Solubility and dissolution enhancement of poorly aqueous soluble drug atorvastatin calcium using modified gum karaya as carrier: In vitro-In vivo evaluation

Solid dispersion is a unique and promising approach for improving the oral absorption and oral bioavailability of BCS class II drugs. Modified gum karaya a recently developed excipient was evaluated as a carrier for solubility and dissolution enhancement of poorly water soluble drug atorvastatin calcium. Physical mixtures along with solid dispersions of drug and polymer was  prepared using three methods kneading, solvent evaporation and solvent wetting method in 5 different ratios (1:1,1:3,1:5,1:7,1:9). Among the three methods used atorvastatin calcium solid dispersions prepared by kneading method in 1:3 ratio showed most promising results in terms of  percent yield, percent drug content, solubility of solid dispersions in phosphate buffer pH 6.8, XRD, DSC, SEM and In vitro release studies. These solid dispersions were selected to prepare tablets using Ac-di-sol as superdisintegrant (T1, T2, T3, T4 and T5). Tablets were characterized for hardness, friability, disintegration time, percent drug content, drug release studies and stability studies. Tablets T5 showed highest dissolution rate and best dissolution efficiency at (DE30) and (DE120) minutes. Release data of T5 tablet was subjected to various release kinetics models to know the type and order of drug release. Order was found to be Korsemeyer–Peppas>Hixson–Crowell cube root law >zero-order >first-order >Higuchi. The similarity factor was calculated for comparison of the dissolution profile before and after stability studies. The f2 value was found to be more than 50 (~ 90.9) thereby indicating a close similarity between both the dissolution profiles. In vivo studies was conducted on healthy albino rats and formulation given by oral route showed that at the end of 14 days solid dispersion 1:3 performed better than pure atorvastatin calcium in reducing total cholesterol and TG level and increasing HDL- cholesterol levels

Psychological well-being and burden in caregivers of patients with schizophrenia

Background: There is a definite paucity of Indian studies looking into the caregiver burden, psychological well-being, and the interface between them. Objectives: This work aims to study the correlation between these variables. Materials and Methods: The study sample included 100 patients with a diagnosis of schizophrenia and their caregivers, randomly selected from the patients admitted in the male and female wards of psychiatric center, Jodhpur, as per inclusion and exclusion criteria. Burden Assessment Schedule and Psychological General Well-Being Index were used for the study. Results: Eighty percent of the caregivers experienced moderate levels of burden. The burden was higher among older (r = 0.334) caregivers and spouse (p o 0.0001). Psychological well-being was low in older caregivers (r = -0.44) and those with lower educational status, and higher in the siblings (p = 0.002). A strong negative correlation was found between burden and psychological well-being (r = -0.81). Conclusion: Quality of care given to the individuals with schizophrenia depends on their primary caregiver. It thus becomes essential to plan interventions that would reduce their burden of care and thus improve their psychological well-being

Oral Mucosal Immunization Recent Advancement and Exploit Dendritic Cell Targeting

Oral mucosal vaccine thrive significant interest in developing vaccines that evoke mucosal moreover systemic immune response i.e. induction of IgA. Oral immunization consistently preferred over conventional immunization because it provides strengthens inpatient acquiescence, needle-free delivery, cost-effective. Thereby strong antibody production at the mucosal site is not refreshing by parenteral administration of the vaccines. Antibodies produced on the mucosal surface instead of it also start common mucosal immune system (CMIS). Vaccines allow particulate delivery protection of antigen. Polylactic-co-glycolic acid, poly lactic acid loaded nanoparticles, liposomes, niosomes, dendrimers; proteosomes are some of the nanocarriers which protect the antigen from their degradation. Authentication concepts of various studies on the mucosal vaccine by using nanotechnology for targeting to dendritic cell presenting on Peyer's patch elicit antibody production. This review sums up current studies on mucosal vaccination by using nanocarrier. More of the studies have been done on mucosal for improvement in methodology. Keywords: Antigen, Nanotechnology, Dendritic cells, Peyer’s patch, Vaccin

The co-occurrence of anemia and cardiometabolic disease risk demonstrates sex-specific sociodemographic patterning in an urbanizing rural region of southern India.

BACKGROUND/OBJECTIVES: To determine the extent and sociodemographic determinants of anemia, overweight, metabolic syndrome (MetS) and the co-occurrence of anemia with cardiometabolic disease risk factors among a cohort of Indian adults. SUBJECT/METHODS: Cross-sectional survey of adult men (n=3322) and nonpregnant women (n=2895) aged 18 years and older from the third wave of the Andhra Pradesh Children and Parents Study that assessed anemia, overweight based on body mass index, and prevalence of MetS based on abdominal obesity, hypertension and blood lipid and fasting glucose measures. We examined associations of education, wealth and urbanicity with these outcomes and their co-occurrence. RESULTS: The prevalence of anemia and overweight was 40% and 29% among women, respectively, and 10% and 25% among men (P<0.001), respectively, whereas the prevalence of MetS was the same across sexes (15%; P=0.55). The prevalence of concurrent anemia and overweight (9%), and anemia and MetS (4.5%) was highest among women. Household wealth was positively associated with overweight and MetS across sexes (P<0.05). Independent of household wealth, higher education was positively correlated with MetS among men (odds ratio (95% confidence interval): MetS: 1.4 (0.99, 2.0)) and negatively correlated with MetS among women (MetS: 0.54 (0.29, 0.99)). Similar sex-specific associations were observed for the co-occurrence of anemia with overweight and MetS. CONCLUSIONS: Women in this region of India may be particularly vulnerable to co-occurring anemia and cardiometabolic risk, and associated adverse health outcomes as the nutrition transition advances in India

Identification of Nucleic Acid Binding Sites on Translin-Associated Factor X (TRAX) Protein

Translin and TRAX proteins play roles in very important cellular processes such as DNA recombination, spatial and temporal expression of mRNA, and in siRNA processing. Translin forms a homomeric nucleic acid binding complex and binds to ssDNA and RNA. However, a mutant translin construct that forms homomeric complex lacking nucleic acid binding activity is able to form fully active heteromeric translin-TRAX complex when co-expressed with TRAX. A substantial progress has been made in identifying translin sites that mediate its binding activity, while TRAX was thought not to bind DNA or RNA on its own. We here for the first time demonstrate nucleic acid binding to TRAX by crosslinking radiolabeled ssDNA to heteromeric translin-TRAX complex using UV-laser. The TRAX and translin, photochemically crosslinked with ssDNA, were individually detected on SDS-PAGE. We mutated two motifs in TRAX and translin, designated B2 and B3, to help define the nucleic acid binding sites in the TRAX sequence. The most pronounced effect was observed in the mutants of B3 motif that impaired nucleic acid binding activity of the heteromeric complexes. We suggest that both translin and TRAX are binding competent and contribute to the nucleic acid binding activity

A rare case of primary mesenteric gastrointestinal stromal tumor with metastasis to the cervix uteri

<p>Abstract</p> <p>Background</p> <p>Gastrointestinal stromal tumors are CD117 (C Kit) positive mesenchymal neoplasms, that may arise anywhere in the gastrointestinal tract. Their current therapy is imatinib mesylate before or after surgery.</p> <p>Case presentation</p> <p>We describe a case of 17-year-old female with metastasis to the cervix uteri of a primary mesenteric gastrointestinal tumor.</p> <p>Conclusion</p> <p>Surgery remains the mainstay of known curative treatment. The manifestations of GIST are not restricted to the typical locations within the bowel; may have very unusual metastatic sites or infiltrations per continuitatem.</p

The Impact of a 4th Generation on Mixing and CP Violation in the Charm System

We study D0-D0 mixing in the presence of a fourth generation of quarks. In particular, we calculate the size of the allowed CP violation which is found at the observable level well beyond anything possible with CKM dynamics. We calculate the semileptonic asymmetry a_SL and the mixing induced CP asymmetry eta_fS_f which are correlated with each other. We also investigate the correlation of eta_fS_f with a number of prominent observables in other mesonic systems like epsilon'/epsilon, Br(K_L -> pi0 nu nu), Br(K+ -> pi+ nu nu), Br(B_s ->mu+ mu-), Br(B_d -> mu+ mu-) and finally S_psi phi in the B_s system. We identify a clear pattern of flavour and CP violation predicted by the SM4 model: While simultaneous large 4G effects in the K and D systems are possible, accompanying large NP effects in the B_d system are disfavoured. However this behaviour is not as pronounced as found for the LHT and RSc models. In contrast to this, sizeable CP violating effects in the B_s system are possible unless extreme effects in eta_fS_f are found, and Br(B_s ->mu+ mu-) can be strongly enhanced regardless of the situation in the D system. We find that, on the other hand, S_psi phi > 0.2 combined with the measured epsilon'/epsilon significantly diminishes 4G effects within the D system.Comment: 22 pages, 23 figures, v2 (references added

Discriminative motif discovery in DNA and protein sequences using the DEME algorithm

<p>Abstract</p> <p>Background</p> <p>Motif discovery aims to detect short, highly conserved patterns in a collection of unaligned DNA or protein sequences. Discriminative motif finding algorithms aim to increase the sensitivity and selectivity of motif discovery by utilizing a second set of sequences, and searching only for patterns that can differentiate the two sets of sequences. Potential applications of discriminative motif discovery include discovering transcription factor binding site motifs in ChIP-chip data and finding protein motifs involved in thermal stability using sets of orthologous proteins from thermophilic and mesophilic organisms.</p> <p>Results</p> <p>We describe DEME, a discriminative motif discovery algorithm for use with protein and DNA sequences. Input to DEME is two sets of sequences; a "positive" set and a "negative" set. DEME represents motifs using a probabilistic model, and uses a novel combination of global and local search to find the motif that optimally discriminates between the two sets of sequences. DEME is unique among discriminative motif finders in that it uses an informative Bayesian prior on protein motif columns, allowing it to incorporate prior knowledge of residue characteristics. We also introduce four, synthetic, discriminative motif discovery problems that are designed for evaluating discriminative motif finders in various biologically motivated contexts. We test DEME using these synthetic problems and on two biological problems: finding yeast transcription factor binding motifs in ChIP-chip data, and finding motifs that discriminate between groups of thermophilic and mesophilic orthologous proteins.</p> <p>Conclusion</p> <p>Using artificial data, we show that DEME is more effective than a non-discriminative approach when there are "decoy" motifs or when a variant of the motif is present in the "negative" sequences. With real data, we show that DEME is as good, but not better than non-discriminative algorithms at discovering yeast transcription factor binding motifs. We also show that DEME can find highly informative thermal-stability protein motifs. Binaries for the stand-alone program DEME is free for academic use and is available at <url>http://bioinformatics.org.au/deme/</url></p

Evolution of the Multi-Domain Structures of Virulence Genes in the Human Malaria Parasite, Plasmodium falciparum

The var gene family of Plasmodium falciparum encodes the immunodominant variant surface antigens PfEMP1. These highly polymorphic proteins are important virulence factors that mediate cytoadhesion to a variety of host tissues, causing sequestration of parasitized red blood cells in vital organs, including the brain or placenta. Acquisition of variant-specific antibodies correlates with protection against severe malarial infections; however, understanding the relationship between gene expression and infection outcome is complicated by the modular genetic architectures of var genes that encode varying numbers of antigenic domains with differential binding specificities. By analyzing the domain architectures of fully sequenced var gene repertoires we reveal a significant, non-random association between the number of domains comprising a var gene and their sequence conservation. As such, var genes can be grouped into those that are short and diverse and genes that are long and conserved, suggesting gene length as an important characteristic in the classification of var genes. We then use an evolutionary framework to demonstrate how the same evolutionary forces acting on the level of an individual gene may have also shaped the parasite's gene repertoire. The observed associations between sequence conservation, gene architecture and repertoire structure can thus be explained by a trade-off between optimizing within-host fitness and minimizing between-host immune selection pressure. Our results demonstrate how simple evolutionary mechanisms can explain var gene structuring on multiple levels and have important implications for understanding the multifaceted epidemiology of P. falciparum malaria