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Biomedical subjects

K Balasubramanian

Publications and source records attributed to K Balasubramanian.

At least 19 recordsLinked to original sources
PubMed1999

Effects of ethanol treatment on epididymal secretory products and sperm maturation in albino rats.

Alcoholics are often associated with fertility disturbances with low sperm count and impaired sperm motility. Spermatozoa attains forward motility and fertilizing capacity during their transit through the epididymis. Epididymal secretory products form a suitable microenvironment, which favors sperm maturation. To study the effects of ethanol on epididymal sperm maturation, ethanol (3 g/kg body weight as 25%, v/v) was given by gastric intubation twice daily for 30 days, and in another group, rats given treatment for 30 days were withdrawn of treatment for a further period of 30 days to assess the reversibility of ethanol-induced changes. Serum and epididymidal testosterone and dihydrotestosterone (DHT), epididymidal tissue and sperm carnitine, acetyl carnitine, glycerylphosphoryl choline (GPC), and sialic acid were studied along with epididymidal sperm count and cauda epididymidal sperm motility. Ethanol treatment significantly reduced the epididymal tissue/sperm carnitine, acetyl carnitine, GPC, and sialic acid, suggesting its adverse effect on these secretory products. Impaired cauda epididymidal sperm motility and fertility (in vivo) of ethanol-treated rats imply the defective sperm maturation. All these changes were reverted back to normalcy after withdrawal of ethanol treatment, indicating the transient effects of ethanol. In conclusion, it is evident that ethanol has an adverse effect on sperm maturation, which may be affected due to the decrease in serum/epididymal testosterone and DHT level and epididymal secretory products.

Acetylcarnitine↗
PubMed1998

Characterization of phosphatidylserine-dependent beta2-glycoprotein I macrophage interactions. Implications for apoptotic cell clearance by phagocytes.

The binding and uptake of phosphatidylserine (PS)-expressing cells appears to involve multiple receptor-mediated systems that recognize the lipid either directly or indirectly through intermediate proteins that form a molecular bridge between the cells. Here we show that beta2-glycoprotein I (beta2GPI), a 50-kDa serum glycoprotein, binds PS-containing vesicles and serves as an intermediate for the interaction of these vesicles with macrophages. Chemical modification of lysines and cysteines abolished beta2GPI-dependent PS uptake by inhibiting the binding of PS to beta2GPI and the binding of PS.beta2GPI complex to macrophages, respectively. Recognition was mediated by beta2GPI and not by the lipid because antibodies to beta2GPI inhibited binding of the complex to macrophages. These results indicate that human (THP-1-derived) macrophages bind beta2GPI only after it is bound to its lipid ligand. Competition experiments with monosaccharides that inhibit lectin-dependent interactions, and PS.beta2GPI binding experiments using deglycosylated beta2GPI, suggested that carbohydrate residues were not required for macrophage recognition of the complex. Antibodies to putative macrophage PS receptors (CD36, CD68, and CD14) did not inhibit uptake of the complex. These data suggest that beta2GPI can bind cells that fail to maintain membrane lipid asymmetry and generate a specific bridging moiety that is recognized for clearance by a phagocyte receptor that is distinct from CD36, CD68, and CD14.

Apoptosis↗
PubMed1998

Estimation of plasma beta-2-glycoprotein levels by competitive ELISA.

Beta-2-glycoprotein I (beta2GPI), a 50-kDA serum glycoprotein that binds negatively charged phospholipids plays a role in coagulation, thrombosis, and the clearance of phosphatidylserine expressing cells. Because of its recently recognized role in several autoimmune responses, we have developed a method that quantifies plasma beta2GPI levels by using a competitive ELISA assay. When combined with data from a standard ELISA, this method determines the concentration of free beta2GPI and the fraction of antibody-bound beta2GPI thereby facilitating quantification of total antigen in individuals with autoimmune antibodies. Standard competitive inhibition ELISA was compared with this method, which uses known amounts of standard beta2GPI added to the plasma as an internal standard. Identical results were obtained with both methods for plasma samples from normal individuals that did not contain blocking antibodies. Analysis of plasma from antiphospholipid syndrome patients (patients with autoantibodies to beta2GPI) by the internal standard method, however, resulted in significantly lower apparent beta2GPI levels indicating that a substantial fraction of the plasma beta2GPI was bound by antibody.

Binding, Competitive↗
PubMed1998

Effects of ethanol ingestion on epididymal glycosidases and fertility in the rat.

Epididymal glycosidases play a role in sperm maturation by modifying sperm surface glycoproteins. To study the effects of ethanol on epididymal sperm maturation, ethanol (3 g/kg body weight as 25%, v/v) was administered to a group of rats by gastric-intubation twice daily for 30 days. In another group, rats were also treated with alcohol for 30 days but were then withdrawn from treatment for 30 days to assess the reversibility of ethanol-induced effects. Ethanol-induced changes in epididymal tissue and sperm glycosidases, cauda epididymal sperm motility and the fertility of rats were assessed. Ethanol treatment caused a marked decrease in the specific activities of glycosidases in both tissues and spermatozoa from epididymal segments. Cauda epididymal sperm motility and the fertility of ethanol-treated rats were significantly impaired compared to control rats fed an isocaloric diet. These changes are likely to be the consequence of direct and indirect effects of ethanol mediated through subnormal testosterone and dihydrotestosterone. Most of these changes were found to be reversible. The present study suggests that impaired activity of sperm glycosidases may be one of the factors responsible for defective sperm motility and fertilizing potential in ethanol-treated rats.

Animals↗
PubMed1998

Effects of ethanol ingestion on insulin binding to rat Leydig cells.

Effects of ethanol treatment and its withdrawal on insulin binding to isolated rat Leydig cells were studied. Mature rats were given ethanol by gastric intubation for 30 days at a dose of 3.0 g/kg body weight, twice daily, as a 25% (v/v) aqueous solution and treatment was withdrawn for the subsequent 30 days in an another group. Ethanol treatment markedly increased serum insulin and reduced the 125I-insulin binding to Leydig cells and the activities of Leydig cellular steroidogenic enzymes such as 3 beta-HSD and 17 beta-HSD. Withdrawal of ethanol treatment restored these changed values to their normal levels. The results suggest the possible involvement of subnormal insulin actions, as that of LH, in the ethanol-induced impairment of Leydig cellular steroidogenesis and the resulting hypoandrogenization associated with alcohol abuse.

Animals↗
PubMed1997

Immune clearance of phosphatidylserine-expressing cells by phagocytes. The role of beta2-glycoprotein I in macrophage recognition.

The function of beta2-glycoprotein I (beta2GPI), a 50-kDa serum glycoprotein, is not completely understood but has been suggested to be involved in the regulation of thrombosis (Brighton, T. A., Hogg, P. J., Dai, Y.-P., Murray, B. H., Choing, B. H., and Chesterman, C. N. (1996) Br. J. Haematol. 93, 185-194) and the clearance of phosphatidylserine (PS)-expressing cells (Chonn, A., Semple S. C., and Cullis P. R. (1995) J. Biol. Chem. 270, 25845-25849). To further understand the role of this protein, we characterized the ability of beta2GPI to interact with PS vesicles and influence their uptake by macrophages in vitro. beta2GPI bound to and precipitated vesicles containing anionic but not zwitterionic phospholipids in a gel diffusion assay. beta2GPI also inhibited the procoagulant activity of PS liposomes. In vitro phagocytosis studies showed 20-fold greater uptake of PS liposomes over phosphatidylcholine liposomes. This enhanced uptake was maintained even after PS was "shielded" with beta2GPI and further increased upon the addition of beta2GPI antibodies. Similar to liposomes, PS-expressing apoptotic thymocytes and lipid symmetric red blood cell ghosts bound beta2GPI. Macrophage uptake of these cells was also maintained or enhanced in the presence of beta2GPI and further increased upon the addition of beta2GPI antibodies. It is concluded that beta2GPI can play a critical role in hemostasis by influencing both thrombosis and the clearance of PS-expressing cells.

Apolipoproteins↗
PubMed1997

Regulation of porcine granulosa cell steroidogenic acute regulatory protein (StAR) by insulin-like growth factor I: synergism with follicle-stimulating hormone or protein kinase A agonist.

The transfer of cholesterol from the outer to the inner mitochondrial membrane, where side-chain cleavage occurs to form pregnenolone, is a crucial event in the regulation of steroidogenesis and recently has been demonstrated to be mediated by steroidogenic acute regulatory protein (StAR). We generated a partial porcine StAR complementary DNA (280 bp) by RT-PCR and used the corresponding antisense riboprobe to quantify the control of StAR gene expression by FSH and insulin-like growth factor I (IGF-I) in hormonally responsive swine granulosa cells, which typically manifest synergistic steroidogenic stimulation by these two dominant intrafollicular regulators. RNase protection assays were implemented to investigate the time course of the actions of FSH (100 ng/ml), IGF-I (100 ng/ml), and FSH plus IGF-I on StAR messenger RNA accumulation in serum-free cultures granulosa cells. Treatment with FSH (1.6-fold) or IGF-I (2.7-fold) alone had a small but consistent stimulatory effect on StAR message accumulation (corrected for 18S ribosomal RNA in each lane) at 48 h, whereas only IGF-I stimulated StAR protein expression (at least 6-fold as assessed by Western blot). Notably, the combined effect of FSH plus IGF-I was strongly synergistic and already significant by 24 h and maximal at 48 h (P < 0.001). Protein kinase A agonist, 8-bromoadenosine 3',5'-cAMP (8-bromo-cAMP) (1 mM) alone elicited a 3.5-fold increase in StAR message and more than 3.7-fold increase in StAR protein expression by 48 h. The combination of IGF-I and FSH or 8-bromo-cAMP evoked a 26- to 40-fold (P < 0.001) synergistic rise in StAR message accumulation. StAR protein also showed a similar synergistic pattern of expression driven by IGF-I and FSH or 8-bromo-cAMP, namely a greater than 56- to 60-fold increase. In summary, two distinct first messenger regulatory molecules, FSH and IGF-I, interact synergistically to induce amplification of StAR messenger RNA and protein expression in serum-free monolayer cultures of immature (swine) granulosa cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Transbilayer phosphatidylethanolamine movements in the yeast plasma membrane. Evidence for a protein-mediated, energy-dependent mechanism.

Aminophospholipid movements in the plasma membrane of higher eukaryotic cells seem to be regulated by an ATP-dependent, protein-mediated process. To examine whether similar mechanisms exist in yeast cells, we have analysed phosphatidylethanolamine (PtdEtn) distributions in Saccharomyces cerevisiae (A184D) cells under a variety of conditions, with trinitrobenzenesulfonic acid and fluorescamine as the external membrane probes. The levels of external PtdEtn in the intact cells were reduced to about 50% by pretreatment of the cells with inhibitors of mitochondrial ATP synthesis, ATPase inhibitors or protein-sulfhydryl-group-modifying reagents, or by depletion of the cells of ATP by metabolic starvation. The levels of external PtdEtn could be restored to normal by repletion of the energy-depleted cells with ATP. Furthermore, treatment of the energy-depleted cells with sulfhydryl-modifying reagents did not cause further reduction in the external PtdEtn levels but decreased the accessibility of PtdEtn to fluorescamine after restoration of the cellular ATP levels to normal in these cells. These results demonstrate an involvement of an ATP-dependent, protein-mediated process(es) in the regulation of the PtdEtn distribution across the plasma-membrane bilayer of yeast cells. The results are discussed with regard to possible models that can generate and maintain the transbilayer phospholipid asymmetry in the yeast plasma membrane.

Adenosine Triphosphatases↗
PubMed1995

Effects of ethanol treatment on Leydig cellular NADPH-generating enzymes and lipid profiles.

Effects of ethanol treatment on Leydig cell NADPH-generating enzymes and lipid profiles were studied. Ethanol treatment (3.0 g/kg b.wt.) twice daily as a 25% (v/v) aqueous solution given to adult Wistar rats reduced the body weight, testis weight and relative weights of the seminal vesicles and ventral prostate. Serum LH and testosterone were also decreased. Similarly, the NADPH-generating enzymes such as G-6-PDH, 6-PGDH, NADP-ICDH were reduced, but malic enzyme was unaltered. Leydig cell total lipid was decreased: neutral lipids such as esterified cholesterol and triacyl glycerol were decreased but free cholesterol and diacyl glycerol were increased. The reduction in total phospholipid was contributed to by fractions such as phosphatidyl inositol, phosphatidyl serine, phosphatidyl choline and phosphatidyl ethanolamine. Withdrawal of ethanol treatment for 30 days restored these to the normal level. The present findings suggest that the ethanol treatment impairs Leydig cellular NADPH generation which may be one of the biochemical mechanisms mediating the direct and indirect effects of ethanol resulting in hypoandrogenization.

Animals↗
PubMed1995

Preliminary study of androgen, thyroid & adrenal status in alcoholic men during deaddiction.

To evaluate the status of the testes, thyroid, and adrenals in male alcoholics during the period of voluntary abstinence and therapy, chronic male drinkers undergoing a 4 wk inpatient deaddiction programme in a social hospital were recruited. Levels of a few serum and urinary hormones/metabolites viz., serum testosterone, total triiodothyronine (T3) and thyroxine (T4) and urinary total 17-ketosteroids (17-KS), estrone, estradiol, and 17-hydroxy corticosteroids (17-OHCS) were assessed in alcoholics thrice during the treatment programme at hospital i.e., on the zero (day of admission), 10th, and 20th day and compared to those of non-alcoholic controls. Alcoholics registered elevated serum total T3, and reduced total T4 and testosterone levels at admission, which persisted even after 20 days of the rehabilitative programme. Markedly high urinary levels of total 17-KS, estrone, and 17-OHCS were observed on zero day of admission. Urinary estrone and 17-OHCS, unlike total 17-KS, showed a trend to return to the normal range during the 20 days period. Urinary estradiol levels, however, recorded no significant alteration. The results of this preliminary study are suggestive of alcohol-induced perturbations on the functional integrity of the testes, thyroid, and adrenal in male alcohol addicts, wherein 20 days period of total alcohol abstinence and rehabilitative programme failed to reverse alcohol-induced hypoandrogenization and altered thyroidal status, but only partially restored certain biochemical events associated with the excretion of steroid metabolites.

17-Hydroxycorticosteroids↗
PubMed1994

Integration of graph theory and quantum chemistry for structure-activity relationships.

The objective of this article is to outline both graph-theoretically based and quantum chemically based structural indices of potential use in quantitative structure activity correlations. We consider graph-theoretical indices such as the connectivity index, topological index, Wiener index and molecular ID indices. Several structural and geometry-dependent indices can be derived from semiempirical and ab initio quantum calculations based on the charge densities, overlap matrices, frontier orbitals, molecular hardness, free valence, density matrices, quantum spectral difference indices, quantum spectral indices and bond matrices. Finally, the use of electrostatic potentials and charge densities for the prediction of reactive sites will be discussed.

Butadienes↗
PubMed1994

Ethanol induced changes in prostatic lipid profiles of albino rats.

Alcohol induced changes in the ventral and dorsolateral prostatic lipid profiles were studied. The results obtained from the present study indicate that alcohol consumption leads to significant alterations in the ventral and dorsolateral prostatic lipids. An increase in the ventral prostate total cholesterol and total glyceride glycerol was observed, but a reverse trend was seen in total phospholipid. However total lipids remained unaltered. Dorsolateral prostatic total lipids, glyceride glycerol and phospholipids were increased but a decrease in total cholesterol was observed. Withdrawal of ethanol treatment for a period of 30 days brought back most of the changes to normalcy. The abnormalities in lipid profiles of both ventral and dorsolateral prostates may be responsible for the altered semen quality prevalent in chronic alcoholics.

Alcoholism↗
PubMed1993

Effect of chronic alcoholism on semen--studies on lipid profiles.

The effect of chronic alcoholism on various seminal parameters (sperm concentration, rate of forward motility, percentage of abnormal spermatozoa, lipid profiles of seminal plasma and spermatozoa) was studied together with the serum levels of testosterone and oestradiol. In chronic alcoholics there was a marked reduction in sperm concentration and in the rate of their forward motility, and increase in the number of spermatozoa with morphological abnormalities when compared to age-matched normal fertile subjects. Serum levels of testosterone were decreased while oestradiol levels were increased in chronic alcoholic men. Studies of lipid profiles showed a marked decrease in the total phospholipid concentration in spermatozoa, primarily in sphingomyelin, phosphatidyl choline and ethanolamine fractions. The cholesterol:phospholipid ratio in spermatozoa was increased in alcoholics. In the seminal plasma of chronic alcoholics, there was a decrease in total lipid, in glyceride glycerol and in free and esterified cholesterol. Of the phospholipid classes, sphingomyelin and phosphatidyl ethanolamine showed a significant reduction. In general, the present study provides evidence for the adverse effects of chronic alcoholism on serum hormones, sperm count, morphology, motility and seminal lipid profiles. These may be responsible for the fertility disorders common in chronic alcoholics.

Alcoholism↗
PubMed1993

Specific activities of seminal vesicular phosphomonoesterases and Mg2+-,Ca2+- and Na+/K(+)-adenosine triphosphatases in hypo- and hyperthyroid albino rats.

Hypothyroidism (surgical thyroidectomy) inhibited the activities of acid phosphatase and Mg(2+)-ATPase in seminal vesicular tissue and fluid and that of Ca(2+)- and Na+/K(+)-ATPases in fluid alone, and T4 supplementation restored normalcy in all, except acid phosphatase. Hyperthyroidism (T4 25 micrograms/100g body weight/day for 60 days, im) enhanced the activities of alkaline phosphatase and ATPases in seminal vesicular tissue and fluid, and decreased acid phosphatase activity in tissue alone. Withdrawal of T4 treatment from hyperthyroid rats (after 30 days) augmented the activity of ATPases in tissue and impaired the same in fluid, while phosphomonoesterases remained at hyperthyroid level. The results suggest specific responses of various seminal vesicular phosphatases to altered thyroid hormone status. Modification in the specific threshold of androgen/estrogen action on different phosphatases in seminal vesicles appears to be the plausible mechanism underlying these changes in hypo- and hyperthyroid conditions.

Adenosine Triphosphatases↗
PubMed1993

Effects of prolactin and androgens on enzymes of carbohydrate metabolism in seminal vesicles of castrated mature bonnet monkeys, Macaca radiata.

Effects of prolactin(Prl), bromocriptine(Br), testosterone propionate (TP), dihydrotestosterone (DHT) and combinations of these androgens with Prl/Br on the maximum catalytic capacities of seminal vesicular enzymes involved in the glycolytic and pentose phosphate pathways in castrated mature monkeys were studied. Castration decreased the activities of all of the enzymes studied such as hexokinase(HK), 6-phosphofructokinase(PFK), glyceraldehyde-3-phosphate dehydrogenase(G3PD), pyruvate kinase(PK), glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase(6PGD) in the seminal vesicles. Prl restored the activities of all of the enzymes to their normal values except G3PD. TP/DHT maintained all the enzyme activities at the normal tissue intact level. Prl given along with androgens further enhanced the androgen action with regard to all the enzymes activities except G3PD. Br decreased all of the enzymes but Br with androgens maintained all the enzyme activities at the normal level. Castration decreased significantly serum T/DHT titres but Prl did not alter Prl levels. Prl+TP/DHT elevated Prl levels. Br alone decreased serum Prl, T and DHT titres, but Br+TP/DHT decreased only Prl, elevated T and maintained DHT levels. These results suggest that Prl has a direct as well as a synergistic action with androgens on the activities of the enzymes of glycolysis and pentose phosphate pathways in the seminal vesicles of castrated monkeys.

Androgens↗
PubMed1993

Primary biliary cirrhosis associated with ulcerative colitis.

Hepatobiliary diseases are frequently associated with ulcerative colitis. The most commonly reported syndromes are primary sclerosing cholangitis, chronic active hepatitis and cirrhosis. Recently, the association of primary biliary cirrhosis and ulcerative colitis has been reported. We present a case of primary biliary cirrhosis in a young man with left-sided ulcerative colitis and review the previous reported cases, noting some unique similarities between them.

Adult↗
PubMed1992

Increased intragastric acid-resistant lipase activity and lipolysis in pancreatic steatorrhoea due to cystic fibrosis.

We measured gastric lipase activity and lipolysis in postprandial gastric samples from 10 adults with steatorrhoea due to cystic fibrosis (CF) and from 10 healthy volunteers of similar age and sex. Gastric samples were aspirated for 2 h following a meal consisting of emulsified long-chain triglyceride. Mean acid-resistant lipase activity was twice as high in CF patients as in controls (596 vs. 299 nmol/ml/min fatty acid released; p = 0.028 for area under the curve). Lipolysis rose from 5 to 10% during the postprandial period in CF patients, compared with a constant 5% in controls (p = 0.036 for area under the curve). We conclude that, in healthy adults, lipolysis of long-chain triglyceride starts in the stomach, while in adults with pancreatic steatorrhoea due to CF, gastric lipase activity and intragastric lipolysis are increased, perhaps in compensation for pancreatic insufficiency.

Adult↗