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Biomedical subjects

G Chandrakasan

Publications and source records attributed to G Chandrakasan.

At least 37 records · Page 2Linked to original sources
PubMed1996

The possible relevance of autoxidative glycosylation in glucose mediated alterations of proteins: an in vitro study on myofibrillar proteins.

The present work was carried out to examine the role of glycation and transition metal catalysed autoxidation of sugars in glucose-mediated alterations of myofibrillar proteins. Myofibrils were prepared from rat skeletal muscle and incubated with 1) sugar alone 2) sugar and micromolar concentrations of transition metals (Cu2+ or Fe3+) 3) transition metals alone and the control remained without sugar or transition metals. A significant increase in extent of glycation and decrease in ATPase activity of myofibrils incubated under autoxidative conditions were observed over the other three incubations. Reducing agent 2-mercaptoethanol was highly effective in preventing the alterations induced by glucoxidation, compared to EDTA and aminoguanidine, suggesting the involvement of thiol group oxidation in the reduced function of the protein. Free radical scavengers like catalase, benzoic acid and mannitol were also effective in preventing glucose mediated alterations. Although a high concentration of glucose alone has an insignificant effect on myofibrils in vitro, the results from the present work suggest that glucose in combination with transition metals could lead to functional alterations of myofibrils, and this process by generating free radicals may contribute to the overall complications of diabetes and aging.

Animals↗
PubMed1996

Glycoprotein metabolism in dimethylnitrosamine induced hepatic fibrosis in rats.

Glycoproteins play a major role in the pathogenesis of hepatic fibrosis by accumulating in the sinusoids and the space of Disse. In order to obtain more information about the altered metabolism of glycoproteins during the development of human hepatic fibrosis, the carbohydrate moieties of the glycoproteins were monitored in experimentally induced hepatic fibrosis. The liver injury was induced by injecting dimethylnitrosamine intraperitoneally in male albino rats. The injections were given on the first 3 consecutive days of each week over a period of 21 days. Glycoprotein moieties such as total hexose, hexosamine, fucose and sialic acid were estimated in liver, serum and urine samples on days 7, 14 and 21 of the experiment. The results indicated a significant decrease in total hexose and an increase in fucose levels in the liver tissue during dimethylnitrosamine administration. While protein bound hexose in the serum showed a significant decrease, sialic acid levels were notably increased. The other glycoprotein moieties both in liver and serum also showed an increase in the later periods of study, especially on day 21. All glycoprotein moieties exhibited a significant increase in the rate of urinary excretion on the 14th and 21st days, indicating an increased rate of metabolic degradation in the acute phase of hepatic fibrosis. The results suggest that glycoproteins undergo changes in both synthesis and the degradation during hepatic fibrosis. The relative alterations in these processes will play a vital role in determining the progression of hepatic fibrosis.

Animals↗
PubMed1996

Effects of Centella asiatica extract on dermal wound healing in rats.

Effects of oral and topical administration of an alcoholic extract of C. asiatica on rat dermal wound healing was studied. The extract increased cellular proliferation and collagen synthesis at the wound site, as evidenced by increase in DNA, protein and collagen content of granulation tissues. Quicker and better maturation and crosslinking of collagen was observed in the extract-treated rats, as indicated by the high stability of acid-soluble collagen and increase in aldehyde content and tensile strength. The extract treated wounds were found to epithelialise faster and the rate of wound contraction was higher, as compared to control wounds. The results show that C. asiatica produced different actions on the various phases of wound repair.

Animals↗
PubMed1995

Modulation of cyclophosphamide-induced early lung injury by curcumin, an anti-inflammatory antioxidant.

Cyclophosphamide causes lung injury in rats through its ability to generate free radicals with subsequent endothelial and epithelial cell damage. In order to observe the protective effects of a potent anti-inflammatory antioxidant, curcumin (diferuloyl methane) on cyclophosphamide-induced early lung injury, healthy, pathogen free male Wistar rats were exposed to 20 mg/100 g body weight of cyclophosphamide, intraperitoneally as a single injection. Prior to cyclophosphamide intoxication oral administration of curcumin was performed daily for 7 days. At various time intervals (2, 3, 5 and 7 days post insult) serum and lung samples were analyzed for angiotensin converting enzyme, lipid peroxidation, reduced glutathione and ascorbic acid. Bronchoalveolar lavage fluid was analyzed for biochemical constituents. The lavage cells were examined for lipid peroxidation and glutathione content. Excised lungs were analyzed for antioxidant enzyme levels. Biochemical analyses revealed time course increases in lavage fluid total protein, albumin, angiotensin converting enzyme (ACE), lactate dehydrogenase, N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, acid phosphatase, lipid peroxide levels and decreased levels of glutathione (GSH) and ascorbic acid 2, 3, 5 and 7 days after cyclophosphamide intoxication. Increased levels of lipid peroxidation and decreased levels of glutathione and ascorbic acid were seen in serum, lung tissue and lavage cells of cyclophosphamide groups. Serum angiotensin converting enzyme activity increased which coincided with the decrease in lung tissue levels. Activities of antioxidant enzymes were reduced with time in the lungs of cyclophosphamide groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

In vivo administration of taurine and niacin modulate cyclophosphamide-induced lung injury.

The antiinflammatory, antioxidant activity of taurine and niacin against cyclophosphamide-induced early lung injury in rats was investigated. A single intraperitoneal injection of cyclophosphamide markedly altered the levels of several biomarkers in bronchoalveolar lavage fluid: total protein, albumin, angiotensin converting enzyme, lactate dehydrogenase, lactate, N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, acid phosphatase and lipid peroxidation product were significantly elevated. In contrast, decreased levels of total reduced glutathione (GSH) and ascorbic acid were observed. Cyclophosphamide significantly increased malondialdehyde levels in serum and lung. Significant increases in lung content of lipid hydroperoxides were seen that paralleled the decreased levels of total reduced glutathione and total sulfhydryl groups. Pretreatment of rats with daily intraperitoneal injection of taurine plus niacin 7 days prior to and 2 days after cyclophosphamide insult significantly inhibited the development of lung injury, prevented the alterations in lavage fluid biomarkers associated with inflammatory reactions, with less lipid peroxidation and restoration of antioxidants. In conclusion, our results suggest that taurine and niacin in combination is efficient in blunting cyclophosphamide-induced pulmonary damage.

Acid Phosphatase↗
PubMed1994

Cyclophosphamide induced early biochemical changes in lung lavage fluid and alterations in lavage cell function.

The present investigation evaluated the changes in bronchoalveolar lavage fluid (BALF) biochemical constituents and indices of bronchoalveolar lavage cell functions to detect early lung injury in rats following intraperitoneal administration of cyclophosphamide (CP). Rats were exposed to a single intraperitoneal injection of CP (200 or 300 mg/kg body weight). Experimental and control rats were sacrificed at various time intervals (2, 3, 5, 7, 11, 21, and 42 days after cessation of exposure), and lung lavage was performed to examine several markers of lung injury. Biochemical analyses revealed dose-related increases in BALF angiotensin converting enzyme activity, total protein, lactate, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase (NAG) levels on days 2, 3, 5, 7, and dose-related increases in albumin, alkaline phosphatase, acid phosphatase, and lipid peroxidation on days 2, 3, 5, 7, and 11 after CP treatment. In contrast, reduced levels of ascorbic acid and glutathione (GSH) content were observed in lung lavage fluid. We also examined bronchoalveolar lavage cells for acid hydrolases (acid phosphatase, beta-glucuronidase, NAG) and GSH content. Activity of acid hydrolases was slightly elevated on day 2 and peaked on days 3, 5, and 7. However, lavage cell GSH content was decreased. Thus, measurements of pulmonary changes by analyzing lavage fluid and lavage cell functions seems to be a useful marker for assessing the early onset and development of CP-induced lung injury.

Animals↗
PubMed1993

Angiotensin I converting enzyme activity in adriamycin induced nephrosis in rats.

Activity of the dipeptidyl hydrolase angiotensin converting enzyme (ACE) has been observed to be altered by treatment with adriamycin (ADR). We used an animal model of ADR nephrotoxicity to study the effects on ACE in serum, urine and tissues on days 5, 10, 15, 20, 25 and 30 after ADR administration. Both glomerular and tubular injury occurred as evidenced by heavy proteinuria, albuminuria and increased urine N-acetyl glucosaminidase (NAG) excretion. Serum ACE was significantly elevated on days 20, 25 and 30. Of great interest was the excretion of ACE in urine of treated rats which ran parallel with the total protein excretion above the barely detectable levels found in controls. ACE activity increased in kidney, adrenal gland and liver on days 15, 20, 25 and 30. Heart and brain ACE levels increased on days 25 and 30. Increased ACE activity in aorta and lungs occurred on days 20, 25 and 30. ACE activity decreased in kidney, aorta, heart and brain on days 5 and 10. These observations strongly suggest a contribution of various tissues to elevate the serum ACE level. Urinary ACE may be of potential use as an index for renal glomerular and tubular damage.

Animals↗
PubMed1991

Stimulation of collagen synthesis in fibroblast cultures by superoxide.

Exposure of diploid fetal human fibroblasts (IMR-90) to superoxide generated by dihydroxyfumarate resulted in increased collagen synthesis. The synthesis of type III collagen was stimulated to a greater extent than the synthesis of type I collagen. The stimulation of collagen synthesis was abolished by superoxide dismutase. Our observations suggest that superoxide may play a role in the regulation of collagen synthesis and may modulate differential collagen gene expression. These observations may explain the increased synthesis of collagen in tissues following inflammation or exposure to oxidant conditions.

Cells, Cultured↗
PubMed1991

Keratin expression in cultures of adult human epidermal cells.

Keratins are complex fibrous proteins characteristic of epithelial cells. We have developed a procedure that allows us to culture and passage adult human dermal keratinocytes in the absence of mesenchymal substrates. Electron microscopic examination of stratifying cultures showed the presence of numerous filament bundles, desmosomes and electron dense granules. The expression of different classes of keratin was examined by immunofluorescence, SDS-PAGE and immunoblots using monoclonal antibodies. The analysis of water-insoluble proteins revealed the presence of keratins of molecular weights 40 Kda, 50-52 Kda, 56 Kda and 65-67 Kda. Our results indicate that the terminal differentiation of keratinocytes may not require dermal factors.

Blotting, Western↗
PubMed1989

Studies on the metabolism of glycosaminoglycans under the influence of new herbal anti-inflammatory agents.

The in vivo effect of an herbal based, non-steroidal anti-inflammatory product, salai guggal, prepared from the gum resin exudate of Boswellia serrata and its active principle "boswellic acids" on glycosaminoglycan metabolism has been studied in male albino rats. The biosynthesis of sulfated glycosaminoglycans, as evaluated by the uptake of [35S]sulfate, and the content of glycosaminoglycans were measured in specimens of skin, liver, kidney and spleen. Statistical analysis of the data obtained with respect to the boswellic acids and salai guggal were compared with those of ketoprofen. A significant reduction in glycosaminoglycan biosynthesis was observed in rats treated with all of the drugs. Glycosaminoglycan content was found to be decreased in the ketoprofen-treated group, whereas that of the boswellic acids or salai guggal treated groups remained unaltered. The catabolism of glycosaminoglycans was followed by estimating the activities of lysosomal glycohydrolases, namely beta-glucuronidase, beta-N-acetylglucosaminidase, cathepsin B1, cathepsin B2 and cathepsin D, in tissues and by estimating the urinary excretion and hexosamine and uronic acid. The degradation of glycosaminoglycans was found to be reduced markedly in all drug-treated animals as compared to controls. The potential significance of boswellic acids and salai guggal was discussed in the light of changes in the metabolism of glycosaminoglycans.

Animals↗
PubMed1989

In vivo glycosylation of dermal and tendon type I collagen.

Recent studies show that native collagen fibers in the extracellular space can be subject to nonenzymatic glycosylation and that the extent of such glycosylation increases in clinical hyperglycemia and aging. In the present study, a comparison was made on the extent of glycosylation in rat tail tendon and in the soluble and insoluble fractions of collagen separated from rat skin after in vivo labeling with [14C]glucose. It was observed that nonenzymatic glycosylation occurred maximally in the salt-soluble fraction as measured by the level of ketoamine linked hexose. 14C radioactivity incorporation as well as the number of free amino groups was also increased in this fraction. However, the amounts of O-glycosidically linked sugars did not show much variation between the soluble and insoluble fractions. These findings could be correlated to the enhanced metabolic turnover of newly synthesized collagen in diabetics.

Animals↗
PubMed1989

Influence of monosaccharides on the fibrillogenesis of type I collagen.

The in vitro self-assembly of Type I rat tail tendon collagen in the presence of monosaccharides was studied turbidimetrically. D(+)glucose and D(+)mannose delayed fibril formation significantly while D(-)fructose showed no variation. The effect of glucose was concentration dependent. Binding of glucose during fibrillogenesis was shown by the incorporation of [14C]glucose and also by SDS-polyacrylamide slab gel electrophoresis of the product. The results indicate that in vitro nonenzymatic glycosylation can take place in the short duration required for fibril formation.

Animals↗
PubMed1989

Separation and evaluation of changing pattern of glycosaminoglycans in 3-methyl cholanthrene induced fibrosarcoma.

The present study evaluates the glycosaminoglycans (GAGs) pattern associated with transplantable rat fibrosarcoma induced by 3-methylcholanthrene. The quantitative analysis of fractionation of GAGs in fibrosarcoma and fetal tissues was performed by enzymatic digestion. The average value of total GAGs in fibrosarcoma and fetal tissue was found to be 4 times higher than its value in the tissue of origin. GAG content showed a steady increase from 7th day onward to 25th day. Hyaluronic acid content in tumor tissue was observed to increase markedly (8-fold) against that of the normal tissue and was equivalent to that of the fetal tissue. Chondroitin sulfate level was also increased in the tumor as well as fetal tissue. The increase in the chondroitin sulfate and hyaluronic acid contents might possibly be due to the abnormal GAG metabolism in the increased production of both sulfated and nonsulfated GAGs.

Animals↗
PubMed1987

Alterations in lung and skin compositions of rat in bleomycin-induced fibrosis.

Male albino rats were given bleomycin subcutaneously (5 mg potency/kg body weight twice a week) for a period of 6 weeks. At this dosage, mortality was found to be nil with marked fibrotic changes. Pulmonary and cutaneous changes at the end of 2, 4, and 6 weeks of treatment were investigated both by light microscopy and analyses of the intra- and extracellular components. Histologically, fibrosis set in as early as 2 weeks of treatment with bleomycin and was pronounced with increasing duration of treatment. Biochemically, total collagen and hexosamine contents of lung and skin increased significantly compared to control toward the end of treatment period. Thus, this animal model can be conveniently used to mimic the human condition and to test effective antifibrotic agents.

Animals↗
PubMed1984

Distribution of different molecular species of collagen in the vertebral cartilage of shark (Carcharius acutus).

It is known that cartilage collagen in higher vertebrates conforms to Type II collagen but very little is known of the nature of shark cartilage. This study was undertaken to determine the differences, if any, between shark cartilage collagen and that of higher vertebrates. Collagen was obtained from shark cartilage by pepsin solubilization and characterized by amino acid analysis and determination of chain composition by SDS-polyacrylamide gel electrophoresis and CM-cellulose chromatography. Results indicated the presence not only of Type II collagen but also of Type I collagen. Type I collagen accounted for about one third of the total collagen content of shark cartilage.

Amino Acids↗