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N C Saxena

Publications and source records attributed to N C Saxena.

At least 19 recordsLinked to original sources
PubMed2000

Inhibition of GABA(A) receptor (GABAR) currents by arachidonic acid in HEK 293 cells stably transfected with alpha1beta2gamma2 GABAR subunits.

Agonist-stimulated liberation of arachidonic acid and subsequent generation of active metabolites are established components of several signal transduction pathways including pathways that regulate ion channels. We evaluated the role of arachidonic acid and some related unsaturated and saturated fatty acids in the modulation of a stably expressed recombinant gamma-aminobutyric acidA receptor (GABAR) isoform, the alpha1beta2gamma2 isoform. Whole-cell currents evoked by 10 microM GABA were inhibited in a concentration-dependent manner by arachidonic acid (0.1-100 microM). This effect of arachidonic acid to inhibit GABAR currents was not reproduced by the non-metabolizable analog of arachidonic acid, 5,8,11,14-eicosatetraynoic acid (ETYA) or by other monounsaturated or saturated fatty acids. However, another polyunsaturated fatty acid, linoleic acid, which is an essential fatty acid and an effective reductant like arachidonic acid, inhibited GABAR currents in a manner similar to arachidonic acid. Nordihydroguaiaretic acid (NDGA), indomethacin and 1-amonibenzotriazole (1-ABT) did not block the inhibitory effect of arachidonic acid, suggesting that arachidonic acid metabolites of the lipoxygenase, cyclooxygenase or P-450 pathways are unlikely to play a major role in the inhibitory effect of arachidonic acid on GABAR currents. However, the antioxidant N-acetyl cysteine (NAC), a scavenger of active oxygen radicals, reduced the inhibitory effect of arachidonic acid on GABAR currents significantly (P<0.01), suggesting that active oxygen radicals might mediate inhibition of GABAR currents by arachidonic acid.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed2000

Evaluating contraceptive choice through the method-mix approach. An Indian Council of Medical Research (ICMR) task force study.

The method-mix approach was used to evaluate informed contraceptive choices in the present study. A total of 8,077 potential clients were given a balanced presentation of all available contraceptive methods in the national program, ie, the CuT 200 intrauterine device (IUD), low-dose combined oral pills (OC), condom, and sterilization (female/male) along with a new method, Norplant(R).(1) The majority of women opted for spacing methods; among them, the IUD was preferred by about 60% of clients, followed by condoms (9%), OC (6%), and Norplant (5%). Sterilization, mainly female, was accepted by about 17% of the women making an informed choice. The economic status of couples did not influence the contraceptive choices, as all the methods were offered free of cost in the present study, which is the current practice in the national program. Illiterate women more often accepted sterilization (about 25%) than did literate women (15%). This is because illiterate women had more children; about 30% of illiterate women had three or more children, as opposed to 16.2% of literate women. However, literacy status did not influence the choice of any specific spacing method. The study also revealed that, by encouraging potential clients to make an informed choice, they could override the provider's bias while accepting a particular type of spacing method. This is evident from the observation that Norplant was the first choice of the provider for 35% of the women, whereas only 5% of women preferred and accepted Norplant. The present study stresses an urgent need to promote the practice of informed choices in the national program with a variety of contraceptive options-especially, spacing methods for improving contraceptive prevalence and reproductive health in the country.

Adolescent↗
PubMed1997

Effects of elevating [Na]i on membrane currents of canine ventricular myocytes: role of intracellular Ca ions.

OBJECTIVES: Our first objective was to study how elevating [Na]i can modify the background membrane conductance in canine ventricular myocytes (CVM). In particular, we wanted to find evidence for a Nai-activated K current (IK,Na) in these cells. The second objective was to compare the effects of elevating [Na]i on membrane currents without and with intracellular Ca buffering. METHODS: Whole-cell currents were recorded and [Na]i was elevated either by using a pipette perfusion device that allowed [Na] in the pipette solution to be varied (from 0 to 50 mM), or by 50 microM ouabain. RESULTS: Although an outward current attributable to IK,Na was confirmed in guinea-pig ventricular myocytes (GPVM) under our recording conditions, no such current was seen in 29 CVM examined. With Cai buffering, the main effect of elevating [Na]i on CVM was an increase in inward current around and negative to the resting membrane potential. Based on the dependence of this Nai-induced inward current on K ions and its pharmacological properties, especially the effects of low concentrations of external Ba ions (< or = 5 microM) at strongly hyperpolarized voltages, we hypothesize that this current was carried by extracellular K ions through the inward rectifier (IK1) channels that had been modified by the high level of [Na]i. With Cai buffering, elevating [Na]i by ouabain had few or no effects on the L-type Ca channel current (ICa) or the slow delayed rectifier current (IKs). Without Cai buffering, ouabain induced a rapid reduction of both currents along with an increase in a time-independent outward current at voltages positive to -60 mV. CONCLUSION: Our data suggest that there are species variations in K channel expression and/or K channel modulation by intracellular Na ions. Furthermore, intracellular Ca ions play a crucial role in mediating the effects of Nai loading on membrane currents in canine ventricular myocytes.

Animals↗
PubMed1997

Contrasting actions of lanthanum on different recombinant gamma-aminobutyric acid receptor isoforms expressed in L929 fibroblasts.

Functional studies have indicated that, unlike most divalent cations, lanthanum increases both native and recombinant gamma-aminobutyric acid (GABA) receptor (GABAR) currents. In the present study, we have examined whether lanthanum shows subunit-dependent selectivity for modification of currents from different GABAR isoforms. The effects of lanthanum on three different GABAR isoforms, alpha1beta3gamma2L, alpha6beta3gamma2L, and alpha6beta3delta, were determined by transient expression of combinations of alpha1, alpha6, beta3, gamma2L, and delta subunit cDNAs in L929 fibroblasts. Whole-cell recording was used to determine the concentration-response curves for lanthanum for the three different isoforms at submaximal concentrations of GABA. Lanthanum displayed strong potentiation of alpha1beta3gamma2L GABAR currents consistent with earlier reports of potentiation of GABAR currents by lanthanum in neurons and recombinant GABAR isoforms. However, in contrast to the potentiation of alpha1beta3gamma2L GABAR currents by lanthanum, alpha6beta3delta GABAR currents were strongly inhibited and alpha6beta3gamma2L GABAR currents were weakly inhibited by lanthanum. Interaction of lanthanum with GABAR isoforms was competitive, with lanthanum decreasing the EC50 value for GABA of alpha1beta3gamma2L GABARs without changing the maximum current and increasing the EC50 value for GABA of alpha6beta3delta and alpha6beta3gamma2L GABAR currents (greater shift in EC50 value in the alpha6beta3delta compared with the alpha6beta3gamma2L GABARs) without changing the maximum GABAR current. Neither potentiation nor inhibition of GABAR currents by lanthanum showed any voltage dependence. These results suggest that 1) changing the alpha-subunit subtype from alpha1 to alpha6 altered the effect of lanthanum from potentiation to inhibition, 2) changing the gamma2L subunit to the delta-subunit changed the level of maximal inhibition of alpha6 subtype-containing GABAR currents by lanthanum, and 3) the site for interaction with lanthanum probably was on the extracellular surface of GABARs.

Animals↗
PubMed1996

Properties of putative cerebellar gamma-aminobutyric acid A receptor isoforms.

Analysis of the composition of cerebellar gamma-aminobutyric acidA (GABAA) receptors (GABARs) with in situ hybridization of GABAR subunit subtype mRNAs [J. Neurosci 12:1063-1076 (1992)] and Western blot analysis and quantitative binding of radioligands to immunopurified receptors from the rat cerebellum [J. Biol. Chem. 269:16020-16028 (1994)] have suggested that GABAR isoforms likely to occur in the cerebellum of adult rats are alpha1betaxgamma2, alpha6betaxgamma2, and alpha6betaxdelta isoforms. Based on these data, GABARs composed of different combinations of rat alpha1, alpha6, beta2, beta3, gamma2L, and delta subunits, corresponding to the three putative cerebellar GABAR isoforms, were transiently expressed in mouse fibroblast cells (L929 cells). Whole-cell currents were recorded from acutely transfected cells to determine whether the alpha1beta2/3gamma2L, alpha6beta2/3gamma2L, and alpha6beta2/3delta GABAR isoforms could form functional receptor channels in L929 cells and to compare their electrophysiological and pharmacological properties. All three putative cerebellar GABAR isoforms showed a high efficiency of expression of functional GABARs. We chose to study the beta3 and gamma2L subtypes as major representatives of the native subunit subtype proteins. The recombinant alpha1beta3gamma2L, alpha6beta3gamma2L, and alpha6beta3delta GABAR isoforms displayed different affinities (EC50 values) for GABA, differential sensitivity to block by the divalent cation zinc and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, and differences in enhancement by diazepam. Our results provide an initial characterization of the electrophysiological and pharmacological properties of possible in vivo cerebellar GABAR isoforms and demonstrate that subunit compositions of different GABAR isoforms play a crucial role in determining their properties.

Animals↗
PubMed1996

Functional expression of recombinant GABAA receptor channels in L929 fibroblasts.

While GABAergic inhibition plays a major role in the regulation of neuronal excitability, a role for altered GABAergic inhibition in the pathogenesis of epilepsy remains to be proven. The demonstration that GABAA receptors are composed of multiple subunits and that the properties and pharmacology of GABAA receptors are different for different subunit combinations, suggests that GABAA receptor heterogeneity may be of importance in determining the properties of GABAergic inhibition in different regions of the nervous system. While it is clear that GABAA receptor heterogeneity is present in the nervous system, a role for receptor heterogeneity in the pathogenesis of epilepsy remains uncertain. GABAA receptor heterogeneity may have implications for the treatment of epilepsy. It is quite possible that drugs which regulate GABAergic function may have variable efficacy in different regions of the nervous system due to expression of receptors with subunits that have different sensitivity to allosteric regulators. In situ hybridization studies indicate the colocalization of alpha 1 beta 1 gamma 2L and delta subunit mRNAs in hippocampal dentate gyrus granule cells while only the alpha 1, beta 1 and gamma 2L and not the delta subunit mRNAs colocalize in the pyramidal cells of the hippocampus. The reduced rate of acute desensitization and the slow recovery of GABA-evoked currents typical of delta-containing subunit combinations could generate tonic inhibition via long-lasting IPSPs in the dentate gyrus and thus play a role in preventing seizures. By the same rationale, a reduction in the level of expression of the delta subunit mRNA in the dentate gyrus or its absence as in the hippocampal pyramidal cells could be associated with a reduced seizure threshold. Furthermore, it is likely that there are developmental changes in the stoichiometry or subunit composition of GABAA receptors rendering the developing nervous system more or less sensitive to the effects of GABAergic anticonvulsant drugs. In addition to the heterogeneous expression of GABAA receptors, other issues concerning the regulation of GABAergic function are of potential importance. The regulatory events that control the expression of specific receptor subtypes and levels of GABA receptors are unknown. To understand the role of GABAA receptor heterogeneity in the pathogenesis of epilepsy will require the combination of biophysical and molecular biological techniques. It will be important to determine not only whether the properties of GABAA receptors have been altered in a specific form of epilepsy but also whether gene expression has been altered.

Animals↗
PubMed1995

Effects of n-dodecylguanidine on A-type potassium channels: role of external surface charges in channel gating.

n-Dodecylguanidine (C12-G) is an amphipathic compound with a guanidine moiety, which is positively charged at physiological pH, and a hydrophobic side chain. Its effects on an A-type K+ channel clone (rKv1.4) expressed in Xenopus oocytes were examined. C12-G caused a concentration-dependent (1-20 microM) positive shift in the voltage dependences of the following channel properties: activation, inactivation, rate of decay during depolarization, and rate of recovery from inactivation. C12-G was effective when added to the bath solution but was without effect when applied to the cytoplasm of oocytes, indicating an extracellular site of action. The effects of C12-G were antagonized by elevation of the extracellular Mg2+ concentration and by external guanidine ions but were augmented by lowering of the ionic strength of the external solution. C12-G did not affect the instantaneous current-voltage relationship for rKv1.4 or the time constant of decay during strong depolarizations, when the voltage dependence of channel activation approached a plateau. Our observations suggest that C12-G exerts its actions by causing a positive shift in the external surface potential around rKv1.4, without altering the ion permeation process or voltage-independent transition steps. In canine ventricular myocytes, C12-G caused changes in the function of a native A-type K+ channel similar to those seen with rKv1.4. However, C12-G had negligible effects on the voltage dependence of the slow delayed-rectifier K+ channel in the same cell type, suggesting that the actions of C12-G are not nonspecific.

Animals↗
PubMed1994

Assembly of GABAA receptor subunits: role of the delta subunit.

GABAA receptor channels (GABARs) composed of different combinations of rat alpha 1, beta 1, gamma 2L, and delta subunits were expressed transiently in mouse fibroblast cells (L929 cells). Whole-cell recordings were obtained from transfected cells to determine which combinations of GABAR subunits formed functional receptor channels, and to compare the electrophysiological and pharmacological characteristics of GABAR channels expressed in the presence and absence of the delta subunit. Only alpha 1 beta 1 gamma 2L, alpha 1 beta 1 gamma 2L delta, and alpha 1 beta 1 delta subunit combinations assembled to form functional GABAR channels and the presence of the delta-subunit slowed the rate of acute desensitization of GABA-evoked current during GABA application and the rate of recovery of GABA-evoked current following GABA application. These three different GABAR channel isoforms also showed distinct pharmacological profiles with differential sensitivity to block by zinc. Zinc was a potent blocker of alpha 1 beta 1 delta GABAR channels, a moderate-strength blocker of alpha 1 beta 1 gamma 2L delta GABAR channels, and did not block the alpha 1 beta 1 gamma 2L GABAR channels. These findings suggest that GABAR isoforms containing the delta subunit constitute a novel GABAR channel with distinct electrophysiological and pharmacological characteristics.

Animals↗
PubMed1992

Estimation of parity progression ratios from the truncated distribution of closed and open birth intervals.

A procedure to estimate parity progression ratios in a population from the truncated distribution of open and closed birth intervals is presented. The approach is quite simple in computation and data needs. It does not require any separate data on age at last birth to the women of completed fertility as in earlier methods. The procedure is illustrated with an observed set of data.

Biometry↗
PubMed1986

Phase II randomized comparative clinical trial of Norplant (six capsules) with Norplant-2 (two covered rods) subdermal implants for long-term contraception: report of a 24-month study. National Programme of Research in Human Reproduction.

In a randomized clinical study, contraceptive efficacy and bleeding patterns were studied in a group of healthy, regularly menstruating, non-lactating women (n = 84) using two 4.4 cm covered silastic rods containing levonorgestrel, Norplant(R)-2, and compared with another group of women (n = 88) using six 3.4 cm capsules also containing levonorgestrel, Norplant(R). The silastic rods or capsules were placed subdermally in the medial aspect of the upper arm. No method failure was reported up to 24 months of use in this study with either of the device. The bleeding pattern was also similar for both devices as indicated by average episode length, number of bleeding runs and number of spotting days. The continuation rates with both devices were over 80 per 100 users at the end of 12 months and over 65 per 100 users at the end of 24 months. Discontinuations due to expulsion of the device, bleeding problems or personal reasons were few and similar for both devices. The results suggest that silastic-covered rods, Norplant(R)-2, which are comparatively easier to insert and remove and have similar clinical effect, could replace capsules, Norplant(R), as a long-term reversible subdermal contraceptive.

Adolescent↗
PubMed1985

Indian Council of Medical Research. Task Force on Hormonal Contraception: Phase II randomized clinical trial with norethisterone oenanthate 50 mg alone and in combination with 5 mg or 2.5 mg of either estradiol valerate or cypionate as a monthly injectable contraceptive.

A Phase II multicentric study was carried out to compare the different contraceptive treatment schedules of the monthly injectable consisting of norethisterone oenanthate (NET OEN) 50 mg either given alone or in combination with estrogen esters, 2.5 or 5 mg of estradiol valerate (E2 Val.) or estradiol cypionate (E2 Cyp.). A total of 364 women were observed for 1686 months of use. Analysis of the bleeding pattern data indicated that NET OEN 50 mg when given alone gave rise to delayed cycles and/or amenorrhoea. However, the addition of estrogen esters in a dose of either 2.5 or 5 mg provided significantly better bleeding patterns. Of the different treatment schedules investigated, the combination of NET OEN 50 mg with E2 Val. 5 mg provided more consistent and better cycle control. These findings however need further validation on a larger study sample.

Adult↗
PubMed1978

Relationship between platelet count and cardiotomy suction return.

A simple, inexpensive, accurate method of measuring the amount of blood returned by the cardiotomy suction system was devised and calibrated. Preoperative and postoperative platelet counts were obtained in 76 patients with congenital heart disease in whom the amount of cardiotomy suction return was measured. The mean percentage of total perfusate returned by the cardiotomy suction system was 8.9%. Both postoperative platelet count and the percentage change between preoperative and postoperative platelet counts correlated with the amount of blood returned by the cardiotomy suction system, time on bypass, and the percentage of total perfusate aspirated by the system.

Adolescent↗
PubMed1976

Transatrial resection of the obstructed right ventricular infundibulum.

Obstructions of the right ventricular infundibulum were resected through the orifice of the tricuspid valve in 21 patients, 15 of whom had tetralogy of Fallot. At operation the systolic pressure difference between the right ventricle and pulmonary artery after repair averaged 18 mm Hg (range 0-40 mm Hg). In patients with tetralogy, cardiac index four hours after operation averaged 2.8 L/M2/min. One patient with tetralogy and severe pulmonary hypertension died. Twelve patients with tetralogy were recatheterized 10 to 186 days after operation. The mean systolic pressure difference between right ventricle and pulmonary artery was 23 mm Hg. Residual obstructions were in the pulmonary valvular annulus. Cineangiograms did not show paradoxical motion of the right ventricular wall. Transatrial resection of right ventricular infundibular obstructions carries with it none of the consequences that often follow right ventriculotomy and this surgical approach satisfactorily relieves infundibular obstructions.

Adolescent↗
PubMed1976

Transatrial repair of tetralogy of Fallot.

In 12 months since March, 1975, 25 of 27 patients with tetralogy of Fallot have had corrective operations without ventriculotomy. Infundibular obstructions were excised and ventricular septal defects were closed through a right artiotomy with retraction of the anterior leaflet of the tricuspid valve. Pulmonary valve stenosis was relieved through a pulmonary arteriotomy. In five patients the pulmonary annulus was patched 0.5 to 1.5 cm. into the right ventricle. Immediately after repair peak right ventricular-pulmonary arterial systolic pressure difference averaged 17 mm. Hg and ranged between zero and 40 mm. Hg. Cardiac indices averaged 2.85 L. per square meter per minute 4 hours after operation. All but two patients developed right bundle branch block. One patient with severe pulmonary hypertension died. Fourteen patients have been recatheterized. Right ventricular-pulmonary peak systolic pressure differences ranged between zero and 45 mm. Hg (mean, 22). Cineangiograms show contraction of the free right ventricular wall during systole. Transatrial repair of tetralogy of Fallot is feasible technically in many patients, avoids muscle necrosis and coronary arterial injury, and improves cardiac output in the immediate postoperative period.

Adolescent↗
PubMed1975

First reported successful management of Serratia marcescens bacteremia after open heart surgery in a child.

A 7 and one-half yr-old girl developed bacteremia from S. marcescens following debanding of the pulmonary artery and closure of multiple ventricular septal defects with a Dacron patch and multiple Teflon pledgets. The site of entry was probably a radial arterial catheter left in place for 8 days. Infection was eradicated by a combination of gentamicin and carbenicillin over a 4-wk period. Of 12 cases of postoperative Serratia bacteremia in adults following valve replacement, only four survived. Antibiotics of proven effectiveness against the specific isolated Serratia strain, prompt therapy sustained for 6 wk offers the prospect for cure of this serious complication of cardiac surgery.

Anti-Bacterial Agents↗