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Biomedical subjects

A Bhardwaj

Publications and source records attributed to A Bhardwaj.

At least 55 records · Page 3Linked to original sources
PubMed1998

Potent sigma1-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine modulates basal and N-methyl-D-aspartate-evoked nitric oxide production in vivo.

BACKGROUND AND PURPOSE: final sigma-Receptor ligands ameliorate ischemic neuronal injury and modulate neuronal responses to N-methyl-D-aspartate (NMDA) receptor stimulation. Because NMDA-evoked synthesis of nitric oxide (NO) may play an important role in excitotoxic-mediated injury, we tested the hypothesis that final sigma-receptor ligands attenuate basal and NMDA-evoked NO production in the striatum in vivo. METHODS: Microdialysis probes were placed bilaterally into the striatum of halothane-anesthetized adult Wistar rats. Rats were divided into 7 treatment groups and perfused with artificial cerebrospinal fluid (aCSF) containing 3 micromol/L [14C]L-arginine for 2 to 3 hours followed by NMDA in various combinations with the following drugs: L-nitroarginine (L-NNA); the final sigma1-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP); the selective final sigma1-receptor antagonist 1-(cyclopropylmethyl)-4-(2'-oxoethyl) piperidine hydrobromide (DuP 734); and the noncompetitive NMDA receptor blocker MK-801 in aCSF. Right-left differences between [14C]L-citrulline in the effluent from rats treated with different drug combinations were assumed to reflect differences in NO production. RESULTS: After a 3-hour loading period with [14C]L-arginine, addition of 1 mmol/L NMDA increased [14C]L-citrulline recovery compared with aCSF alone. This NMDA-evoked increase was inhibited by 1 mmol/L of L-NNA and PPBP. Perfusion of 1 mmol/L of the final sigma1-receptor antagonist DuP 734 with 1 mmol/L PPBP augmented NMDA-evoked [14C]L-citrulline recovery compared with perfusion with PPBP and NMDA. MK-801 attenuated the basal as well as NMDA-evoked [14C]L-citrulline recovery. PPBP did not cause any further attenuation in the basal and NMDA-evoked [14C]L-citrulline recovery in the presence of MK-801. CONCLUSIONS: These data indicate that a final sigma1-receptor ligand attenuates basal as well as NMDA-evoked NO production. Because the attenuated NO production was reversed by DuP 734, PPBP appears to act as an agonist at the final sigma1-receptor. Attenuated NO production by final sigma1-receptor agonists provides one possible mechanism for focal ischemic neuroprotection.

Animals↗
PubMed1997

Characterization of metabotropic glutamate receptor-mediated nitric oxide production in vivo.

We tested the hypothesis that stimulation of metabotropic glutamate receptors (mGluRs) increases nitric oxide (NO) production in the hippocampus in vivo. Microdialysis probes were placed bilaterally into the CA3 region of the hippocampus of adult Sprague-Dawley rats under pentobarbital anesthesia. Probes were perfused for 5 h with artificial cerebrospinal fluid (CSF) containing 3 microM [14C]-L-arginine. Recovery of [14C]-L-citrulline in the effluent was used as a marker of NO production. In nine groups of rats, increases in [14C]-L-citrulline recovery were compared between right- and left-sided probes perfused with various combinations of the selective mGluR agonist, trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD); the mGluR antagonist, (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG); the NO synthase inhibitor, N-nitro-L-arginine (LNNA); the ryanodine sensitive calcium-release channel inhibitor dantrolene, the non-N-methyl-D-aspartate (NMDA); receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK-801); and the Na+ channel blocker, tetrodotoxin. Recovery of [14C]-L-citrulline during perfusion with artificial CSF progressively increased to 90 +/- 21 fmol/min (+/-SD) over 5 h. Perfusion in the contralateral hippocampus with 1 mM ACPD augmented [14C]-L-citrulline recovery to 250 +/- 81 fmol/min. Perfusion of 1 mM nitroarginine + ACPD inhibited [14C]-L-citrulline recovery compared to that with ACPD alone. Perfusion with 1 mM MCPG + ACPD attenuated ACPD enhanced [14C]-L-citrulline recovery. Perfusion of 1 mM dantrolene + ACPD inhibited the ACPD-evoked increase in [14C]-L-citrulline recovery. Perfusion of 1 mM MCPG or dantrolene without ACPD did not decrease [14C]-L-citrulline recovery as compared to CSF alone. ACPD-enhanced [14C]-L-citrulline recovery was not attenuated by CNQX, MK-801, or tetrodotoxin (TTX). Using an indirect method of assessing NO production in vivo, these data demonstrate that mGluR stimulation enhances NO production in rat hippocampus. Inhibition with dantrolene suggests that calcium-induced calcium release amplifies the inositol triphosphate-mediated calcium signal associated with mGluR stimulation, thereby resulting in augmented calcium-dependent NO production.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

Neither L-arginine nor L-NAME affects neurological outcome after global ischemia in cats.

BACKGROUND AND PURPOSE: We attempted to determine whether N-nitro-L-arginine methyl ester (L-NAME) would improve neurological outcome and whether L-arginine (L-ARG) would worsen neurological outcome after transient global ischemia. METHODS: Halothane-anesthetized cats (n = 6 for each group) were treated with intravenous saline, L-NAME (5 mg/kg or 10 mg/kg), or L-arginine (300 mg/kg) 30 minutes before 10 minutes of ischemia (temporary ligation of the left subclavian and brachiocephalic arteries with hemorrhagic hypotension to 50 mm Hg). At 30 minutes of reperfusion, cats in the L-ARG group were administered an additional 300 mg/kg dose of intravenous L-arginine. RESULTS: Time (mean +/- SE) to isoelectric electroencephalography was similar among groups (saline, 26 +/- 11 seconds; L-NAME-5, 15 +/- 4 seconds; L-NAME-10, 36 +/- 27 seconds; and L-ARG, 22 +/- 7 seconds). At 72 hours, reperfusion pathological injury was severe and neurological deficit score (mean, range) was similar among groups (saline, 38[11 to 70]; L-NAME-5, 52 [40 to 73]; L-NAME-10, 47 [23 to 70]; and L-ARG, 40 [0 to 79]). CONCLUSIONS: Nitric oxide is not important in the mechanism of brain injury after global ischemia in cats.

Animals↗
PubMed1997

Characterization of ionotropic glutamate receptor-mediated nitric oxide production in vivo in rats.

BACKGROUND AND PURPOSE: Glutamate receptor activation can stimulate nitric oxide (NO) production and possibly play a role in long-term potentiation and excitotoxic-mediated injury. We studied the differential effect of agonist-induced activation of ion channel-linked N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subtypes on NO production in vivo in rat hippocampus. We also studied whether dantrolene, a ryanodine calcium channel inhibitor previously shown to attenuate metabotropic glutamate receptor stimulation of NO production, also attenuated ionotropic glutamate receptor-mediated stimulation of NO production. METHODS: Microdialysis probes were placed bilaterally into the CA3 region of the hippocampus of pentobarbital-anesthetized adult Sprague-Dawley rats and were perfused for 5 hours with artificial cerebrospinal fluid (CSF) containing 3 mumol/L [14C]L-arginine. Recovery of [14C]L-citrulline in the effluent was used as a marker of NO production. In 13 groups of rats, increases in [14C]L-citrulline recovery were compared between right- and left-sided probes perfused with no additional drugs versus combinations of NMDA, AMPA, the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the non-competitive glutamate receptor blocker MK-801, the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and dantrolene. RESULTS: Recovery of [14C]L-citrulline during perfusion with artificial CSF progressively increased to 272 +/- 73 fmol/min (+/-SEM) over 5 hours. Contralateral perfusion with 1 mmol/L L-NAME inhibited [14C]L-citrulline recovery. Perfusion with 1 mmol/L MK-801 or 1 mmol/L CNQX reduced [14C]L-citrulline recovery compared with contralateral perfusion with CSF alone. Perfusion with 1 mmol/L NMDA enhanced [14C]L-citrulline recovery, and this enhancement was attenuated by L-NAME, MK-801, and CNQX but not by dantrolene. Perfusion with 1 mmol/L AMPA enhanced [14C]L-citrulline recovery, and this enhancement was also attenuated by L-NAME, MK-801, and CNQX but not by dantrolene. CONCLUSIONS: Through an indirect method of assessing NO production in vivo, results with MK-801 and CNQX indicate that NMDA and AMPA receptor activation contribute to basal NO production in the rat hippocampus. Enhanced NO production with NMDA and AMPA agonists appears to involve a complex neuronal interaction because the effect of NMDA was attenuated by both MK-801 and CNQX and because the effect of AMPA was attenuated by both CNQX and MK-801. In contrast to metabotropic glutamate receptor activation, release of calcium from intracellular ryanodine calcium channels does not appear to be a prominent mediator of ionotropic glutamate receptor stimulation of NO production.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

Critical care monitoring for cerebrovascular disease.

Frequent or continuous monitoring of crucial variables in patients with cerebrovascular disease allows the intensive care team to identify progression of the pathophysiologic mechanisms involved, intervene to halt or reverse this progression, and identify the response to treatment in order to modify the intervention if necessary. Central nervous system physiologic monitoring modalities include: a) the clinically-apparent function, b) physical and mechanical variables, c) circulation or perfusion, d) bioelectrical measures, and e) biochemical measures. The neurologic examination of the critically ill patient is an indispensable monitoring tool in the ICU. Patterns of neurologic signs and the trend of the examination, whether worsening or improving, are the most important factors to follow because there is no single sign or symptom which forecasts impending disaster. Intracranial pressure monitoring is applicable to all subsets of cerebrovascular disease, providing information about cerebral perfusion pressure and risk of secondary cerebral injury. Cerebral blood flow is not easily quantified in the ICU, but transcranial Doppler sonography is a reliable bedside technique that can be used for intermittent or continuous monitoring. Neurophysiologic monitoring with electroencephalography (EEG) and evoked potential (EP) testing can be used as a supplement to the neurologic exam and other diagnostic studies. EEG and EP can provide an early indication of clinically relevant change due to evolving disease or in response to therapy, which is especially helpful when the neurologic examination is limited due to severe coma, therapeutic barbiturate coma, or neuromuscular blockade. Neurometabolic monitoring in cerebrovascular disease with microdialysis is a promising technique that may be able to identify markers of cellular energy state or excitotoxicity in carefully selected areas of the brain.

Cerebrovascular Circulation↗
PubMed1996

Stimulus-evoked sinus arrest in severe Guillain-Barré syndrome: a case report.

Guillain-Barré syndrome, or acute inflammatory demyelinating polyradiculoneuropathy, is frequently accompanied by cardiac and autonomic dysfunction. We report a patient in whom minor autonomic stimulation by upgaze, tongue protrusion, opening the mouth against resistance, eyeball pressure, and carotid sinus massage produced asystole. The frequency of potentially lethal dysrhythmias in Guillain-Barré syndrome, coupled with the relative ease of cardiac pacing, makes recognition of these phenomena of utmost importance in affected patients.

Adult↗
PubMed1995

Selective labeling of membrane protein sulfhydryl groups with methanethiosulfonate spin label.

Electron paramagnetic resonance was used to characterize the first use of a thio-specific spin label in membranes. Procedures for use of the spin-label, 1-oxyl-2,2,5,5-tetramethyl-delta 3-pyrroline-3-methyl (methanethiosulfonate MTS) covalently attached to membrane proteins in human erythrocyte membranes are reported. The major findings are: (1) MTS was found to be thiol-specific in membranes as it is for soluble proteins; (2) MTS labels ghost proteins in as few as 30 min at room temperature, providing a distinct advantage when sensitive or fragile membranes are to be used; (3) the distribution of the spin label suggests that the major cytoskeletal protein, spectrin, and the major transmembrane protein (Band 3) incorporate the highest percentage of spin label. This procedure expands the tools with which the researcher can investigate the physical state of membrane proteins and its alteration upon interaction of membrane perturbants or in pathological conditions.

Acetylcholinesterase↗
PubMed1995

Consequences of cometary aurora on the carbon chemistry at comet P/Halley.

Various experimental data acquired during the visit of Halley's comet in 1986 have shown that the amount of carbon produced due to photodissociation of parent carbon bearing species is not ample enough to explain the observations. This requires the presence of an additional source of atomic carbon. One of the possible source could be auroral-type activities resulting from the precipitation of high-energy "auroral electrons" of solar wind origin, the evidence of which have been inferred from many observations at comet Halley. We have developed a coupled chemistry-transport model to study the role of auroral and photoelectron impact as well as of chemistry on the modelling of carbon in the inner coma (< or = 10(4) km) of comet Halley. Our study suggest that electron impact dissociation of CO is the major source of carbon production in the inner coma, not the recombination of CO+ as suggested by earlier workers, while transport is the main loss process.

Carbon↗
PubMed1995

A questionnaire to evaluate disability in osteoporotic patients with vertebral compression fractures.

BACKGROUND: Few studies have reported on the functional disability due to vertebral compression factors in osteoporosis. The Osteoporosis Functional Disability Questionnaire (OFDQ) was developed to assess disability in patients with osteoporosis and back pain due to vertebral fractures. The domains of the OFDQ include: quantitative indices of pain, a standard 20-item depression scale, 26 items relating to functional abilities, a scale of social activities, and confidence in the ability of prescribed osteoporosis treatment to reverse disability. METHODS: Reliability of the OFDQ was assessed using test-retest and internal consistency methods. Criterion validity was demonstrated by correlating disability against radiographic evidence of vertebral fractures. Construct validity was demonstrated through comparisons of 81 patients with osteoporosis and fractures to 37 healthy age-matched controls. Additional evidence was found in comparing 45 of the 81 cases who were actively engaged in an exercise program with 36 cases who were sedentary. RESULTS: The test-retest reliabilities ranged from .76 to .93, with internal consistencies from .57 to .96. The OFDQ correlated significantly with relevant spinal pathology, and showed significant improvements in activities of daily living and socialization when active exercisers were compared to inactive patients with osteoporosis. CONCLUSIONS: The OFDQ is a reliable instrument which correlates well with objective measures of osteoporotic spinal damage. It is also sensitive to changes in disability brought about by participation in our aerobic exercise program. The OFDQ may be a useful adjunct to measuring outcomes in other osteoporotic treatment protocols.

Activities of Daily Living↗
PubMed1995

Adenosine modulates N-methyl-D-aspartate-stimulated hippocampal nitric oxide production in vivo.

BACKGROUND AND PURPOSE: Adenosine acts presynaptically to inhibit release of excitatory amino acids (EAAs) and is thus considered to be neuroprotective. Because EAA-stimulated synthesis of nitric oxide (NO) may play an important role in long-term potentiation and excitotoxic-mediated injury, we tested the hypotheses that adenosine agonists attenuate basal and EAA-induced NO production in the hippocampus in vivo and that adenosine A1 receptors mediate this response. METHODS: Microdialysis probes were placed bilaterally into the CA3 region of the hippocampus of adult Sprague-Dawley rats under pentobarbital anesthesia. Probes were perfused for 5 hours with artificial cerebrospinal fluid containing 3 mumol/L [14C]L-arginine. Recovery of [14C]L-citrulline in the effluent was used as a marker of NO production. In 10 groups of rats, time-dependent increases in [14C]L-citrulline recovery were compared between right- and left-sided probes perfused with various combinations of N-methyl-D-aspartate (NMDA), adenosine agonists, adenosine antagonists, and the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). RESULTS: Recovery of [14C]L-citrulline during perfusion with artificial cerebrospinal fluid progressively increased to 141 +/- 27 fmol/min (+/- SEM) over 5 hours. Contralateral perfusion with 1 mmol/L NMDA augmented [14C]L-citrulline recovery to 317 +/- 62 fmol/min. Perfusion of 1 mmol/L L-NAME with NMDA inhibited [14C]L-citrulline recovery compared with NMDA alone. Perfusion with 0.1 mmol/L 2-chloroadenosine attenuated basal as well as NMDA-enhanced [14C]L-citrulline recovery. This action of 2-chloroadenosine was reversed by infusion of 0.1 mmol/L 8-cyclopentyl-1,3-dipropylxanthine, a specific A1 receptor antagonist. Infusion of 0.1 mmol/L (2S)-N6-[2-endo-norboryl]adenosine, a specific A1 receptor agonist, also attenuated the 0.1 mmol/L and 1 mmol/L NMDA-enhanced [14C]L-citrulline recovery. CONCLUSIONS: Using an indirect method of assessing NO production in vivo, these data are consistent with in vitro results showing that NMDA receptor stimulation enhances NO production. Furthermore, we conclude that stimulation of A1 receptors can attenuate the basal as well as NMDA-induced production of NO. Because NMDA receptor stimulation amplifies glutamate release, our data are consistent with presynaptic A1 receptor-mediated inhibition of EAA release and consequent downregulation of NO production.

2-Chloroadenosine↗
PubMed1995

Ifosfamide-induced nonconvulsive status epilepticus.

OBJECTIVE: To describe a patient with ifosfamide-induced nonconvulsive status epilepticus. CASE SUMMARY: A 71-year-old woman with a history of malignant mixed mesodermal tumor involving the uterus, cervix, and vagina was admitted because of local recurrence. After receiving 3 doses of ifosfamide/mesna, she was found to be unresponsive. Physical examination and laboratory data revealed no significant changes. An electroencephalogram was consistent with the diagnosis of nonconvulsive status epilepticus. The patient's mental status returned to baseline after treatment with intravenous phenytoin and discontinuation of ifosfamide therapy. DISCUSSION: Central nervous system (CNS) toxicity has been described with ifosfamide, with most cases reported in the pediatric population. Among CNS toxicities, generalized tonic-clonic seizures have been reported in both children and adults. This represents the first report of nonconvulsive status epilepticus induced by ifosfamide. CONCLUSIONS: There was a temporal relationship between the onset of nonconvulsive status epilepticus and initiation of ifosfamide infusion. No other identifiable factor contributed to the unresponsiveness.

Aged↗
PubMed1994

Primary care physicians and the cost of drugs: a study of prescribing practices based on recognition and information sources.

Rapidly inflating health care costs limit patient care, and prescription drug costs constitute a major component of this expenditure. This study examines attitudes toward and knowledge of prescription drug costs of primary care physicians. Access to information about drug costs and implications for medical education are also explored. A questionnaire survey was sent to 137 internists, family, and general practitioners, randomly selected from a list provided by the Ohio State Medical Board. The questionnaire elicited information on demographic characteristics of respondents, influence of drug costs on prescribing habits, actual knowledge of prices of the 20 most commonly used drugs, attitudes toward generic drug use, sources of information on costs, and desire for emphasis on drug costs in medical education. Responding physicians indicated consideration of drug costs in therapeutic decisions, but lacked information and often made inaccurate assumptions about costs of drugs prescribed. Most felt they could provide better service and reduce costs if information about drug prices was readily available. Most agreed medical education should address drug costs. Drug cost estimates varied widely; correct responses ranged from 9% to 53%. No statistically significant pattern emerged regarding demographics of respondents or information sources used. Primary care physicians consider drug costs important and realize that cost-effective prescribing may lower health care costs. However, because physician knowledge of drug costs is inadequate and costs are not readily accessible, implications for better physician education and improved abscess are substantial.

Drug Costs↗
PubMed1991

Serum lipase levels in chronic alcoholics.

Using an elevated serum amylase level to diagnose acute pancreatitis in an alcoholic patient with abdominal pain may not be appropriate, because hyperamylesemia is common in asymptomatic alcoholics without acute pancreatitis. To determine whether serum lipase also suffers from the same drawback, we undertook a prospective study involving 202 asymptomatic alcoholics admitted to the detoxification unit of our hospital. Sixty-six of the 202 patients had serum lipase levels above the normal range (0-213 U/L). Of these 66, 55 (83%) had levels that were one to two times normal, while 11 patients had levels ranging between two and three times normal. No patient exceeded three times the normal level. This background information is important in the interpretation of serum lipase levels in alcoholic patients with abdominal pain.

Acute Disease↗
PubMed1990

Ischemia in the dorsal hippocampus is associated with acute extracellular release of dopamine and norepinephrine.

The cerebral dialysis technique was employed to monitor extracellular concentrations of dopamine (DA), norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the dorsal hippocampus of gerbils before and after cerebral ischemia induced by carotid artery occlusion. Extracellular concentrations of DA and NE in the dorsal hippocampus increased from baseline levels of less than 35 fmol/collection interval to 180 and 200 fmol/collection, respectively, within 36 minutes following carotid artery ligation (n = 8 animals). Extracellular concentrations of the DA metabolites, DOPAC and HVA, did not change significantly following carotid artery ligation. These data demonstrate that ischemia in the dorsal hippocampus is associated with a mared release of DA and NE. This release may contribute to the selective vulnerability of the dorsal hippocampus to neuronal damage during ischemia.

Animals↗