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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 829 records · Page 46Linked to original sources
PubMed1996

Effect of ranitidine hydrochloride (150 mg twice daily) on the pharmacokinetics of increasing doses of ethanol (0.15, 0.3, 0.6 g kg-1).

1. The interaction of ranitidine hydrochloride (150 mg twice daily for 15 doses) with single doses (0.15, 0.3 and 0.6 g kg-1) of ethanol was investigated in a placebo controlled study in 24 male subjects. Ethanol was given 1 h after a standard breakfast to maximise a drug ethanol effect if there is one. A balanced incomplete block design was used in that each subject received two of the three ethanol doses in the presence or absence of ranitidine. Blood samples (n = 18) were taken for 8 h after dosing and blood ethanol concentrations (BAC) were determined by head space analysis using a validated gas liquid chromatographic method. 2. At the lowest dose of ethanol studied the pharmacokinetic profile was largely first order but at the higher doses the usual zero order kinetics were seen. Using the technique of simultaneous fitting across all doses the Km and Vmax constants were similar and close to literature value of 100 mg l-1 and 200-300 mg h l-1 respectively. 3. Ranitidine, in common with other H2-receptor antagonists tested under the same experimental conditions, caused a small rise in BAC. However this was only evident at the smallest dose of ethanol studied and in common with many other publications, no effects were seen at the higher doses. The mean rise in blood ethanol following the 0.15 g kg-1 dose was 2.6 mg dl-1 (13.3 mg dl-1 for placebo and 15.9 mg dl-1 for ranitidine) and this change is of no clinical relevance.

Adolescent↗
PubMed1996

The glutamate transport inhibitor L-trans-pyrrolidine-2,4-dicarboxylate indirectly evokes NMDA receptor mediated neurotoxicity in rat cortical cultures.

Because of the well-documented importance of glutamate uptake in protecting neurons against glutamate toxicity, we were interested in testing the effects of L-trans-pyrrolidine-2,4-dicarboxylate (PDC) on rat cortical cultures. This compound is a substrate for glutamate transporters and is a potent glutamate transport inhibitor that does not interact significantly with glutamate receptors. Using a 30 min exposure, and assessing neuronal survival after 20-24 h, PDC was neurotoxic in conventional astrocyte-rich cortical cultures, with an EC50 in these cultures of 320 +/- 157 microM. In astrocyte-poor cultures, an EC50 for PDC of 50 +/- 5 microM was determined. The neurotoxicity of PDC in both astrocyte-rich and astrocyte-poor cultures was blocked by the NMDA antagonist MK-801, but not by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). We tested the possibility that the neurotoxicity of PDC might be due to release of excitatory amino acids using several approaches. After pre-loading cells with the non-metabolizable analogue of glutamate, [3H]-D-aspartate, first we demonstrated that PDC caused significant efflux of [3H]-D-aspartate. This effect of PDC was dependent upon extracellular sodium. In contrast with glutamate neurotoxicity, PDC neurotoxicity was inhibited by removal of extracellular sodium. In the presence of 1 mM PDC, sodium caused neurotoxicity with an EC50 of 18 +/- 7.6 mM. Tetrodotoxin had no effect on either PDC neurotoxicity or on PDC-evoked [3H]-D-aspartate release. PDC-evoked release of [3H]-D-aspartate was demonstrable in astrocyte cultures with no neurons present. PDC also evoked release of endogenous glutamate. Finally, the neurotoxicity of PDC was blocked by coincubation with glutamate-pyruvate transaminase plus pyruvate to degrade extracellular glutamate. These results demonstrate the neurotoxicity of PDC, and suggest that the mechanism of this toxicity is the glutamate transporter-dependent accumulation of glutamate in the extracellular space.

Animals↗
PubMed1996

Altered contractility of urinary bladder in diabetic rabbits: relationship to reduced Na+ pump activity.

We studied the effect of alloxan-induced diabetes on Na+ pump activity in isolated rabbit bladder strips. In addition, the effects of diabetes and the Na+ pump inhibitor ouabain on contractions induced by carbachol (CCh) and KCl were studied. In bladder strips from diabetic rabbits, ouabain-sensitive 86Rb+ uptake (a measure of Na+ pump activity) was approximately 50% less compared with strips from normal bladder. Diabetes also reduced the maximum contractions induced by CCh and KCl. Treatment of bladder strips with ouabain alone caused an acute concentration-dependent increase in tone. In contrast, longer incubation with ouabain inhibited CCh- and KCl-induced contractions in normal and diabetic bladders. Furthermore, differences in agonist-mediated contractions observed between normal and diabetic bladders were abolished in the presence of the maximally effective concentration of ouabain (10 microM). The ability of CCh to cause contraction in normal and diabetic rabbit bladders was also significantly inhibited by the Na+ ionophore monensin but not by the Ca2+ ionophore A-23187 or by depolarization with KCl. Monensin also inhibited KCl-induced contractions in normal bladder strips. These results indicate that 1) Na+ pump activity is an important modulator of bladder smooth muscle tone, 2) diabetes diminishes Na+ pump activity and inhibits agonist-induced contractions in bladder, and 3) an increase in intracellular Na+ concentration, secondary to inhibition of bladder smooth muscle Na+ pump activity, is associated with reduced responsiveness to contractile agonists. Diminished Na+ pump activity in diabetes may, in part, contribute to the development of bladder cystopathy.

Animals↗
PubMed1996

Differential stimulation of Na+ pump activity by insulin and nitric oxide in rabbit aorta.

The effect of insulin on Na+ pump activity, measured as ouabain-sensitive (OS) 86Rb uptake, was studied in the rabbit aorta. In the absence of insulin, incubation of endothelium-intact rings for 3 h in a medium containing a high concentration of glucose (44 mM) decreased OS 86Rb uptake by 42% compared with that observed at 5.5 mM glucose. Addition of insulin (0.1-10 microU/ml) increased OS86 86Rb uptake at both glycose concentrations and eliminated the differences between the groups. Insulin also increased OS 86Rb uptake in endothelium-intact and -denuded (ED) rings in the presence of the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine. Removal of the endothelium before the incubations did not diminish the insulin-induced increase in OS 86Rb uptake, which was concentration dependent. The NO donor sodium nitroprusside increased OS 86Rb uptake in ED rings, and its effect and that of insulin were additive. Phorbol 12,13-dibutyrate, a direct activator of protein kinase C (PKC), also increased OS 86Rb uptake in ED rings; however, its effect and that of insulin were not additive. The PKC inhibitor bisindolylmaleimide totally inhibited insulin-induced, but not sodium nitroprusside-induced, increases in OS 86Rb uptake. The results suggest that insulin activates the Na+ pump in the aorta and reverses the inhibition of the pump caused by hyperglycemia. This effect of insulin can occur at physiological concentrations, is independent of endothelium-derived NO, and is presumably mediated by an increase in PKC activity, In contrast, activation of the Na+ pump by NO appears to be independent of PKC.

Animals↗
PubMed1996

Intra-alveolar macrophage-inflammatory peptide 2 induces rapid neutrophil localization in the lung.

Endotoxin-induced lung injury is characterized by neutrophil infiltration of the lungs. The various mechanisms which mediate movement of neutrophils from vascular space to lung interstitium and alveoli remain unclear. Macrophage-inflammatory protein 2 (MIP-2) is a potent chemoattractant for neutrophils and may play a significant role in recruiting neutrophils in acute lung injury in rats. Experiments were performed in male Sprague Dawley rats to: (1) evaluate the kinetics of neutrophil influx in the lung following intraperitoneal administration of Salmonella enteritidis lipopolysaccharide (LPS); (2) determine the expression of transcripts for chemokines and adhesion molecules in the lung following intraperitoneal LPS; and (3) elucidate the effects of intra-alveolar instillation of recombinant rat MIP-2 on neutrophil influx into the lung. Intraperitoneal LPS resulted in an increase in neutrophil sequestration in the lung capillaries of rats as early as 45 min following administration, and there was a parallel increase in lung myeloperoxidase activity. There were also major increases in mRNA in whole-lung homogenates of LPS-treated rats for chemokines MIP-2 and KC (cytokine-induced neutrophil chemoattractant) and adhesion molecules P- and E-selectin at 1 and 2 h following LPS. When recombinant rat MIP-2 was instilled into the alveolar space of rats through a catheter wedged into a bronchus, there was profound neutrophil localization both in the vascular and alveolar space which significantly differed (P < 0.05) from the contralateral lungs of the same animals, and lungs of control animals instilled with control buffer. These observations reveal that MIP-2 is a potent chemoattractant in rat lungs, and suggest that chemoattractants locally released in alveoli can recruit neutrophils to those alveoli. This suggests that alveolar macrophages may play an important role in neutrophil sequestration in sepsis and other inflammatory lung diseases which produce a neutrophilic alveolitis.

Animals↗
PubMed1996

Soft signs and neuropsychological performance in schizophrenia.

OBJECTIVE: Both neuropsychological impairment and neurological soft signs have been documented in at least a subset of patients with schizophrenia. The purpose of the present study was to examine the relationship between soft signs and neuropsychological performance in patients with schizophrenia in order to address the issue of whether soft signs are related to global or more selective cognitive impairment. METHOD: Patients with a DSM-III-R diagnosis of schizophrenia (N=176) were given a standardized neuropsychological battery and underwent a neurological examination. The study group was dichotomized on the basis of presence or absence of neurological soft signs. RESULTS: Patients with neurological soft signs (N=68) demonstrated significantly poorer performance on neuropsychological tasks that assessed timed motor speed and motor coordination (e.g., finger tapping, the Purdue Pegboard task, and part B of the Trail Making Test). These findings continued to be significant even after lifetime medication exposure, extrapyramidal symptoms, and abnormal involuntary movements were used as covariates. CONCLUSIONS: These findings support the notion that soft signs are a manifestation of a localizable behavioral deficit of the systems that are involved in motor speed, coordination, and sequencing and are not indicative of global cognitive impairment. The specific deficit in motor abilities is consistent with the types of neurological soft signs that are most frequently reported and suggests involvement of frontal/subcortical circuitry in schizophrenia.

Adolescent↗
PubMed1996

Polypharmacy among nursing home geriatric Medicaid recipients.

OBJECTIVE: To determine the factors that influence the number of different drugs prescribed to geriatric Medicaid recipients residing in Louisiana's intermediate care facilities I (ICFs I). DESIGN: Observational and cross-sectional with descriptive and analytic components. PARTICIPANTS: All geriatric Medicaid recipients in Louisiana ICFs I during 1994 (n = 19932). METHODS: Relevant data on sex, age, race, geographic region of a recipient, number of prescribing physicians, number of pharmacies used, and the number of drugs prescribed to a recipient were extracted from the state Medicaid files. Frequencies for the seven study variables were calculated. Regression analysis was used to evaluate the influence of the six predictor variables on the number of drugs prescribed. RESULTS: The study population was 73.63% women, 60.07% 81 years of age and older, 70.65% white, 23.21% African-American, 6.14% other races, and 29.83% from predominantly rural north Louisiana. A total of 44.60% of the residents received prescriptions from one physician, 8.41% of the residents were single pharmacy users, and 45.65% were prescribed more than 10 drugs during the year. The regression model accounted for 20.53% of the total variation in the number of drugs prescribed to a recipient. Race, geographic region, number of prescribing physicians, and number of pharmacies used by a recipient influenced the number of drugs prescribed. CONCLUSIONS: To reduce the number of drugs prescribed and polypharmacy among geriatric Medicaid recipients, Louisiana's ICFs I should minimize the number of physicians and pharmacies used in this population.

Aged↗
PubMed1996

Role of animal danders as inhalant allergens in bronchial asthma in India.

The etiological significance of animal danders in Indian patients with nasobronchial disorders has not yet been investigated. In the present study, the role of animal danders in the etiology of bronchial asthma was studied. Extracts of danders from 6 animals along with guinea pig whole pelt were prepared. Intradermal and bronchial provocation tests with these extracts were performed on (i) 68 asthmatics and (ii) 20 nonallergic healthy volunteers. In patients, significant positive skin reactions (2+ to 4+) ranged from 1.4% each with guinea pig whole pelt and ox dander to 8.8% with dog dander extracts. None of the healthy volunteers elicited such a response. On bronchial provocation, 20% and 53.8% of the tests were positive in asthmatics showing 1+ and 2+ skin reactivity, respectively. All the patients as well as controls eliciting negative intradermal responses demonstrated uniformly negative bronchial provocation tests to different dander extracts. Analysis of various clinical features of asthmatics with respect to skin positivity to dander/pelt extract was also carried out. Radioallergosorbent tests (RASTs) were performed to estimate dander-specific IgE levels in the sera of patients showing different grades of skin response to dander extracts of dog, horse, and goat. Sixty percent of sera from the patients showing 2+ to 4+ skin reactivity to various animal dander extracts showed positive RASTs. RAST positivity as well as RAST ratio increased with increase in the intensity of skin response. All the patients with positive cutaneous as well as positive bronchial responses also showed positive RASTs. Similarly, all the patients with positive skin and positive RASTs showed positive bronchoprovocation tests. These results suggested that animal danders play an important role in the etiology of bronchial asthma. Some of the clinical characteristics of asthmatics, such as (i) early age at onset of asthma, (ii) positive family history, and (iii) asthma with associated allergies, have significant bearing on the cutaneous response to various dander extracts.

Adult↗
PubMed1996

The relationship of irritable bowel syndrome (IBS) and panic disorder.

Irritable bowel syndrome (IBS) has been reported in 10 to 22% of adults. Using a semi-structured clinical interview to study the prevalence of irritable bowel syndrome, we compared 41 patients seeking treatment for panic disorder in an outpatient setting to an age- and sex-matched control group of 40 patients who were seeking treatment in a general physician's office for other medical illnesses. The control group did not have any Axis I disorders. IBS was diagnosed according to the criteria of Drossman et al. Nineteen (46.3%) patients with panic disorder met the criteria for IBS, in contrast to one (2.5%) patient in the control group (p < 0.000005). Patients with panic disorder and IBS were more likely to report symptoms of back pain as well as a personal history of bowel disease compared to patients with panic disorder but without IBS. IBS is fairly common in patients seeking treatment for panic disorder. Prospective studies should address the question whether treatment of panic disorder leads to an improvement or resolution of the symptoms of IBS.

Adult↗
PubMed1996

Improvement of debilitating tardive dyskinesia with risperidone.

This case vignette illustrates dramatic improvement of tardive dyskinesia (TD) in an elderly female with a long history of neuroleptic exposure, following treatment with low-dose risperidone. The TD continued to be in remission at 1-year follow-up. This observation calls for well-designed randomized studies to evaluate the efficacy of risperidone in treating TD.

Aged↗
PubMed1996

Unmonitored apexification of wide open apex in nonvital, immature incisor: a case report.

Apexification is the accepted procedure to form an apical stop in nonvital teeth with incomplete root formation. A case is presented in which apexification with calcium hydroxide was performed on erupting maxillary central incisor in 7-year-old female child with immature root (half root) formation and wide open apex. Although it was an induced procedure, but unmonitored. Patient did not return until 18 months after his first visit. Treatment then concluded with gutta percha obturation against firm "cap shaped" apical stop.

Calcium Hydroxide↗