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Biomedical subjects

M R Rao

Publications and source records attributed to M R Rao.

At least 55 records · Page 3Linked to original sources

Breastfeeding and the risk of life-threatening enterotoxigenic Escherichia coli diarrhea in Bangladeshi infants and children.

OBJECTIVE: To assess the relationship between breastfeeding and the risk of life-threatening enterotoxigenic Escherichia coli (ETEC) diarrhea among Bangladeshi infants and young children <36 months of age. DESIGN: Case-control study. SETTING: A rural Bangladesh community. PARTICIPANTS: A total of 168 cases with clinically severe ETEC diarrhea detected in a treatment center-based surveillance system during 1985 to 1986 and 3679 controls selected in three surveys of the same community during the same calendar interval. OUTCOMES: Cases and controls were compared for the frequency of antecedent breastfeeding patterns. RESULTS: Compared with other feeding modes, exclusive breastfeeding of infants was associated with significant protection against severe ETEC diarrhea (relative risk [RR] = 0.51; 95% confidence interval [CI]: 0.28,0.96). However, during the second and third years of life, the risk of this outcome was similar in both breastfed and nonbreastfed children (RR = 0.98; 95% CI: 0.45,2.12), and no significant overall protective association between breastfeeding and severe ETEC diarrhea was evident during the first 3 years of life (RR = 0.86; 95% CI: 0.43,1. 74). CONCLUSIONS: Exclusive breastfeeding appeared to protect infants against severe ETEC diarrhea, but breastfeeding was not associated with protection after infancy, nor was it associated with a major overall reduction of severe ETEC disease during the first 3 years of life. Although not diminishing the importance of breastfeeding, our findings suggest that other interventions, such as immunization and education about proper food hygiene, may also be required in efforts to prevent this major pediatric disease.

Bangladesh↗

Epidemiology of shigellosis among children exposed to cases of Shigella dysentery: a multivariate assessment.

We followed 1,756 young, rural Bangladeshi children less than five years of age for one month after identification of sentinel Shigella patients in their neighborhoods. Two hundred nineteen (12%) children developed Shigella diarrhea (shigellosis) and 227 (13%) developed culture-negative dysentery. Shigella flexneri (60%) and S. dysenteriae, type 1 (15%) were the most common isolates among shigellosis cases. Within individual neighborhoods, there was poor agreement (Kappa = 0.21) between Shigella species isolated from sentinel patients and from additional cases detected during surveillance. The risk of shigellosis increased substantially after infancy and peaked in the second year of life. Severe stunting, as assessed by height-for-age, was associated with an increased risk of shigellosis (adjusted odds ratio [ORa] = 1.67, 95% confidence interval [CI] = 1.09-2.57, P < 0.05), while breast-feeding was protectively associated (ORa = 0.40, 95% CI = 0.24-0.69, P < 0.001). Only 43% of the shigellosis cases reported bloody stools; frank dysentery occurred more frequently in S. dysenteriae 1 infections than in S. flexneri infections (ORa = 5.04, 95% CI = 1.76-14.48, P < 0.01), and was also associated with severe stunting (ORa = 2.16, 95% CI = 1.01-4.58, P < 0.05). Our findings show that the high risk of shigellosis in residentially exposed Bangladeshi children results from multiple Shigella strains circulating concurrently within the same neighborhood; demonstrate that the risk is notably modified by host age, nutritional status, and dietary patterns; and illustrate that the classic picture of dysentery is relatively infrequent and is correlated with the infecting species and with host nutritional status.

Adolescent↗

Effect of praeruptorin C on spontaneous [Ca2+]i transients in cultured myocardial cells of neonatal rats.

AIMS: To study the effects of praeruptorin C (Pra-C) on [Ca2+]i transients in cultured neonatal myocardiocytes. METHOD: Using Ca(2+)-sensitive fluorescent indicator, Fura 2-AM, spontaneous cytosolic Ca2+ transients were measured in cultured myocardial cells of neonatal rats. RESULTS: Pra-C 10, 30 mumol.L-1 caused a decrease in the peak of Ca2+ transients. Pra-C 30 mumol.L-1 and 10-30 mumol.L-1 inhibited partly the stimulatory effects of CaCl2 4.8 mmol.L-1 and Bay k 8644 100 nmol.L-1 on peak Ca2+ transients, respectively. Pra-C did not cause any marked change in the basal [Ca2+]i level between beats. Pra-C inhibited the reduced [Ca2+]i transients after inhibition of sarcoplasmic reticulum Ca2+ release in ryanodine pretreated cells. CONCLUSIONS: Pra-C inferred with the Ca2+ influx responsible for excitation-contraction coupling in myocardiocytes.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Effects of praeruptorine C on the intracellular free calcium in normal and hypertrophied rat ventricular myocytes.

AIM: To study the intracellular free calcium ([Ca2+]i) in normal and hypertrophic left ventricular myocytes isolated from adult rat hearts and the effects of praeruptorine C (Pra-C) on them. METHODS: [Ca2+]i of single myocyte was measured with Fura 2-AM. RESULTS: The resting [Ca2+]i was 87 +/- 4 nmol.L-1 in normal left ventricular myocytes, 123 +/- 7 nmol.L-1 in hypertrophied myocytes. After exposure to KCl (20, 40, and 60 mmol.L-1), the [Ca2+]i were increased by 66%, 141%, and 268% in normal myocytes, and 77%, 185%, and 243% in hypertrophic myocytes, respectively. Pra-C (1, 10, and 100 mumol.L-1) concentration-dependently inhibited the [Ca2+]i elevation caused by KCl (35 mmol.L-1) or norepinephrine (20 mumol.L-1) in both normal and hypertrophied myocytes. All of the effects of Pra-C were similar to that of nifedipine. CONCLUSION: [Ca2+]i of hypertrophied myocytes was higher than that of normal ones and Pra-C decrease the [Ca2+]i elevation in left ventricular myocytes resulted from its calcium channel blockade.

Animals↗

Inhibitory effects of nifedipine on DNA and protein synthesis in cultured cardiac nonmyocytes of neonatal rats.

AIM: To observe the inhibitory effects of nifedipine (Nif) on cardiac nonmyocytes growth and proliferation. METHODS: Using nonmyocytes in culture as a model, [3H]thymidine and [3H]leucine incorporation were measured. RESULTS: There was a significant decrease in cell number and in total cellular protein after 72-h exposure to Nif 1 mumol.L-1 in the presence of angiotensin II (Ang II). A 48-h exposure to 1, 10, 100, 1000 nmol.L-1 of Ang II caused a 19%, 35%, 46%, 48% increase in protein synthesis and 27%, 46%, 56%, 57% increase in DNA synthesis. Nif 1, 3, and 10 mumol.L-1 were able to reduce the Ang II 100 nmol.L-1-induced increase of protein synthesis and DNA synthesis. CONCLUSION: Nif had a direct inhibitory action on the growth of nonmyocytes, which was related to the regression of cardical hypertrophy.

Angiotensin II↗

[Effect of sanchinoside Rg1 on experimental thrombosis and its mechanisms].

The effect of sanchinoside Rg1 on generation of thrombosis and its mechanism was studied. Rg1 was shown to markedly inhibit experimental thrombosis formation induced by extra corporeal shunt between the carotid artery and jugular vein. After Rg1 infusion, the activity of t-PA was found to be increased, so did the percentage of active-type t-PA, but the activity of PA-I decreased. Further data in our study indicate that incubation of endothelial cells with Rg1 for 24 h caused significant increase of NO production. This effect was found to be dose-dependent. These observations suggest that Rg1 is a potent anti-thrombosis substance and can enhance the function of fibrinolysis system and stimulate vascular endothelial cells to release NO.

Animals↗

[Effects of praeruptorin C on cardiac dysfunction, myocardial compliance and collagen content in renovascular hypertensive rats].

The effects of praeruptorin C (Pra-C) on cardiac dysfunction, myocardial compliance, and collagen content in renovascular hypertensive rats have been studied. In rats with left ventricular hypertrophy (LVH), the ratio of cardiac flow (CF)/heart wet weight (HWW) and cardiac output (CO)/HWW decreased by 20.1% and 35.5%; LVSP and -dp/dtmax decreased by 19.4% and 42.1%, while LVEDP and T value were increased by 186.4% and 226%. The left ventricular diastolic pressure-volume (P-V) curve was shifted to the left and down ward compared with that of sham-operated rats. The hydroxyproline content was 5.93 +/- 0.82 mg.g-1 dry weight in the left ventricular myocardial tissue of rats with LVH which was higher than that of sham-operated rats(e.g. 4.01 +/- 0.47 mg.g-1). The content did not change in the right ventricular myocardium. After treated with Pra-C for nine weeks, the CF/HWW and CO/HWW increased by 31.3% and 25.1%, the LVSP and -dp/dtmax increased by 16.7% and 27.8%. The LVEDP and T value was reduced by 34.9% and 36.5%, respectively, compared with those of LVH. The P-V curves of these rats were shifted to the right and in the up-ward direction. The hydroxyproline content was 4.52 +/- 0.3 mg.g-1 dry weight in the left ventricular tissue. These results indicate that Pra-C improved the cardiac contractility and relaxation by increasing the coronary flow and cardiac output, and decreasing the collagen content in the ventricular myocardium.

Animals↗

Protection from amphotericin B-induced lipid peroxidation in rats by fructose-1,6-diphosphate.

Amphotericin B's (Amp B) usefulness is associated with a number of toxic cellular side effects. We investigated the in vivo effects of Amp B on the lipid peroxide (malondialdehyde [MDA]) levels in various organs of rats infused with 1.5 mg/kg body weight of Amp B. The rats (n = 8) experienced cardiac arrest following Amp B infusion. Among the organs, the kidney exhibited higher levels of MDA and was followed by brain > liver > lung > heart. Pretreatment of rats with 0.35 g/kg body weight of fructose-1,6-diphosphate (FDP) prior to Amp B infusion reduced the extent of MDA formation in all organs. These studies suggest that Amp B-associated toxicity in rats may involve the formation of lipid peroxide damage and FDP, in part by reducing these effects, may afford partial protection.

Amphotericin B↗

Zinc dependent recognition of a human CpG island sequence by the mammalian spermatidal protein TP2.

Rat spermatidal protein TP2 is a zinc metalloprotein with two atoms of zinc coordinated to cysteine and histidine residues and condenses alternating GC copolymer preferentially in a zinc dependent manner [Kundu, T. K., & Rao, M. R. S. (1995) Biochemistry 34,5143-5150]. In the present study, we have used a 40-mer oligonucleotide containing a human CpG island sequence to study its interaction with TP2 by gel mobility shift assays. A specific complex was observed in the presence of poly(dI).poly(dC). Preincubation of TP2 with 10 mM EDTA or 1 mM 1, 10-o-phenanthroline inhibited the complex formation by more than 90%. Competition experiments with various polynucleotides revealed the following order of efficiency: poly(dG-dC).poly(dG-dC) > cold homologous oligonucleotide > poly(dA-dT).poly(dA-dT). Homoduplexes poly(dG).poly(dC) and poly(dA).poly(dT) had no effect on the complex formation. Chromomycin A3, a GC minor groove binding drug, inhibited the complex formation. Methylation of the CpG doublet within the CpG island sequence by SssI methylase (CpG methylase) completely abolished the complex formation. Methylation of G at the N-7 position with dimethyl sulfate did not affect the recognition of CpG island by TP2. Thus, CpG islands, widely distributed in the mammalian genome, may serve as specific loci for initiation of chromatin condensation by TP2 during the later stages of spermiogenesis.

Animals↗

Characterisation of a DNA pairing activity copurifying with DNA ligase in a partially purified extract from rat testis.

Rat testicular nuclear extracts were fractionated sequentially on phosphocellulose, heparin-agarose and ssDNA-cellulose columns, in order to isolate and characterise a strand-transfer activity from a mammalian meiotic tissue. A partially purified fraction, eluting at 0.6 M KCl from ssDNA-cellulose column, catalyzed the formation of two classes of products migrating slowly on an agarose gel. The formation of one of these classes of products-the aggregates-was dependent on the presence of both the substrates (M13mp19 RF III and M13mp19 ssDNA) and on homology. The presence of ATP was essential for the formation of aggregates, though its hydrolysis was not required. EM analysis of the products indicated the presence of structures which resembled paired DNA molecules: duplex-duplex paired (Y-shaped and ds-ds paired structures) and ss-ds paired (duplex DNA paired with the single-stranded DNA) structures, indicating the presence of a pairing protein in the fraction. However, alpha- and sigma-structures were not observed. The other class of products, seen as discrete bands, were identified biochemically and by electron microscopy as ligated products. A DNA ligase-adenylate adduct of molecular weight 100 kDa was formed by the fraction. Both 5' to 3' and 3' to 5' exonucleases were absent and hence did not contribute to the formation of the products.

Adenosine Triphosphate↗

Cloning of cDNA encoding rat spermatidal protein TP2 and expression in Escherichia coli.

Rat spermatidal protein TP2 is a basic nuclear protein containing two atoms of zinc bound per molecule. We report here cloning of complementary DNA encoding rat TP2 by the RT-PCR method. The nucleotide sequence of cloned TP2 cDNA differs at a few positions from the sequence already reported in the literature. We have cloned rat TP2 cDNA into the expression vector pTrc 99A. Upon induction with 1 mM IPTG, there was a low level of expression of TP2 which could be recovered in the soluble form. Recombinant TP2 was purified from the soluble form. Recombinant TP2 was purified from the soluble extract of E. coli using nickel-agarose and heparin-agarose chromatography and was shown to be identical to native rat TP2 as revealed by immunoblotting with anti-rat TP2 antibodies and radioactive 65Zn-blotting.

Amino Acid Sequence↗

Field trial of inactivated oral cholera vaccines in Bangladesh: results from 5 years of follow-up.

To determine the protective efficacy (PE) of three doses of oral B subunit-killed whole cell (BS-WC) or killed whole cell-only (WC) vaccines against cholera, a clinical trial was conducted among 62285 children over 2 years and adult women in rural Bangladesh. During 5 years of follow-up, there were 144 cases of cholera in the BS-WC group (PE = 49%; P < 0.001), 150 in the WC group (PE = 47%; P < 0.001), and 283 in the K12 group. Protection by each vaccine was evident only during the first three years of follow-up; long-term protection of young children was observed only against classical but not El Tor cholera; 3-year protection against both cholera biotypes occurred among older persons, but at a higher level against classical cholera.

Administration, Oral↗

High seroprevalence of hepatitis A, B, C, and E viruses in residents in an Egyptian village in The Nile Delta: a pilot study.

Hepatitis C virus (HCV) infection is hyperendemic in Egypt, with seroprevalence rates of 10-20% among volunteer blood donors, and even higher rates reported among segments of the general population. We attempted to confirm the high seroprevalence of HCV and to compare it with the age-specific seroprevalence rates for hepatitis A, hepatitis B, and hepatitis E among 155 nonrandomly selected residents of a semiurban village in the Nile River delta. Of the two orally transmitted viruses (HAV and HEV), all 1-3-year-old children had been infected by HAV and the seroprevalence rate of 100% persisted until age 67. In contrast, HEV infections were not detected until children were 4-9-years old, and the 57% seroprevalence rate in this age group did not increase appreciably in older age groups. Of the two parenterally transmitted viruses, HBV was first detected in 1-3-year-olds, whereas HCV was first detected later, in 10-19-year-olds. The seroprevalence rates of both viruses increased progressively with age, peaking in the 40-67-year-old group at 66% for HBV and at 51% for HCV. The number of persons who had only one infection, or no infection at all, was too small to allow meaningful statistical analysis of serologically pure groups infected only by HBV, HCV, or HEV. The results of this pilot study revealed extraordinarily high seroprevalence rates of HBV, HCV, and HEV in this village, and distinctive age-specific seroprevalence rates suggesting different patterns of transmission.

Adolescent↗

Cyclosporin A-induced changes in nitric oxide synthase activity in the rat kidney: in vitro and in vivo assay.

Cyclosporin A (CsA) is a cyclic undecapeptide that has been used extensively as an immunosuppressive drug in transplantation medicine and is known to interact with L-arginine dependent pathways. We studied the in vitro and in vivo effects of CsA on nitric oxide synthase (NOS) activity in the rat kidney. CsA in concentrations of 44-2200 nM in vitro, and 12.5 or 25 mg/kg body weight per 4 weeks treated rat kidneys in vivo, significantly stimulated NOS activity. CsA may alter the Ca2+/Cam-dependent NOS activity by interacting with rat kidney Ca2+/calmodulin dependent events.

Animals↗

Inhibition of rat brain nitric oxide synthase activity by cyclosporin-A.

Cyclosporin-A, a potent immunosuppressive agent is known to induce cellular toxic side effects by way of altering calcium homeostasis, including calcium/calmodulin mediated events. We studied the in vitro and in vivo effects of cyclosporin-A on rat brain nitric oxide synthase activity (the enzyme that mediates the conversion of L-arginine to citrulline and NO). CsA in concentrations of 22-4400 nM inhibited rat brain NOS activity in vitro and in 10 or 25 mg/kg wt/4 weeks of CsA treated rat brains in vivo. We report here that CsA by way of interfering with rat brain Ca2+/CaM mediated events may inhibit its NOS activity which ultimately may result in neurotoxicity.

Animals↗

Effects of m-nifedipine on dihydropyridine binding sites in hypertrophied left ventricular cell membranes from deoxycorticosterone acetate-salt hypertensive rats.

m-Nifedipine(m-Nif 20 mg.kg-1.d-1 ig) was administered orally to male deoxycorticosterone-acetate-salt(DOCA) hypertensive rats for 9 or 12 wk, the affinity and density of dihydropyridines (DHP) binding sites in the membranes of left ventricle (LV) were investigated. Treatment with m-Nif, whether for prevention (6 wk postoperation) or regression (9 wk postoperation) lowered systolic blood pressure, decreased the weight of left ventricle and the Ca2+ concentration in mitochondria in hypertrophied LV. The density (Bmax) and the total number of DHP binding sites in hypertrophied LV were also markedly decreased (450 +/- 25, 462 +/- 36 fmol.mg-1 vs 836 +/- 47 fmol.mg-1 protein, P < 0.001). There was no difference between groups in constant (KD) values of DHP binding sites. These results indicate that m-Nif prevented and regressed cardiac mass in DOCA hypertensive rats through mechanisms that may be associated with their density of DHP binding sites and control of blood pressure.

Animals↗

[Effects of Peucedanum praeruptorum extractum on blood pressure, left ventricular hypertrophy and hemodynamic changes in left ventricular hypertrophied hypertensive rats].

After intragastric administration of Peucedanum praeruptorum (PPE) 0.6 g/100 g body weight, the blood pressure was decreased significantly in both the normal and the left ventricular hypertrophied hypertensive (LVH) rats. The PPE could still prevent the formation of the left ventricular hypertrophy in renovascular hypertensive rats, the ratio of weight of left ventricular over the weight of body was reduced markedly than that of the LVH group, and was nearly the same of the sham-operated group. The PPE could improve both the systolic and diastolic function than that of the LVH group in the isolated heart, especially, the flow of the coronary artery was increased significantly.

Animals↗

Effects of menidipine on dihydropyridines binding sites in cardiac and cerebral membranes from old rats with left ventricular hypertrophy.

AIM: To study the effects of menidipine (Men) on the affinity and density of dihydropyridines (DHP) binding sites in the cell membranes of left ventricle (LV) and brain in elderly renovascular hypertensive rats (RVHR) with LV hypertrophy. METHODS: Renovascular hypertension was produced by clipping the left renal artery in 20-month-old rats. The affinity and density of DHP binding sites in the cell membranes of LV and brain were assessed by radioligand assay. RESULTS: Men (20 mg.kg-1.d-1 ig for 9 wk) decreased markedly the systolic blood pressure and the LV weight (P < 0.01). Though not affecting the density of DHP receptor (Bmax), Men markedly decreased the total number of DHP binding sites in hypertrophied LV (from 5.95 +/- 0.62 to 4.0 +/- 1.1 pmol.LV). Men also reduced Bmax of DHP binding sites in the thalamus (from 522 +/- 27 to 371 +/- 24 pmol/g protein) and hippocampus (from 498 +/- 26 to 332 +/- 32 pmol/g protein). CONCLUSION: Men reversed the LV hypertrophy from renovascular hypertension accompanied with reduced total number of DHP binding sites in the cell membranes of LV and Bmax of the cell membranes of thalamus and hippocampus from elderly LV hypertrophied rats.

Animals↗