Biomedical subjects

V S Rao

Publications and source records attributed to V S Rao.

At least 19 recordsLinked to original sources

PubMed1998

Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study.

BACKGROUND: There is controversy regarding the association of the angiotensin-converting enzyme deletion-insertion (ACE D/I) polymorphism with systemic hypertension and with blood pressure. We investigated these relations in a large population-based sample of men and women by using association and linkage analyses. METHODS AND RESULTS: The study sample consisted of 3095 participants in the Framingham Heart Study. Blood pressure measurements were obtained at regular examinations. The ACE D/I polymorphism was identified by using a polymerase chain reaction assay. In logistic regression analysis, the adjusted odds ratios for hypertension among men for the DD and DI genotypes were 1.59 (95% confidence interval [CI], 1.13 to 2.23) and 1.18 (95% CI, 0.87 to 1.62), respectively, versus II (chi2 P=.02). In women, adjusted odds ratios for the DD and DI genotypes were 1.00 (95% CI, 0.70 to 1.44) and 0.78 (95% CI, 0.56 to 1.09), respectively (P=.14). In linear regression analysis, there was an association of the ACE DD genotype with increased diastolic blood pressure in men (age-adjusted P=.03, multivariate-adjusted P=.14) but not women. Quantitative trait linkage analyses in 1044 pairs of siblings, by using both ACE D/I and a nearby microsatellite polymorphism of the human growth hormone gene, supported a role of the ACE locus in influencing blood pressure in men but not in women. CONCLUSIONS: In our large, population-based sample, there is evidence for association and genetic linkage of the ACE locus with hypertension and with diastolic blood pressure in men but not women. Our data support the hypothesis that ACE, or a nearby gene, is a sex-specific candidate gene for hypertension. Confirmatory studies in other large population-based samples are warranted.

Adult↗

PubMed1998

Angiotensinogen gene and hypertension in Chinese.

The renin-angiotensin system plays a major role in regulating blood pressure and maintaining electrolyte and volume homeostasis. Previously, the angiotensinogen gene, which encodes the key substrate for renin within this system, has been reported linked to and associated with essential hypertension in White Europeans, African-Caribbeans, and Japanese. Therefore, we investigated whether the angiotensinogen gene might be similarly implicated in the pathogenesis of essential hypertension in Chinese by carrying out linkage analysis in 310 hypertensive sibling pairs. Genotypes for two diallelic DNA polymorphisms observed at amino acid residues 174 (T174M) and 235 (M235T) within the coding sequence and for two highly informative dinucleotide (GT)-repeat sequences (one in the 3' flanking region, and one at a distance of 6.1 cM from the gene) were determined. Affected sibpair analysis conducted according to three different algorithms (S.A.G.E./SIBPAL, MAPMAKER/ SIBS, and APM methods) revealed no evidence for linkage of the angiotensinogen gene to hypertension. Our data indicate that molecular variants of this gene do not appear to contribute materially to the pathogenesis of primary hypertension among Chinese (a notion supported by concomitant, direct estimates of power), and that the disease relevance of this gene may vary therefore depending on ethnicity.

Alleles↗

PubMed1998

Gastroprotective effect of Copaifera langsdorffii oleo-resin on experimental gastric ulcer models in rats.

The effects of oleo-resin obtained from the stem bark of Copaifera langsdorffii on ethanol, indomethacin and hypothermic restraint-stress induced gastric lesions were studied in rats. Oral administration of oleo-resin at doses of 200 and 400 mg/kg provided dose-dependent significant protection against gastric damage caused by ethanol and restraint stress, and at a dose of 400 mg/kg it also prevented the gastric ulceration induced by indomethacin. Further, in the 4 h pylorus ligated rats, the accumulation of gastric juice volume and the mucus secretion was significantly enhanced by oleo-resin whereas the total acidity was inhibited. These results highlight the gastroprotective potential of C. langsdorffii oleo-resin and the need for a systematic study on this traditional remedy.

Animals↗

PubMed1998

Three dimensional structure of the soybean agglutinin Gal/GalNAc complexes by homology modeling.

Complexes of soybean agglutinin (SBA) with galactose (Gal) and N-acetyl galactosamine (GalNAc) have been modeled based on its homology to erythrina corallodendron (EcorL) lectin. The three dimensional structure of SBA-Gal modeled with homology techniques agrees well with SBA-(beta-LacNAc)2Gal-R complex determined by X-ray crystallographic techniques at the beta-sheet regions and the regions where Ca2+ and Mn2+ ions bind. However, significant deviations have been observed between the modeled and the X-ray structures, particularly at the loop regions where the polypeptide chain could not be unequivocally traced in the X-ray structure. The hydrogen bonding scheme, predicted from the homology model, shows that the invariant residues i.e. Asp, Gly, Asn, and aromatic residues (Phe) found in all other legume lectins, bind Gal, slightly in a different way than reported in X-ray structure of SBA-pentasaccharide complex. The higher binding affinity of GalNAc over Gal to SBA is due to additional hydrophobic interactions with Tyr107 rather than a hydrogen bond between N-acetamide group of the sugar and the side chain of Asp88 as suggested from X-ray crystal structure studies. Our modeling also suggest that the variation in the length of the loop D observed among galactose binding legume lectins may not have any effect on the binding of sugar at the monosaccharide specific site of the lectins. Soybean agglutinin (SBA) is a member of the leguminous family of lectins. They generally possess a single carbohydrate binding site, besides the tightly bound Ca2+ and Mn2+ ions which are required for their carbohydrate binding activity. They possess a high degree of sequence homology and about 50% of the amino acid residues are invariant. Some of these invariant amino acid residues are involved in the binding of sugar moieties and in metal ion coordination. X-ray crystallographic studies showed that their three-dimensional structures are very similar, though they differ in their carbohydrate binding specificity (1-6). Three of the invariant residues Asp, Gly, and Asn, besides an aromatic residue (Phe or Tyr), are involved in carbohydrate binding. Independent of their sugar specificity, these four residues in legume lectins provide the basic frame for the sugar to bind.

Acetylgalactosamine↗

PubMed1998

Molecular modeling studies on binding of bFGF to heparin and its receptor FGFR1.

Sugar induced protein-protein interactions play an important role in several biological processes. The carbohydrate moieties of proteoglycans, the glycosaminoglycans, bind to growth factors with a high degree of specificity and induce interactions with growth factor receptors, thereby regulate the growth factor activity. We have used molecular modeling method to study the modes of binding of heparin or heparan sulfate proteoglycans (HSPGs) to bFGF that leads to the dimerization of FGF receptor 1 (FGFR1) and activation of receptor tyrosine kinase. Homology model of FGFR1 Ig D(II)-D(III) domains was built to investigate the interactions between heparin, bFGF and FGFR1. The structural requirements to bridge the two monomeric bFGF molecules by heparin or HSPGs and to simulate the dimerization and activation of FGFR1 have been examined. A structural model of the biologically functional dimeric bFGF-heparin complex is proposed based on: (a) the stability of dimeric complex, (b) the favorable binding energies between heparin and bFGF molecules, and (c) its accessibility to FGFR1. The modeled complex between heparin, bFGF and FGFR1 has a stoichiometry of 1 heparin: 2 bFGF: 2 FGFR1. The structural properties of the proposed model of bFGF/heparin/FGFR1 complex are consistent with the binding mechanism of FGF to its receptor, the receptor dimerization, and the reported site-specific mutagenesis and biochemical cross-linking data. In the proposed model heparin bridges the two bFGF monomers in a specific orientation and the resulting complex induces FGF receptor dimerization, suggesting that in the oligosaccharide induced recognition process sugars orient the molecules in a way that brings about specific protein-protein or protein-carbohydrate interactions.

Amino Acid Sequence↗

PubMed1998

A study of the anti-pyretic effect of quinine, an alkaloid effective against cerebral malaria, on fever induced by bacterial endotoxin and yeast in rats.

The effect of quinine on fever induced by lipopolysaccharide and brewer's yeast has been investigated in rats. Oral administration of 50 or 100 mg kg(-1) quinine, doses which had no effect on normothermic rats, significantly reduced lipopolysaccharide- (50 microg kg(-1), i.m.) and yeast- (2 g kg(-1)) induced fever in rats. Pentoxifylline (100 mg kg(-1)), a tumour necrosis factor antagonist also attenuated the febrile response induced by lipopolysaccharide, but not that by yeast, in a manner similar to quinine. Piroxicam (5 mg kg(-1)), a cyclooxygenase inhibitor suppressed both types of fever with a longer duration of action. In addition to its anti-pyretic effect, quinine had a significant anti-inflammatory effect in the carrageenan model of acute inflammation in the hind-paw of rats. The results indicate the anti-inflammatory and anti-pyretic potential of quinine which might be important in addition to its anti-plasmodial action in the therapy of cerebral malaria.

Analgesics, Non-Narcotic↗

PubMed1998

Three candidate genes and angiotensin-converting enzyme inhibitor-related cough: a pharmacogenetic analysis.

Unexplained, persistent cough limits the use of angiotensin-converting enzyme (ACE) inhibitors in a significant number of patients. It has been speculated that occurrence of this adverse effect is genetically predetermined; in particular, variants of the genes encoding ACE, chymase, and B2-bradykinin receptor have been implicated. To investigate this question, we determined genotypes for common polymorphisms for these three genes in subjects with a history of ACE inhibitor-related cough. Specificity of the adverse effect was confirmed by a blinded, double-crossover design protocol in which subjects were rechallenged with either lisinopril or placebo. In 99 case subjects and 70 control subjects (who failed to develop cough on rechallenge with ACE inhibitor) thus selected, frequencies for the ACE D and I alleles were 0.56 and 0.44 (cases) and 0.56 and 0.44 (controls), respectively; frequencies for chymase A and B alleles (absence/presence of BstXI site) were 0.56 and 0.44 (cases) and 0.46 and 0.54 (controls), respectively; frequencies for B2-bradykinin receptor + and - alleles (presence/absence of a 21 to 29 nonanucleotide sequence) were 0.52 and 0.48 (cases) and 0.53 and 0.47 (controls), respectively. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for association between genotype at either gene examined and cough (adjusted for gender and age). Our data indicate that common genetic variants of ACE, chymase, and B2-bradykinin receptor do not explain the occurrence of ACE inhibitor-related cough.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Mast cell involvement in the rat paw oedema response to 1,8-cineole, the main constituent of eucalyptus and rosemary oils.

The present studies tested the ability of 1,8-cineole to produce inflammatory oedema in the hind paw of the rat and verified the possible involvement of mast cells in the response. Subplantar injection of 1,8-cineole (10, 15 and 20 microl/paw) induced a dose-dependent paw oedema which was apparent within 30 min. At higher doses the oedema effect was persistent, peaked at 2 h, and then decreased gradually but was still pronounced at 24 h post injection. In contrast, the oedema produced by mast cell degranulator compound 48/80 (10 microg/paw) had a rapid onset with a peak effect at the first hour, followed by a gradual decrease thereafter and at 24 h post injection it was almost absent. The oedema response to 20 microl 1,8-cineole was significantly inhibited throughout its time-course in rats pretreated with antihistaminic and antiserotonergic drugs such as diphenhydramine, methysergide and cyproheptadine or with ketotifen, a mast cell stabilizer. A more effective blockade of the oedema response was, however, observed in rats depleted of mast cell granules by systemic treatment with compound 48/80. Furthermore, 1,8-cineole was able to cause rat peritoneal mast cell degranulation (94%) in vitro, in a concentration as low as 0.3 microl/ml, which was almost comparable to that produced by 0.1 microg/ml of compound 48/80. The data provide evidence of a key role for the mast cell in 1,8-cineole-induced hind paw oedema in the rat.

Animals↗

PubMed1997

The leaf essential oil of Psidium guyanensis offers protection against pentylenetetrazole-induced seizures.

The essential oil obtained from the leaves of Psidium guyanensis Pers. (Myrtaceae) was studied against lethal seizures induced by intraperitoneal injection of pentylenetetrazole (80 mg/kg), picroptoxin (6 mg/kg), and strychnine (2 mg/kg) in mice. At oral doses of 100, 200, and 400 mg/kg, the essential oil attenuated the severity of pentylenetetrazole-induced seizures and offered a dose-related protection but it was found to be ineffective against convulsions induced by picrotoxin and strychnine. The blockade of its protective effect on pentylenetetrazole lethal seizures by caffeine (10 and 50 mg/kg, i.p.) suggests a probable participation of endogenous adenosine in its mechanism. Furthermore, a peripheral mechanism also appears to be involved as the essential oil (5-20 micrograms/ml) was able to block selectively the acetylcholine (1.65 x 10(-6) M) induced contractions but not those evoked by high potassium (80 mM) or caffeine (2 x 10(-3) M) on isolated toad rectus abdominis muscle.

Animals↗

PubMed1997

Investigations on the gastroprotective and antidiarrhoeal properties of ternatin, a tetramethoxyflavone from Egletes viscosa.

The study was designed to verify the gastroprotective and antidiarrhoeal effects of ternatin, tetramethoxyflavone isolated from Egletes viscosa Less. The gastroprotective function of ternatin was evaluated in rats against gastric mucosal damage induced by hypothermic restraint stress, absolute ethanol, and indomethacin, whereas the antidiarrhoeal activity was investigated by studying its influence on gastrointestinal transit as measured by a charcoal marker and on castor oil-induced accumulation of intestinal fluid in mice and also on contractile responses evoked by acetylcholine, histamine, serotonin, and barium chloride in isolated guinea-pig ileum. The results demonstrate that pretreatment of animals with the plant flavonoid (25 and 50 mg/kg, i.p.) produces a significant inhibition of gastric lesions induced by ethanol but not those induced by restraint stress or indomethacin and suggest a probable involvement of a prostaglandins-independent mechanism of gastroprotection. At similar doses, both the intestinal transit as well as the accumulation of intestinal fluids induced by castor oil in mice were significantly inhibited by ternatin. Furthermore, the flavonoid antagonised the contractile responses evoked by different agonists on guinea-pig ileum in vitro and its inhibitory potential for the drugs are in the order of acetylcholine > histamine > serotonin > barium chloride. Taken together, these results point out a possible antidiarrhoeal effect of ternatin since inhibition of intestinal motility and secretion can greatly control clinical diarrhoea.

Animals↗

PubMed1997

Hypoglycemic effect of trans-dehydrocrotonin, a nor-clerodane diterpene from Croton cajucara.

trans-Dehydrocrotonin (t-DCTN), a 19-nor-clerodane diterpene isolated from the bark of Croton cajucara Benth. (Euphorbiaceae) demonstrated a significant hypoglycemic activity in alloxan-induced diabetic rats but not in normal rats, at oral doses of 25 and 50 mg/kg body weight. The drug also effectively lowered the blood sugar levels in glucose fed normal rats. The hypoglycemic effect of t-DCTN was almost comparable to that produced by glibenclamide (2 mg/kg), a clinically useful drug. The results indicate the antihyperglycemic potential of t-DCTN.

Animals↗

PubMed1997

Disease outbreak in laying hens arising from the consumption of fumonisin-contaminated food.

1. During the last quarter of 1995 an unusual disease outbreak characterised by black sticky diarrhoea, severe reduction in food intake, egg production and body weight follow by lameness and death was observed in 2 layer farms in Andhra Pradesh. A total of 6700 hens of 64 weeks age and 3000 hens of 36 weeks age were affected. 2. Around 10% mortality and a 20% reduction in egg production was observed. Postmortem examinations showed pale yellow coloured livers with peripheral congestion, mild haemorrhage in the proventriculus and watery accumulations in the intestine. 3. The disease was traced to a new batch of food and its withdrawal improved the health status of the flocks. 4. Analysis of the diet indicated contamination with fumonisin B1 up to 8.5 mg/kg and aflatoxin B1 up to 0.1 mg/kg. 5. Diarrhoea was induced in day old cockerels by feeding the suspect diet containing 8.5 mg/kg fumonisin B1, and in laying hens by feeding a normal diet with fumonisin B1 additions of 8 and 16 mg/kg.

Animal Feed↗

PubMed1997

Identification of actin as an estradiol 17-beta-stimulated protein in the human placenta.

Addition of estradiol 17-beta to first trimester human placental minces resulted in an increased synthesis of a protein of apparent molecular weight 45 kDa. The specific involvement of estrogen in the stimulation of this protein was established by demonstrating a reduction in the level of this protein by the addition of CGS 16949 A, an inhibitor of aromatase, a key enzyme in the biosynthesis of estradiol 17-beta and ICI 182,780, an estrogen receptor antagonist. The protein was purified to homogeneity and N-terminal sequencing of two of the internal peptides obtained by enzymatic digestion of the protein, as well as the absence of a free N-terminal indicated that it could be actin. This was confirmed by Western blotting using commercially available actin antiserum. The role of estradiol 17-beta in the stimulation of actin synthesis in human placenta was also established by monitoring the quantitative inhibition of DNase I by actin.

Actins↗

PubMed1997

Mapping of both autosomal recessive and dominant variants of pseudoxanthoma elasticum to chromosome 16p13.1.

Pseudoxanthoma elasticum (PXE) is a classic inherited disorder of the elastic tissue characterized by progressive calcification of elastic fibers with a pathognomonic histological appearance. The clinical manifestations of PXE typically involve the skin, the eye and the cardiovascular system, resulting in skin lesions, decreased vision and vascular disease. Clinically, a more common autosomal recessive and a less common autosomal dominant pattern of inheritance, with high penetrance, have been described; the estimated prevalence of the disease is 1 in 70,000-100,000. Previous failure to link the disease to any of several candidate genes prompted us to conduct a genome-wide screen on a collection of 38 families with two or more affected siblings, using allele sharing algorithms. Excess allele sharing was found on the short arm of chromosome 16 and confirmed by conventional linkage analysis, localizing the disease gene under a recessive model with a maximum two point lod score of 21.27 on chromosome 16p13.1, an area so far devoid of any obvious candidate genes. Under a dominant transmission pattern linkage with a maximum two point lod score of 14.53 was observed to the same region. Linkage heterogeneity analysis predicted the presence of allelic heterogeneity with different variants of a single gene that resides in this chromosomal region accounting for recessive and dominant forms of PXE.

Adult↗

PubMed1997

Effects of misoprostol on pentylenetetrazol-induced seizures in mice.

The effects of prostaglandin E-analogue misoprostol on the susceptibility to pentilenetetrazol (PTZ)-induced seizures were examined in mice. Misoprostol (200-800 micrograms/kg), given subcutaneously 45 min before the subconvulsive dose of PTZ (30 mg/kg, i.p) provoked dose-dependent clonic-tonic seizures (30 to 100%) and mortality in mice. At 300 g/kg, s.c., misoprostol pretreatment significantly (p < 0.05) lowered the onset latency to first convulsion as well as the latency to mortality induced by a convulsive dose of PTZ (60 mg/kg, i.p.). At this dose misoprostol was found to lower the CD50 and Ld50 values for PTZ by 21% and 36% respectively. The results suggest that prostaglandins are likely to lower the threshold for convulsions.

Abortifacient Agents, Nonsteroidal↗

PubMed1996

Absence of association or genetic linkage between the angiotensin-converting-enzyme gene and left ventricular mass.

BACKGROUND: Homozygous carries of the D allele of the angiotensin-converting-enzyme (ACE) gene have been reported to be at increased risk for various cardiovascular disorders, including left ventricular hypertrophy. We investigated the potential role of the ACE gene in influencing left ventricular mass. METHODS: Quantitative echocardiographic data and DNA samples were available for 2439 subjects from the Framingham Heart Study. ACE genotypes were determined by an assay based on the polymerase chain reaction. (The D allele of the ACE gene contains a deletion, whereas the I [insertion] allele does not.) Left ventricular mass and the prevalence of left ventricular hypertrophy, adjusted for clinical covariates, were analyzed according to genotype. Genetic linkage between the ACE locus and left ventricular mass was evaluated by quantitative analysis of pairs of siblings. RESULTS: The ACE genotype was associated neither with left ventricular mass nor with the prevalence of left ventricular hypertrophy. Mean (+/-SE) left ventricular mass (adjusted for sex) among subjects carrying the DD, DI, and II genotypes was 165+/-1.6, 165+/-1.3, and 166+/-2.0 g, respectively (P=0.90). The prevalence of left ventricular hypertrophy among the three genotype groups was 15.6 percent, 13.6 percent, and 15.6 percent, respectively (P=0.36), and the adjusted relative risk of left ventricular hypertrophy associated with the DD genotype was 1.10 (95 percent confidence interval, 0.86 to 1.19). Linkage analysis in 759 pairs of siblings using both the ACE D/I marker and a microsatellite polymorphism at the neighboring locus for the human growth hormone gene failed to support any role of ACE in influencing left ventricular mass. CONCLUSIONS: The ACE genotype showed no association with echocardiographically determined left ventricular mass, nor did it confer an increased risk of left ventricular hypertrophy. We found no appreciable role of the ACE gene in influencing left ventricular mass.

Adult↗

PubMed1996

Molecular dynamics simulations of hybrid and complex type oligosaccharides.

Conformational preferences of hybrid (GlcNAc1Man5GlcNAc2) and complex (GlcNAc1Man3GlcNAc2; GlcNAc2Man3GlcNAc2) type asparagine-linked oligosaccharides and the corresponding bisected oligosaccharides have been studied by molecular dynamics simulations for 2.5 ns. The fluctuations of the core Man-alpha 1,3-Man fragment are restricted to a region around (-30 degrees, -30 degrees) due to a 'face-to-face' arrangement of bisecting GlcNAc and the beta 1,2-GlcNAc on the 1,3-arm. However, conformations where such a 'face-to-face' arrangement is disrupted are also accessed occasionally. The orientation of the 1,6-arm is affected not only by changes in chi, but also by changes in phi and psi around the core Man-alpha 1,6-Man linkage. The conformation around the core Man-alpha 1,6-Man linkage is different in the hybrid and the two complex types suggesting that the preferred values of phi, psi, and chi are affected by the addition or deletion of saccharides to the alpha 1,6-linked mannose. The conformational data are in agreement with the available experimental studies and also explain the branch specificity of galactosyltransferases.

Asparagine↗

PubMed1996

Aflatoxin B1 contamination in groundnut samples collected from different geographical regions of India: a multicentre study.

Under a multicentre study conducted by the Indian Council of Medical Research, 2062 samples of groundnut were collected from rural and urban areas of 11 states representing different geographical regions of the country. These samples were analysed for aflatoxin B1 using the AOAC method. Analytical quality assurance between various participating laboratories was ensured through analysis of check-samples. Twenty-one per cent of groundnut samples collected from 11 states exceeded the permissible Indian regulatory limit of 30 micrograms/kg. No statistically significant difference in percentage of samples contaminated (> 30 micrograms/kg) were observed between pooled rural (22.9%) and urban (19.9%) data. Amongst the 11 states, the minimum and maximum per cent contamination respectively (> 30 micrograms/kg) was observed to be 15.2 in the state of Andhra Pradesh and 28.3 in the state of Haryana. The maximum level of contamination of 833 micrograms/kg was observed in the state of Gujarat. The median level of < 5 micrograms/kg was observed in the states of Gujarat, Haryana, Punjab, Andhra Pradesh and Karnataka. In all other states studied, the median level was found to vary between 10 and 20 micrograms/kg. The 90th percentile values were high in Andhra Pradesh (125 micrograms/kg), Gujarat (111 micrograms/kg) and Haryana (110 micrograms/kg). In the remaining states the 90th percentile value ranged from 60 to 93 micrograms/kg. Analysis of pooled data showed the percentages of samples exceeding the level of contamination of 5 micrograms/kg and 15 micrograms/kg, respectively were 44.9% and 37.4% which therefore, showed a marked increase when compared with the per cent of samples exceeding 30 micrograms/kg in the overall data.

Aflatoxin B1↗