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Biomedical subjects

M M Singh

Publications and source records attributed to M M Singh.

At least 19 recordsLinked to original sources
PubMed1995

Early abortifacient action of RU 486 by continuous intravenous infusion in rat.

RU 486 administered through constant intravenous infusion at 20 mg/kg dose on day 8 of pregnancy induced frank vaginal bleeding and resorption of all implantations in 100% rats. This was associated with an almost 4-fold reduction in progesterone secretion rate by the dispersed luteal cells ex-vivo. At 12 mg/kg dose, an incomplete resorption of implantations was observed in all treated animals. Results indicate that slow and continuous intravenous infusion of this antiprogestin was highly effective in terminating pregnancy shortly after implantation in the rat and this could, at least partially, be related to its luteolytic action in this species.

Abortion, Induced↗
PubMed1995

Time-related effects of a triphenylethylene antiestrogen on estrogen-induced changes in uterine weight, estrogen receptors, and endometrial sensitivity in rats.

Time-related estrogen antagonistic action of a single oral contraceptive (1.25 mg/kg) dose of the triphenylethylene antiestrogen centchroman was determined in ovariectomized immature rats. Tamoxifen and nafoxidine were used for comparison. A single oral administration of centchroman followed by three doses of estradiol-17 beta (1 microgram/d, s.c.) caused significant dose-dependent inhibition in estradiol-17 beta-induced increase in uterine weight and nuclear and cytosolic estrogen receptors. But the inhibition at antiimplantation dose was evident only if estradiol-17 beta treatment was initiated not later than 48 h post-antiestrogen. Alternatively, when antiestrogen treatment was followed by a single dose of estradiol-17 beta between days 2-7, a synergistic action, typical of antiestrogens possessing weak estrogen agonistic activity, was observed. In immature rats in which a condition mimicking preimplantation was produced by estradiol-17 beta (0.5 microgram/d, s.c.) priming on days -2 and -1, followed by progesterone (1 mg/d, s.c.) and an endometrial sensitizing dose (0.5 microgram/d, s.c.) of estradiol-17 beta at 1600 h on day 4, anti-implantation dose of centchroman administered on day 1, too, failed to inhibit uterine weight gain induced by sensitizing dose of estradiol-17 beta, but caused marked inhibition in endometrial sensitivity to a deciduogenic stimulus and decidualization and weight gain of traumatized uterine horn 96 h post-traumatization over non-traumatized horn was only about 150% (725% in controls). Inhibition in endometrial sensitivity and decidualization was evident when the interval between antiestrogen treatment and sensitizing estradiol was < 126 h. Pinopods were present on endometrial surface on day 5 whether or not priming and/or sensitizing doses of estradiol were administered, but decidual response was mild if either of these doses of estradiol-17 beta was deferred. Findings suggest that: (a) duration of antiestrogenic action of single anti-implantation dose of centchroman in rat was about 126 h, which in ovariectomized immature rats was evident only when a condition mimicking preimplantation was produced and the antiestrogenic response was based on inhibition in estradiol-induced endometrial sensitivity and not uterine weight gain; (b) priming as well as sensitizing estrogen were essential to get optimal decidual responses; (c) appearance of pinopods on endometrial surface may not be related to endometrial sensitivity; and (d) tamoxifen and nafoxidine appear slightly longer acting with duration of antiestrogenic action of approximately 150 h.

Administration, Oral↗
PubMed1995

Reversibility of antigestagenic action of antiprogestin onapristone by exogenous progestagens during early pregnancy in guinea pig.

Ability of progesterone, gestodene, promegestone and cyproterone acetate (CPA) to reverse antigestagenic action of onapristone in adult female guinea pigs was investigated. Onapristone (10 mg/kg, s.c.) administered on post-conception days 8-11 caused resorption of implantations and vaginal bleeding in all animals. Simultaneous administration of progesterone, gestodene or promegestone on days 7-13 successfully reversed antigestagenic action of this antiprogestin, since most animals supplemented with these progestagens had viable implantations at autopsy on day 14. CPA was, however, ineffective and animals supplemented with it had only resorbed implantations and blood in uterus and vagina like that in onapristone per se treated animals. High plasma progesterone and low PGFM concentration were generally observed in all pregnant animals bearing viable implantations. PGFM (13, 14-dihydro-15-keto PGF2 alpha) was significantly elevated by day 14 in onapristone-treated (Group II) and CPA-supplemented (Group X) animals. No discernible effect on pregnancy or post-implantation embryonic development was observed in animals treated per se with these progestagens.

Animals↗
PubMed1995

Post-coital contraceptive efficacy of the seeds of Nigella sativa in rats.

Hexane extract of the seeds of Nigella sativa L. prevented pregnancy in Sprague-Dawley rats treated orally at 2 g/kg daily dose on days 1-10 post-coitum. Significant antifertility activity was also observed in its column fractions and subfractions. At contraceptive dose, the active hexane extract exhibited only mild uterotrophic activity comparable almost to 0.002 mg/kg dose of 17 varies; is directly proportional to-Ethinylestradiol, but was devoid of any estrogenicity in the immature rat bioassay.

Animals↗
PubMed1994

Assessment of location-specific human exposure to dichloro-diphenyl trichloroethane and benzenehexachloride in Gujarat state, India.

On the basis of the use of insecticides in agriculture and vector control programmes, two locations were selected in Gujarat state, India. In location 1 the insecticides are used in both agriculture and vector control programmes while in location 2 they are used only in agriculture. Raw food commodities, water, soil and blood samples were collected from the people residing in these locations, and analysed for total dichloro-diphenyl trichloroethane and total benzenehexachloride residues. Residue levels were significantly lower in location 2 than in location 1.

Adult↗
PubMed1993

Effect of a pure nonsteroidal antiestrogen, CDRI-85/287, on implantation--associated histological and biochemical changes in the rat uterus.

The effect of compound CDRI-85/287, a pure, nonsteroidal antiestrogen, on implantation-associated changes in rat uterus were studied. Results provide a clear correlation between the antideciduogenic action of 85/287 (0.05 mg/kg in days 1-5 post-coitum or 2.5 mg/kg on day 1 post-coitum) and the time of its administration in relation to the secretion of prenidatory luteal phase estrogen. The antiestrogenic nature of the compound is further highlighted by inhibition of estradiol-induced increase in vascular permeability. In the present study, differences in the pattern of biochemical maturation of the pregnant, pseudopregnant and 85/287-treated rat uterus have also been illustrated. As compared to the pregnant rat uterus, absence of (the blastocyst and) decidualizing tissue in the pseudopregnant rat uterus accounts for the low uterine weight, protein, RNA, phospholipids and alkaline phosphatase at the time of implantation. Post-coital treatment with 85/287 (2.5 mg/kg, oral) inhibited increase in these parameters at the time of implantation. Glycogen levels which were lowered in the pregnant rat uterus on days 5 and 6, remain unaltered in the pseudopregnant and 85/287-treated rat uteri, suggesting nonutilization of this energy substrate. These findings provide sufficient evidence that the antiimplantation activity of 85/287 is due to its antiestrogenic property.

Alkaline Phosphatase↗
PubMed1992

CDRI-85/287, a novel antiestrogen and antiimplantation agent: biological profile and interaction with the estrogen receptors in immature rat uterus.

Postcoital antifertility efficacy, estrogenic and antiestrogenic activities of compound 85/287 were determined by the subcutaneous route in rats. It was 100% effective in preventing implantation at 0.5 mg/kg dose when administered within 24 h of mating and at 0.05 mg/kg in the days 1-5 post-coitum regimen. In the immature rat bioassay, it exhibited mild uterotrophic effect at the contraceptive dose but when administered along with estradiol (E2), it caused almost complete inhibition of uterine weight gain and vaginal cornification at the 2 mg/kg dose. E2 administration to immature rats (0.1 microgram, s.c., 3 days) caused 3-5 fold increase in the nuclear as well as cytoplasmic estradiol receptor (ER) content as compared to controls. In contrast, 85/287 (0.5 mg/kg and 2 mg/kg; s.c.), only translocated the ER to the nuclear compartment resulting in a depletion of cytoplasmic ER levels. Concurrent administration of 85/287 and E2 inhibited E2-induced increase in cytoplasmic ER. It is suggested that compound 85/287 exerts its antiestrogenic and antiimplantation action by interfering with the formation of E2-receptor complexes in the uterus.

Animals↗
PubMed1992

Fetal resorption in rats treated with an antiestrogen in relation to luteal phase nidatory estrogen secretion.

Centchroman was administered to rats in relation to luteal phase nidatory estrogen secreted between 21.00 on day 4 and 10.00 on day 5 of pregnancy. A single oral dose of 1.25 mg/kg before the secretion of nidatory estrogen, i.e. until 21.00 on day 4, prevented implantation in 100% of the rats without altering plasma estradiol or progesterone concentration. Administration of a dose of up to 62.5 mg/kg at 10.00 on day 5 even failed to inhibit implantation, but caused dose-dependent resorption of implantations. Resorption of all implantations at a dose of 62.5 mg/kg was associated with a decrease in circulating progesterone levels, but was only partially reversed by progesterone or progesterone + estrone supplementation. Apparently normal morulae and blastocysts recovered between days 4 and 10 from rats treated with anti-implantation doses before release of nidatory estrogen, when transferred to the uteri of control rats exhibited lower pregnancy, implantation and development rates with increasing confinement in the genital tract of treated donors. None of the embryos recovered from control or centchroman treated females implanted in the uteri of treated rats. Centchroman administration on day 1, but not on day 5, abolished endometrial receptivity to an artificial stimulus for decidualization. All term fetuses were apparently normal and their weight comparable to that of control fetuses. The study provides evidence of post-implantation fetal resorption, occurring primarily between days 10 and 19 post-coitum, in rats treated with a potent antiestrogen before or immediately after the prenidatory estrogen secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Duration of antiestrogenecity of compound CDRI-85/287: a new orally active nonsteroidal antiimplantation agent.

Duration of antiestrogenic and antiimplantation action of CDRI-85/287, (2-(4-(2-N-piperidino)ethoxy phenyl)-3-phenyl(2H)benzo(2)pyran), was studied in rat. Pretreatment of ovariectomized immature rats with this compound caused translocation of cytoplasmic estrogen receptor (ER) to the nucleus and a marked depletion of cytoplasmic ER pool resulting in a nonresponsive state of the uterus to subsequent estrogen administration until day 4. While in rats pretreated with estradiol, increased cytoplasmic ER level made the uterus responsive to a second injection of estrogen. In the delayed implantation model, 85/287 pretreated rats were given estrone on days 4, 5 or 6 post-antiestrogen treatment. No implantations were observed after estrone administration on day 4, but were present when estrone was given on days 5 or 6. Summation of these results suggests the duration of action of 85/287 to be 3-4 days in rat.

Administration, Oral↗
PubMed1992

CDRI-85/287: studies on competition to estrogen binding sites in the immature rat uterus.

Ability of compound CDRI-85/287, a new nonsteroidal antiestrogen with negligible inherent estrogenicity, to inhibit uptake of 3H-estradiol (3H-E2) by the immature rat uterus in vivo was investigated. Different doses of 85/287 were administered either intraperitoneally 30 min before 3H-E2 or orally 1 and 6 hr before 3H-E2. A dose dependent inhibition in 3H-E2 uptake was observed after administration of the compound by either route and was 69% at 50 micrograms/rat ip dose and 80% at 2.5 mg/kg po dose. In in vitro competitive binding assay, however, the compound showed poor affinity (RBA 0.42% of estradiol-17 beta) for cytosolic estrogen receptors. Considering the potent anti-estrogenic as well as anti-implantation efficacy of the compound, its action in vivo appears to be mediated via its active metabolite(s).

Animals↗
PubMed1991

Synthesis and pregnancy-inhibiting activity of 7-substituted androst-5-ene derivatives.

Synthesis of 7-aryl/allyl-substituted androstene derivatives 3a through 3g has been carried out by Grignard reaction on 3 beta,17 beta-diacetoxyandrost-5-en-7-one (2) with aryl/allyl magnesium bromide. Isomeric mixture of products 3b and 3c/3e and 3f/3h was separated by column chromatography. Stereochemical assignment at C-7 has been made on the basis of 13C nuclear magnetic resonance studies and chemical considerations. Compounds 6a and 6b were synthesized by alkylation of compound 5 with beta-(N,N-diethylamino)ethyl chloride hydrochloride and 1-(2-chloroethyl)pyrrolidine hydrochloride, respectively. Compound 3g (isomeric mixture) prevented pregnancy in 60% of rats at 10 mg/kg daily dose administered orally on days 1 to 7 of pregnancy; however, its only isolable 7 beta-hydroxy isomer, 3h, was inactive at this dose.

Androstenes↗
PubMed1991

Determination of mevalonolactone in capsules by capillary gas-liquid chromatography.

A wide bore capillary gas chromatographic method was developed to determine mevalonolactone in capsule formulations. The method uses beta,beta-dimethyl-gamma-hydroxymethyl-gamma- butyrolactone as an internal standard and has been validated for its accuracy, precision and linearity. The method has been applied for stability testing of the capsule formulation. High-performance liquid chromatographic and gas chromatographic studies demonstrated cyclization of mevalonic acid (open-chain form) to mevalonolactone (cyclic form) under the described gas chromatography conditions. Mass spectrometric analysis indicated that mevalonolactone prepared in water or an organic solvent emerged from the gas chromatographic column as the intact cyclic lactone.

Capsules↗
PubMed1991

Effect of prolonged centchroman treatment on pituitary gonadotrophic activity in rhesus monkeys.

Daily oral administration of antiestrogen centchroman at 6.25, 12.5 and 25 mg/kg doses to adult female rhesus monkeys continuously for one year caused no significant effect on their total pituitary gonadotrophin content as evidenced by an almost similar extent of uterine weight gain, premature opening of vagina and cornification of vaginal epithelium in immature female mice treated with pituitary homogenates from control and centchroman treated monkeys.

Animals↗
PubMed1990

Psychopathology of delayed resumption of sexual activity after myocardial infarction.

A total of 300 male cases of myocardial infarction were analyzed to evaluate the effect of myocardial infarction on sexual activity with particular stress on resumption of sexual activity and to determine the factors in cases of delayed resumption. Sexual activity decreased with age and correlated negatively to total sexual activity. 26 per cent cases developed one or other symptoms which occurred during all the phases of sexual activity but were more marked during resolution phase. Sexual activity returned to normal within six months only in 11.33 per cent cases and in the remaining cases resumption was delayed. In 27.8 per cent cases phobia of marked exertion involved in sex act, created by physicians in 12.7 per cent was the factor responsible for the delayed resumption. Quality of sexual activity decreased in 39 per cent cases and it was due to change in position from Male on top to male on bottom position in 31 per cent cases. Counselling for sexual rehabilitation has been discussed.

Adult↗
PubMed1990

Serum cholesterol binding reserve and its ratio to serum cholesterol in first degree relatives of patients with ischaemic heart disease.

Serum total cholesterol and serum cholesterol binding reserve (SCBR) were estimated in 50 healthy subjects and 25 cases with ischaemic heart disease (IHD) and their seventy asymptomatic first degree relatives. In normal subjects mean values of SCBR tended to expand with increasing levels of serum cholesterol, while this relationship was reversed in cases with IHD. The relatives showed a direct correlation between serum cholesterol and SCBR upto serum cholesterol level of 220 mg/dl, but the correlation was lost beyond this level. The critical levels for predicting risk of IHD were 30 mg/dl for SCBR and 8 for cholesterol: SCBR ratio. The latter was found to be a more sensitive index for predicting the risk of IHD as compared to SCBR alone.

Adult↗
PubMed1990

Right precordial mapping. Diagnostic sensitivity and specificity of leads V3R to V6R in different intercostal spaces in cases with right ventricular infarction.

Twelve lead conventional electrocardiography and right precordial mapping including precordial leads V2R to V6R in the 2nd to 5th intercostal spaces were obtained in 150 cases with acute myocardial infarction. There were 27 (18%) cases with right ventricular infarction: 24 associated with inferior wall infarction and 3 with anterior wall infarction. In the right precordial mapping, leads V3R to V6R in all intercostal spaces had equal sensitivity of 100%; 3rd intercostal space recording, however, had the maximum specificity of 92.6%.

Electrocardiography↗
PubMed1989

The positive-negative distinction in drug-free schizophrenic patients. Stability, response to neuroleptics, and prognostic significance.

Fundamental questions about the validity and significance of positive and negative syndromes in schizophrenia were addressed by a prospective, double-blind longitudinal study that involved a drug-free placebo baseline, three to four months of neuroleptic treatment, and a three-year poststudy follow-up. From pooled data on 62 schizophrenics, the following findings were observed: (1) a high stability of both syndromes during drug-free conditions; (2) significant correlations of syndrome ratings between the placebo baseline and final neuroleptic week; (3) significant neuroleptic-related improvement in both positive and negative syndromes, with a marginally greater reduction of positive features; (4) independence of the two syndromes during the drug-free baseline but not under neuroleptic conditions; (5) greater symptomatic improvement but more residual disorder portended by both positive and negative syndromes in the drug-free baseline; and (6) poorer functional reconstitution and earlier relapse predicted by a positive syndrome alone. These data supported the validity of the positive-negative distinction in schizophrenia but challenged basic assumptions about its import.

Adolescent↗