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Vasudeva Reddy Netala,1 Murali Satyanarayana Bethu,2,3 Bobbu Pushpalatha,1 Vijaya Bhaskar Baki,4 Sani Aishwarya,1 J Venkateswara Rao,2 Vijaya Tartte5 1Department of Biotechnology, Sri Venkateswara University, Tirupati, 2Biology Division, Indian Institute of Chemical Technology, Hyderabad, 3Academy of Scientific and Innovative Research, New Delhi, 4Department of Bioinformatics, 5Department of Botany, Sri Venkateswara University, Tirupati, India Abstract: An endophytic fungal strain isolated from the leaves of Gymnema sylvestre was identified as Pestalotiopsis microspora VJ1/VS1 based on nucleotide sequencing of internal transcribed spacer region (ITS 1-5.8S-ITS 2) of 18S rRNA gene (NCBI accession number KX213894). In this study, an efficient and ecofriendly approach has been reported for the synthesis of silver nanoparticles (AgNPs) using aqueous culture filtrate of P. microspora. Ultraviolet-visible analysis confirmed the synthesis of AgNPs by showing characteristic absorption peak at 435 nm. Fourier transform infrared spectroscopy analysis revealed the presence of phenolic compounds and proteins in the fungal filtrate, which are plausibly involved in the biosynthesis and capping of AgNPs. Transmission electron microscopy (TEM) showed that the AgNPs were spherical in shape of 2–10 nm in size. Selected area electron diffraction and X-ray diffraction studies determined the crystalline nature of AgNPs with face-centered cubic (FCC) lattice phase. Dynamic light scattering analysis showed that the biosynthesized AgNPs possess high negative zeta potential value of -35.7 mV. Biosynthesized AgNPs were proved to be potential antioxidants by showing effective radical scavenging activity against 2,2'-diphenyl-1-picrylhydrazyl and H2O2 radicals with IC50 values of 76.95±2.96 and 94.95±2.18 µg/mL, respectively. The biosynthesized AgNPs exhibited significant cytotoxic effects against B16F10 (mouse melanoma, IC50 =26.43±3.41 µg/mL), SKOV3 (human ovarian carcinoma, IC50 =16.24±2.48 µg/mL), A549 (human lung adenocarcinoma, IC50 =39.83±3.74 µg/mL), and PC3 (human prostate carcinoma, IC50 =27.71±2.89 µg/mL) cells. The biosynthesized AgNPs were found to be biocompatible toward normal cells (Chinese hamster ovary cell line, IC50 =438.53±4.2 µg/mL). Cytological observations on most susceptible SKOV3 cells revealed concentration-dependent apoptotic changes that include cell membrane blebbing, cell shrinkage, pyknotic nuclei, karyorrhexis followed by destructive fragmentation of nuclei. The results together in this study strongly provided a base for the development of potential and versatile biomedical applications of biosynthesized AgNPs in the near future. Keywords: AgNPs, Pestalotiopsis microspora, 18S rRNA, SKOV3, B16F10, AO-EB staining

Background: The increasing rate of maternal obesity in reproductive age group is a major challenge to obstetricians, as it can result in adverse outcomes for both women and foetuses making the pregnancy a high risk one. Aim and objectives of the study: Aim of the study is to evaluate the effect of obesity on maternal and perinatal outcome, in obesity complicating pregnancies. Objective is to assess the risk of obesity related complications in pregnancy by comparing with pregnancies with normal BMI. Methodology: Prospective cohort study done between January 2017 – January 2018 in the Department of Obstetrics and Gynecology at Gitam Institute of Medical Sciences and Research - hospital, deemed to be University, Visakhapatnam. Results: One hundred and five pregnant (105) women with BMI > 30kg/m2 and two hundred and ten (210) pregnant women with BMI 18.5kg/m2 to 25kg/m2 were selected and were followed prospectively. Obese group had 9.35 fold increased risk of gestational diabetes, 7.0 fold increased risk of preeclampsia and increased caesarean delivery rate (56.57%). There were increased admissions to NICU among newborns of obese women (25.26%) when compared to control group (8.37%). Conclusion: Pregnancies in obese women should be regarded as high risk pregnancies and appropriate antenatal, intranatal and post-natal care should be provided with heightened surveillance, with anticipation, early diagnosis and prompt intervention.

Background: Neonatal pneumonia contributes significantly to mortality due to pneumonia in the under-five age group, but the predictors of mortality are largely unknown., Objectives: To evaluate the clinical and microbiological characteristics and other risk factors that predict mortality in neonates admitted with pneumonia in tertiary care centres., Study Design: Prospective observational cohort study., Participants: Term and preterm (32 weeks to 36 6/7 weeks) neonates (<28 days of life) admitted with clinical and radiological features suggestive of pneumonia., Intervention: Baseline sociodemographic data, clinical details, blood culture and nasopharyngeal swabs for virologic assay (RT PCR for RSV, Influenza) were collected at admission and the neonates were observed throughout their hospital stay., Outcome: The primary outcome was predictors of mortality in neonatal pneumonia., Results: Five hundred neonates were enrolled in the study. Out of 476 neonates with known outcomes, 39 (8.2%) died. On multivariate analysis, blood culture positive sepsis was independently associated with mortality (adjusted OR 2.51, 95% CI1.23 to 5.11; P-0.01)., Conclusions: Neonates with blood culture positive pneumonia positive are at a higher risk of death.

L-Asparaginase (L-asparagine aminohydrolase, E.C. 3.5.1.1) has been proven to be competent in treating Acute Lymphoblastic Leukaemia (ALL), which is widely observed in paediatric and adult groups. Currently, clinical L-Asparaginase formulations are derived from bacterial sources such as Escherichia coli and Erwinia chrysanthemi. These formulations when administered to ALL patients lead to several immunological and hypersensitive reactions. Hence, additional purification steps are required to remove toxicity induced by the amalgamation of other enzymes like glutaminase and urease. Production of L-Asparaginase that is free of glutaminase and urease is a major area of research. In this paper, we report the screening and isolation of fungal species collected from the soil and mosses in the Schirmacher Hills, Dronning Maud Land, Antarctica, that produce L-Asparaginase free of glutaminase and urease. A total of 55 isolates were obtained from 33 environmental samples that were tested by conventional plate techniques using Phenol red and Bromothymol blue as indicators. Among the isolated fungi, 30 isolates showed L-Asparaginase free of glutaminase and urease. The L-Asparaginase producing strain Trichosporon asahii IBBLA1, which showed the highest zone index, was then optimized with a Taguchi design. Optimum enzyme activity of 20.57 U mL -1 was obtained at a temperature of 30 °C and pH of 7.0 after 60 hours. Our work suggests that isolation of fungi from extreme environments such as Antarctica may lead to an important advancement in therapeutic applications with fewer side effects.

Introduction: A sensitive and rapid method for quantitation of Sofosbuvir in human plasma has been established using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS)., Materials and Methods: Sofosbuvir d3 was used as an internal standard. Sofosbuvir and internal standard in plasma sample were extracted using ethyl acetate (liquid liquid extraction). A centrifuged upper layer was then evaporated and reconstituted with the mobile phase of 0.5% formic acid: methanol (30:70, v/v). The reconstituted samples were injected into a Gemini C18 (50×4.6mm, 5μm) column., Results: Using MS/MS in the multiple reaction monitoring mode, Sofosbuvir and Sofosbuvir d3 were detected without severe interferences from human plasma matrix. Sofosbuvir produced a protonated precursor ion ([M+H] + ) at m/z 428.35 and a corresponding product ion at m/z 279.26. The internal standard produced a protonated precursor ion ([M+H] + ) at m/z 431.38 and a corresponding product ion at m/z 282.37. The calibration curves for the analyte was linear (R 2 ≥0.9956, n=4) over the concentration range of 4.063-8000.010ng/mL. Stability studies revealed that Sofosbuvir was stable in plasma during bench top (7h at room temperature), in injector (20h), at the end of five successive freeze and thaw cycles and long term at -70°C±15°C for 15 days., Conclusion: The developed method was validated as per the guidelines of USFDA and the obtained results were found to be within the limits and could be successfully employed for the determination of Sofosbuvir in human plasma for regular and pharmacokinetic studies., (Copyright © 2017 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

This study outlines the toxic effects of Quinalphos (QP), an organophosphrous insecticide on the development of zebrafish (Danio rerio) embryos, with special emphasis on toxicomorphomics and toxicokinetics of target enzyme, AChE. A range of concentrations was used to elucidate the median lethal concentration (LC 50 ) of Quinalphos. Furthermore, embryos were exposed to two sub-lethal concentrations LC 10 (0.66mg/L) and LC 20 (1.12mg/L) along with a median lethal concentration (3.0mg/L) for 96h. Several morphological aberrations like lordosis, kyphosis, scoliosis, heart edema, breaks in the neuronal tube and underdeveloped facial parts were noticed, which were of concentration and time dependent. The QP has adequately hindered hatching process during the course of exposure which was upheld by the in silico docking studies with hatching enzyme, ZHE1. The length of hatchlings at 96h in LC 50 concentration was significantly reduced to 47% compared to control. A significant pericardial effusion (5 to 16 fold) was observed in >90% of LC 50 treated groups. Morphological changes in heart lead to the bradycardia, which ultimately leading to heart failure in some cases. The swimming behavior was significantly diminished in relation to the inhibition of AChE levels. From the in vitro kinetic studies, the kinetic constants K m , V max and inhibitory concentration K i (4.45×10 -5 M) was determined which supported the competitive nature of QP., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Studies on the effect of curcumin/PLGA ratio (CPR), stabilizer (PVA) concentration, homogenization speed, homogenization time, and sonication time on mean particle size (MPS) and percentage drug encapsulation (PDE) were performed using the multivariate technique. MPS and PDE were found to be more dependent on the interaction of sonication time with the other variables. Curcumin was released in a sustained manner from curcumin-PLGA nanoparticles (CPN). CPN improved the survival rate of Ehrlich ascites carcinoma (EAC)-bearing mice and controlled the EAC-induced change in hematological parameters. Histopathology of vital organs showed that the formulation was safe. Polycaprolactone was used in preparing an in situ implant containing CPN.

Context: The study was aimed to develop a polymeric nanoparticle formulation of anticancer drug carboplatin using biodegradable polymer polycaprolactone (PCL). The formulation is intended for intranasal administration to treat glioma anticipating improved brain delivery as nasal route possess direct access to brain and nanoparticles have small size to overcome the mucosal and blood-brain barrier., Objective: Development and evaluation of carboplatin-PCL nanoparticles for brain delivery by nasal route., Methodology: Carboplatin-loaded PCL nanoparticles (CPCs) were prepared by double emulsion-solvent evaporation technique and characterized by particle size, zeta potential, entrapment efficiency, scanning electron microscopy and differential scanning calorimetry. The CPCs were assessed for in vitro release kinetics, ex vivo permeation and in situ nasal perfusion. Cytotoxic potential of CPCs in vitro was evaluated on LN229 human glioblastoma cells., Results and Discussion: The optimized formulation of carboplatin-PCL nanoparticle CPC-08 with particle size of 311.6 ± 4.7 nm and zeta potential -16.3 ± 3.7 mV exhibited percentage entrapment efficiency of 27.95 ± 4.21. In vitro drug release showed initial burst release followed by slow and continues release indicating biphasic pattern. The ex vivo permeation pattern through sheep nasal mucosa also exhibited a similar release pattern as for in vitro release studies. In situ nasal perfusion studies in Wistar rats demonstrate that CPCs show better nasal absorption than carboplatin solution. In vitro cytotoxicity studies on LN229 cells showed an enhancement in cytotoxicity by CPCs compared to carboplatin alone., Conclusion: CPC-08 effectively improves nasal absorption of carboplatin and can be used for intranasal administration of carboplatin for improved brain delivery.

In order to exploit the potential benefits of antimicrobial combination therapy, we need a better understanding of the circumstances under which pharmacodynamic interactions expected. In this study, Pharmacodynamic interactions between silver nanoparticle (SNP) and topical antibiotics such as Cefazolin (CEF), Mupirocin (MUP), Gentamycin (GEN), Neomycin (NEO), Tetracycline (TET), Vancomycin (VAN) were investigated using the MIC test, Combination assay followed by Fractional Inhibitory concentration Index and Agar well diffusion method. SNP + MUP, SNP + NEO, SNP + VAN combinations showed Synergism (SN) and SNP + CEF, SNP + GEN, SNP + TET showed Partial synergism (PS) against Staphylococcus aureus. Four combinations (SNP + CEF, SNP + MUP, SNP + GEN, SNP + VAN) showed SN, SNP + TET showed PS and Indifferent effect (ID) were observed for SNP + NEO against Pseudomonas aeruginosa. SN was observed for SNP + CEF, SNP + GEN, SNP + NEO, SNP + TET and SNP + MUP showed ID, SNP + VAN showed PS against Escherichia coli. In addition, we elucidated the possible mechanism involved in the pharmacodynamic interaction between SNP-topical antibiotics by increased ROS level, membrane damage following protein release, K(+) leakage and biofilm inhibition. Thus, our findings support that conjugation of the SNP with topical antibiotics have great potential in the topical formulation when treating complex resistant bacterial infections and where there is a need of more concentration to kill pathogenic bacteria.

Lercanidipine is a vasoselective dihydropyridine calcium antagonist, mainly used for the treatment of hypertension and angina pectoris. However, it suffers from food dependent absorption, poor solubility, low permeability and considerable first pass metabolism, resulting in highly variable and low bioavailability of 10%. Nanoparticles of lercanidipine were incorporated in fast dissolving oral films (FDO) via preparation of nanosuspension by evaporative antisolvent precipitation method. Prepared nanosuspensions were incorporated in FDO without lyophilizing or spray drying. Two nanosuspensions containing PEG 400 and TPGS 1000 as stabilizers, were selected further for incorporation in FDO. Physicochemical and mechanical properties of the optimized films were observed to be within acceptance criteria. SEM images as well as FTIR chemical images of oral films show uniform distribution of nanoparticles in polymeric matrix. The DSC and XRD results proved the poorly crystalline nature of lercanidipine. However thermal processing of film induces crystallinity in hypromellose which results in embedding of amorphous drug nanoparticles in semicrystalline polymeric matrix. Superior dissolution and permeability properties of nanoparticles were confirmed by in vitro dissolution studies and about 4.5-folds higher ex vivo drug permeation was observed from formulation through porcine buccal mucosa. This may give the clue for enhancement of bioavailability in vivo via improving orotransmucosal absorption., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The current study is aimed to study cytotoxicity and oxidative stress mediated changes induced by copper oxide nanoparticles (CuO NPs) in Chinook salmon cells (CHSE-214). To this end, a number of biochemical responses are evaluated in CHSE-214 cells which are as follows [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] MTT, neutral red uptake (NRU), lactate dehydrogenase (LDH), protein carbonyl (PC), lipid peroxidation (LPO), oxidised glutathione (GSSG), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione sulfo-transferase (GST), superoxide dismutase (SOD), catalase (CAT), 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and reactive oxygen species (ROS), respectively. The 50% inhibition concentration (IC50) of CuO NPs to CHSE-214 cells after 24 h exposure was found to be 19.026 μg ml(-1). Viability of cells was reduced by CuO NPs, and the decrease was dose dependent as revealed by the MTT and NRU assay. CHSE-214 cells exposed to CuO NPs induced morphological changes. Initially, cells started to detach from the surface (12 h), followed by polyhedric, fusiform appearance (19 h) and finally the cells started to shrink. Later, the cells started losing their cellular contents leading to their death only after 24 h. LDH, PC, LPO, GSH, GPx, GST, SOD, CAT, 8-OHdG and ROS responses were seen significantly increased with the increase in the concentration of CuO NPs when compared to their respective controls. However, significant decrease in GSSG was perceptible in CHSE-214 cells exposed to CuO NPs in a dose-dependent manner. Our data demonstrated that CuO NPs induced cytotoxicity in CHSE-214 cells through the mediation of oxidative stress. The current study provides a baseline for the CuO NPs-mediated cytotoxic assessment in CHSE-214 cells for the future studies.

Context: Polymeric delivery system is useful in reducing pharmacokinetic limitations viz., poor absorption and rapid elimination associated with clinical use of curcumin. Design of experiment is a precise and cost effective tool useful in analyzing the effect of independent variables and their interaction on the product attributes., Objective: To evaluate the effect of process variables involved in preparation of curcumin-loaded polycaprolactone (PCL) nanoparticles (CPN)., Materials and Methods: In the present experiment, CPNs were prepared by emulsification solvent evaporation technique. The effect of independent variables on the dependent variable was analyzed using design of experiments. Anticancer activity of CPN was studied using Ehrlich ascites carcinoma (EAC) model. In-situ implant was developed using PLGA as polymer., Results and Discussion: The effect of independent variables was studied in two stages. First, the effect of drug-polymer ratio, homogenization speed and surfactant concentration on size was studied using factorial design. The interaction of homogenization speed with homogenization time on mean particle size of CPN was then evaluated using central composite design. In the second stage, the effect of these variables (under the conditions optimized for producing particles <500 nm) on percentage drug encapsulation was evaluated using factorial design. CPN prepared under optimized conditions were able to control the development of EAC in Swiss albino mice and enhanced their survival time. PLGA based in-situ implant containing CPN prepared under optimized conditions showed sustained drug release., Conclusion: This implant could be further evaluated for pharmacological activities.

Background: Polio eradication needs a new routine immunisation schedule--three or four doses of bivalent type 1 and type 3 oral poliovirus vaccine (bOPV) and one dose of inactivated poliovirus vaccine (IPV), but no immunogenicity data are available for this schedule. We aimed to assess immunogenicity of this vaccine schedule., Methods: We did an open-label, randomised controlled trial in four centres in India. After informed consent was obtained from a parent or legally acceptable representative, healthy newborn babies were randomly allocated to one of five groups: trivalent OPV (tOPV); tOPV plus IPV; bOPV; bOPV plus IPV; or bOPV plus two doses of IPV (2IPV). The key eligibility criteria were: full-term birth (≥37 weeks of gestation); birthweight ≥2·5 kg; and Apgar score of 9 or more. OPV was administered at birth, 6 weeks, 10 weeks, and 14 weeks; IPV was administered intramuscularly at 14 weeks. The primary study objective was to investigate immunogenicity of the new vaccine schedule, assessed by seroconversion against poliovirus types 1, 2, and 3 between birth and 18 weeks in the per-protocol population (all participants with valid serology results on cord blood and at 18 weeks). Neutralisation assays tested cord blood and sera collected at 14 weeks, 18 weeks, 19 weeks, and 22 weeks by investigators masked to group allocation. This trial was registered with the India Clinical Trials Registry, number CTRI/2013/06/003722., Findings: Of 900 newborn babies enrolled between June 13 and Aug 29, 2013, 782 (87%) completed the per-protocol requirements. Between birth and age 18 weeks, seroconversion against poliovirus type 1 in the tOPV group occurred in 162 of 163 (99·4%, 95% CI 96·6-100), in 150 (98·0%, 94·4-99·6) of 153 in the tOPV plus IPV group, in 153 (98·7%, 95·4-99·8) of 155 in the bOPV group, in 155 (99·4%, 96·5-100) of 156 in the bOPV plus IPV group, and in 154 (99·4%, 96·5-100) of 155 in the bOPV plus 2IPV group. Seroconversion against poliovirus type 2 occurred in 157 (96·3%, 92·2-98·6) of 163 in the tOPV group, 153 (100%, 97·6-100·0) of 153 in the tOPV plus IPV group, 29 (18·7%, 12·9-25·7) of 155 in the bOPV group, 107 (68·6%, 60·7-75·8) of 156 in the bOPV plus IPV group, and in 121 (78·1%, 70·7-84·3) of 155 in the bOPV plus 2IPV group. Seroconversion against poliovirus type 3 was achieved in 147 (90·2%, 84·5-94·3) of 163 in the tOPV group, 152 (99·3%, 96·4-100) of 153 in the tOPV plus IPV group, 151 (97·4%, 93·5-99·3) of 155 in the bOPV group, 155 (99·4%, 96·5-100) of 156 in the bOPV plus IPV group, and 153 (98·7%, 95·4-99·8) of 155 in the bOPV plus 2IPV group. Superiority was achieved for vaccine regimens including IPV against poliovirus type 3 compared with those not including IPV (tOPV plus IPV vs tOPV alone, p=0·0008; and bOPV plus IPV vs bOPV alone, p=0·0153). 12 serious adverse events occurred (six in the tOPV group, one in the tOPV plus IPV group, three in the bOPV group, zero in the bOPV plus IPV group, and two in the bOPV plus 2IPV group), none of which was attributed to the trial intervention., Interpretation: The new vaccination schedule improves immunogenicity against polioviruses, especially against poliovirus type 3., Funding: WHO, through a grant from Rotary International (grant number 59735)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aim: Quantitative estimation of lercanidipine HCl in bulk material as well as from nanosuspension formulations via a developed reverse phase HPLC method., Materials and Methods: Optimized chromatographic condition was used to achieve separation on a Kromasil (100-5c18 250 × 4.6 mm) column using Shimadzu HPLC system. The mobile phase consisted of a mixture of acetate buffer (20 mM pH 4.5) and acetonitrile in the ratio of 10:90, v/v. It is pumped through the chromatographic system at a flow rate of 1 ml/min. The detection was carried out at 240 nm using ultraviolet-visible spectrophotometry detector. The method was validated as per Q2 (R1) guidelines, and suitability of the developed method was established by optimized nanosuspension formulation., Results: The method is specific to lercanidipine (RT: 7.7 min), and has ability to resolve the analyte peak from excipient interferences. It is linear (regression coefficient: 0.9993), accurate (average recovery: 100%), and passed all the system suitability requirements., Conclusion: Developed method was found applicable for evaluation of drug content, content uniformity, and analyzing samples of dissolution studies of nanosuspension.

Introduction: Malrotation of midgut is considered to be a condition of childhood. This study evaluated malrotation in adults with recurrent abdominal pain (RAP)., Methods: Sixty-four consensus-confirmed cases of intestinal malrotation were reviewed. The diagnosis was based on radiological criteria, and the consensus was arrived at by at least three of the five authors in any individual case., Results: Abnormal duodenojejunal junction (DJJ) was a consensus finding in 64 cases referred for RAP. Most were in their fourth decade of life, and 12 were beyond 60 years. Besides RAP, intolerance to food was the next common symptom. Acute intestinal obstruction was seen in 16. Forty-two of 64 patients consented for surgery. Ladd's procedure was the commonest. All patients who underwent surgery were symptom free except for two, of which, one had liver cyst and the other had hernia. Of those who refused surgery (22), all had continued symptoms and 10 patients took alternative therapies. On follow up of initially unwilling patients (for surgery) with abnormal DJJ, only eight consented for surgery; three underwent open Ladd's procedure, and one had laparoscopic Ladd's done., Conclusion: Malrotation is not uncommon as a cause of RAP in adults.

Titanium oxide nanoparticles (TiO2 NPs) have received wide attention in diverse application, but the potential impact of these nanomaterials on the environment, aquatic life and especially on fish cell lines is lacking. The present study aimed to investigate the cytotoxicity and oxidative stress induced by TiO2 NPs on Chinook salmon cells derived from Oncorhynchus tshawytscha embryos (CHSE-214). The The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] and neutral red (NR) assays in CHSE-214 cells exposed to TiO2 NPs revealed concentration-dependent cytotoxic effect in the range of 10 to 60 μg/ml for 24 h. CHSE-214 cells exposed to TiO2 NPs (10-60 μg/ml) exhibited significant decline in superoxide dismutase (SOD), catalase (CAT) glutathione (GSH) content and increased lipid peroxidation (LPO) in a concentration-dependent manner. TiO2 NPs induced cytotoxicity and oxidative stress in CHSE-214 cells which serve as a base line studies for future studies.

Background: Japanese encephalitis (JE) is a vaccine-preventable acute disease. We report the results of a phase 2/3 trial of JENVAC, a Vero cell-derived vaccine developed using an Indian strain of JE virus (JEV)., Methods: JENVAC was administered in 2 doses 28 days apart, and immunogenicity was compared to that from a single dose of SA-14-14-2, the only approved JE vaccine and regimen at the time in India., Results: After both the doses, seroconversion and seroprotection were >90% for JENVAC. For SA-14-14-2, seroconversion and seroprotection were 57.69% and 77.56%, respectively, on day 28 and 39.74% and 60.26%, respectively, on day 56. The geometric mean titers at day 28 and day 56 were 145.04 and 460.53, respectively, for JENVAC and 38.56 and 25.29, respectively, for SA-14-14-2. With a single dose of JENVAC, seroprotection titers lasted at least 12 months in >80% of the subjects. Following receipt of 2 doses, 61.17% of subjects retained seroprotection titers at 24 months, and immunogenicity criteria were higher than that for SA-14-14-2 at 12, 18, and 24 months each. Sera from JENVAC subjects neutralized JEV genotypes I, II, III, and IV equally well. Adverse events were not significantly different between the 2 vaccines., Conclusions: JENVAC elicits long-lasting, broadly protective immunity., Clinical Trials Registration: CTRI/2011/07/001855., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Purpose: This paper describes a simple, precise and accurate RP-HPLC method for simultaneous estimation of atorvastatin and ezetimibe in plasma., Methods: The chromatographic separation of the drugs were performed on an X-Terra C8 (4.6 x 150 mm, 3.5 mm), with phosphate buffer [pH 3.5 with Ortho Phosphoric Acid] - acetonitrile 40:60 (v/v) as mobile phase. The detection was performed at 235 nm. The flow rate was maintained at 1.2 mL/min. The run time was 8.0 min., Results: The accuracy and reliability of the method was assessed by evaluation of linearity (5-25 µg/mL for both atorvastatin calcium and ezetimibe), precision (intra-day RSD 0.57 % and inter-day RSD 0.02 % for atorvastatin calcium and intra-day RSD 0.56 % and inter-day RSD 0.1 % for ezetimibe), accuracy (100.08- 100.84 % for atorvastatin calcium and 100.56- 101.00 % for ezetimibe), and specificity, in accordance with ICH guidelines. The LLOQ obtained by the proposed method were 1.294 and 1.384 µg/mL for atorvastatin and ezetimibe respectively., Conclusion: Overall the proposed method was found to be suitable and accurate for the quantitative determination in plasma. The method was effectively separated the drug from plasma.

The study was conducted to explore the modulatory effects of chlorpyrifos and protective role of vitamin C in tissues of Clarias batrachus. Treatments include E1 group (basal diet plus 1.65mgL(-1) CPF) and E2 group (basal diet+200mgkg body weight vitamin C and 1.65mgL(-1) CPF) along with a control group of fishes (fed on basal diet only). After 1, 7, 15, and 30d of treatment, fish tissues (brain, blood and liver) were used for the estimation of growth, biochemical and haematological parameters. The results of E1 group indicated significantly lower weight gain and survival rate. Brain AChE activity was inhibited. The RBC, Hb, respiratory burst activity, total protein and HSI were also reduced whereas WBC count, plasma glucose and haematocrit were elevated. In contrast, liver glycogen content, lactate dehydrogenase, alkaline and acid phosphatase activities were inhibited and malate dehydrogenase, aspartate, alanine amino transferase were enhanced. The E2 group of fish exhibited significant improvement in growth, survival, haematological indices, brain AChE, liver glycogen and oxidative enzyme activity. The findings support that dietary vitamin C supplementation might be helpful in abrogation of chlorpyrifos toxicity and improves growth, survival, biochemical and haematological conditions in fishes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A comprehensive investigation of chemical constituents from brown algae Stoechospermum marginatum yielded ten known spatane compounds (1-10). To develop the compound libraries on these scaffolds, a series of semi synthetic derivatives was prepared (1a-1d, 2a, 4a, 11 and 12) and investigated for their anti-microbial and anticancer activities. The results indicated that compounds 2a, 4, 1b and 4a exhibited potent cytotoxic activities against B16F10 cancer cell line with IC50 values of 3.28, 3.45, 3.62 and 4.11 μg/ml respectively, which are comparable to the standard drug (etoposide IC50=4.12 μg/ml). In addition, 4 and 1b were also manifested potent antimicrobial activities against tested bacterial and fungal strains. This is the first Letter on the synthesis and biological activities of these novel derivatives., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

1H-1,2,3-Triazolylbenzohydrazides (6a-h and 11a-l) were synthesized from 2-chloronicotinaldehydes and evaluated for anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv strain (ATCC-27294). Seven compounds 6b, 6e,f, 11d, 11h, 11j and 11l displayed potent anti-mycobacterial activity (MIC 2.8-6.2 μM). Potent anti-mycobacterial compounds were chosen for cytotoxicity studies by MTT protein assay against normal cell lines (PBMC and Raw 264.7) and shown low cytotoxicity. This is the first Letter assigning anti-mycobacterial activity, cytotoxicity and structure activity relationship for 1H-1,2,3-triazolylbenzohydrazides., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Context: Delivery of a drug into the central nervous system (CNS) is considered difficult. Most of the drugs discovered over the past decade are biological, which are high in molecular weight and polar in nature. The delivery of such drugs across the blood-brain barrier presents problems., Objective: This review discusses some of the options available to reach the CNS by systemic route. The focus is mainly on the recent developments in systemic delivery of a drug to the CNS., Materials and Methods: Databases such as Scopus, Google scholar, Science Direct, SciFinder and online journals were referred for preparing this article including 89 references., Results: There are at least nine strategies that could be adopted to achieve the required drug concentration in the CNS., Conclusion: The recent developments in drug delivery are very promising to deliver biologicals into the CNS.

Objectives: To evaluate the efficacy of liraglutide with pioglitazone for prevention of dexamethasone induced hepatic steatosis, dyslipidemia and hyperglycemia in Albino rats., Materials and Methods: There were four groups of six rats each. First group received dexamethasone alone in a dose of 8 mg/kg intraperitoneally for 6 days to induce metabolic changes and considered as dexamethasone control. Second group received liraglutide 1.8 mg/kg subcutaneously 6 days before dexamethasone and 6 days during dexamethasone administration. Third group received pioglitazone 45 mg/kg orally 6 days before dexamethasone and 6 days during dexamethasone administration. Fourth group did not receive any medication and was considered as normal control. Fasting blood sugar, lipid profile, blood sugar 2 h after glucose load were measured. Liver weight, liver volume, and histopathological analysis were done., Results: Dexamethasone caused hepatomegaly, dyslipidemia, and hyperglycemia. Both pioglitazone and liraglutide significantly reduced hepatomegaly, dyslipidemia and hyperglycemia (P < 0.01). Reduction of blood sugar levels after glucose load was significant with pioglitazone when compared with liraglutide (P < 0.01)., Conclusion: Liraglutide has comparable efficacy to pioglitazone in prevention of dexamethasone induced hepatomegaly, dyslipidemia and fasting hyperglycemia.

The aim of the present study was to evaluate the developmental toxicity of profenofos to early developing Zebrafish (Danio rerio) embryos (4h post fertilization) in a static system at 1.0 to 2.25mg/L. Median lethal concentrations (LC50) of profenofos at 24-h, 48-h, 72-h and 96-h were determined as 2.04, 1.58, 1.57 and 1.56 mg/L, respectively. The hatching of embryos were recorded at every 12h interval and the median hatching time (HT50) was also calculated for each concentration. In a separate set of experiments, 96-h LC10 (0.74 mg/L) and LC50 (1.56 mg/L) concentrations were used to assess the developmental toxicity in relation to behavior, morphology, and interactions with the targeted enzyme acetylcholinesterase. Live video-microscopy revealed that the profenofos exposed embryos exhibited an abnormal development, skeletal defects and altered heart morphology in a concentration-dependent manner, which leads to alterations in the swimming behavior of hatchlings at 144-h, which indicate that developing zebrafish are sensitive to profenofos., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Cyclodextrins (CDs) are carrier molecules produced by cyclization of α-1,4-glucans by Cyclodextrin Glycosyl Transferase (CGTase). These torus shaped molecules have hydrophobic cavity and hydrophilic shell making them useful in pharmaceutical, food, textile, pesticide and cosmetic industries. In this study, culture conditions for the production of CGTase by organism belonging to Arthrobacter genus obtained from a paddy field soil were optimized by single parameter mode. Soluble starch, yeast extract and magnesium sulphate played an important role in CGTase production. Percentage increase in CGTase yield under optimized conditions was 396.77%. The enzyme precipitated by 60% ammonium sulphate was purified using DEAE-sepharose. The molecular weight of the purified protein as determined by SDS-PAGE was 75 kDa. Purified CGTase was thermostable and stable over a wide pH range. Dissolution studies on β -cyclodextrin-Irbesartan complex revealed that β -CDs formed were useful in preparing immediate release oral dosage forms.

Background and Objective: There has been relatively little investigation of the effect of temperature on skin permeation compared to other methods of penetration enhancement. A principal physicochemical factor which controls the passive diffusion of a solute from a vehicle into the skin arises from the skin temperature. The aim of this ex vivo study was to probe into the effect of heat on transdermal absorption of alfuzosin hydrochloride from ethyl cellulose-polyvinyl pyrrolidone (EC-PVP) based transdermal systems., Materials and Methods: Principles of design of experiment (DoE) were used to systematically study the influence of temperature on transdermal permeation of alfuzosin. Ex vivo transdermal permeation studies were carried out at varied donor compartment temperatures. Permeation data analysis was carried out and activation energy for transdermal permeation was estimated., Results: Temperature found to enhance ex vivo permeation parameters of alfuzosin hydrochloride from its transdermal systems. It was also noted that chemical permeation enhancers potentiate permeation enhancing effect of temperature. The permeation flux values approximately doubled after exposure to 45°C. The activation energy for transdermal permeation was found lower for the runs with chemical permeation enhancers indicating existence of a lower energy barrier in the presence of chemical permeation enhancers., Conclusion: The method reported here is a simple and useful tool for studying the effect of heat on percutaneous absorption. Such temperature dependent enhancement of flux can be more pronounced at skin surface temperatures >45°C., (Copyright © 2015 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Every year more than 12,000 people in US alone suffer from spinal cord injury. However, complete recovery of physical function is difficult due to multiple factors involved in disease progression. Currently available therapeutic regimens do not address all the factors concerned with the disease progression. The present review focuses mainly on the role of immune cells in progression of spinal cord injury and the drugs that target these immune cells. Literature search shows that inflammatory reactions and subsequent reactions that follow direct injury to spinal cord are sometimes responsible for the severity of the disease. Therefore, for design of proper treatment regimen a deep understanding in this area is required. Understanding the pathophysiology will help in creating delivery system that can target multiple factors involved in progression of spinal cord injury. A combination of various treatment strategies is required to reduce the disability in patients with spinal cord injury.

Background: Rotavirus is the leading cause of severe, dehydrating diarrhea in children aged <5 years globally, with an estimated 25 million outpatient visits and 2 million hospitalizations attributable to rotavirus infections each year. The aim of this hospital-based surveillance was to summarize the local epidemiological and virological features of rotavirus and to estimate the disease burden in the population under surveillance in India., Methods: During the 16 months surveillance period from April 2011 through July 2012, a total of 4711 children under the age of 5 years were admitted with acute diarrhea at 12 medical centers attached to medical schools throughout India. Stool samples were randomly collected from 2051 (43.5%) subjects and were analyzed for rotavirus positivity using commercial enzyme immunoassay kit (Premier Rotaclone Qualitative Elisa) at the respective study centers. Rotavirus positive samples were genotyped for VP7 and VP4 by reverse-transcription polymerase chain reaction (RT-PCR) at a central laboratory., Results: During the study period, maximum number of rotavirus related hospitalizations were reported from December 2011 through February 2012. Out of the 2051 stool samples tested for rotavirus, overall 541 (26.4%) samples were positive for rotavirus VP6 antigen in stool. The highest positivity was observed in the month of December, 2011 (52.5%) and lowest in the month of May, 2011 (10.3%). We found that majority of the rotavirus positive cases (69.7%) were in children <24 months of age. The most common genotypes reported were G1 (38%), G2 (18%), G9 (18%), G12 (9%) and mixed strains (17%)., Conclusions: The results of this study confirm the significant burden of acute rotavirus gastroenteritis as a cause of hospitalizations in under five children in India., (Copyright © 2014. Published by Elsevier Ltd.)

The current study aimed to investigate the modulation of glutathione (GSH) and its dependent enzymes (glutathione reductase, GR; glutathione peroxidase, GPx; glutathione sulfotransferase, GST) from 0 to 72 h in the gill cells of Anguilla anguilla under in vitro condition exposed to silica coated iron oxide nanoparticles functionalized with dithiocarbamate (Fe₃O₄@SiO₂/SiDTC, hereafter called 'IONPs'; 100 nm; 2.5 mgL(-1)) with or without mercury (Hg) coexposure. Significantly decreased TGSH content under IONP alone exposure from 0 to 72 h indicated increased utilization of the TGSH in response to IONP stress. Significant increases in the activity of GR, GPx and GST were depicted when exposed to IONP alone. Lipid peroxidation (LPO), a membrane damage trait also significantly increased under IONP alone exposure indicating the efficient role of antioxidant induction abolishing the IONP-mediated enhanced reactive oxygen species. Under Hg exposure, gill cells displayed significantly increased activity of the studied enzymes (GR, GPx and GST) and LPO which was accompanied by significantly decreased TGSH content. Concomitant (IONPs+Hg) exposure displayed a synergistic response to that of individual responses of either IOPN or Hg which was evident by significant increases in GR, GPx, GST and LPO. Overall, our findings revealed a fine tuning among the GSH and its dependent enzyme modulation under IONP, Hg and its concomitant (IONPs+Hg) exposure in A. anguilla gill cells under in vitro condition., (Copyright © 2014 Elsevier Inc. All rights reserved.)