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Biomedical subjects

A Shukla

Publications and source records attributed to A Shukla.

At least 73 records · Page 4Linked to original sources
PubMed1993

Alterations in free radical scavenging mechanisms following blood-brain barrier disruption.

It has been reported earlier that rat microvessels which constitute the blood-brain barrier (BBB) are rich in free radical scavenging enzymes. In the present investigation, BBB of rat was disrupted by intravenous infusion of the hypertonic saline and changes in enzymes--namely, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR)--were evaluated in the brain microvessels at 30 min after the intravenous administration of hypertonic saline, being the time of peak effect. There was a significant increase in the activities of CAT (40%), GPx (26%), and SOD (16%) over the control values. In addition, within 90 min BBB was found to be reestablished and the levels of enzymes reverted to normal. Malondialdehyde (MDA) levels and activity of lactate dehydrogenase (LDH) remained unaltered during and following disruption, suggesting that there was no change in the membrane lipid environment. Similarly, there was no cell lysis. The results suggest that the disruption of BBB following hypertonic saline administration might be due to an increase in the generation of free radicals in the brain microvessels.

Animals↗
PubMed1993

Phenotype of 49,XXYYY.

A 7-year-old boy with 49,XXYYY karyotype is reported. Physical examination revealed facial dysmorphism, mild microcephaly, limitation of supination at the elbows, delayed bone age and moderate mental retardation.

Child↗
PubMed1993

Evaluation of vanillic acid analogues as a new class of antifilarial agents.

A number of vanillic acid analogues (1-14) have been synthesised and evaluated against experimental filarial infections using cotton rats (Sigmodon hispidus) infected with Litomosoides carinii, a primary screening model, at a dose of 30 mg/kg, ip for 5 days. Of the 8 compounds tested, 4 (5,7, 11 and 12) exhibited high micro- and macro-filaricidal activity with sterilization of surviving female worms. Compounds 5, 7, 12 showed remarkable adulticidal action (> 80%). Sterilization of the female worms by compounds 11 and 12 was highly significant (80-100%).

Animals↗
PubMed1992

Electrophysiologic basis of dynamic extensor splinting.

The use of dynamic extension splinting in the rehabilitation of extensor tendon injuries is gaining interest because of its apparent ability to improve clinical results. With such splinting, the extensor musculature is theoretically quiescent during both active flexion and rubber band-mediated extension; the gliding produced thereby decreases adhesion formation. Our initial intent was to perform electromyographic studies on volunteers in dynamic extension splinting to test this electrophysiologic principle. It was found, however, that only 16% of normal volunteers have quiescent extensor digitorum communis muscle activity within the dynamic extension splint typically used in this type of rehabilitation. A second splint was developed with a dorsal hood to keep the metacarpophalangeal joints in approximately 15 degrees of flexion. In this splint, 18 of 19 volunteers (95%) showed no extensor activity. The explanation for this phenomenon is not yet clear, but it shows that splint design plays a more significant role than previously expected. The expected electrophysiologic principle of dynamic extension splinting for extensor tendon injuries has been validated, but only in a splint design that is not commonly used.

Electromyography↗
PubMed1992

Control of kidney size by sex hormones: possible involvement of glucosylceramide.

Because androgenic hormones produce an increase in kidney size and the production of kidney glycosphingolipids and because the level of tissue glucosylceramide (GlcCer) has been implicated as a modulator of organ size, we measured the activities of two enzymes in mouse kidney that (in part) determine the level of this glycolipid. GlcCer synthase was found to rise in specific activity with age and increased kidney size, whereas GlcCer glucosidase was found to decrease with age; both enzyme changes act to elevate the level of kidney GlcCer and point to the level of this lipid as a determinant of kidney size. The increase in synthase was especially rapid in male kidney, consistent with the more rapid growth of male kidney. Testosterone injection into both males and females produced elevated levels of GlcCer synthase, decreased levels of the hydrolase, and more rapid growth. Injection of 17 beta-estradiol, which produced slow or negative kidney growth, caused the synthase activity to decrease in female mouse kidney and the glucosidase activity to rise in both sexes. Thus the changes in kidney size produced by the two hormones paralleled the changes in GlcCer level predicted by the hormone effects on the two enzymes. In liver, estradiol produced increases in both enzymes but only the male liver increased in size. Testosterone did not affect the liver. The testes grew with age but the activities of both enzymes decreased.

Animals↗
PubMed1991

Rapid kidney changes resulting from glycosphingolipid depletion by treatment with a glucosyltransferase inhibitor.

The ceramide analog, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, inhibits the glucosylation of ceramide and thus, by virtue of the normal catabolism of the higher glucosphingolipids, leads to a general depletion of cellular glucolipids. In a previous study with chronic administration of this inhibitor in mice, it was found that the kidneys and liver, particularly the former, grew more poorly than the organs of control mice. This study shows that the inhibitor produces rapid decreases in glucolipid concentration in kidney which are maintained for at least 5 days without noticeable harm. The changes were enhanced by inclusion of L-cycloserine in the injection scheme. Cycloserine blocks ketosphinganine synthase and thus slows the synthesis of all sphingolipids. However, sphingomyelin levels did not drop significantly in this study. The glucosyltransferase inhibitor also produced a small decrease in kidney beta-D-glucuronidase and distinct increases in the levels of glucocerebrosidase, galactocerebrosidase and sphingomyelinase. It also produced a small but distinct decrease in the level of glucosyltransferase, after a delay of a few hours, possibly because the inhibitor was metabolized to a covalently inactivating product. Comparison with kidney, liver and brain showed that the kidney was more sensitive to the action of the morpholino inhibitor.

Animals↗
PubMed1991

Congenital monomelic hypertrophy with progressive myopathy.

We describe a patient with congenital monomelic hypertrophy who later developed progressive footdrop due to a degenerative myopathy. The clinical, electrophysiologic, and pathologic features of the case are described and compared with those of a previously reported case.

Adult↗
PubMed1991

Occupational health and the environment in an urban slum in India.

The Indo-Dutch Environmental & Sanitary Engineering Project under the Ganga action Plan in Kanpur and Mirzapur is being executed within the Indo-Dutch bilateral development cooperation framework. The project aims to integrate physical, social and health related improvements. It is expected that the development approach and methodology can be replicated in other urban settlements in India. The project is being supplemented by a training and institutional strengthening programme to facilitate the transfer of new technologies and improvement of operation and maintenance of the new facilities. The project is also aimed at the improvement of the living conditions of the population, by installing drinking water and drainage systems. A socio-economic unit in the project supports the technical interventions by enhancing the community to participate in project activities. The Occupational Health Programme in Jajmau, an industrial slum of Kanpur, aims to improve the working conditions of tannery workers. Four hundred and ninety-seven tannery workers and 80 employees not engaged in leather work, from 20 tanneries, were interviewed and underwent physical examination. The mean age of tannery workers was 32 years, about half of them recently migrated to Kanpur. The majority of the workers are illiterate, have temporary jobs and 85% have a monthly income between 300 and 600 Rs. Occupational morbidity was 28.2%. Regular meetings with tannery owners, the training of tannery workers in first aid, and support for the installation of safety and health councils in tanneries are the main programme activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Gangliosides inhibit glucosylceramide synthase: a possible role in ganglioside therapy.

Gangliosides stimulate the hydrolysis of glucosylceramide (GlcCer), their precursor, and therefore may lower the level of cellular GlcCer and exert a feedback control effect to slow the formation of gangliosides. Tests were made to see if a similar effect on GlcCer levels can be exerted by the action of gangliosides on GlcCer synthesis. Using a new assay procedure, we showed that gangliosides do inhibit the synthase in brain membranes quite effectively, the most active being those lipids with more sugar and sialic acid moieties. Mice injected with a mixture of brain gangliosides for 5 days were found to have a lower level of ceramide:UDP-Glc glucosyltransferase activity in brain, liver, and kidney. The inhibition seems to be exerted by competition for the active site and binding to effector site(s) on the enzyme. It is possible that the reported therapeutic actions of gangliosides on the nervous system are, in part, the result of lowered levels of GlcCer. Malignant tumors shed gangliosides into the extracellular fluid, which are believed to block the generation of antibodies by the host's immunodefense system; this effect also may be due, in part, to reduction in the GlcCer level of immunogenic cells. A new finding is that a ceramide containing phytosphingosine is a markedly better substrate for GlcCer synthase than one containing the more common base.

Animals↗
PubMed1991

The effects of long-term non-fatiguing resistance exercise in subjects with post-polio syndrome.

Measures of torque were used to evaluate changes in muscle strength and endurance in 17 patients with post-polio syndrome who did prescribed resistance exercise for up to 2 years. Exercise compliance averaged 75%, with 16 subjects increasing the weight lifted in training. Maximum torque was significantly increased in the exercised muscle compared to the control muscle; no difference was seen in muscle endurance. Individuals with post-polio syndrome can increase muscle strength by doing non-fatiguing resistance exercise, but they should undergo quantitative testing of muscle strength a minimum of every 3 months to guard against overwork weakness.

Exercise Therapy↗
PubMed1991

Spontaneous gastrointestinal perforation in the neonate.

Twenty seven cases of spontaneous gastro-intestinal perforation were treated from 1981 to 1990. Four perforations were in the stomach, 17 in the small bowel and seven in the large bowel. One of them had dual perforation, one in the stomach and another in the duodenum. The exact etiology remained obscure. Various factors observed were maternal obstetric complications, prematurity and perinatal asphyxia. Stress should be laid on early diagnosis by following up 'at risk neonates' thus, giving a better overall survival rate.

Female↗
PubMed1991

Cytogenetic studies in Down syndrome.

Cytogenetic studies were carried out in 645 patients with Down syndrome. Free trisomy of chromosome 21 was present in 600 cases (93%). Translocation karyotypes were observed in 26 cases (4%). Seventeen patients (2.6%) had mosaicism. Two (0.3%) patients had additional karyotypic abnormalities along with trisomy 21.

Chromosome Aberrations↗
PubMed1991

Metabolism of D-[3H]threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of glucosylceramide synthesis, and the synergistic action of an inhibitor of microsomal monooxygenase.

D-Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) is an effective inhibitor of the glucosyltransferase that makes glucosylceramide. Virtually all of the hundreds of naturally occurring glycolipids are formed from this primary glycolipid, so the inhibitor acts to lower their concentrations by the process of attrition (hydrolytic catabolism). Trials with mice carrying ascites carcinoma cells showed that PDMP could produce a permanent cure in some of the animals and marked prolongation of life in the others (Inokuchi, J., I. Mason, and N.S. Radin. 1987. Cancer Lett. 38: 23-30). In order to maximize the effect, we studied the metabolism of PDMP by labeling it with [3H] on carbon one, using a labeling method that discriminated against the unwanted erythro-isomer. The active enantiomer of the inhibitor (D-) was isolated by chromatography of the camphanate esters, followed by methanolytic cleavage. Examination of the fate of the labeled drug after a single injection showed that it was very rapidly converted to several polar products that were rapidly excreted. The drug penetrated all of the organs readily and a small portion was oxidized at the C-1 position to yield 3H2O. From these findings it appeared likely that the amine is attacked by a mixed function oxidase based on cytochrome P450. This conclusion was confirmed by showing that the tissue levels of PDMP could be greatly elevated, for a much longer time, when the mice were pretreated with piperonyl butoxide or cimetidine. The amount of conversion to polar metabolites was substantially reduced and tissue levels of PDMP were maintained much longer. Analysis of mice injected with one or both drugs showed that piperonyl butoxide augmented the effects of PDMP on ceramide, glucosylceramide, and dihexosylceramide levels, as well as on the activity of glucosylceramide synthase. It is suggested that piperonyl butoxide be used as an adjuvant for the many useful drugs that are inactivated by the P450 system.

Animals↗
PubMed1990

Effect of latent iron deficiency on the levels of iron, calcium, zinc, copper, manganese, cadmium and lead in liver, kidney and spleen of growing rats.

Feeding a marginally low iron content diet (18-20 mg iron/kg diet) to weaned (21-day-old) rats for 8 weeks produced a significant decrease in liver non-heme iron (66%, p less than 0.001) but no change in blood hemoglobin. Total iron contents of liver (56%, p less than 0.01), spleen (20%, p less than 0.05), and kidney (19%, p less than 0.05) were also found to decrease along with increased zinc, copper, calcium, manganese lead and cadmium in various organs. The magnitude of alteration of a metal was different in different organs. However, liver was found to be the most affected organ. Two weeks of rehabilitation with iron-sufficient diet (390 mg iron/kg diet) normalized these altered levels.

Animals↗
PubMed1989

Heat-stable protein that stimulates acid alpha-glucosidase.

A hot-water extract of bovine spleen and guinea pig liver exhibited the ability to enhance acid alpha-glucosidase activity, with methylumbelliferyl alpha-glucoside, glycogen or maltose as substrate. The level of activator required for maximal stabilization was similar for all three substrates, indicating direct action on the enzyme rather than on substrate. The stimulator was partially purified by chromatography with gel-permeation (apparent Mr 20,000-24,000), ion-exchange and C4 reverse-phase columns. It was retained by a narrow-pore dialysis tubing and destroyed by treatment with Pronase, and is presumably a protein. The stimulating protein protected the enzyme against denaturation by heat or incubation with a buffer of high ionic strength in the absence of substrate. RNA inhibited the enzyme, and the activator protein was able to counteract the effect. Activating material was found in a variety of mouse and rat tissues, as well as human urine.

Animals↗