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Biomedical subjects

A Kulkarni

Publications and source records attributed to A Kulkarni.

18 recordsLinked to original sources
PubMed1992

A novel model to assess developmental toxicity of dihaloalkanes in humans: bioactivation of 1,2-dibromoethane by the isozymes of human fetal liver glutathione S-transferase.

Glutathione S-transferase (GST) isozymes from human fetal liver (16-18 weeks gestation) were purified by affinity chromatography followed by ion-exchange high performance liquid chromatography (HPLC). The purified isozymes were used to investigate toxicity of 1,2-dibromoethane(EDB) in an in vitro model of rat embryos in culture as passive targets. At least five isozymes of GST were found in the human fetal liver. Two anionic forms [pI values 5.5 (P-2) and 4.5 (P-3)] and one basic form [pI value 8.7 (P-6)] were clearly separated. The presence of two near-neutral forms was also identified. All the isozymes of the human fetal liver GSTs tested metabolized EDB (specific activities were 2.1, 7.0, and 2.0 mumol of GSH consumed/min/mg protein for P-2, P-3, and P-6 isozymes, respectively). Covalent binding of EDB to DNA and protein was 144% and 212% higher, respectively, with the P-3 anionic isozyme when compared to the P-6 basic isozyme of GST. No covalent binding to either protein or DNA was observed with the P-2 isozyme. EDB bioactivation by the GST isozyme P-3 (15 units; 1 unit = 1 nmol of GSH consumed/min) resulted in toxicity to cultured rat embryos. Significant reductions of crown rump length, yolk sac diameter, and the composite score of morphological parameters (Brown and Fabro method) were observed. The central nervous system, optic and olfactory systems, and the hind limb were most significantly affected. The results of this investigation suggest that EDB may be classified as a suspected developmental toxicant in humans.

Animals↗
PubMed1992

Rat hepatic glutathione S-transferase-mediated embryotoxic bioactivation of ethylene dibromide.

The embryotoxic effects of ethylene dibromide (EDB) bioactivation, mediated by purified rat liver glutathione S-transferases (GST), were investigated using rat embryos in culture. Significant EDB metabolism was observed with rat liver GST purified by affinity chromatography (specific activity of 188 +/- 11.3 nmol/min/mg protein). The reaction was enzymatic in nature and the conjugation rate was proportional to the concentration of EDB (up to 0.75 mM) and the enzyme present in the reaction medium. EDB activation by 100 units (1 unit = 1 nmol of glutathione consumed per min) of purified rat liver GST caused a significant reduction in general development as measured by crown-rump length, yolk sac diameter, somite number, and the composite score for different morphological parameters (Brown and Fabro methodology). Structures most significantly affected were the central nervous and olfactory systems as well as the yolk sac circulation and allantois. The results of this study clearly indicate that under in vitro conditions, bioactivation of EDB by GST can lead to embryotoxicity.

Animals↗
PubMed1992

Inhibition of human term placental and fetal liver glutathione-S-transferases by fatty acids and fatty acid esters.

Glutathione-S-transferase (GST) activity from human term placenta and human fetal liver towards 1-chloro-2,4-dinitrobenzene as the second substrate was significantly inhibited by the saturated fatty acids, stearic (SA) and palmitic (PA) acids and fatty acid esters, ascorbyl stearate (Asc-S) and ascorbyl palmitate (Asc-P). The nature of inhibition of human placental GST was competitive towards CDNB with Ki values of 3.1, 10.0, 13.5 and 18.5 microM for Asc-S, Asc-P, PA and SA, respectively. The inhibitory effect of Asc-S on human term placental GST was reversible. I50 values for Asc-S, Asc-P, SA and PA were 15, 45, 83 and 78 microM, respectively, for partially purified human fetal liver GSTs and 21, 6, 88 and 117 microM, respectively, for partially pure rat liver GSTs. The evidence suggests that Asc-S, Asc-P, SA and PA are potent inhibitors especially of the pi-class of GST.

Animals↗
PubMed1991

Human fetal tracheal smooth muscle produces spontaneous electromechanical oscillations that are Ca2+ dependent and cholinergically potentiated.

Although the electromechanical properties of, and the cholinergic innervation to adult airway smooth muscle has been extensively studied, the little information is available on developing human airway smooth muscle, and the role of cholinergic mechanisms in regulating bronchomotor tone. A total of 7 tracheae obtained at the time of elective abortion and between 12-16 weeks of gestational development were used in this study. For each trachea, muscle tension and transmembrane potentials were measured simultaneously using an isometric force transducer and a standard 3-M KCl-filled glass microelectrode. All preparations showed spontaneous electrical oscillations approximately 8 mV in amplitude, which could be increased using electrical field stimulation, or exogenously applied acetylcholine. This was accompanied by a corresponding increase in muscle tension. Atropine (0.1 microM) abolished this potentiation, but had no apparent effect on the oscillations. Slow-wave activity was completely suppressed in the absence of extracellular Ca2+, or in the presence of verapamil (1 microM) or quinidine (1 microM). It appears that these oscillations of membrane potential may be potentiated by cholinergic mechanisms which regulate cell membrane ion channels, thus serving to change excitability in a rhythmic manner.

Acetylcholine↗
PubMed1990

Azelastine and desmethylazelastine suppress acetylcholine-induced contraction and depolarization in human airway smooth muscle.

We examined the effects of a new anti-asthmatic drug, azelastine, and its principal metabolite, desmethylazelastine, on the in vitro electromechanical response of human airway smooth muscle during cholinergic stimulation. Membrane potential and isometric force were simultaneously measured using an intracellular microelectrode and a microforce transducer. Desmethylazelastine significantly suppressed acetylcholine-induced depolarization and contraction at 10(-6) M, whereas azelastine produced similar results at 10(-4) M, suggesting that the metabolite may be the principal compound acting upon the airway smooth muscle cell.

Acetylcholine↗
PubMed1990

Occult spinal dysraphism: clinical and urodynamic outcome after division of the filum terminale.

A highly select group of 31 patients presenting with urinary incontinence failed to respond to conservative management and were found to have unstable bladders and spina bifida occulta. After thorough evaluation they were suspected of having neurogenic bladder dysfunction possibly due to a tethered cord. Following division of the filum terminale daytime incontinence resolved in 72%, urodynamic detrusor hyperreflexia disappeared in 59% and bladder compliance improved in 66% of the patients. The operation was well tolerated and did not result in any neurological complications. The clinical, radiological and urodynamic characteristics of these patients before and after treatment are reported.

Adolescent↗
PubMed1989

Hemodynamic effects of dilevalol in patients with systemic hypertension and left ventricular dysfunction.

Hemodynamic and left ventricular function parameters were measured in patients with mild to moderate hypertension and compromised left ventricular function who were given dilevalol, an antihypertensive agent with selective beta 2-agonism and nonselective beta-antagonist activity. After a 2- to 3-week placebo washout period, 9 patients were given dilevalol titrated upward from 100 to 600 mg twice daily over a 7-week period to achieve a supine diastolic blood pressure of less than 90 mm Hg with a decrease of greater than or equal to 10 mm Hg from baseline. Multigated radionuclide ventriculography and systolic and diastolic time intervals were performed after the pretreatment placebo washout, at the end of 2 weeks' maintenance dosing, and after a 7- to 10-day post-treatment discontinuation and placebo washout period. At an average daily dose of dilevalol, 444 mg, heart rate at rest decreased significantly (p less than 0.01) during treatment and increased during post-treatment placebo. Systolic and diastolic blood pressures at rest decreased significantly (p less than 0.01) during treatment and increased during post-treatment placebo. At maximal exercise, changes in blood pressure and heart rate were significantly blunted (p less than 0.05) during treatment. Ejection fraction at rest increased significantly (p less than 0.01) during treatment, with no significant change occurring during exercise, and decreased during post-treatment placebo. Preejection period decreased significantly during treatment (p less than 0.005) and increased during post-treatment placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Suppression of opiate withdrawal by cyclosporin A and dietary modification.

It has been demonstrated in a murine model that a defined diet (Purina Basal Diet 5755) has immunosuppressive effects similar to cyclosporin A (CsA). It was also shown that CsA treatment in opiate dependent rats can attenuate the severity of opiate withdrawal. In this study, an opiate dependence model was established in Balb/c mice to assess the effects of the 5755 diet and CsA on morphine withdrawal - a CNS mediated phenomenon. Three groups of mice were used; a chow-fed control group (Purina 5008), a chow fed CsA treated group, and a group maintained on the 5755 diet. Morphine dependence was established by subcutaneous implantation of a 100 mg morphine base pellet under ether anesthesia. Seventy-two hours after pellet implantation, withdrawal was precipitated by a single injection of the opiate antagonist naloxone (2 mg/kg ip). Two indicators of withdrawal were assessed; jumping and diarrhea. The data demonstrated that both CsA and the 5755 diet resulted in significant attenuation of withdrawal symptoms with the 5755 diet being the most effective of the two. These findings suggest that immune modulation elicited by the 5755 diet and CsA treatment has a direct impact on the CNS opioid function.

Animals↗
PubMed1989

A moderate concentration of ethanol alters cellular membrane potentials and decreases contractile force of human fetal heart.

The effects of ethanol, although well studied in the adult myocardium, have been little studied in fetal tissue. Experiments in pregnant animals suggest that ethanol compromises fetal myocardial performance, in utero; however, the physiological mechanism(s) remains obscure. The present report examines, in vitro, the effects of a moderate concentration of ethanol (20 mM) directly on cell membrane potentials and contractility of human fetal left ventricle as determined using intracellular microelectrodes and microforce transducers. We observed significant decreases in action potential amplitude, upstroke velocity, duration of repolarization, and the force of contractions. These effects were reversible. As ethanol crosses the placenta, our findings suggest that moderate concentrations of ethanol, as occur during 'social drinking', may temporarily compromise fetal myocardial performance in utero.

Action Potentials↗
PubMed1988

Dexamethasone suppression test, schizophrenia and movement disorder.

The dexamethasone suppression test (DST) was administered to 20 patients with schizophrenic illness. Ten of these patients also had tardive dyskinesia (TD). The scores on TD and parkinsonism scales were significantly higher in DST nonsuppressors. There was also a significant positive correlation between the post-dexamethasone cortisol level and the movement disorder scales.

Adult↗