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Biomedical subjects

M R Rao

Publications and source records attributed to M R Rao.

At least 127 records · Page 7Linked to original sources

Field trial of oral cholera vaccines in Bangladesh: evaluation of anti-bacterial and anti-toxic breast-milk immunity in response to ingestion of the vaccines.

In a field trial conducted in Bangladesh, ingestion of either B subunit-killed whole cell (BS-WC) or killed whole cell (WC) oral cholera vaccines by mothers was associated with a 47% reduction of the risk of cholera in their non-vaccinated children aged under 36 months. Because vaccine-induced breast-milk immunity seemed a possible explanation for these findings, we evaluated anti-lipopolysaccharide (LPS) and anti-cholera toxin (CT) IgA antibody responses in breast milk collected during the trial from 53 lactating women who ingested three doses of BS-WC, WC, or an Escherichia coli K12 strain (K12). Despite induction of moderate vibriocidal (1.4 to 2.0-fold) and anti-CT (4.5-fold) serum antibody responses, the vaccines did not elicit significant rises of anti-LPS or anti-CT IgA breast-milk antibodies. The failure of the vaccines to elicit significant levels of breast-milk anti-cholera antibodies suggests an alternative explanation for protection of young children by maternal vaccination, such as interruption of maternal-child transmission of Vibrio cholerae 01.

Administration, Oral↗

Low gastric acid as a risk factor for cholera transmission: application of a new non-invasive gastric acid field test.

Although gastric acid is thought to be an important host defense against certain enteric infections, field studies of the role of gastric acid in preventing enteric infections have been hampered by the lack of a suitable non-invasive test. Because low gastric acid output (GAO) is an established risk factor for cholera, we assessed after validation, whether a new non-invasive test which estimates GAO by measuring breath hydrogen excess after ingestion of magnesium and a stimulant of gastric acid secretion, could discriminate between persons at high and at low risk of developing cholera. Fifteen age-matched pairs, participants in the field trial of two oral cholera vaccines in rural Bangladesh, were tested. In each pair the "case" was a person who had recovered from severe cholera at least 6 months before testing and the "control" was a person who resided in the home of a cholera patient but remained uninfected. The stimulated breath hydrogen was higher in controls (median hydrogen excess = 369 mumol/80 min) than in cases (median hydrogen excess = 150 mumol/80 min) (p less than 0.05) and was higher in controls in 12 out of 15 pairs. The results, which are consistent with past invasive assessments of the association between hypochlorhydria and cholera, suggest that this non-invasive test may be useful in evaluating GAO in epidemiological field studies.

Adult↗

Breast feeding and the risk of severe cholera in rural Bangladeshi children.

The association between breast feeding and the risk of severe cholera was examined in a case-control study of rural Bangladeshi children under 36 months of age who were studied in 1985-1986 during a field trial of killed oral cholera vaccines. A total of 116 cases who were treated for severe cholera were compared with 464 age-matched community controls without severe cholera. Overall, the odds ratio relating breast feeding to severe cholera (0.30, p less than 0.0001) reflected a 70% reduction in the risk of severe cholera among breast-fed children. The estimated reduction of risk declined with age, but was clearly evident in children up to 30 months of age. Although the association between breast feeding and a reduced risk of severe cholera was not significantly greater in children of mothers who had received cholera vaccine than in children whose mothers had received placebo during the trial, maternal vaccination per se was suggestively associated with a reduced risk of severe cholera in their nonvaccinated children (odds ratio = 0.53, p = 0.05). These results indicate that breast feeding was associated with a substantial reduction of the risk of severe cholera and raise the possibility that vaccination of mothers may provide protection to their young children in endemic settings.

Bangladesh↗

[Effects of praeruptorin C on isolated guinea pig atrium and myocardial compliance in patients].

Praeruptorin C (Pra-C, 2-methyl-,10-(acetyloxy)-9,10- dihydro-8,8-dimethyl-2-oxo-2H, 8H-benzo[1,2-b:3,4-b'] dipyran-9-ol ester of 2-butenoic acid) was first isolated by Chinese researcher. Pra-C 10 mumol/L reduced automatic rhythm and positive chronotropic effects of CaCl2 in right atrium. Its antagonistic effects on isoproterenol-mediated increase in beat rate were non-competitive with a pD'2 of 4.8. Pra-C 5-50 mumol/L shortened functional refractory period with little effects on the excitability and epinephrine-induced ecotopic automaticity. Modification of myocardial compliance during 2 wk oral Pra-C therapy in patients with hypertrophic cardiomyopathy was also investigated.

Animals↗

[Protecting effects of m-nifedipine on isoproterenol-induced myocardial injury in rats].

To test whether m-nifedipine (m-Nif) protects heart against myocardial injury induced by a single subcutaneous injection of isoproterenol (Iso) 30 mg/kg, male rats were injected subcutaneously twice daily with m-Nif 6 mumols/kg for 4 d. Hemodynamic changes, serum creatine kinase activity and ion contents of myocardial tissue and mitochondria were assessed about 6 h after Iso injection. While it did not notably influence blood pressure, heart rate and left ventricular contracting function of rats, m-Nif markedly attenuated calcium accumulation in myocardial tissue and mitochondria, reduced magnesium and potassium loss in myocardial tissue, depressed the release of creatine kinase and prevented the elevation of left ventricular end diastolic pressure. These beneficial effects of m-Nif were similar to those of nifedipine (Nif). However, m-Nif decreased minute tension-time index more significantly than the same dose of Nif. It is possible that m-Nif protects the rat heart from isoproterenol-induced injury by inhibiting transsarcolemmal calcium influx.

Animals↗

Characterization of poly(ADP-ribosyl)ated domains of rat pachytene chromatin.

Poly(ADP-ribosyl)ation of nuclear proteins was several-fold higher in the pachytene spermatocytes than in the premeiotic germ cells of the rat. Among the histones of the pachytene nucleus, histone subtypes H2A, H1 and H3 were poly(ADP-ribosyl)ated. Based on the immunoaffinity fractionation procedure of Malik, Miwa, Sugimara & Smulson [(1983) Proc. Natl. Acad. Sci. U.S.A. 80, 2554-2558] we have fractionated DNAase-II-solubilized chromatin into poly(ADP-ribosyl)ated chromatin (PAC) and non-poly(ADP-ribosyl)ated chromatin (non-PAC) domains on an anti-[poly(ADP-ribose)] IgG affinity matrix. Approx. 2.5% of the pachytene chromatin represented the PAC domains. A significant amount of [alpha-32P]dATP-labelled pachytene chromatin (labelled in vitro) was bound to the affinity matrix. The DNA of pachytene PAC domains had internal strand breaks, significant length of gaps and ligatable ends, namely 5'-phosphoryl and 3'-hydroxyl termini. On the other hand, the PAC domains from 18 h regenerating liver had very few gaps, if any. The presence of gaps in the pachytene PAC DNA was also evident from thermal denaturation studies. Although many of the polypeptides were common to the PAC domains of both pachytene and regenerating liver, the DNA sequences associated with these domains were quite different. A 20 kDa protein and the testis-specific histone H1t were selectively enriched in the pachytene PAC domains. The pachytene PAC domains also contained approx. 10% of the messenger coding sequences present in the DNAase-II-solubilized chromatin. The pachytene PAC domains, therefore, may represent highly enriched DNA-repair domains of the pachytene nucleus.

Animals↗

Testis-specific histone H1t is truly a testis-specific variant and not a meiotic-specific variant.

Immunoblotting studies using highly specific polyclonal anti-histone H1t-IgG, which was extensively characterized by us previously, did not produce a signal with any of the histone H1 subtypes of either 1-day-old or adult rat ovarian nuclei. The absence of histone H1t in ovarian nuclei was also confirmed by indirect immunofluorescence studies. It is concluded, therefore, that histone H1t is truly a testis-specific histone variant and not a meiotic-specific variant.

Animals↗

Immunochemical detection of Z-DNA in rat pachytene spermatocytes.

Rat testicular nuclei have been probed for the presence of Z-DNA conformation by employing indirect immunofluorescence technique using anti-Z-DNA antibodies. Pachytene nuclei, in which meiotic recombination takes place, showed brighter fluorescence than the premeiotic and postmeiotic spermatogenic nuclei. Moreover, utilizing a novel chromatin immunoblotting technique, Z-DNA conformation was found to be enriched in the poly(ADP-ribosyl)ated chromatin domains of the pachytene nucleus.

Animals↗

Exclusion of clinically atypical or microbiologically mixed diarrhoeal episodes from outcome events in a field trial of oral cholera vaccines.

We investigated whether alternative clinical and microbiological criteria for outcome events affected estimates of vaccine efficacy in a randomized, double-blind field trial of B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) oral cholera vaccines among 62,285 rural Bangladeshi participants. At one year of follow-up estimates of vaccine protective efficacy (PE = 60%, P less than 0.0001 for BS-WC; PE = 54%, P less than 0.0001 for WC) against all treated diarrhoeal episodes associated with V. cholerae 01 were similar to estimates of efficacy against only those episodes which were clinically typical and unassociated with additional enteric pathogens (PE = 62%, P less than 0.0001 for BS-WC; PE = 52%, P less than 0.0001 for WC). In contrast, estimates of vaccine cross-protection against episodes associated with each of several agents antigenically related to V. cholerae 01 (LT-ETEC, non-cholera Vibrio sp, Aeromonas sp) were substantially reduced when mixed infections with V. cholerae 01 were excluded. We conclude that restrictive criteria intended to improve the specificity of the definition of cholera did not increase the detectability of vaccine efficacy against V. cholerae 01, but that exclusion of mixed infections with V. cholerae 01 was necessary to avoid false-positive conclusions about vaccine cross-protection against other potential target pathogens.

Administration, Oral↗

[Comparison of actions of m-nifedipine and nifedipine on isolated guinea pig atria and rabbit aortic strips].

m-Nifedipine (m-Nif) had weaker inhibitory effects than nifedipine (Nif) on the staircase phenomenon, functional refractory period and contraction (IC50: m-Nif/Nif = 18) of isolated guinea pig left atria at concentrations of 0.1-1.0 mumol/L. At the same concentrations, both m-Nif and Nif could hardly change the post-rest potentiation, excitability and ectopic automaticity induced by epinephrine. m-Nif 0.05 mumol/L, had no effect on the automatic contractile force of isolated right atria but could slow down the automatic rhythm. On the contrary, Nif had little effect on the automatic rhythm but potently inhibited the contractile force. Furthermore, in isolated rabbit aorta strips, m-Nif had an equal or somewhat stronger inhibitory effect on the tension induced by KCl. These results suggest that m-Nif might be superior to Nif in treating myocardial ischemia, arterial hypertension and congestive heart failure.

Animals↗

[Protective effects of m-nifedipine and nifedipine on ischemic-reperfused injury in working guinea pig hearts].

The effects of m-nifedipine (m-Nif) on global myocardial ischemia and reperfusion have been compared with those of nifedipine (Nif) in the isolated working guinea pig hearts. Stronger coronary vasodilatation and less prominent cardiac depression were observed in the nonischemic hearts treated with m-Nif (8 and 25 nmol/L) than in those treated with the same doses of Nif. Hearts treated with m-Nif or Nif before and during low-flow ischemia, which lasted 50 min followed by 35 min reperfusion, showed significant preservation of contractility and relaxation, especially relaxation. These treatments resulted in a greater recovery of coronary flow and cardiac output, improvement of left ventricular work and efficiency, a reduction in creatine kinase release, and attenuation of myocardial edema. The treatments (m-Nif 25 and Nif 8 nmol/L), which were equiactive in nonischemic hearts, provided equivalent myocardial protection in reperfused ischemic hearts.

Animals↗

Effects of praeruptorin C and E isolated from 'Qian-Hu' on swine coronary artery and guinea-pig atria.

Praeruptorin C and E isolated from Peucedanum praeruptorum Dunn. decreased the maximum contractile effect of Ca2+ in potassium-depolarized swine coronary strips and shifted the concentration-response curve to the right in a non-parallel manner. The calcium antagonistic activity of praeruptorin C and E expressed as pD'2 value was 5.7 and 5.2, respectively. Nifedipine, with a pD'2 value of 6.88, was used as a known calcium antagonistic drug to compare the potency of the drugs studied. The relaxation induced by praeruptorin C was concentration-dependent and the IC50 value was 79 microM. Praeruptorin C also reduced the maximum contractile response and shifted the concentration-response curve for calcium to the right in a non-parallel manner in potassium-depolarized guinea-pig left atria (pD'2 = 5.52) but its potency was much less than that of nifedipine (pD'2 = 7.19). The results suggest that praeruptorin C and E relaxed swine coronary artery and decreased contractility in guinea-pig left atria. These effects are similar in many respects to those displayed by drugs that have calcium entry blocking activity.

Animals↗

Discontinuation of breast-feeding during episodes of diarrhoea in rural Bangladeshi children.

Discontinuation of breast-feeding during an episode of childhood diarrhoea is widely regarded as a common, high-risk practice in the developing world. We studied cessation of breast-feeding in a rural Bangladeshi population under comprehensive surveillance for medically treated diarrhoeal episodes. Among 2129 episodes in children aged under 36 months and breast-fed before the onset of diarrhoea, there were only 33 (2%) in whom breast-feeding had stopped before presentation for care. Children in whom breast-feeding had stopped (cases) differed little from those in whom it had not (controls) in respect to exclusive vs partial breast-feeding, age, gender, or several maternal characteristics (maternal age, education, and recent maternal diarrhoeal illness). In contrast, cases were more likely to have presented with clinically severe illness or to have died within 30 d of presentation (odds ratio = 2.20, P less than 0.05). We conclude that discontinuation of breast-feeding during diarrhoea is an infrequent phenomenon in this population. However, the association of cessation of breast-feeding with severe clinical outcomes may be of considerable importance, particularly in countries where discontinuation of breast-feeding is more common.

Bangladesh↗

Measles vaccination and childhood mortality in rural Bangladesh.

To ascertain whether measles vaccination was associated with reduced mortality rates in rural Bangladeshi children, the authors conducted a case-control study in four contiguous areas, two of which had participated in an intensive measles vaccination program which began in the spring of 1982. Cases were 536 children who had died in the four-area region at the age of 10-60 months between April 1982 and December 1984. Two age- and sex-matched controls were selected from the four-area region for each case; each control had survived at least through the date of death of the matched case. Measles vaccination was associated with a 36% (95% confidence interval 21%-48%) proportionate reduction in the overall rate of death and a 57% (95% confidence interval 43%-67%) reduction in the rate of deaths directly attributed to measles or ascribed to diarrhea, respiratory illness, or malnutrition. The association of measles vaccination and reduced mortality remained unchanged after the authors restricted controls to children who had survived at least one year after the deaths of their matched cases. Moreover, children vaccinated in 1982 exhibited a sustained reduction in the rate of death in 1983 and 1984. The authors concluded that measles vaccination was associated with a pronounced and sustained reduction in the rate of death among children in this study.

Bangladesh↗