In vivo pathogenicity of hydropericardium hepatitis syndrome (Angara disease)

This study was conducted on 175 one day old broiler chicks in order to observe in vivo pathogenicity of hydropericardium hepatitis syndrome (Angara disease). Chicks were grouped into A (25 chicks; reared at the Poultry Research institute (PRI), Rawalpindi) and B groups (150 chicks; reared at National Veterinary Laboratories (NVL) Islamabad in poultry rearing units). Feed and water were provided adlibitum to all the birds in both groups. The LD50 (lethal dose 50) of the virus was determined at the age of 26 days of broiler chickens divided into sub-groups a, b, c, d and e (each having 5 birds). The LD50 titre of the viral suspension (10%) was prepared from liver extract and determined as 10-2.5 per ml. During the study, potency of the vaccines was determined by vaccinating 150 chicks of sub-group k, l, m, n and o (each having 30 birds) with a dose of 0.2 ml. The vaccinated and non-vaccinated chicks of sub-groups were challenged with viral dose of 2 ml at day 17 post-vaccination to know the protection potency of the vaccines. No chick showed clinical manifestation of disease up to five days post challenge. On the 6th day post challenge, all the chicks were slaughtered and subjected to postmortem. Some of the chicks showed the lesions of hydropericarium. Histopathological findings of liver of all sub-groups revealed different stages of necrosis, cloudy swelling, liquefactive necrosis, cytoplasmic blabing, fatty degeneration and intranuclear inclusion bodies of virus.Key words: In vivo pathogenicity, hydropericardium hepatitis syndrome, Angara disease

Pheno4J: a gene to phenotype graph database

Efficient storage and querying of large amounts of genetic and phenotypic data is crucial to contemporary clinical genetic research. This introduces computational challenges for classical relational databases, due to the sparsity and sheer volume of the data. Our Java based solution loads annotated genetic variants and well phenotyped patients into a graph database to allow fast efficient storage and querying of large volumes of structured genetic and phenotypic data. This abstracts technical problems away and lets researchers focus on the science rather than the implementation. We have also developed an accompanying webserver with end-points to facilitate querying of the database

Evaluation of biochemical effects of diclofenac sodium in goats

ABSTRACT Diclofenac sodium is one of the most commonly using Non steroidal anti -inflammatory drugs (NSAID) worldwide in medical as well as veterinary practices. Use of anti-inflammatory drugs may affect liver function which may or may not be reversible in various livestock breeds. In this study effect of diclofenac sodium on Alanin transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALK), serum creatinine, serum uric acid, blood urea and total protein of liver and kidney of local dairy goats has been evaluated at Sindh Agriculture University, Tandojam since 2007. The drug was administered in six goats in two phases with adequate wash out period of 21 days between each phase. Dose rates, 2.5mg/kg (b.w) and 1 mg/kg (b.w), of diclofenac was administered in Phase-1 and Phase-2 respectively. For biochemical analysis the blood samples were collected at different intervals up to 96 hrs post drug administration. Significant change (p<0.05) with high dose was documented at 2, 3, 6, 12, 24 48 hrs in blood serum level of ALT, AST, ALK.PO4, creatinine, uric acid, and blood urea respectively. Where as highly significant change (p<0.01) was monitored at 6, 12, 24, 48 hrs in ALT and AST, ALK.PO4, and blood urea respectively. Significant increase in serum level of Alanin transaminase, Aspartate transaminase and Alkaline phosphatase was noticed at 12 and 24 hrs with low dose of diclofenac respectively. No significant change in serum creatinine and uric acid was observed but blood urea significantly increased at 48 hrs with low dose. No change was examined in total serum protein with both the doses. The effect of diclofenac was short-lived and most of the parameters went back to normal after 72hrs of drug administration

Broken R Parity Contributions to Flavor Changing Rates and CP Asymmetries in Fermion Pair Production at Leptonic Colliders

We examine the effects of the R parity odd renormalizable interactions on flavor changing rates and CP violation asymmetries in the production of fermion-antifermion pairs at $e^-- e^+$ leptonic colliders. The produced fermions may be leptons, down-quarks or up-quarks, and the center of mass energies may range from the Z-boson pole up to $1000$ GeV. Off the Z-boson pole, the flavor changing rates are controlled by tree level amplitudes and the CP asymmetries by interference terms between tree and loop level amplitudes. At the Z-boson pole, both observables involve loop amplitudes. The lepton number violating interactions, associated with the coupling constants, \l_{ijk}, \l'_{ijk}, are only taken into account. The consideration of loop amplitudes is restricted to the photon and Z-boson vertex corrections. We briefly review flavor violation physics at colliders. We present numerical results using a single, species and family independent, mass parameter, $\tilde m$, for all the scalar superpartners and considering simple assumptions for the family dependence of the R parity odd coupling constants.Comment: Latex File. 23 pages. 4 postscript figures. 1 table. Revised version with new results and several corrections in numerical result

Current pre-clinical and clinical advances in the BCR-ABL1-positive and -negative chronic myeloproliferative neoplasms

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Mutations in HNF1A Result in Marked Alterations of Plasma Glycan Profile

A recent genome-wide association study identified hepatocyte nuclear factor 1-α (HNF1A) as a key regulator of fucosylation. We hypothesized that loss-of-function HNF1A mutations causal for maturity-onset diabetes of the young (MODY) would display altered fucosylation of N-linked glycans on plasma proteins and that glycan biomarkers could improve the efficiency of a diagnosis of HNF1A-MODY. In a pilot comparison of 33 subjects with HNF1A-MODY and 41 subjects with type 2 diabetes, 15 of 29 glycan measurements differed between the two groups. The DG9-glycan index, which is the ratio of fucosylated to nonfucosylated triantennary glycans, provided optimum discrimination in the pilot study and was examined further among additional subjects with HNF1A-MODY (n = 188), glucokinase (GCK)-MODY (n = 118), hepatocyte nuclear factor 4-α (HNF4A)-MODY (n = 40), type 1 diabetes (n = 98), type 2 diabetes (n = 167), and nondiabetic controls (n = 98). The DG9-glycan index was markedly lower in HNF1A-MODY than in controls or other diabetes subtypes, offered good discrimination between HNF1A-MODY and both type 1 and type 2 diabetes (C statistic ≥ 0.90), and enabled us to detect three previously undetected HNF1A mutations in patients with diabetes. In conclusion, glycan profiles are altered substantially in HNF1A-MODY, and the DG9-glycan index has potential clinical value as a diagnostic biomarker of HNF1A dysfunction

Exendin-4 Ameliorates Motor Neuron Degeneration in Cellular and Animal Models of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by a progressive loss of lower motor neurons in the spinal cord. The incretin hormone, glucagon-like peptide-1 (GLP-1), facilitates insulin signaling, and the long acting GLP-1 receptor agonist exendin-4 (Ex-4) is currently used as an anti-diabetic drug. GLP-1 receptors are widely expressed in the brain and spinal cord, and our prior studies have shown that Ex-4 is neuroprotective in several neurodegenerative disease rodent models, including stroke, Parkinson's disease and Alzheimer's disease. Here we hypothesized that Ex-4 may provide neuroprotective activity in ALS, and hence characterized Ex-4 actions in both cell culture (NSC-19 neuroblastoma cells) and in vivo (SOD1 G93A mutant mice) models of ALS. Ex-4 proved to be neurotrophic in NSC-19 cells, elevating choline acetyltransferase (ChAT) activity, as well as neuroprotective, protecting cells from hydrogen peroxide-induced oxidative stress and staurosporine-induced apoptosis. Additionally, in both wild-type SOD1 and mutant SOD1 (G37R) stably transfected NSC-19 cell lines, Ex-4 protected against trophic factor withdrawal-induced toxicity. To assess in vivo translation, SOD1 mutant mice were administered vehicle or Ex-4 at 6-weeks of age onwards to end-stage disease via subcutaneous osmotic pump to provide steady-state infusion. ALS mice treated with Ex-4 showed improved glucose tolerance and normalization of behavior, as assessed by running wheel, compared to control ALS mice. Furthermore, Ex-4 treatment attenuated neuronal cell death in the lumbar spinal cord; immunohistochemical analysis demonstrated the rescue of neuronal markers, such as ChAT, associated with motor neurons. Together, our results suggest that GLP-1 receptor agonists warrant further evaluation to assess whether their neuroprotective potential is of therapeutic relevance in ALS