Molecular modelling studies on adamantane-based Ebola virus GP-1 inhibitors using docking, pharmacophore and 3D-QSAR.

The pathogenic Ebola virus (EBOV) causes a potential health risk and global spread. To date, few drugs are available for the treatment of Ebola virus disease (EVD) that allow researchers to use computational methods for designing potential drugs. The developed PHASE-based common six-point pharmacophore hypothesis (AADHPR_1) showed the necessity of two hydrogen bond acceptor features, one hydrogen bond donor feature, one hydrophobic group feature, one positively ionizable and one aromatic ring feature for further designing. We developed best 3D-QSAR models with high regression coefficients for the training (r2>0.82) and test (Q2>0.5) sets for both atoms-based and field-based 3D-QSAR models. The molecule 1A-4 (docking score = -4.711 kcal/mol) was obtained as best docked (SP mode) on Ebola virus envelope glycoprotein (PDB ID-3CSY) as compared with the standards oseltamivir (docking score = -4.39 kcal/mol) and zanamivir (docking score = -3.392 kcal/mol). The obtained ZINC hit ZINC58935541 showed a good docking score of -4.892 kcal/mol. The ZINC58935541 molecule also showed a strong binding affinity towards the receptor cavity of Ebola virus envelope glycoprotein when simulated for 1.2 ns. The good QikProp parameters reflect the fact that this molecule, upon optimization into a lead, might become a good candidate for the treatment of EVD.

Morbidly Adherent Placenta: Its Management and Maternal and Perinatal Outcome.

OBJECTIVES: The aim of the study was to identify the risk factors predisposing to morbidly adherent placenta and to study the different modes of management and the obstetric and neonatal outcome of these patients. METHODS: This was a retrospective cum prospective observational study conducted in the Department of Obstetrics and Gynaecology in a tertiary care referral hospital in Mumbai from January 2012 to November 2014. RESULTS: The incidence of morbidly adherent placenta was 1.32 per 1000 pregnancies with patient profile comprising second gravida in the age group 26-28 years; 90 % of the patients in this study had previous Caesarean section and co-existing placenta praevia was diagnosed in 63 %. Fifty-three per cent of the women delivered between 35 and 38 weeks and 40 % had elective deliveries. Caesarean section was the mode of delivery in 90 % of the patients. Prophylactic balloon placement in the internal iliac artery followed by classical Caesarean section, uterine artery embolization and post-operative methotrexate was done in 27 % which preserved the uterus and was associated the blood loss of 1000-2000 mL. CONCLUSION: Antenatal diagnosis of morbidly adherent placenta allows for multidisciplinary planning in an attempt to minimize potential maternal or neonatal morbidity and mortality.

Expression and localization of collectins in feto-maternal tissues of human first trimester spontaneous abortion and abortion prone mouse model.

Dysregulation of immune response at the feto-maternal interface during first trimester of pregnancy is one of the leading causes of spontaneous abortion. Previously, we reported differential expression of collectins, soluble pattern recognition molecules involved in immunoregulation, in placental and decidual tissues during spontaneous labor. In the present pilot study, the expression of collectins was analyzed in the inflamed human gestational tissues of spontaneous abortion ('SA') and in 13.5 dpc placental tissues from resorption survived embryos of murine model (CBA/J X DBA/2J). Transcripts of SP-A were significantly down-regulated and SP-D were significantly up-regulated in placental and decidual tissues of 'SA' group compared to that of 'normal' group. Immunostaining for SP-D and MBL proteins was positive in placental and decidual tissues. However, levels of SP-D and MBL proteins were not significantly altered in placental as well as in decidual tissues of 'SA' group in comparison to the 'normal' group. Placental tissues of viable embryos from the abortion prone mouse model showed significantly enhanced expression of mSP-A and mSP-D transcripts at 13.5 day post coitus (dpc) and 14.5 dpc compared to the control group (CBA/J X Balb/c). Mouse collectins were localized in placental tissues (13.5 dpc), with increased staining in murine model compared to control. Human and murine data together indicate that SP-A, SP-D and MBL are synthesised in early gestational tissues, and may contribute to regulation of immune response at the feto-maternal interface during pregnancy.

Characterization and Fungal Inhibition Activity of Siderophore from Wheat Rhizosphere Associated Acinetobacter calcoaceticus Strain HIRFA32.

Acinetobacter calcoaceticus HIRFA32 from wheat rhizosphere produced catecholate type of siderophore with optimum siderophore (ca. 92 % siderophore units) in succinic acid medium without FeSO4 at 28 °C and 24 h of incubation. HPLC purified siderophore appeared as pale yellow crystals with molecular weight [M(+1)] m/z 347.18 estimated by LCMS. The structure elucidated by (1)H NMR, (13)C NMR, HMQC, HMBC, NOESY and decoupling studies, revealed that siderophore composed of 2,3-dihydroxybenzoic acid with hydroxyhistamine and threonine as amino acid subunits. In vitro study demonstrated siderophore mediated mycelium growth inhibition (ca. 46.87 ± 0.5 %) of Fusarium oxysporum. This study accounts to first report on biosynthesis of acinetobactin-like siderophore by the rhizospheric strain of A. calcoaceticus and its significance in inhibition of F. oxysporum.

Gender-dimorphic regulation of antioxidant proteins in response to high-fat diet and sex steroid hormones in rats.

Despite the fact that gender dimorphism in diet-induced oxidative stress is associated with steroid sex hormones, there are some contradictory results concerning roles of steroid hormones in gender dimorphism. To evaluate the role of gender dimorphism as well as the effects of sex steroid hormones in response to high-fat diet (HFD)-induced oxidative stress, we measured cellular levels of major antioxidant proteins in the liver, abdominal white adipose tissue, and skeletal muscles of Sprague-Dawley rats following HFD or sex hormone treatment using Western blot analysis. Animal experiments revealed that 17ß-estradiol, (E2) and dihydrotestosterone (DHT) negatively and positively affected body weight gain, respectively. Interestingly, plasma levels of malondialdehyde (MDA) increased in both E2- and DHT-treated rats. We also observed that cellular levels of classical antioxidant proteins, including catalase, glutathion peroxidase, peroxiredoxin, superoxide dismutase, and thioredoxin, were differentially regulated hormone- and gender-dependent manner in various metabolic tissues. In addition, tissue-specific expression of DJ-1 protein with respect to HFD-induced oxidative stress in association with sex steroid hormone treatment was observed for the first time. Taken together, our data show that females were more capable at overcoming oxidative stress than males through feasible expression of antioxidant proteins in metabolic tissues. Although the exact regulatory mechanism of sex hormones in diet-induced oxidative stress could not be fully elucidated, the current data will provide clues regarding the tissue-specific roles of antioxidant proteins during HFD-induced oxidative stress in association with sex steroid hormones.

Modulation of drug release from nanocarriers loaded with a poorly water soluble drug (flurbiprofen) comprising natural waxes.

In this study, flurbiprofen (FLB) Solid Lipid Nanoparticles (SLN) composed from a mixture of beeswax and carnauba wax, Tween 80 and egg lecithin as emulsifiers have been prepared. FLB was incorporated as model lipophilic drug to assess the influence of matrix composition in the drug release profile. SLN were produced by microemulsion technique. In vitro studies were performed in Phosphate Buffered Saline (PBS). The FLB loaded SLN showed a mean particle size of 75 +/- 4 nm, a polydispersity index approximately 0.2 +/- 0.02 and an entrapment efficiency (EE) of more than 95%. Suspensions were stable, with zeta potential values in the range of -15 to -17 mV. DSC thermograms and UV analysis indicated the stability of nanoparticles with negligible drug leakage. Nanoparticles with higher beeswax content in their core exhibited faster drug release than those containing more carnauba wax.

Validated high performance thin layer chromatographic determination and content uniformity test for rosiglitazone in tablets.

A simple, rapid, precise and economical high performance thin layer chromatographic method has been developed and validated for determination of rosiglitazone in its tablet dosage form using caffeine as an internal standard. It was performed on silica gel 60 GF(254) thin layer chromatographic plates as a stationary phase using mobile phase methanol:toluene:chloroform:triethylamine (1:8:0.5:0.5 v/v/v/v) and the detection was carried out in the absorbance mode at 264 nm showing R(f) value 0.31 for rosiglitazone and 0.52 for caffeine. The linear regression data curve shows good linear relationship in the concentration range 1.0-7.0 µg/µl. The content uniformity test was carried out as per USP specification of the content uniformity test of 85-115%. The percent drug estimated of rosiglitazone from two different marketed formulations were found to be in the range 99.83-100.21. The recovery of drugs was carried out by standard addition method were found to be 100.21±1.06 and 100.04±0.30 by height and area respectively. The method was validated with the determination of accuracy, precision, specificity, linearity detector response and ruggedness. The proposed method provides a faster and cost effective quality control tool for routine analysis of content uniformity test for rosiglitazone in tablet formulation.

Angular ectopic pregnancy presenting as rupture of lateral wall of the uterus.

This is a case report of a 32-year-old woman, being treated for secondary infertility, with history of previous ectopic pregnancy, who presented to the emergency obstetrical room in a state of hypovolemic shock. A diagnosis of ruptured ectopic pregnancy was confirmed in view of history of 14 weeks amenorrhea with a positive urine pregnancy test and positive colpopunture. She was immediately shifted for an emergency exploratory laparotomy. Intraoperatively, the authors were surprised to encounter a right lateral wall rupture uterus and ~14 weeks foetus with the placenta lying freely in the peritoneal cavity. That was suggestive of a right interstitial ectopic which had grown up to 14 weeks, invaded the uterine cavity thus forming an angular ectopic, which ended up as the catastrophic event. The authors here wish to highlight that angular pregnancy is rare but it has catastrophic consequences including maternal mortality. Had the patient presented early, in view of history of previous ectopic, an ultrasonography and color Doppler would have been useful in early detection. And a fertility conserving management in the form of Methotrexate therapy or Selective Uterine artery embolization could have been done.