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Biomedical subjects

M Bhatnagar

Publications and source records attributed to M Bhatnagar.

At least 37 records · Page 2Linked to original sources

Neonatal mortality in Meerut district.

A study of neonatal mortality in Meerut district revealed an infant mortality rate of 50.1 per 1000 live births. Neonatal mortality accounted for 37.8% of infant mortality with a neonatal mortality rate of 19.0 per 1000 live births. 90.5% of these neonates were delivered at home largely by untrained personnel (57.2%). Only 28.6% of these neonates were treated by qualified doctors and only 30.9% of their mothers were fully immunized against tetanus. At least 2/3rd of neonatal mortality was due to exogenous factors with tetanus neonatorum and septicaemia being the principal causes of mortality each accounting for a mortality rate of 4.7 per 1000 live births.

Cause of Death↗

Ranitidine--rifampicin interaction.

Newly diagnosed patients of pulmonary tuberculosis (n = 112) were put on a rifampicin-containing drug regimen. Fifty six patients were also given a placebo tablet twice daily while the other fifty-six were given ranitidine 150 mg twice daily. Gastric pH, gastric emptying time, serum rifampicin levels, urinary total and unchanged rifampicin, serum bilirubin and ALT levels were measured serially. Clinical record of adverse symptoms was maintained. Ranitidine increased the basal as well as post-drug gastric pH without altering the gastric emptying time. Concomitant administration of ranitidine and rifampicin did not alter the absorption, metabolism or excretion of the latter but reduced the frequency of gastrointestinal symptoms.

Adult↗

Influence of prior information of drug toxicity on patient compliance.

Sixty patients with pulmonary tuberculosis, who had not received any chemotherapy in the past, were divided into two groups. All the patients were put on isoniazid, rifampicin and pyrazinamide for 8 weeks followed by isoniazid and rifampicin for another 18 weeks. Group A patients were informed of the likely occurrence of anorexia and/or vomiting but Group B patients were not. Routine and default retrieval home visits were given to ensure maximal drug compliance. Drug toxicity related early defaults were significantly less common in Group A patients (1 of 30) as compared to Group B (6 of 30).

Adult↗

Cross-axis synchronous flow-through coil planet centrifuge (type XLL). I. Design of the apparatus and studies on retention of stationary phase.

The fourth prototype holds a pair of column holders in the lateral position at 15 cm from the center of the rotary shaft horizontally mounted on the rotary frame at 7.6 cm from the central axis of the apparatus. Using short coils of 2.6 mm I.D. PTFE (polytetrafluoroethylene) tubing with 7.6 cm and 24 cm helical diameters, retention of the stationary phase was measured in ten pairs of two-phase solvent systems under various experimental conditions. Satisfactory retention was obtained by choosing proper combinations of three factors, i.e., the direction of planetary motion, head-tail elution mode, and inward-outward elution mode. The polar butanol solvent systems showed excellent retention from 65 to 80% in the 7.6 cm helical diameter left-handed coil.

Centrifugation↗

Separation of rare earth elements by high-speed counter-current chromatography.

Besides being widely used in electronic and glass industries, rare earth elements have recently been found to have important biological effects including the ability to stabilize and enhance interferon activity [J.J. Sedmak and S.E. Grossberg, J. Gen. Virol, 52 (1981) 195]. In this paper, the rare earth elements have been separated using a high-speed counter-current chromatography (HSCCC) centrifuge equipped with three multilayer coils connected in series. Two-phase solvent systems were composed of n-heptane containing di-(2-ethylhexyl)phosphoric acid (stationary phase) and dilute hydrochloric acid (mobile phase) where the partition coefficient of each can be optimized by selecting the proper hydrochloric acid concentration. The mobile phase was eluted through the column at a flow-rate of 5 ml/min, while the apparatus was rotated at 900 rpm. Continuous detection of the rare earth elements was effected by means of a post-column reaction with arsenazo III and the elution curve was obtained by on-line monitoring at 650 nm. Excellent isocratic separations of closely related rare earth elements were achieved at high partition efficiencies up to several thousand theoretical plates. Versatility of the present method was demonstrated in an exponential gradient elution of hydrochloric acid concentration where fourteen rare earth elements were all resolved in about 4.5 h.

Centrifugation↗

Improved cross-axis synchronous flow-through coil planet centrifuge for performing counter-current chromatography. II. Studies on retention of stationary phase in short coils and preparative separations in multilayer coils.

Performance of the apparatus was evaluated in terms of stationary phase retention, partition efficiency and sample loading capacity. Preliminary studies with short coils revealed high retention of the stationary phase under a proper combination of the head-tail elution and planetary motion. Preparative capability of the apparatus was successfully demonstrated on efficient multigram separations of 2,4-dinitrophenyl amino acids, indole auxins, and bacitracin in a pair of large multilayer coils with a total capacity of 1.5 l.

Amino Acids↗

Localisation of mRNA and co-expression and molecular forms of GRP gene products in endocrine cells of fetal human lung.

The presence of bombesin (gastrin-releasing peptide, GRP)-like immunoreactivity in mucosal endocrine cells of human fetal lung is well established. In this study we have investigated the localisation of pro-GRP mRNA and GRP gene products and compared the distribution and levels of extractable GRP- and C-terminal flanking peptide of human pro-GRP-like immunoreactivity in order to verify synthesis and to investigate their coexistence and molecular forms. Human fetal lungs (14 to 23 weeks gestation) were immunostained, and extracts were assayed using region-specific antisera to pro-GRP. Additional antisera to chromogranin and protein gene product 9.5 (PGP 9.5) were used for immunostaining by the peroxidase anti-peroxidase technique and for double immunofluorescence staining using antisera raised in two species. Immunoreactivity for both bombesin (GRP) and flanking peptide was seen mainly in the same endocrine cells, but more cells were stained with antisera to flanking peptide than with antiserum to bombesin (GRP). In situ hybridisation showed that pro-GRP mRNA was present and thus synthesis of the peptides was taking place. Endocrine cells and nerve fibres were PGP 9.5-immunoreactive, and a subset of cells was immunoreactive for bombesin gene products. Radioimmunoassay and chromatography show that pro-GRP is present in both the uncleaved and cleaved forms, and, in agreement with immunocytochemistry results, that an excess of C-terminal peptide of pro-GRP is detectable. It is therefore concluded that GRP-like peptides and flanking peptide are co-localised in human pulmonary endocrine cells, but the latter is found in larger concentrations than free GRP. Thus GRP-like peptides may be secreted separately from the flanking peptide(s) of pro-GRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Gel↗

Expression of the atrial natriuretic peptide gene in the cardiac muscle of rat extrapulmonary and intrapulmonary veins.

Atrial natriuretic peptide is a peptide regulating salt and water balance, originally isolated from the cardiac atrium, where it is synthesised as part of a precursor molecule in specialised myocardial cells. The myocardium extends into the extrapulmonary part of the pulmonary veins in many species, including man. In some small mammals, however, such as the rat, mouse, and bat, it extends further to veins in the peripheral parts of the lung. Since this myocardial layer is continuous with that in the atrium, we have looked for the possible expression of the atrial natriuretic peptide gene in this tissue in rats. Strong immunoreactivity was seen for both the peptide and the N terminal sequence (cardiodilatin) of its precursor in extrapulmonary veins and in intrapulmonary veins extending into the lung as far as the second branching point, where it was localised in the dense cored granules by electron microscopy; in situ hybridisation showed atrial natriuretic peptide messenger RNA at identical sites. Chromatography and radioimmunoassay of extracts of extrapulmonary and intrapulmonary veins showed most of the atrial natriuretic peptide immunoreactivity to be in the uncleaved (precursor molecule) form. Thus the peptide is synthesised in veins both outside and inside the lung, and these extra-atrial sites may be an important additional source of circulating atrial natriuretic peptide.

Animals↗

Enhancement of reactive oxygen-dependent mitochondrial membrane lipid peroxidation by the anticancer drug adriamycin.

Mitochondrial degeneration is a consistently prominent morphological alteration associated with adriamycin toxicity which may be the consequence of adriamycin-enhanced peroxidative damage to unsaturated mitochondrial membrane lipids. Using isolated rat liver mitochondria as an in vitro model system to study the effects of the anticancer drug adriamycin on lipid peroxidation, we found that NADH-dependent mitochondrial peroxidation--measured by the 2-thiobarbituric acid method--was stimulated by adriamycin as much as 4-fold. Marker enzyme analysis indicated that the mitochondria were substantially free of contaminating microsomes (less than 5%). Lipid peroxidation in mitochondria incubated in KCl-Tris-HCl buffer (pH 7.4) under an oxygen atmosphere was optimal at 1-2 mg of mitochondrial protein/ml and with NADH at 2.5 mM. Malonaldehyde production was linear with time to beyond 60 min, and the maximum enhancement of peroxidation was observed with adriamycin at 50-100 microM. Interestingly, in contrast to its stimulatory effect on NADH-supported mitochondrial peroxidation, adriamycin markedly diminished ascorbate-promoted lipid peroxidation in mitochondria. Superoxide dismutase, catalase, 1,3-dimethylurea, reduced glutathione, alpha-tocopherol and EDTA added to incubation mixtures inhibited endogenous and adriamycin-augmented NADH-dependent peroxidation of mitochondrial lipids, indicating that multiple species of reactive oxygen (superoxide anion radical, hydrogen peroxide and hydroxyl radical) and possibly trace amounts of endogenous ferric iron participated in the peroxidation reactions. In submitochondrial particles freed of endogenous defenses against oxyradicals, lipid peroxidation was increased 7-fold by adriamycin. These observations suggest that some of the effects of adriamycin on mitochondrial morphology and biochemical function may be mediated by adriamycin-enhanced reactive oxygen-dependent mitochondrial lipid peroxidation.

Animals↗

Effect of centhaquine on spontaneous and evoked norepinephrine release from isolated perfused rabbit heart.

1-[Bis(2-quinolyl)-ethyl]-4-m-tolylpiperazine (centhaquine), a centrally acting hypotensive agent, was studied for its effect on spontaneous and evoked release of norepinephrine (NE) from the rabbit heart. Spontaneous release of NE as well as its release evoked by potassium chloride (81 X 10(-3) mol/l), tyramine hydrochloride (2.88 X 10(-5) mol/l), dimethyl phenyl piperazinium iodide (DMPP, 3.18 X 10(-5) mol/l), acetylcholine chloride (1 X 10(-4) mol/l) and amphetamine sulfate (7.48 X 10(-5) mol/l) from isolated perfused rabbit heart was studied. Centhaquine (0.1, 1.0 and 10.0 micrograms/ml) caused an initial increase followed by inhibition of spontaneous NE output. It also significantly inhibited the NE release evoked by KCl, DMPP and acetylcholine but not tyramine and amphetamine evoked release. It is concluded that centhaquine predominantly inhibits the neuronal NE release.

Acetylcholine↗

Supra spinal influence on ventricular fibrillation threshold and cardiac stores of norepinephrine in the cat.

The relationship between ventricular fibrillation threshold (VFT) as measured by voltage required to evoke ventricular fibrillation and the concentration of norepinephrine (NE) in different parts of the myocardium under experimental interventions has been studied in anaesthetized cats. A selective increase in VFT and a marked reduction in NE content have been observed after spinal transection, removal of spinal cord from cervical 6 to thoracic 6 or carotid sinus denervation. Reserpine pretreatment significantly reduces NE content of myocardium but fails to affect VFT. The fibrillating left ventricle shows a marked decline in NE content from the control level of 1.55 +/- 0.32 to 0.82 +/- 0.09 micrograms/g and there is also a similar concomitant reduction in NE content of the entire heart. Defibrillation brings back normal rhythm, but does not restore the NE content immediately. The results suggest that a marked reduction in cardiac stores of norepinephrine significantly affect VFT and that the central nervous system plays an important role in the genesis of sustained ventricular arrhythmia.

Animals↗