DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING LIQUID CHROMATOGRAPHIC METHOD FOR THE SIMULTANEOUS ESTIMATION OF PAROXETINE AND CLONAZEPAM IN BULK AND ITS PHARMACEUTICAL FORMULATIONS

A novel stability indicating reversed-phase liquid chromatographic method has been developed and validated for simultaneous estimation of paroxetine and clonazepam in combined pharmaceutical dosage form. An Agilent zorbax sb-c18 (250mmx4.6mmx5 µm) column with the mobile phase containing 0.2 % Orthophosphoric acid and Methanol (60:40 v/v) was used. The flow rate was maintained at 0.8 ml/min, column temperature was 30°C and effluents were monitored by using a photodiode array detector at 270 nm. The retention times of paroxetine and clonazepam were found to be 3.478min and 3.964 min, respectively. Correlation co-efficient for paroxetine and clonazepam were found to be 0.99 and 0.99, respectively. The proposed method was validated with respect to linearity, accuracy, precision, specificity, and robustness. Recovery of paroxetine and clonazepam in formulations was found to be in a range of 97-103% and 97-103% respectively. Paroxetine and clonazepam were also subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. The degradation products were well resolved from and peak purity test results confirmed that paroxetine and clonazepam peaks were homogenous and pure in all stress samples, thus proving stability-indicating power of the method. Due to its simplicity, rapidness and high precision, this method can be applied for regular analysis

EFFECT OF DIETARY SUPPLEMENTATION OF TULASI (OCIMUM SANCTUM) AND SELENIUM ON ALANINE TRANSAMINASE (ALT) AND ASPARTATE TRANSAMINASE (AST) LEVELS IN BROILERS

ABSTRAC

Performance of broilers on sorghum-based diets

The effect of replacing maize with sorghum grain on the performance of broilers was studied. Grain from 4 improved Sorghum bicolor cultivars (CSH 16, CSV 15, PSV 16 and S 35) and one traditional yellow variety were used to replace maize (control diet) in the starter (1-4 weeks) and finisher rations (5-6 weeks) of broilers by 50, 75 and 100% levels. All diets were isonitrogenous and isocaloric and were homogeneous for lysine, methionine and cystine levels. One-day-old 512 commercial Cobb female broilers were divided into 64 groups with 16 dietary treatments and 4 replicates per treatment, with 8 birds in each. In a second trial, sorghum replacement was conducted without homogenizing the diets for nitrogen and energy contents. The study lasted for 6 weeks. It was shown that the liveweight gain and feed intake of broilers was statistically similar in sorghum diets at all inclusion levels compared to the control diet. However, the feed conversion efficiency of broilers in the 100% sorghum diet was significantly higher compared to the maize diet (P=0.05). A better feed conversion efficiency was found with the CSV 15, CSH 16, PSV 16 and the local cultivars at 100% inclusion levels. However, the yellow pigmentation of the skin and carcass of the broilers was better in the maize diet compared to the sorghum diets. Cost varied among and within cultivars at different inclusion levels, and was lower in CSV 15, PSV 16, S 35 and local sorghum cultivar-based diets. Cost was also much lower in CSV 15, PSV 16 and local sorghum cultivars at 100% inclusion level compared to maize. Feed cost per kg liveweight gain was lower with CSV 15 (Rs 17.16) and PSV 16 cultivars (Rs 17.62) compared to maize (Rs 18.02). Although pelleting increased feed costs (by Rs 0.25/kg), it also improved broiler production efficiency compared to mash in sorghum diets. Inclusion of Stylosanthes sp. leaf meal at 3% in 100% sorghum-based diets favourably improved the shank and skin colour of the carcass. Carcass yield and abdominal fat of broilers fed sorghum, sorghum + Stylosanthes sp. and maize diets were similar. In conclusion, the inclusion/replacement of sorghum in maize-based diets and pelleting improves the feed conversion ratio and decreases the total feed costs in broiler production

Unsteady flow of a nanofluid over a sphere with nonlinear Boussinesq approximation

A theoretical study is presented of transient mixed convection boundary layer flow of a nanofluid in the forward stagnation region of a heated sphere which is rotating with time dependent angular velocity. The effect of the non-linear Boussinesq approximation is taken into account. The nanofluid is treated as a two-component mixture i.e. nano-particles distributed homogenously in a base fluid (water or gas). The effects of the Brownian motion and thermophoresis are included for the nanofluid and constant wall temperature is imposed at the sphere surface. The first and second laws of thermodynamics are employed in order to study thermophysics as well as heat and mass transfer phenomena. By introducing appropriate similarity variables the governing equations are transformed into a system of dimensionless, nonlinear, coupled, ordinary differential equations which are solved numerically by applying the second-order accurate implicit finite difference Keller box method. The reliability and efficiency of the obtained numerical results are validated via comparison with the previously published results for special cases. The effects of various parameters on primary and secondary velocities, temperature, nanofluid volume fraction (concentration), primary and secondary shear stress functions, Nusselt number function (wall heat transfer rate) and Sherwood number function (wall nanoparticle mass transfer rate) are visualized. Furthermore the influence of non-linear temperature parameter, Brinkman parameter (ratio of Brinkman number to dimensionless temperature ratio), local Reynolds number and unsteadiness parameter on entropy generation number is computed. A strong elevation in entropy generation number is computed with both increasing Brinkman parameter and unsteadiness parameter. Primary and secondary surface shear stresses, Nusselt number and Sherwood number also increase with unsteadiness and rotation parameters. Primary shear stress is boosted with increasing mixed convection parameter and Brownian motion effect whereas secondary shear stress is depressed. Temperatures are suppressed with increasing nonlinear temperature parameter whereas nano-particle concentrations are elevated. Increasing thermophoresis parameter enhances both temperatures and nano-particle concentration values. The simulations find applications in rotating chemical engineering mixing systems and nano-coating transport phenomena

Austro-Asiatic Tribes of Northeast India Provide Hitherto Missing Genetic Link between South and Southeast Asia

Northeast India, the only region which currently forms a land bridge between the Indian subcontinent and Southeast Asia, has been proposed as an important corridor for the initial peopling of East Asia. Given that the Austro-Asiatic linguistic family is considered to be the oldest and spoken by certain tribes in India, Northeast India and entire Southeast Asia, we expect that populations of this family from Northeast India should provide the signatures of genetic link between Indian and Southeast Asian populations. In order to test this hypothesis, we analyzed mtDNA and Y-Chromosome SNP and STR data of the eight groups of the Austro-Asiatic Khasi from Northeast India and the neighboring Garo and compared with that of other relevant Asian populations. The results suggest that the Austro-Asiatic Khasi tribes of Northeast India represent a genetic continuity between the populations of South and Southeast Asia, thereby advocating that northeast India could have been a major corridor for the movement of populations from India to East/Southeast Asia

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Algorithms for effective querying of compound graph-based pathway databases

<p>Abstract</p> <p>Background</p> <p>Graph-based pathway ontologies and databases are widely used to represent data about cellular processes. This representation makes it possible to programmatically integrate cellular networks and to investigate them using the well-understood concepts of graph theory in order to predict their structural and dynamic properties. An extension of this graph representation, namely hierarchically structured or compound graphs, in which a member of a biological network may recursively contain a sub-network of a somehow logically similar group of biological objects, provides many additional benefits for analysis of biological pathways, including reduction of complexity by decomposition into distinct components or modules. In this regard, it is essential to effectively query such integrated large compound networks to extract the sub-networks of interest with the help of efficient algorithms and software tools.</p> <p>Results</p> <p>Towards this goal, we developed a querying framework, along with a number of graph-theoretic algorithms from simple neighborhood queries to shortest paths to feedback loops, that is applicable to all sorts of graph-based pathway databases, from PPIs (protein-protein interactions) to metabolic and signaling pathways. The framework is unique in that it can account for compound or nested structures and ubiquitous entities present in the pathway data. In addition, the queries may be related to each other through "AND" and "OR" operators, and can be recursively organized into a tree, in which the result of one query might be a source and/or target for another, to form more complex queries. The algorithms were implemented within the querying component of a new version of the software tool P<smcaps>ATIKA</smcaps><it>web </it>(Pathway Analysis Tool for Integration and Knowledge Acquisition) and have proven useful for answering a number of biologically significant questions for large graph-based pathway databases.</p> <p>Conclusion</p> <p>The P<smcaps>ATIKA</smcaps> Project Web site is <url>http://www.patika.org</url>. P<smcaps>ATIKA</smcaps><it>web </it>version 2.1 is available at <url>http://web.patika.org</url>.</p

Elevated miR-499 Levels Blunt the Cardiac Stress Response

The heart responds to myriad stresses by well-described transcriptional responses that involve long-term changes in gene expression as well as more immediate, transient adaptations. MicroRNAs quantitatively regulate mRNAs and thus may affect the cardiac transcriptional output and cardiac function. Here we investigate miR-499, a microRNA embedded within a ventricular-specific myosin heavy chain gene, which is expressed in heart and skeletal muscle.We assessed miR-499 expression in human tissue to confirm its potential relevance to human cardiac gene regulation. Using a transgenic mouse model, we found that elevated miR-499 levels caused cellular hypertrophy and cardiac dysfunction in a dose-dependent manner. Global gene expression profiling revealed altered levels of the immediate early stress response genes (Egr1, Egr2 and Fos), ß-myosin heavy chain (Myh7), and skeletal muscle actin (Acta1). We verified the effect of miR-499 on the immediate early response genes by miR-499 gain- and loss-of-function in vitro. Consistent with a role for miR-499 in blunting the response to cardiac stress, asymptomatic miR-499-expressing mice had an impaired response to pressure overload and accentuated cardiac dysfunction.Elevated miR-499 levels affect cardiac gene expression and predispose to cardiac stress-induced dysfunction. miR-499 may titrate the cardiac response to stress in part by regulating the immediate early gene response

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013

Background: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks