Biomedical subjects

K Balasubramanian

Publications and source records attributed to K Balasubramanian.

At least 37 records · Page 2Linked to original sources

PubMed2004

Relativistic double group spinor representations of nonrigid molecules.

The character theory of relativistic double group spinor representations is developed in order to represent the total rovibronic states of nonrigid molecules. It is shown that the double groups can be represented in terms of wreath products and powerful matrix cycle type generators that are used to construct their character tables. It is shown that these tables are of use when spin-orbit coupling is included in the Hamiltonian even for molecules containing lighter atoms. Applications to nonrigid molecules such as Tl2H4/Tl2H4+ are considered. It is shown that the tunneling splittings and the nuclear spin statistical weights can be obtained for such species using the character tables thus constructed. The spinor double groups of several other molecules such as hexamethyl dilead and heavy weakly bound clusters such as (PoH2)4 are also considered.

Journal Article↗

PubMed2004

Effects of Vitamin C and E on PCB (Aroclor 1254) induced oxidative stress, androgen binding protein and lactate in rat Sertoli cells.

The effect of Aroclor 1254 and the ameliorative effect of Vitamin C and E on Sertoli cell function were studied in adult male rats. The rats were administered Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received Vitamin C (100 mg/kg bw/day) while the other group received Vitamin E (50 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Necropsy was performed at 24 h after the last injection. Sertoli cells were isolated for the estimation of enzymatic antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GST), and gamma-glutamyl transpeptidase (gamma-GT). Lipid peroxidation (LPO), hydrogen peroxide and hydroxyl radical were estimated. Sertoli cellular androgen binding protein (ABP) and lactate were also quantified. Whereas body weight, testis weight, relative weight of testis, ABP, lactate and specific activities of SOD, CAT, GPx, GR, GST, gamma-GT were all decreased, the levels of hydrogen peroxide, hydroxyl radical and LPO were significantly increased in the Sertoli cells of Aroclor 1254 treated rats. Simultaneous administration of Vitamin C or E restored these parameters to a normal range. Thus, the present study suggests that Aroclor 1254 exposure induces oxidative stress in rat Sertoli cells and furthermore that simultaneous administration of Vitamin C or E ameliorated these effects.

Androgen-Binding Protein↗

PubMed2004

Etiology and outcome of childhood and adolescent diabetes mellitus in North India.

The etiology of childhood onset diabetes mellitus (DM) varies between regions and races, and its long-term outcome is affected by social and economic factors. There are scant data on the etiology of childhood DM and outcome of multidisciplinary team management from developing countries. We retrospectively analyzed case records of 160 predominantly middle socio-economic group patients with onset of DM < or =18 years of age for etiology and features at presentation. In addition, we prospectively studied acute and chronic complications and metabolic control in a subset of 67 patients. Type 1 DM comprised 81%, type 2 DM 8%, and fibrocalculous pancreatic DM 9% of patients. Mean HbA1c was 8.0+/-1.5%. Retinopathy was present in 22% and nephropathy in 18% of those with DM duration > or =5 years (mean age 21.2+/-6.8 years, mean duration 10.2+/-4.6 years). The frequency of ketoacidosis and severe hypoglycemia was 5.0 and 3.3 episodes per 100 patient years. Mortality was 7% over 823 person years of follow up. We conclude that fairly good metabolic control is achievable in a middle socio-economic population in India, with the assistance of a diabetes education program. The frequency of microvascular complications is comparable to that in the literature. However, mortality remains unacceptably high.

Adolescent↗

PubMed2003

The role of luteinizing hormone and prolactin in the regulation of insulin receptors in Leydig cells of the adult rat.

The role of luteinizing hormone (LH), prolactin and their combination in the regulation of insulin receptors in Leydig cells was studied. Leydig cells were isolated from adult male Wistar rats and measurement of insulin binding and internalization was done by incubating the cells with a saturating concentration of 125I-insulin in the presence or absence of different doses of unlabeled LH/insulin. LH exposure (100 and 200 ng dose) caused a significant increase in Leydig cell surface and internalized insulin receptor concentrations. Prolactin at all doses was ineffective in inducing a significant change in insulin receptor concentration. Under basal condition, Leydig cell surface binding of 125I-insulin was greater than the internalization at 34 degrees C but at 4 degrees C, surface binding remained lower than that at 34 degrees C with negligible internalization. Internalization of insulin receptors was measured by incubating the cells at 4 degrees C for 16h and then rapidly incubating at 34 degrees C for various time intervals (60, 120, and 180 min). LH/PRL or LH + PRL did not induce any significant change in the internalization of 125I-insulin at 60 and 120 min. The rate of internalization was greater at 120 min in basal as well as LH/PRL exposed Leydig cells, compared to 60 min of incubation. Prolactin alone did not evoke any appreciable change in internalization of 125I-insulin compared to basal at all three time points tested. Total and acid soluble release of 125I-insulin recorded a significant increase in Leydig cells exposed to LH, which was marginally potentiated when prolactin was added along with LH. Monensin treatment of Leydig cells prevented the recycling of insulin receptors to the cell surface and thereby suppressed the surface binding and enhanced the internalized 125I-insulin. Under cycloheximide treatment, neither surface bound nor internalized 125I-insulin recorded a significant change compared to their respective basal values. It is concluded from the present study that LH has dose-dependent biphasic effects on insulin receptors in Leydig cells by modulating the internalization and intracellular processing of hormone-receptor complexes but prolactin has no such effects.

Animals↗

PubMed2003

Varying role of vitamin D deficiency in the etiology of rickets in young children vs. adolescents in northern India.

The relative importance of calcium vs. vitamin D deficiency in the etiology of nutritional rickets in the tropics may be different in children compared with adolescents. We studied calcium intake, sun exposure, serum alkaline phosphatase, and 25 hydroxyvitamin D in 24 children and 16 adolescents with rickets/osteomalacia. The values were compared with those obtained in control subjects (34 children and 19 adolescents). We found that young children with rickets had lower calcium intake compared with controls (285 +/- 113 vs. 404 +/- 149 mg/day, p < 0.01), but similar sun exposure (55 +/- 28 vs. 56 +/- 23 min x m2/day) and 25 hydroxyvitamin D (49 +/- 38 vs. 61 +/- 36 nmol/l). Sixteen of 24 children with rickets had 25 hydroxyvitamin D above the rachitic range (> 25 nmol/l), in contrast to one of 16 adolescents. Adolescent patients had low calcium intake vs. controls (305 +/- 196 vs. 762 +/- 183 mg, p < 0.001), and lower sunshine exposure (16 +/- 15 vs. 27 +/- 17 min x m2/day, p < 0.01) and serum 25 hydroxyvitamin D (12.6 +/- 7.1 vs. 46 +/- 45.4 nmol/l, p < 0.001). The odds ratio for developing rickets with a daily calcium intake below 300 mg was 4.8 (95 per cent CI, 1.9 - 12.4, p = 0.001). Subjects with rickets were randomized to receive 1 g calcium daily, with or without vitamin D. Children showed complete healing in 3 months, whether they received calcium alone or with vitamin D. Adolescents showed no response to calcium alone, but had complete healing with calcium and vitamin D in 3-9 months (mean 5.3 months). Thus deficient calcium intake is universal among children and adolescents with rickets/osteomalacia. Inadequate sun exposure and vitamin D deficiency are important in the etiology of adolescent osteomalacia.

Adolescent↗

PubMed2001

Binding of annexin V to membrane products of lipid peroxidation.

There is increasing evidence that endogenously generated aldehydes formed as a result of lipid peroxidation are involved in the pathophysiological effects associated with oxidative stress in cells and tissues. Malondialdehyde (MDA), a major product of lipid peroxidation, can modify amines present on the cell surface and thereby introduce negative charges that can affect the interfacial ionic layer. We show that lipid peroxidation of RBC generates MDA adducts that, similar to phosphatidylserine (PS), bind annexin V in a Ca(2+)-dependent manner. Like PS, these adducts also promote the "PS-dependent" prothrombinase assays, albeit to lower levels. These results indicate that annexin V binding cannot be used as an exclusive indicator of cell surface PS and raise the possibility that some phenomenon attributed to PS may, in fact, also involve aldehyde-lipid adducts.

Animals↗

PubMed2001

Structures and electron attachment properties of halomethanes (CX(n)Y(m), X=H, F; Y=Cl, Br, I; n=0,4; m=4-n).

Theoretical studies of structures of neutral molecules and their anions as well as dissociative electron attachment properties are presented for the halomethanes of general formula CX(n) Y(m); X=H, F; Y=Cl, Br, I; n=0,4; m=4-n. The dissociative electron attachment seems to be the primary process resulting in toxicity of these species. The halomethane anions containing hydrogens are formed as radical-anion adducts. When H is replaced by F, these species become true sigma* radicals. The electron affinities are computed using a variety of computational techniques including the four-order Møller-Plesset (MP4) technique that included 250 basis functions. It is challenging to compare the computed results with experiment due to dearth of experimental data and uncertainties in the existing experimental data. Thus in certain cases larger differences are found between the computed and experimental values.

Anions↗

PubMed2000

beta(2)-glycoprotein I-dependent alterations in membrane properties.

beta(2)-Glycoprotein I (beta(2)GP1), a 50 kDa serum glycoprotein, binds anionic phospholipids and plays a role in phosphatidylserine (PS)-dependent coagulation and apoptotic processes. To characterize the molecular consequences that occur to target membranes upon binding of beta(2)GP1, the interaction between beta(2)GP1 and PS-containing vesicles was investigated by fluorescent spectroscopy. Membranes containing pyrene-labeled lipid showed that binding of beta(2)GP1 induced a decrease in excimer/monomor ratios (E/M) of the target membrane. Although these membrane alterations occurred in isotonic buffer, the effects were greater in low ionic strength buffer and were coincident to membrane precipitation. In contrast, increases in membrane polarization were only seen in low ionic strength buffer. Analysis of beta(2)GP1 binding kinetics by resonance energy transfer between fluorescein-labeled beta(2)GP1 and rhodamine-containing PS vesicles revealed a two-component process: (1) a primary and rapid binding via the C-terminus that occurred <2 s in both isotonic and low ionic strength buffers, and (2) a sequential binding of the N-terminus that was approximately 100-fold slower in low ionic strength solution. Taken together, these data suggest that beta(2)GP1 alters the fluidity and membrane polarization of its target membrane, which in low ionic strength buffer is of sufficient magnitude to induce precipitation.

Chemical Precipitation↗

PubMed2000

Phosphatidylserine expression on cell surfaces promotes antibody-dependent aggregation and thrombosis in beta2-glycoprotein I-immune mice.

Beta-2-glycoprotein I (beta2GP1) has been implicated as the primary antigenic target in antiphospholipid syndrome. To study the role beta2GP1 antibodies play in thrombosis associated with this syndrome, the clearance and binding of phosphatidylserine (PS)-containing target membranes were monitored in beta2GP1-immune mice. Clearance in immune mice (T(1/2)4.8 min) was faster than in normal mice (T(1/2)11.0 min). Analysis of PS vesicles recovered from immune mice by sequencing and Western blotting showed the presence of bound beta2GP1 and autologous antibody, respectively. Bleeding times in immune mice were approximately 30% shorter than in control mice. In vitro clotting times, however, were the same in both populations. To determine if the in vivo results could be attributed to the interaction of autoantibodies with the vascular endothelium, the binding of PS-containing target membranes to normal and apoptotic endothelial cells was studied. While endothelial cells bound PS vesicles, beta2GP1 reduced uptake by approximately 50% in both normal and apoptotic endothelium. In the presence of beta2GP1 antibodies, however, uptake in apoptotic cells, but not normal cells, increased by more than two-fold. These results suggest that thrombosis in antiphospholipid syndrome could, in part, be due to antibody-dependent cross-linking of beta2GP1 bound to PS-expressing cells and the vascular endothelium.

Animals↗

PubMed2000

Chronic administration of corticosterone impairs LH signal transduction and steroidogenesis in rat Leydig cells.

The mechanism involved in the inhibitory actions of chronic corticosterone treatment on Leydig cell steroidogenesis was studied in adult Wistar rats. Rats were treated with corticosterone-21-acetate (2 mg/100 g body weight, i.m., twice daily) for 15 days and another set of rats was treated with corticosterone plus ovine luteinizing hormone (oLH) (100 microg/kg body weight, s.c., daily) for 15 days. Chronic treatment with corticosterone increased serum corticosterone but decreased serum LH, testosterone, estradiol and testicular interstitial fluid (TIF) testosterone and estradiol concentrations. Administration of LH with corticosterone partially prevented the decrease in serum and TIF testosterone and estradiol. Leydig cell LH receptor number, basal and LH-stimulated cAMP production were diminished by corticosterone treatment which remained at control level in the corticosterone plus LH treated rats. Activities of steroidogenic enzymes, 3beta- and 17beta-hydroxysteroid dehydrogenase (3beta-HSD and 17beta-HSD) were significantly decreased in corticosterone treated rats. LH plus corticosterone treatment did not affect 3beta-HSD activity but decreased 17beta-HSD activity, indicating a direct inhibitory effect of excess corticosterone on Leydig cell testosterone synthesis. The indirect effect of corticosterone, thus, assume to be mediated through lower LH which regulates the activity of 3beta-HSD. Basal, LH and cAMP-stimulated testosterone production by Leydig cells of corticosterone and corticosterone plus LH treated rats were decreased compared to control suggesting the deleterious effect of excess corticosterone on LH signal transduction and thus steroidogenesis.

Animals↗

PubMed2000

Influence of streptozotocin-induced diabetes and insulin treatment on the pituitary-testicular axis during sexual maturation in rats.

Effects of streptozotocin (STZ)-diabetes and insulin treatment on the functioning of pituitary-testicular axis during sexual maturation was studied. Prepubertal (30 days old) and pubertal (50 days old) male Wistar rats were made diabetic by a single injection of STZ. A group of diabetic rats was given insulin (3U/100 g b.wt./day in 2 equally divided doses), 3 days after STZ treatment. Prepubertal and pubertal rats of all groups were killed on postnatal days 51 and 71, respectively. STZ-diabetes caused marked reduction in serum LH, FSH, prolactin, testosterone and testicular interstitial fluid testosterone as well as the activities of Leydig cellular steroidogenic enzymes (3beta-and 17beta-hydroxysteroid dehydrogenases). Insulin treatment to diabetic rats maintained these changes at control range except FSH and prolactin in prepubertal rats. The results indicate that (i) diabetes-induced steroidogenic lesions in Leydig cells represent a direct consequence of dysfunctioning of pituitary-testicular axis, (ii) the adverse effects of diabetes on pituitary-testicular functions are influenced by age of its induction and (iii) optimum insulin level is essential for the acquisition of Leydig cellular steroidogenic efficacy during sexual development.

17-Hydroxysteroid Dehydrogenases↗

PubMed2000

Chronic corticosterone treatment impairs Leydig cell 11beta-hydroxysteroid dehydrogenase activity and LH-stimulated testosterone production.

The effects of excess corticosterone on luteinizing hormone (LH)-stimulated Leydig cell testosterone production and activity of 11beta-HSD was studied. Adult male rats (200-250 g body weight) were treated with corticosterone-21-acetate (2 mg/100 g body weight, i.m., twice daily) for 15 days. Another set of rats was treated with corticosterone (dose as above) plus LH (ovine LH 100 microg/kg body weight, s.c., daily) for 15 days. Corticosterone administration significantly increased serum and testicular interstitial fluid (TIF) corticosterone but decreased testosterone levels. Administration of LH with corticosterone partially prevented the decrease in serum and TIF testosterone. The oxidative activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) was significantly decreased in Leydig cells of rats treated with corticosterone alone and in combination with LH. The direct effect of corticosterone on Leydig cell steroidogenic potency was also studied in vitro. Addition of corticosterone to Leydig cell culture showed a dose dependent effect on LH-stimulated testosterone production. Corticosterone at 50 and 100 ng/ml did not alter LH-stimulated testosterone production, but at high doses (200-400 ng/ml), decreased basal and LH-stimulated testosterone production. Basal and LH-stimulated cAMP production was not altered by corticosterone in vitro. It is concluded from the present study that elevated levels of corticosterone decreased the oxidative activity of 11beta-HSD and thus resulting in impaired Leydig cell steroidogenesis and the inhibitory effects of corticosterone on testosterone production appear to be mediated through inhibition of LH signal transduction at post-cAMP level.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

PubMed1999

Streptozotocin-diabetes impairs prolactin binding to Leydig cells in prepubertal and pubertal rats.

Prolactin (PRL) binding to Leydig cells in prepubertal and pubertal streptozotocin (STZ)-diabetic and insulin-treated rats was studied. Prepubertal (30-day-old) and pubertal (50-day-old) rats were made diabetic by single injection of STZ (120 and 100 mg/kg b.wt, respectively). After 3 days of STZ administration, a group of rats was given insulin injections subcutaneously (3 U/100 g b.wt/day in 2 equally divided doses). Animals of prepubertal and pubertal groups were killed on postnatal days 51 and 71, respectively. Age-dependent increase in serum testosterone, PRL levels and PRL receptors on Leydig cells were prevented by STZ-diabetes. Insulin administration partly or completely prevented these changes. These results suggest that steroidogenic defects in Leydig cells of prepubertal and pubertal diabetic rats may be associated with decrease in serum PRL levels and its receptors on Leydig cells. Insulin probably has a role in the maintenance of PRL receptor numbers on Leydig cells during pubertal maturation.

Animals↗

PubMed1999

Effects of ethanol ingestion on sperm monosaccharides and fertility.

Chronic alcohol abuse is often associated with reproductive disorders. Sperm monosaccharides play an indispensable role in sperm-egg interactions and fertilization. Ethanol (3 g/kg body weight as 25%, v/v) was given by gastric intubation twice daily for 30 days while in another group, rats which had been treated with ethanol were withdrawn from treatment for a further period of 30 days, in order to assess the reversibility of the ethanol-induced effects. Epididymal ethanol content, sperm monosaccharides and the fertility of ethanol treated and ethanol withdrawn rats were assessed. Ethanol ingestion caused a significant decrease in sperm monosaccharides suggesting defective glycosylation of sperm surface proteins. Sperm monosaccharides and fertility were returned to normal following the withdrawal of ethanol. Ethanol-induced changes in sperm monosaccharides may be one of the reasons for the reduced fertility of ethanol treated rats.

Animals↗

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↗