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Biomedical subjects

R Sharma

Publications and source records attributed to R Sharma.

At least 469 records · Page 26Linked to original sources
PubMed1992

A longitudinal study of plasma cortisol and depressive symptomatology by random regression analysis.

The authors utilized a random regression model to test the longitudinal relationship between depressive symptomatology and plasma cortisol levels obtained before and after the administration of dexamethasone in 62 affectively ill inpatients. This statistical model for longitudinal studies permits the inclusion of subjects with incomplete data as well as subjects measured at different time points. The most significant relationships were found between decreases in depressive symptoms and decreases in the 8:30 AM predexamethasone and the 4:00 PM postdexamethasone cortisol values. Patients were also classified as responders or nonresponders, and the rate of change in several plasma cortisol measures were separately analyzed for these two groups. No differences in the rate of change in plasma cortisol levels were found between responders and nonresponders. These results suggest that the decreases in cortisol production associated with clinical improvement may be partially explained by a regression toward the mean effect. Some of the possible explanations for these results are discussed.

Adult↗
PubMed1992

Clastogenic effect of fenfluramine in mice bone marrow cells in vivo.

Fenfluramine, an amphetamine derivative used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice using two cytogenetic endpoints for assessing its genotoxic and clastogenic potentials. Concentrations of 0.75, 1.5, 3.0, and 5.0 mg/kg b.w. were administered orally for the study of sister chromatid exchange frequencies and chromosome aberrations (CA). SCE frequencies showed a positive dose response; 1.5 mg/kg being the minimum effective concentration. Fen caused a prolongation of cell cycle at all concentrations. Except for the minimum therapeutic dose (0.75 mg), all other doses (1.5, 3.0, and 5.0 mg) showed a significant increase in the percentage of damaged cells over that of the vehicle control. The degree of clastogenicity was directly proportional to the dosage used and inversely related with the duration of treatment. A gradual reduction of the clastogenic potential was observed after 12 and 24 hr of exposure, indicating that the maximum effect occurs at the middle or late synthetic phase of the cell cycle. This study, probably the first detailed screening of the drug for its genotoxicity, shows that Fen is moderately clastogenic and a DNA damaging agent in vivo.

Administration, Oral↗
PubMed1992

Influence of single and concurrent clofibrate and phenobarbital administration on cytochrome P450-dependent mixed function oxidase activities and peroxisome proliferation in male rat liver.

The influence of both single and concurrent administration of phenobarbital and clofibrate on hepatomegaly, cytochrome P450-dependent mixed function oxidase activities, and peroxisome proliferation in male rat liver have been studied. Both xenobiotics separately increase the liver: body weight ratio and their combined administration results in greater hepatomegaly than either compound alone. Both compounds induce NADPH-cytochrome c(P450) reductase activity and laurate omega- and omega-1-hydroxylase activities, but only phenobarbital induces pentoxyresorufin-O-dealkylase. None of the drug treatments induced microsomal cytochrome b5. Phenobarbital did not cause peroxisome proliferation and inhibited the corresponding clofibrate-dependent proliferation. Taken collectively, our studies have demonstrated that concomitant treatment with phenobarbital and clofibrate are largely permissive with respect to the hepatic mixed function oxidase system but have opposing effects on the phenomenon of peroxisome proliferation in the same tissue.

Animals↗
PubMed1992

t-butylated hydroxytoluene enhances intracellular levels of glutathione and related enzymes of rat lens in vitro organ culture.

Studies were undertaken to investigate the effect of t-butylated hydroxytoluene (BHT) on reduced glutathione (GSH) levels and related enzymes in rat ocular tissues. GSH levels were significantly enhanced when 1 microM BHT was included in the medium of rat lens cultures. BHT had a dose-dependent effect on GSH levels of lenses in cultures. Inclusion of 10 microM BHT in the culture medium resulted in a twofold increase in GSH levels of the lens within 24 hr. Increased gamma-glutamylcysteine synthetase activity concomitant with the increased amount of [35S]methionine incorporation in GSH strongly suggested that BHT caused enhanced levels of GSH in lenses by increasing de novo biosynthesis. A significant increase was also observed in glutathione S-transferase (GST) levels of lenses in culture containing BHT in the medium. Present studies also demonstrated that rat lens expresses only the mu and pi class GST isoenzymes and both these classes of isoenzymes were elevated by BHT. Oral administration of BHT to rats also resulted in enhanced in vivo levels of GSH in lens, retina and cornea. In addition, a significant in vivo increase in the levels of GST, GSH-peroxidase, GSH-reductase, gamma-glutamylcysteine synthetase, and glucose 6-phosphate dehydrogenase was observed in the lens, retina, and cornea of BHT-fed rats.

Animals↗
PubMed1992

Reinfection of lambs with bovine respiratory syncytial virus.

Eight lambs which were experimentally infected with bovine respiratory syncytial virus (RSV) when they were six to eight weeks old were challenged with the same virus seven months later. After reinfection, lambs developed mild clinical disease and the virus was isolated from nasal swabs from three lambs and peripheral blood from two lambs. Reinfection resulted in changes in peripheral blood cell populations. There was an early increase in the number of CD8+ T lymphocytes and B (LCA p220+) lymphocytes but the proportions of CD4+ and CD4-CD8- T lymphocytes were significantly reduced. Peripheral blood mononuclear cells obtained from lambs reinfected with bovine RSV showed significantly higher responses to bovine RSV antigen in vitro than those obtained from control lambs but their responses to the mitogen phytohaemagglutinin were significantly lower than in control lambs. RSV-specific IgG, IgM and IgA levels of serum samples obtained 10 days after challenge were significantly higher than those of serum samples obtained before challenge.

Animals↗
PubMed1992

An initial screen of a series of neuroactive peptides for activity on identified central neurones of Helix aspersa.

1. Intracellular recordings were made from identified neurones in the suboesophageal ganglia of Helix aspersa. Seven neuropeptides were tested for activity and their actions compared with acetylcholine and FMRFamide. 2. Three peptides isolated from nematodes, AF-1, AF-2 and PAN-1 had mainly inhibitory effects with thresholds of around 1 nM. This inhibition was due to an increase in potassium conductance. 3. The molluscan neuropeptides LSSFVRIamide, CARP and ACEP-1 were all active on certain neurones; the first two showed only inhibitory effects while ACEP-1 was mainly excitatory. The thresholds in each case were 0.1-10 microM. When norleucine replaced methionine in CARP, the potency was reduced by at least 100 times. 4. The echinoderm peptide, SALMF-1, only excited neurones but with a very low threshold, around 1.0 fM. 5. There was no obvious correlation between the action of these peptides and either acetylcholine or FMRFamide.

Acetylcholine↗
PubMed1992

The action of a series of glutamic acid analogues on Helix neuronal glutamate receptors.

1. Intracellular recordings were made from identified Helix central neurones, sensitive to L-glutamate. 2. Out of a range of substituted glutamate analogues, only the L- and D-isomers of thio-glutamate possessed clear glutamate-like activity. 3. On neurones excited by L-glutamate, the EC50 values for L-glutamate, gamma-thio-L-glutamate and gamma-thio-D-glutamate were 30 microM, 20 microM and greater than 1 mM, respectively. 4. On neurones inhibited by L-glutamate, the EC50 values for L-glutamate, gamma-thio-L-glutamate and gamma-thio-D-glutamate were 6.0 microM, 0.7 microM and greater than 200 microM, respectively. 5. It is concluded that, unlike the situation with thio derivatives of GABA, thio derivatives of glutamate possess potent glutamate-like activity.

Animals↗
PubMed1992

Proton magnetic resonance spectroscopy of the brain in schizophrenic and affective patients.

Water-suppressed 1H magnetic resonance spectra were recorded from two brain regions of psychiatric patients and normal volunteers. The two regions studied were (a) the basal ganglia structures surrounding the anterior horn of the lateral ventricle and (b) the occipital cortex. N-Acetylaspartate (NAA), phosphocreatine-creatine (PCr-Cr), choline and inositol resonances were seen in both regions. Ratios of metabolite peak integrals to PCr-Cr peak integral were calculated for each spectrum. To control for partial volume effects, comparisons between patients and controls were made only from identical regions i.e. basal ganglia vs basal ganglia, and likewise for occipital cortex. Metabolite ratios from the occipital region of patients were similar to those from the occipital region of normal subjects. Bipolar patients being treated with lithium had elevated NAA/PCr-Cr in the basal ganglia region when compared to normals. These patients also demonstrated elevated choline/PCr-Cr and inositol/PCr-Cr ratios in the basal ganglia region.

Adult↗
PubMed1992

Histochemical characterization of carbohydrate residues during the morphogenesis of gastrointestinal and respiratory systems of Caretta caretta.

The distribution of carbohydrates in the gastrointestinal and respiratory tract of Caretta caretta during embryogenesis and postnatal development was investigated by histological and histochemical techniques and using fluorescein-labelled lectins. The results indicate that the compartmentalised expression of glycoconjugates found in the juvenile Caretta caretta is acquired during development. The occurrence of neutral carbohydrates in cells and extracellular matrix was dependent on the developmental stage of the animal. In general, periodic acid Schiff positive glycoconjugates of the respiratory tract occurred at an earlier stage of development than those from the gastrointestinal system. The lectin binding pattern of both organ systems revealed a more refined pattern of the types of carbohydrates present during development. Wheat germ agglutinin showed the broadest binding pattern, whereas Soy bean agglutinin and phythaemagglutinin were more limited in their binding to tissue structures. The terminal carbohydrates detected in the gastrointestinal and respiratory tract of Caretta caretta were similar to those observed in mammals; this finding emphasises the suitability of Caretta caretta as a model system for amniote development.

Animals↗
PubMed1992

Class-specific antibodies to bovine respiratory syncytial virus in experimentally infected lambs.

Enzyme-linked immunoabsorbent assay (ELISA) was used to titrate virus-specific IgG, IgM and IgA levels in nasal secretions, lung lavage fluids and serum samples sequentially obtained from lambs experimentally infected with bovine respiratory syncytial virus (RSV). Virus-specific IgG and IgM responses were measured by the indirect double antibody sandwich ELISA using anti-bovine RSV monoclonal antibody, as capture antibody, and peroxidase-conjugated anti-sheep IgG and anti-sheep IgM. Virus-specific IgA antibodies were measured by antibody capture assay using anti-sheep IgA (alpha-chain specific) and anti-bovine RSV monoclonal antibodies. Bovine RSV-specific IgM and IgA antibodies were detected in the serum samples within 6 days post-inoculation (p.i.). Virus-specific IgC antibodies appeared in serum samples 4 days later. In nasal secretions, IgA antibodies appeared 7 days p.i. but IgM antibodies were not detected until 12-16 days p.i. In serum samples, IgM titres were predominant for the first 2 weeks p.i. IgC titres becoming predominant thereafter. In nasal secretions and lung lavage fluids, IgA titres were significantly higher than IgM or IgG titres up to 21 days p.i. (0.01).

Animals↗
PubMed1992

Aqueous kinetics of sisomicin sulphate.

Sisomicin sulphate is a new-generation aminoglycoside with a broad spectrum of antimicrobial activity that includes Pseudomonas aeruginosa. It is superior to gentamicin against indole-negative Proteus and some resistant strains of Pseudomonas. The ocular pharmacokinetics of sisomicin have not been explored. We used the agar diffusion technique of microbial assay to determine the aqueous penetration and bioavailability of a subconjunctivally placed standard dose of 20 mg/0.4 ml of sisomicin sulphate in 20 human volunteers undergoing elective cataract surgery. A peak concentration of 16.4 mg/l was found in the aqueous humour 78 minutes after injection, which is 65 times the minimum inhibitory concentration for Pseudomonas. The antibiotic was bioavailable up to 1203 minutes after injection in a concentration of 0.9 mg/l, which easily covers the minimum inhibitory concentration of Staphylococcus aureus and Pseudomonas. The antibiotic disappears from the aqueous humour at the 1434 minute interval (approximately 24 hours). The elimination half-life (t1/2 of sisomicin was determined to be 5.16 hours (K = 0.134/hour) and the aqueous clearance was 2.87 microliters/min.

Aqueous Humor↗
PubMed1992

Evidence of immunosuppression by bovine respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a major respiratory pathogen in human infants and calves. Calves and lambs infected with bovine RSV show mild clinical signs but they are more susceptible to secondary infection with Pasteurella haemolytica. Lambs infected with P. haemolytica 6 days after experimental infection with bovine RSV had significantly greater magnitudes of fever, higher disease and lesion scores and higher mortality rates than those infected with P. haemolytica or bovine RSV alone (P less than 0.05). Experimental infection with bovine RSV is characterized by alterations in lymphocyte subpopulations and down-regulation of some of their functions. For example, the number of T helper cells is significantly reduced during the first week of infection and peripheral blood mononuclear cells obtained from bovine RSV-infected lambs were less responsive to the mitogen phytohaemagglutinin but more susceptible to P. haemolytica cytotoxin than those obtained from control lambs. Infection with bovine RSV does not significantly affect the humoral immune responses of lambs against P. haemolytica cytotoxin. Bovine RSV does not appear to affect the capacity of alveolar macrophages to present antigens in vitro.

Animals↗
PubMed1992

Vasoactive substances induce cytoskeletal changes in cultured rat glomerular epithelial cells.

Angiotensin II (ANG II), atrial natriuretic peptide III (ANP), and sodium nitroprusside (SNP) alter capillary hydraulic conductivity in isolated glomeruli. These agents also affect cyclic nucleotide levels of glomerular epithelial cells (GEC). ANG II increases cAMP, whereas ANP and SNP increase cGMP. The effects of these vasoactive substances on GEC cytoskeleton were tested by incubating cells from primary cultures or an established cell line with each agent. Changes in the cytoskeleton were assessed by staining for F-actin with Bodipy phallacidin and for tubulin with NBD-colcemid. Control cells exhibited short bundles of F-actin or stress fibers near the base of the cells. These were frequently arranged in parallel and occasionally appeared to radiate from the center of the cell. Microtubules were arranged in a fine network throughout the cell with increased density adjacent to the nucleus and within the nucleolus. Incubation of GEC with 10(-7) M ANG II, cholera toxin, or 8Br-cAMP for 2 at 37 degrees C resulted in rearrangement of F-actin into distinct stellate patterns with a decrease in the relative intensity of the peripheral staining, all concurrent with a fivefold increase in intracellular cAMP. The incubation of GEC with 10(-6) M ANP or 10(-7) M SNP for 2 h at 37 degrees C resulted in apparent disassembly of stress fibers, sparse and more diffuse fluorescence, and some increase of fluorescence at the periphery of the cells, all concurrent with a 10-fold increase in intracellular cGMP. Cytochalasin D incubation led to complete disassembly of actin filaments.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗
PubMed1992

Measurement of albumin reflection coefficient with isolated rat glomeruli.

Macromolecular permeability of the glomerular capillary has been inferred from the clearance of endogenous protein or infused macromolecules. Permeability is increased after treatment with polycations as well as after renal injury. It has previously been shown that the capillaries of glomeruli isolated from normal mammals expand or collapse in response to transcapillary albumin gradients and that the magnitude of the changes in capillary volume and in total glomerular volume are directly proportional to the applied oncotic gradients. In the experiments presented here, the volume responses of control glomeruli and of glomeruli treated with protamine (100 to 600 micrograms/mL for up to 60 min) were used to calculate the albumin reflection coefficient, sigma albumin, and the convectional permeability, P convectional albumin = (1 - sigma albumin), of the capillary wall. Sigma albumin for normal glomeruli was about 1 (P convectional albumin = 0); sigma albumin fell to a minimum of 0.2 +/- 0.1 (P convectional albumin = 0.8 +/- 0.1) after incubation with protamine sulfate (600 micrograms/mL) for 30 min. Retraction and fusion of podocyte foot processes and denudation of the underlying matrix was seen on scanning electron micrographs of protamine-treated glomeruli. These results confirm that it is possible to study macromolecular permeability of the glomerular capillary in vitro and to calculate sigma albumin independent of hemodynamic and systemic humoral influences. This method will permit the assessment of the effects of individual mediators of glomerular injury and the study of glomeruli from kidneys affected by experimentally induced or naturally occurring renal diseases.

Albumins↗
PubMed1992

Intradural spinal cavernomas.

Intradural cavernomas are rare vascular lesions of the spinal cord. Four cases of histologically verified cavernomas of the cord are reported, of which two were extramedullary and two were intramedullary in location. Progressive neurological deficit was the presenting feature in three cases while one patient had a rapid evolution of neurological deficits and was found at surgery to have had bled from the extramedullary lesion. All the patients were subjected to surgery and total excision of the cavernomas was carried out in each case. While two patients improved after surgery the other two remained static. The available literature on spinal cord cavernomas is reviewed.

Adult↗
PubMed1992

Immunocytochemical and electrophysiological investigations of central neurones in the parasitic nematode Ascaris suum.

Here we report on preliminary investigations into the morphological, neurochemical and electrophysiological characteristics of central neurones in the parasitic nematode Ascaris suum. The neurones do not display all or none action potentials and apparently have low resting membrane potentials. Neurones have been shown to respond to acetylcholine. Immunoreactivity to a diverse range of neuropeptides has been demonstrated.

Acetylcholine↗
PubMed1992

Low concentrations of neuroactive peptides modulate cholinergic transmission and cyclic AMP levels in Helix aspersa.

1. FMRFamide and the Catch relaxing peptide (CARP) at 0.01-0.1 nM modulate acetylcholine (ACh) induced currents of identified neurons of Helix aspersa, but have no direct effect on membrane current and conductivity. 2. Both FMRFamide and CARP noncompetitively inhibit ACh Cl- responses while having either no effect or increasing ACh Na+/K+ response. 3. The inhibitory effect of FMRFamide and CARP on the ACh Cl- response was eliminated following pretreatment with forskolin (20 microM), an activator of adenylate cyclase. 4. Ascaris peptide (ASC) and a synthetic CARP analogue NORL-CARP, in which the amino acid methionine is replaced by either leucine or norleucine, at 1-10 microM, showed no effect on responses to ACh. 5. FMRFamide and CARP, at 10 nM, increased cAMP levels to 240% and 148% respectively above resting basal cAMP levels, while ASC and NORL-CARP had no significant effective. 6. Our results suggest that FMRFamide and CARP, in low concentrations, modulate ACh responses of Helix neurons, possibly through changes in cAMP levels. They also indicate the importance of the presence of methionine in these neuroactive peptides.

Acetylcholine↗