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Biomedical subjects

R Shukla

Publications and source records attributed to R Shukla.

At least 109 records · Page 6Linked 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

Immunostimulant activity of a novel lipopeptide and its protective action against Leishmania donovani.

Novel lipopeptides 84/201 and 86/450 synthesized in this laboratory stimulated antibody and delayed type hypersensitivity (DTH) response to ovalbumin in guinea pigs. Lipopeptide 86/450 also stimulated antibody and DTH responses in albino mice and enhanced nonspecifically macrophage migration index (MMI), phagocytic activity and incorporation of [14C] glucosamine in peritoneal macrophages of the treated animals. Proliferative response of splenocytes from lipopeptide 86/450 treated animals was significantly higher than that from untreated controls. Peritoneal macrophages from lipopeptide 86/450 treated mice were less susceptible to Leishmania donovani promastigote invasion when co-cultured in vitro. The treated animals on challenge with L. donovani promastigote/amastigote showed 80 to 90% lower intake of infection than the control animals.

Adjuvants, Immunologic↗
PubMed1993

Effect of sodium valproate on serum amylase in epileptics.

Thirty-eight patients of generalised tonic-clonic seizures of epileptics in the age group of 15-30 years were included in this study. Of these 20 were started sodium valproate afresh and 18 already taking it for more than one year prior to inclusion. Serum amylase and serum valproic acid levels were measured in all of them, initially and at every 3 months interval for 9 months. Though no clinical evidence was present, there was significant increase in serum amylase levels in both the groups which has no correlation with dose or serum valproic acid levels.

Adolescent↗
PubMed1993

Health status of pesticide applicators: postural stability assessments.

Postural sway testing was performed on 37 pesticide-exposed workers and 35 nonexposed subjects. All subjects were asymptomatic. When ratios of sway measurements in different test conditions were investigated, total length of sway was significantly different between groups (P = .0001). Weight/height (P = .0006), exposure to pesticides (P = .0215), recent organophosphate exposure (P = .0391), and plasma cholinesterase level (P = .1537) were associated with increased body sway. The pattern of sway performance suggested a proprioceptive impairment, well compensated by visual cues, potentially attributable to pesticide exposure. This finding is of unclear clinical significance because results of neurologic examinations and nerve conduction studies that were reported separately did not show evidence of neuropathy. Postural sway testing is a simple, sensitive, noninvasive, and reproducible technique to evaluate subtle neurologic dysfunction. These findings are preliminary. Further studies are required to validate the findings and, if confirmed, to explore their functional or clinical significance.

Adult↗
PubMed1993

Clinical sequelae of Japanese encephalitis in children.

Over a five and a half year period, virological investigations for Japanese encephalitis (JE) were conducted in children admitted with acute encephalitis like illness to a large city hospital. The diagnosis of Japanese encephalitis was made by viral isolation from cerebrospinal fluid and/or a four-fold or higher rise in haemagglutination inhibiting antibodies in paired sera followed by demonstration of specific IgM antibodies by HI test after treatment with 2-mercapto ethanol. All children surviving the illness were contacted by post and followed up for sequelae. A total of 55 children could be followed up after 12-18 months and 22 of these even after 2 yr. A high rate of major sequelae (45.5%) in the form of frank motor deficits (32.7%), mental retardation (21.8%) and/or convulsions (18.2%) was observed. Neurological deficits were of diverse types and improved even after 2 yr of the illness. Fourteen patients (25.4%) had only minor deficits in the form of scholastic backwardness, behavioural problems and/or subtle neurological signs. Only 16 (29.2%) patients were completely normal on follow up. JE may therefore be an important cause of neurological handicap in this area. Sequelae of the disease were more severe if the initial illness was prolonged (P < 0.001, CI 2.45, 12.64), or associated with focal neurological deficits (P < 0.001, CI 1.97, 7.02).

Child↗
PubMed1992

Pregnane derivatives as pregnancy interceptive agents: efficacy determination on growing trophoblasts (in vitro) and in pregnant hamsters (in vivo).

An in vitro test system was standardized to study potentiality of five hormonally inert pregnane derivatives on growing trophoblasts isolated from ectoplacental cone (EPC) of day 8 hamster embryo. Cells were incubated with different concentrations of respective compounds in surface droplets. The response was determined by analyzing the sequence of changes in cell morphology like attachment, growth, proliferation, differentiation and/or degeneration within 24 or 48 h following seeding. The in vivo efficacy of these compounds was determined in hamster during peri- and immediate post-implantation periods (days 3-8 post coitum). Two compounds 88/583 and 88/585 were found to inhibit not only growth and proliferation of the cells but caused total degeneration within 24 h. The same compounds induced partial to complete resorption of the foetuses in treated animals. Whereas, the other three compounds 88/506, 88/594 and 89/43 that showed lack of comparable potentiality in vitro were found to be equally ineffective in vivo. The results indicate a positive correlationship between in vitro and in vivo activity.

Abortifacient Agents, Steroidal↗
PubMed1992

A dihydropyridine-resistant component in the rat adrenal secretory response to splanchnic nerve stimulation.

A study of the effects of dihydropyridine Ca2+ channel modulators on the release of catecholamines from perfused rat adrenal glands, evoked by electrical stimulation of their splanchnic nerves, is presented. Electrically mediated secretory responses were compared to chemically mediated responses (exogenous acetylcholine, nicotine, or high K+). Intensities of stimuli were selected to produce quantitatively similar secretory responses (between 100 and 200 ng per stimulus). The main finding of the study is that responses to transmural stimulation (300 pulses at 1 or 10 Hz) and to acetylcholine were inhibited only partially (about 50%) by isradipine, an L-type Ca2+ channel blocker. In contrast, responses to high K+ (17.5 mM for 2 min) were highly sensitive to isradipine (IC50 = 8.2 nM). Responses to nicotine were also fully inhibited by this drug. Bay K 8644 (an L-type Ca2+ channel activator) potentiated mildly the secretory responses to electrical stimulation at 10 Hz and to acetylcholine, but increased threefold the responses to K+ and nicotine. It is, therefore, likely that responses mediated by high K+ or nicotinic receptors are triggered by external Ca2+ gaining access to the internal secretory machinery through L-type, dihydropyridine-sensitive voltage-dependent Ca2+ channels. However, in addition to nicotinic receptors, the physiological stimulation of adrenal medulla chromaffin cells through splanchnic nerves has other components, i.e., muscarinic receptor stimulation or the release of cotransmitters such as vasoactive intestinal polypeptide. The poorer sensitivity to dihydropyridines of secretory responses triggered by electrical stimulation of splanchnic nerve terminals or exogenous acetylcholine speaks in favor of alternative Ca2+ pathways, probably some dihydropyridine-resistant Ca2+ channels, in modulating the physiological adrenal catecholamine secretory process.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Rhythmic palatal myoclonus.

We report two cases of rhythmic palatal myoclonus (RPM) first presenting with symptoms unrelated to myoclonus and a possible etiology of encephalitis and the second presenting with ear click and palatal myoclonus. The response to treatment was unsatisfactory in both.

Adult↗
PubMed1991

Effect of digoxin on contractility and symptoms in infants with a large ventricular septal defect.

The effect of digoxin on contractility and symptoms in infants with a large ventricular septal defect (VSD) is controversial. Nineteen infants with symptoms of congestive heart failure due to a VSD were studied with load-independent indexes during 4 study periods: (1) before any medication; (2) while on chronic diuretics; (3) while on both diuretics and digoxin; and (4) while on diuretics alone, to determine if digoxin: (a) increases "contractility" when added to diuretic therapy; and (b) improves symptoms. Symptoms, signs (heart and respiratory rates, and weight gain), shortening fraction, preload (left ventricular end-diastolic dimension), afterload (left ventricular end-systolic wall stress) and contractility were measured at each period. The difference between the measured and predicted velocities of circumferential fiber shortening for the measured left ventricular end-systolic wall stress served as an index of contractility. Eighteen infants also underwent catheterization. Mean pulmonary-to-systemic blood flow ratio was 3:1. When digoxin was added to diuretics, contractility index was significantly greater than in control subjects (0.13 +/- 0.15 vs 0.0 +/- 0.12 circ/s, p = 0.04). When patients were again on diuretics alone (after discontinuation of digoxin), contractility index was no longer different. Symptoms and signs were not significantly improved by either diuretics or digoxin. It is concluded that in infants with a large left-to-right VSD shunt and receiving digoxin and diuretics, contractility index was significantly greater than in control subjects. However, neither diuretics alone nor in combination with digoxin improved symptoms significantly.

Digoxin↗
PubMed1991

Pregnancy interceptive efficacy and biological profile of 3-amino-6,7-dimethoxy-1H-pyrazolo [3,4-b] quinoline (compound 85/83) in rodents.

Administration of compound 85/83 during the peri- and post-implantation period intercepted pregnancy in hamster and guinea pig by parenteral route and in hamster by oral route also. The m.e.d. for hamster and guinea pig was 10 and 20 mg/kg, respectively; lower doses were less effective. Restricting the administration to early post-implantation schedule interrupted pregnancy partially in both species. The compound was, however, ineffective in rat and in the pre-implantation schedule (days 1-4 post-coitum) in hamster. When tested in vitro on growing trophoblasts at 13.8 x 10(-5) M concentration, it prevented growth and caused degeneration of the cells within 24 h; lower concentration (9.2 x 10(-5) M) was less effective. The compound was found to be devoid of estrogenic, antiestrogenic, progestational and antiprogestational properties in conventional bioassays. In hormone competition assays, its relative binding affinity (RBA) to estrogen receptor was negligible (0.002% of estradiol-17 beta), while for uterine cytosol progesterone receptors in rabbit and hamster was 0.06 and 0.08% of progesterone, respectively. The compound 85/83 appears to intercept pregnancy by interfering with development of trophoblast cells.

Administration, Oral↗
PubMed1991

Changes in cardiac function during extracorporeal membrane oxygenation for persistent pulmonary hypertension in the newborn infant.

The effects of extracorporeal membrane oxygenation (ECMO) on cardiac function and its determinants (preload, afterload, contractility, and heart rate) are largely unknown, although some evidence exists that function may decrease. To determine whether cardiac function decreases and what changes in the determinants take place during and after ECMO, we observed 26 newborn infants with persistent pulmonary hypertension. Serial echocardiograms were performed before ECMO, during maximum cardiopulmonary bypass, and after ECMO. Cardiac function was assessed by using standard echographic ejection phase indices (shortening fraction and cardiac output). Heart rate, preload (left ventricular end-diastolic dimension and area), afterload (left ventricular end-systolic wall stress), and contractility (relationship between velocity of circumferential fiber shortening and wall stress) were also measured. Ejection phase indices significantly decreased during ECMO (shortening fraction 33% to 25%, cardiac output 205 to 113 ml/kg/min; p less than 0.05) and returned to normal after ECMO (shortening fraction 26% to 34%, cardiac output 107 to 240 ml/kg/per minute; p less than 0.05). Heart rate also significantly decreased during ECMO (158 to 118 beats/min; p less than 0.05). Preload significantly increased after ECMO (left ventricular end-diastolic dimension 1.4 to 1.6 cm, left ventricular end-diastolic area 1.9 to 2.2 cm2; p less than 0.05). There were no significant changes in contractility and afterload during any study period. We conclude that, although left ventricular ejection phase indices and heart rate decreased during ECMO, these changes were transient and resolved when bypass was terminated. Contractility and afterload did not appear affected by bypass.

Bacterial Infections↗
PubMed1991

Benzo[a]pyrene-induced skin damage and tumor promotion in the mouse.

Epidermal cell kinetics and DNA adduct levels, and skin morphological changes were measured following weekly topical applications for 29 weeks of high (16, 32 and 64 micrograms) benzo[a]pyrene (B[a]P) doses to female ICR/Harlan mice, in order to investigate the relationship of these parameters to the timing, incidence and morphology of the elicited tumors. During the tumor latency period, [3H]thymidine labeling index, mitotic index, epidermal cell stacking, incidence of pyknotic and dark basal keratinocytes and labeled mitoses were periodically measured, as were nuclear area and DNA content. DNA adducts in skin epidermis were measured by an ELISA method over a period of 9 weeks of single weekly applications of 64, 32, 16 or 8 micrograms B[a]P. There was an initial linear increase in DNA adducts with dose in the epidermis but the increase was much less steep above 32 micrograms/week. This did not correlate with the sharp rise in tumor response above the 32 micrograms/week dose rate. Cell kinetic changes in response to the 64 micrograms/week dose reached a plateau in the first few weeks of the tumor latent period. There was little epidermal hyperplasia but an associated dose-dependent increase in [3H]thymidine labeling index, mitotic index and incidence of pyknotic and dark cells. This evidence indicated that B[a]P produced extensive cytotoxicity and cell death with regenerative proliferation under these conditions. Giant keratinocytes occurred in all dose groups. Analysis of a labeled mitosis curve indicated that B[a]P produced a G2/M block. There was a marked inflammatory response in the dermis at all B[a]P doses. Mice were observed weekly for tumor formation. Virtually all of the tumors were papillomas on initial appearance and required an average of 8 weeks to convert to carcinomas. The substantial cell killing and regenerative proliferation, and the correspondence between the dose-response patterns for epidermal damage and tumors, together with the initial appearance of tumors in the benign form, a characteristic of the action of promoting agents, provided evidence that the tissue damage associated with the high dose levels of B[a]P used in this study reflected tumor-promoting activity in this mouse epidermal tumorigenesis model. The implication of the results for mathematical models of tumor formation are discussed.

Animals↗
PubMed1991

Functional aspects of calcium channels of splanchnic neurons and chromaffin cells of the rat adrenal medulla.

Effects of the inorganic calcium channel blockers zinc, manganese, cadmium, and nickel on secretion of catecholamines from the perfused adrenal gland of the rat were investigated. Secretion of catecholamines evoked by splanchnic nerve stimulation (1 and 10 Hz) was not affected by nickel (100 microM), partially blocked (50%) by cadmium (100 microM), and almost completely blocked (90%) by zinc (1 mM) or manganese (2 mM). A combination of nickel and cadmium inhibited nerve stimulation-evoked secretion by 80-90%. Catecholamine secretion evoked by direct stimulation of chromaffin cells by acetylcholine (50 micrograms), nicotine (5 microM), muscarine (50 micrograms), and K+ (17.5 mM) was not blocked by either cadmium, nickel, or their combination. However, zinc and manganese almost abolished nicotine- and K(+)-evoked secretion of catecholamines. None of the above agents had any effect on the secretion evoked by muscarine. Acetylcholine-evoked secretion of catecholamines was only partially reduced (50%) by zinc and manganese. We draw the following conclusions from the above findings: (a) cadmium plus nickel selectively blocks the calcium channels of splanchnic neurons but has no effect on calcium channels of the chromaffin cells; (b) zinc and manganese do not discriminate between calcium channels of neurons and calcium channels of chromaffin cells; (c) partial inhibition of acetylcholine-evoked secretion by inorganic calcium channel blockers is consistent with the idea that activation of nicotinic receptors increases Ca2+ influx, and activation of muscarinic receptors mobilizes intracellularly bound Ca2+, which is not affected by calcium channel blockers.

Acetylcholine↗