking of an aqueous acetic acid dispersionSmooth, highly spherical, crosslinked chitosan microspheres in the size range of 45–300 μm loaded with progesterone were prepared by glutaraldehyde crosslinking of an aqueous acetic acid dispersion of chitosan containing progesterone in a non-aqueous dispersion medium consisting of liquid paraffin and petroleum ether stabilized using sorbitan sesquioleate. In vitro release of the drug into phosphate buffer at 37°C was determined as a function of crosslinking density of the microspheres and particle size. The extent of drug release had a remarkable dependence on the crosslinking density of the microspheres, the highly crosslinked spheres releasing only around 35% of the incorporated steroid in 40 days compared to 70% from spheres lightly crosslinked. Determination of the in vivo bioavailability of the steroid from microsphere formulation by intramuscular injection in rabbits showed that a plasma concentration of 1 to 2 ng/ml was maintained up to 5 months without a high `burst effect'. Data obtained suggest that the crosslinked chitosan microspheres would be an interesting system for long term delivery of steroids.