Biomedical subjects
Publications and source records attributed to S Batra.
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BACKGROUND: The continued endeavour to design novel, non-detergent molecules that can be useful as topical, prophylactic contraceptives has led to the discovery of substituted isoxazolecarbaldehydes as a new class of compounds exhibiting both spermicidal and acrosin inhibitory activities simultaneously. METHODS: Normal human semen samples were used to detect the spermicidal and acrosin inhibitory activities of the new compounds. Lactobacillus, HeLa and Candida cultures were used to determine the safety of compounds towards normal vaginal flora, their cytotoxicity and anti-fungal activity. Supravital staining and the hypo-osmotic swelling test (HOST) were used to detect the effect on sperm membrane integrity. Nonoxynol-9 (N-9) was used as a reference standard. RESULTS: The 5- and 3-substituted isoxazolecarbaldehydes showed significant spermicidal [minimum effective concentration (MEC)=0.005-2.5%] and acrosin inhibitory (IC50=3.9-58 x 10(-4) mol/l) activities in several molecules along with weak fungicidal activity against Candida albicans. Lineweaver-Burk and Dixon plot analysis of a representative structure showed non-competitive inhibition of human acrosin enzyme, and the most potent acrosin inhibitors also considerably diminished the induction of the acrosome reaction by Ca2+ ionophore. Some compounds were found to be significantly safer than N-9 towards Lactobacillus acidophilus in vitro at their respective spermicidal MECs. In the cytotoxicity assay, the IC50 of these compounds towards the HeLa cell line was of the same order as N-9 (0.9-0.1 mmol/l); however, in contrast, the compounds exhibited only a moderate effect on sperm membrane integrity. CONCLUSIONS: This study indicates that 5- and 3-substituted isoxazolecarbaldehydes are 'first generation' multifunctional, spermicidal molecules that hold promise for development as topical contraceptives with useful associated activities that can add considerably to their effectiveness, safety and prophylaxis.
OBJECTIVE: Evaluation of visual inspection of the cervix with acetic acid (VIA) for screening cervical intraepithelial neoplasia. METHODS: In this prospective study, 400 women were screened using the Papanicolaou (PAP) smear, VIA and colposcopy. Those who had positive results with any of the screening methods underwent large loop excision of the transformation zone (LLETZ). The sensitivity and specificity of each of the screening methods was analyzed. RESULTS: The sensitivity of VIA (96.7%) was much higher than that of the Pap smear (50%), and almost as high as that of colposcopy (100%). The specificity of VIA (36.4%) was lower than that of the Pap smear (97%) and colposcopy (96.9%), resulting in high false-positive rates for VIA. Two cases of endocervical lesions were missed with VIA. CONCLUSION: Visual inspection of the cervix with acetic acid is very sensitive for ectocervical lesions. The advantages of the VIA method are its low cost and ease of use (it can be used by paramedical workers), its high sensitivity and its immediate results (it is possible to "see and treat" at the first visit). Its main limitation is a high rate of false-positive results, which may lead to overtreatment if a "see and treat" policy is applied.
OBJECTIVE: Non-invasive sampling of human genitals to identify high-risk individuals with subclinical oncogenic HPV infection remains a challenge. The study was designed to see if self-collected urine can be used as a simple, non-invasive sampling for screening HPV, particularly for screening/monitoring general population or young adolescents or infants, if they are to be immunized by HPV vaccines. METHOD: Self-collected urine samples from 100 sexually unexposed college going girls and cervical scrapes from 104 normal healthy sexually active married women were used in this study. Additionally, a group of 55 women were recruited for collecting first urine and later scraped cervical cells to validate urine sampling by directly comparing HPV positivity between the two types of biological specimens. A dry 'paper smear' method for specimen collection and a simple single tube protocol was employed for PCR detection of HPV infection. RESULTS: Out of 100 sexually inexperienced college going girls, only 6 (6%) were positive for HPV infection as revealed by L1 consensus primer and 4 (4%) of them were positive for HPV 16 but none was found positive for HPV 18 DNA. Out of 104 sexually active married women who were cytologically reported as negative by Pap test, 11 (10.5%) were found HPV positive and 7 (6.7%) of them had infection of high-risk HPV type 16. Both urine and later cervical scrapes from a group of 55 women collected as dry 'paper smear' showed perfect matching positivity for HPV between urine and cervical scrape. CONCLUSIONS: The use of urine coupled with its dry collection as 'paper smear' facilitating their easy transport, storage and direct PCR detection of HPV DNA opens up an alternative non-invasive approach for population screening of HPV infection, at least in such cases as children and infants in whom invasive samples are difficult to obtain.
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The solution-phase parallel synthesis involving reactions of Baylis-Hillman products of 3-substituted-5-isoxazolecarbaldehydes with nucleophiles and their in vivo antithrombotic evaluations are described along with the results of in vitro platelet aggregation inhibition assay of a few compounds. Results of the detailed evaluation of one of the compounds as an inhibitor of platelet aggregation are also presented.
The synthesis of isoxazole-based derivatives utilizing Baylis-Hillman chemistry and results of their preliminary bioevaluation as hypolipidemic agents in triton model are described.
For the extrapolation of data obtained from experimental animals to the human situation, it is important to know the similarities and differences between human and animal species. Some important characteristics of nitric oxide synthase (NOS) in myometrium and vagina from human and rat were compared. NOS-activity was measured by the formation of 14C-citrulline from 14C-arginine and the expression of NOS isoforms was examined by Western blotting. NOS activity in human uterus and vagina was significantly lower than in the tissues from rat. In contrast to the rat where NOS activity was predominantly found in the cytosolic fractions, NOS activity in particulate and cytosolic fractions from both human myometrium and vagina was similar. Data from Western blots confirmed that eNOS and nNOS isoforms were concentrated in the particulate and cytosolic fractions, respectively. Estrogen treatment of rats resulted in a down regulation of uterine cytosolic NOS activity. A down regulation of NOS in the cytosolic fraction was also seen in the human pregnant myometrium as compared with the nonpregnant myometrium. The vaginal NOS activity was considerably higher than the uterus in both species. In spite of some clear-cut qualitative and other differences between human and rat tissues, there are some interesting similarities. Downregulation in pregnancy of human uterine NOS is probably due to, at least in part, the influence of estrogen and progesterone.
OBJECTIVES: To compare maternal and fetal outcomes in patients with non-operated valvular heart disease and patients who had surgery before or during pregnancy. METHODS: The 308 women with valvular heart disease who delivered in this hospital in the last 8 years were divided into three groups. The 218 (70.7%) women in group 1 had no surgical intervention; the 42 (13.6%) women in group 2 underwent balloon mitral valvotomy during pregnancy; and the 48 (15.5%) women in group 3 had surgical intervention before pregnancy (35 had balloon mitral valvotomy, eight had mitral valve replacement, and five had mitral valve repair). Maternal and fetal outcomes were compared for these three groups. RESULTS: The antenatal events differed significantly: 175 (80.3%), 40 (94.2%), and 46 (95.8%) patients in groups 1, 2 and 3, respectively, had uneventful pregnancies. In group 1, 14 (6.4%) patients had congestive heart failure (P>0.05) and 24 (11%) patients had cardiac arrhythmias, which was statistically significant. The rate of preterm deliveries did not differ significantly among the three groups. The groups did not differ in mean birth weight, mode of delivery, low birth weight, Apgar scores less than 8, stillbirths, neonatal death, or congenital anomalies. CONCLUSIONS: Mitral valve surgery before or during pregnancy did not significantly improve maternal and fetal outcomes but decreased adverse events such as congestive heart failure and cardiac arrhythmias. It should be therefore performed only in selected cases.
OBJECTIVES: To observe the effect of the antioxidant lycopene on the occurrence of pre-eclampsia and intrauterine growth retardation in primigravida women. METHODS: A total of 251 primigravida women were enrolled in this prospective, randomized controlled study in the second trimester. A total of 116 women were given oral lycopene (Group I) in a dose of 2 mg twice daily while 135 women were given a placebo (Group II) in the same dose until delivery. The criteria for recruitment included gestational age of 16-20 weeks, singleton pregnancy, absence of any medical complication and willingness on the part of the women to participate in the study. The women were followed-up until delivery for development of pre-eclampsia, mode of delivery and fetal outcome. RESULTS: The two groups were comparable in their maternal characteristics. Pre-eclampsia developed in significantly less women in the lycopene group than in the placebo group (8.6% vs. 17.7%, P=0.043 by chi-square test). Mean diastolic blood pressure was significantly higher in the placebo group (92.2+/-5.98 mmHg vs. 86.7+/-3.80 mmHg, P=0.012). Mean fetal weight was significantly higher in the lycopene group (2751.17+/-315.76 g vs. 2657+/-444.30 g, P=0.049). The incidence of intrauterine growth retardation was significantly lower in the lycopene group than in the placebo group (12% vs. 23.7%, P=0.033). CONCLUSIONS: The results of the present study suggest that the antioxidant lycopene reduces the development of pre-eclampsia and intrauterine growth retardation in primigravida women.
BACKGROUND: Pelvic inflammatory disease is a common problem faced by the gynecologists in there out patient department. AIM: The aim of the study was to evaluate the efficacy of three treatment combinations in the syndromic management of pelvic inflammatory disease in the out patient setting. SETTING DESIGN: In the medical college hospital patients presenting in gynecology out patient department were enrolled. MATERIAL AND METHODS: One hundred and sixty five women with diagnosis of pelvic inflammatory disease were randomized into three equal groups getting ciprofloxacin (500 mg) and tinidazole (600 mg) combination twice daily for 7 days (Group 1), a kit containing fluconazole (150 mg), azithromycin (1 gm) and secnidazole (2 mg) as one time dose (Group 2) and Doxycycline 100mg twice daily and metronidazole 200 mg thrice daily for seven days (Group 3). Severity score was determined on first visit and after 1 week and 4 weeks when patients were called for follow up. STATISTICAL ANALYSIS: Chisqare test, Krusker wallis test and Mann Whitney test. RESULTS: There was significant reduction in severity score after 1 week of treatment, which was further reduced after 4 weeks in all the three groups. Cure rate was highest in-group 1 (96%) followed by group 2 (93.5) and group 3 (91.3%) but the difference was not statistically significant. Resolution of inflammatory mass was highest in group 1. The incidence of side effects was highest and compliance was lowest in the doxycycline -metronidazole group, but the difference was not statistically significant. CONCLUSION: All the three treatment combinations were found to be equally effective in the syndromic management of pelvic inflammatory disease.
The use of the triterpenoid lupeol as a scaffold for the synthesis of lupeol-based libraries is described. Lupeol was anchored to a solid support (Rink amide/Sieber Amide) through aliphatic dicarboxylic acid moieties, which also served as a site for introducing diversity. The resulting polymer linked 3beta-O (resin-alkanoyl)-lup-20(29)-ene 3 was used to generate key intermediates 3beta-O (resin-alkanoyl)-30-bromo-lup-20(29)-ene 4 and 3beta-O (resin-alkanoyl)-30-amino-lup-20(29)-ene 6 for the generation of libraries based on disubstituted lupeol derivatives. A 96-member library was screened for its in-vitro antimalarial activity against Plasmodium falciparum.
The 3-substituted phenyl-5-isoxazolecarboxaldehydes have been identified as activated aldehydes for the generation of isoxazole-based combinatorial libraries on solid phase through automation. Three highly functionalized isoxazole-based libraries comprising of 32, 96 and 45 compounds each have been synthesized in parallel format using Baylis Hillman reaction, Michael addition, reductive amination and alkylation reactions. With an objective of lead generation all the three libraries were evaluated for their antithrombin activity in vivo.
Four sets of mixture based nonapeptide libraries derived from an antifungal hexapeptide pharmacophore Arg-D-Trp-D-Phe-Ile-D-Phe-His-NH(2) (II) have been synthesized. The three C-terminal positions 7, 8 and 9 were subject to randomization using 19 genetically coded amino acids. They were then screened for their antifungal activity against Candida albicans and Cryptococcus neoformans in order to quantify inhibition at each step of the nonapeptide sublibrary deconvolution. The studies led to the identification of several novel nonapeptides with potent antifungal activity. Two of the nonapeptides exhibited approximately 17-fold increase in the activity in comparison to the lead hexapeptide motif His-D-Trp-D-Phe-Phe-D-Phe-Lys-NH(2) (I) against C. albicans.
OBJECTIVES: To analyze the maternal and perinatal outcome in varying degrees of anemia. METHODS: A total of 447 pregnant women were divided into group I (Hb>11 g%, n=123 women), group II (Hb 9-10.9 g%, n=214 women), group III (Hb 7-8.9 g%, n=79 women) group IV (Hb<7 g%, n=31 women). Their maternal and perinatal outcome, mode of delivery, duration of labor and postpartum complications were noted and analyzed using multiple logistic regression to calculate odds ratios (95% CI) for duration of labor, mode of delivery and low birth babies. Chi square or Fisher's exact test was employed for difference in proportions and Student's t-test for testing difference between means. RESULTS: Mean age (27+/-4.25 years) and number of women with parity >3 were highest in group IV. The patients with Hb<8.9 g% had a 4-6-fold higher risk of prolonged labor compared to Hb>11 g%. The odds ratios for abnormal delivery (cesarean and operative vaginal deliveries) showed a 4.8-fold higher risk (95% CI 1.82, 12.7) in patients with Hb </=7.5 g%. The mean birth weight was maximum in the 9.6-10.5 g% category that fell with both increasing and decreasing hemoglobin values, being lowest in Group IV. Women in Group II had lowest number of low birth weight and IUGR babies, no stillbirths and neonatal deaths, lowest induction and operative delivery rates. CONCLUSIONS: Mild anemia fared best in maternal and perinatal outcome. Severe anemia was associated with increased low birth weight babies, induction rates, operative deliveries and prolonged labor.
The stereocontrolled reduction of 3-aryl-5-acetylisoxazolines (1) to the corresponding alcohols (2 and 3) in the presence of four different yeast strains, recognized as Baker's yeast (commercial), Candida krusei (ATCC 14243), Pichia farinosa (NRRL Y110) and Sacchromyces sp. (soil isolate) have been attempted. The C. krusei was found to be diastereoselective for the (R)-1 while the Sacchromyces sp. led to complete reduction to yield the RS- and SS-alcohol in 1:1 ratio at 10 g/L scale.