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V Jain

Publications and source records attributed to V Jain.

At least 109 records · Page 6Linked to original sources

Differential regulation of nitric oxide in the rat uterus and cervix during pregnancy and labour.

The aim of this study was to determine if nitric oxide (NO) production and nitric oxide synthase (NOS) isoforms change within the uterus and cervix during pregnancy and labour either at term or preterm. NO production was compared in the rat uterus and cervix of non-pregnant and pregnant rats on days 18-22 prior to labour, day 22 during delivery, 1 day post-partum and after treatment with either 10 mg onapristone or progesterone. Uterine NO synthesis, reflected in nitrite production, increased during gestation (194.2 +/- 22.6 nmol/g on day 19) compared with the non-pregnant state (76.2 +/- 18.4 nmol/g, P < 0.05) and decreased during term labour and post-partum. Furthermore, injection of lipopolysaccharide (LPS) (100 micrograms/rat i.p.) on day 20 of gestation resulted in a significant increase in NO synthesis after 6 h. Conversely, cervical NO synthesis and nitrite production was low in the non-pregnant (65.1 +/- 9.2 nmol/g) and pregnant animals on days 18-22 of gestation (53.2 +/- 9.0 nmol/g on day 22, P > 0.05), but markedly increased during term labour (139 +/- 28.6 nmol/g, P < 0.05). Treatment with the antiprogestin onapristone suppressed uterine NO production and increased cervical production while continuous administration of progesterone from day 19 had the opposite effect. LPS produced a significant increase in cervical NO production in both the pregnant (8-fold) and non-pregnant (4-fold) states. All three known NOS isoforms (i.e., iNOS, nNOS and eNOS) were detected in the cervical samples but only two were present in the uterus (iNOs and eNOS). An increase in the presence of iNOS occurred during labour at term compared with cervices collected from day 19. This was contrary to the measurements of the isoform in the uterus. Also, there was a similar increase of nNOS in the cervix during labour. This isoform seemed absent in the uterus during gestation. No significant changes occurred in the abundance of eNOS in the cervix during labour at term compared with day 19. During preterm labour after onapristone, iNOS concentrations increased significantly in the cervix. In order to examine whether the NO pathway plays a role in cervical ripening, the effects of the nitric oxide synthesis inhibitor L-nitro-arginine methylester (L-NAME) on the duration of delivery and on cervical extensibility were also investigated. The duration of delivery was significantly prolonged in L-NAME-treated rats compared with the control group (2.4-fold). Moreover, cervical extensibility decreased significantly (1.7-fold) after in-vitro incubation with L-NAME (P < 0.005). We conclude that the NO system may have an active role in the cascade of processes involved in preparing the uterus and cervix for parturition.

Animals↗

The stability of estrogen and progesterone receptors in patients receiving preoperative chemotherapy for locally advanced breast carcinoma.

The determination of estrogen (ER) and progesterone receptor (PR) content is routine in the management of carcinoma of the breast. Such data are commonly used to predict responses to endocrine therapy. Preoperative chemotherapy is often utilized in the treatment of patients with locally advanced carcinoma of the breast. However, little attention has been focused upon the effect of preoperative chemotherapy on hormonal receptor expression in that setting. The purpose of this study is to evaluate the effect of preoperative chemotherapy on ER and PR expression in patients with locally advanced breast carcinoma. Patients with T3 or T4 adenocarcinoma of the breast from Charity Hospital in New Orleans were studied. Levels of ER and PR were determined from tissue blocks obtained at diagnostic biopsy, as well as after the preoperative chemotherapy. The receptor levels were determined using immunohistochemistry and quantified using image analysis. We evaluated 21 locally advanced cancer patients who received at least three cycles of standard chemotherpay regimens. Of these patients, 11 achieved a partial response, with 3 achieving a complete response after preoperative chemotherapy. A total of 33 per cent of patients had a significant change in hormonal receptor content after preoperative chemotherapy. ER changed in 17%, PR in 22%, and both ER and PR in 6%. These data show that ER and/or PR expression changed in 33% of patients studied. Further, ER and PR status does not appear to predict or correlate with response to chemotherapy. This suggests that determination of ER and PR may best be performed from definitive resection specimens in patients who receive preoperative chemotherapy.

Adenocarcinoma↗

2-DG induced modulation of chromosomal DNA profile, cell survival, mutagenesis and gene conversion in X-irradiated yeast.

Effects of post-irradiation modulation in presence of 2-deoxy-D-glucose and yeast extract, on chromosomal DNA profile, cell survival, reverse mutation (ILV+) and gene conversion (TRP+), were studied in X-irradiated stationary phase yeast cells (diploid strain D7 of Saccharomyces cerevisiae). The damage and repair in chromosomal DNA bands, resolved by using contour clamped homogeneous electric pulsed-field gel electrophoresis (PFGE) technique, was estimated by calculating intensity ratio, rho n (rho n I(n)/I(t); where I(n) is the intensity of nth band in a lane and I(t) is the sum of intensities of all bands and the well in the lane). The data indicate linear correlation between relative compactness (tau) of a chromosome [chromosome size (Kb)/length of synaptonemal complex (microns)] and DNA damage and repair. The chromosome repair kinetics were biphasic, showing initial decrease followed by an increase in rho n. Variations were observed among different chromosomes with respect to DNA damage, repair and post-irradiation repair modulation. 2-DG inhibited both components of chromosomal DNA repair and also repair of potentially lethal damage but enhanced frequencies of mutants. Relatively the effects on revertants were greater in cells irradiated with lower doses (50 Gy) of X-rays and post-irradiation incubation in presence of phosphate buffer having 2-DG (50 mM) and glucose (10 mM). Yeast extract increased frequencies of revertants and convertants thus promoting error-prone DNA repair. Yeast extract in combination with 2-DG showed complex effects on chromosomal DNA repair and enhanced mutagenesis further.

Cell Survival↗

In vivo NMR spectroscopic studies on the bioenergetic changes induced by metabolic modulators in Ehrlich ascites tumour cells.

Changes in the energy metabolism of Ehrlich ascites tumour (EAT) cells induced by treatment with 2-deoxy-D-glucose (2-DG) alone and in combination with other metabolic modulators, were studied using in vivo nuclear magnetic resonance (NMR) spectroscopy. Accumulation of 2-DG-6-phosphate (2-DG-6-P) and cellular energy status as reflected in the ratio of beta ATP to inorganic phosphate (beta-ATP/Pi) in cells could be monitored as a function of time using P-31 NMR spectroscopy. Presence of 2-DG induced a significant decrease in the levels of nucleotide triphosphates, which continued to reduce for some time even after removing 2-DG from the vicinity of cells. When administered along with 3-O-methyl-D-glucose (3-O-MG), 2-DG phosphorylated at a slower rate and the resultant 2-DG-6-P accumulated to a lesser extent than that obtained with 2-DG alone. Treatment with Photosan II, a haematoporphyrin derivative (Hpd), has been reported to increase the glucose utilisation and rate of glycolysis. Upon concomitant administration of 2-DG along with Hpd (after Hpd pretreatment for 1-2 hr), the extent of phosphorylation of 2-DG increased. The combination of 2-DG with 3-O-MG or Hpd reduced the energy status (beta-ATP/Pi) to a greater extent and the recovery was considerably less upon removal of the treatment, compared to the effects of either drug administered separately. Since metabolic depletion of ATP is known to inhibit the post-irradiation DNA repair processes, it is hypothesized that the use of these drug combinations, as adjuvants to tumour radiotherapy, should enhance the therapeutic efficacy and selectivity.

Animals↗

Radioprotective effects of diltiazem on cytogenetic damage and survival in gamma ray exposed mice.

Diltiazem, a calcium ion channel blocker, already in use in cardiovascular therapeutics, has been observed to protect against bone marrow damage (cytogenetic damage, cell death) and mortality in whole body irradiated mice. The micronuclei fraction in bone marrow cells of whole body irradiated (60Co gamma rays, 2.0 Gy) mice was reduced from 2.24 +/- 0.23% to about 0.74 +/- 0.33% by preirradiation administration (-20 min) of 110 mg/kg body wt. diltiazem (ip). Endogenous colony forming unit counts in spleen of mice administered 110 mg/kg body wt. (-20 min) of diltiazem before 10 Gy whole body irradiation were 6 times more than untreated irradiated controls. Pretreatment with diltiazem accelerated the recovery of radiation induced weight loss also. Diltiazem (110 mg/kg body wt, -20 min) enhanced 30 day survival to about 95% and 85% after lethal whole body absorbed dose of 9 and 10 Gy respectively and also mitigated radiation induced life- span shortening. Post-irradiation (10 Gy) administration of diltiazem (+20 to 30 min) enhanced survival from about 2 to 15% only but was highly significant (P < 0.001). Possible modes of radioprotective action of diltiazem have been discussed.

Animals↗

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Journal Article↗

Safety of intrauterine administration of purified neem seed oil (Praneem Vilci) in women & effect of its co-administration with the heterospecies dimer birth control vaccine on antibody response to human chorionic gonadotropin.

Praneem Vilci (PV), purified neem oil was reported to exercise a reversible antifertility effect after a single intrauterine instillation in rodents and primates without any adverse effects. After toxicology, drug regulatory and ethical clearances, a phase I clinical trial was conducted on PV. Eighteen healthy tubectomised women were enrolled to evaluate the safety of a single intrauterine instillation of PV and to determine the effect of its co-administration on anti-hCG response to the heterospecies dimer (HSD) hCG vaccine. Eight women received PV alone and ten women were given the HSD-hCG vaccine in addition. Base-line and post-treatment haematological and biochemical profiles were determined as also the mid-luteal serum progesterone. Endometrial biopsies were examined to assess ovulatory status and the effect of intrauterine treatment with PV on the endometrium. Anti-hCG antibody titres were estimated in women who were concurrently immunized with the HSD vaccine. No untoward reaction was observed in any woman. Menstrual pattern and ovulatory status remained unaltered. Endometrial biopsy after PV instillation in one woman showed non-specific endometritis but she remained asymptomatic. Mild eosinophilia was seen in two women and this reverted to normal on its own. All women receiving PV and the HSD vaccine generated antibodies against hCG. Our data show that intrauterine administration of PV is safe and does not prevent the antibody response to HSD-hCG vaccine.

Adult↗