Development and Physical Characterization of Meclizine Hydrochloride Solid Dispersions by using Polyethylene Glycol 8000

Development of the meclizine hydrochloride solid dispersions using  polyethylene glycol 8000 is not only to enhance the solubility and  dissolution rate but also to produce rapid onset of action. The objectives of present research are to improve the solubility and dissolution rate of  meclizine hydrochloride using solid dispersion method. In the present study, the solid dispersions were prepared using solvent evaporation  method and evaluated for different physical parameters such as solubility, drug carrier compatibility and powder flow properties. From the results of solubility studies, F4 formulation was selected to prepare the fast  dissolving tablets because it showed highest improvement in the solubility among the all formulations and compared with control tablets (conventional tablets using pure drug). The percent drug release in 15 min (Q15) and  initial dissolution rate for F4 tablets was 98.52±1.34%, 6.56%/min and  these were very much higher compared to control tablets (32.49±1.29 %, 2.17%/min). The relative dissolution rate was found to be 3.03 and  dissolution efficiency was found to be 54.45 and it is increased by 3.5 fold with F4 formulation compared to control tablets (16.55). Hence the  formulation of polyethylene glycol 8000 solid dispersions is a suitable method to enhance the solubility and dissolution rate of meclizine  hydrochloride. Further research warranted to study the efficacy of the developed formulations has to be assessed by pharmacokinetic studies

Angiopoietin-like protein 2 regulates endothelial colony forming cell vasculogenesis

Angiopoietin-like 2 (ANGPTL2) has been reported to induce sprouting angiogenesis; however, its role in vasculogenesis, the de novo lumenization of endothelial cells (EC), remains unexplored. We sought to investigate the potential role of ANGPTL2 in regulating human cord blood derived endothelial colony forming cell (ECFC) vasculogenesis through siRNA mediated inhibition of ANGPTL2 gene expression. We found that ECFCs in which ANGPTL2 was diminished displayed a threefold decrease in in vitro lumenal area whereas addition of exogenous ANGPTL2 protein domains to ECFCs lead to increased lumen formation within a 3 dimensional (3D) collagen assay of vasculogenesis. ECFC migration was attenuated by 36 % via ANGPTL2 knockdown (KD) although proliferation and apoptosis were not affected. We subsequently found that c-Jun NH2-terminal kinase (JNK), but not ERK1/2, phosphorylation was decreased upon ANGPTL2 KD, and expression of membrane type 1 matrix metalloproteinase (MT1-MMP), known to be regulated by JNK and a critical regulator of EC migration and 3D lumen formation, was decreased in lumenized structures in vitro derived from ANGPTL2 silenced ECFCs. Treatment of ECFCs in 3D collagen matrices with either a JNK inhibitor or exogenous rhTIMP-3 (an inhibitor of MT1-MMP activity) resulted in a similar phenotype of decreased vascular lumen formation as observed with ANGPTL2 KD, whereas stimulation of JNK activity increased vasculogenesis. Based on gene silencing, pharmacologic, cellular, and biochemical approaches, we conclude that ANGPTL2 positively regulates ECFC vascular lumen formation likely through its effects on migration and in part by activating JNK and increasing MT1-MMP expression

Development of core collections in soybean on the basis of seed size

Core collections display a large fraction of the diversity contained in large collections in smaller germplasm panels. We used historical data (1973–2015) collected at the World Vegetable Center, Taiwan, for developing soybean (Glycine max L. Merr.) core collections representing the diversity of the whole collection of 7853 accessions held by the Center. The collection was split into two groups on the basis of the 100 seed weight: large seeded (>25 g or equal to 25 g) and small seeded (<25 g). The large-seeded group (vegetable soybean/edamame) comprised 456 accessions, while the small-seeded group contained 7397 accessions. Within these two groups, we developed core collections based on seven quantitative and 14 qualitative traits collected during the autumn season, resulting in a core collection of 112 large-seeded vegetable soybean accessions and 1480 accessions for the small-seeded types

Unravelling the secret of seedbased gels in water: the nanoscale 3D network formation

Chia (Salvia hispanica) and basil (Ocimum basilicum) seeds have the intrinsic ability to form a hydrogel concomitant with moisture-retention, slow releasing capability and proposed health benefits such as curbing diabetes and obesity by delaying digestion process. However, the underlying mode of gelation at nanoscopic level is not clearly explained or explored. The present study elucidates and corroborates the hypothesis that the gelling behavior of such seeds is due to their nanoscale 3D-network formation. The preliminary study revealed the influence of several conditions like polarity, pH and hydrophilicity/ hydrophobicity on fiber extrusion from the seeds which leads to gelation. Optical microscopic analysis clearly demonstrated bundles of fibers emanating from the seed coat while in contact with water, and live growth of fibers to form 3D network. Scanning electron microscope (SEM) and transmission electron microscope (TEM) studies confirmed 3D network formation with fiber diameters ranging from 20 to 50 nm

Heterotic pools in African and Asian origin populations of pearl millet [Pennisetum glaucum (L.) R. Br.]

Forty-five African or Asian origin pearl millet populations bred either in Africa or Asia were investigated to generate information on heterotic pools. They were clustered into seven groups (G1 to G7) when genotyped, using 29 highly polymorphic SSRs. Fourteen parental populations representing these seven marker-based groups were crossed in diallel mating design to generate 91 population hybrids. The hybrids evaluated at three locations in India showed mean panmictic mid-parent heterosis (PMPH) and better-parent heterosis (PBPH) for grain yield ranging from − 21.7 to 62.08% and − 32.51 to 42.99%, respectively. Higher grain yield and heterosis were observed in G2 × G6 (2462 kg ha− 1, 43.2%) and G2 × G5 (2455 kg ha− 1, 42.8%) marker group crosses compared to the most popular Indian open-pollinated variety (OPV) ICTP 8203. Two heterotic groups, Pearl millet Population Heterotic Pool-1 (PMPHP-1) comprising G2 populations and Pearl millet Population Heterotic Pool-2 (PMPHP- 2) comprising G5 and G6 populations, were identified based on hybrid performance, heterosis and combining ability among marker group crosses. Population hybrids from two heterotic groups, PMPHP-1 × PMPHP-2 demonstrated PMPH of 14.75% and PBPH of 6.8%. Populations of PMPHP-1 had linkages with either African or Asian origin populations, whereas PMPHP-2 composed of populations originating in Africa and later bred for Asian environments. Results indicated that parental populations from the two opposite heterotic groups can be used as base populations to derive superior inbred lines to develop high yielding hybrids/cultivars

CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells

The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4+ T cells in peripheral blood or lymphoid tissue; isolated CD32+ resting CD4+ T cells accounted for less than 3% of the total HIV DNA in CD4+ T cells. Cell-associated HIV DNA and RNA loads in CD4+ T cells positively correlated with the frequency of CD32+ CD69+ CD4+ T cells but not with CD32 expression on resting CD4+ T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4+ T cells or of enriched HIV DNA–positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4+ T cells enriched for transcriptionally active HIV after long-term ART

An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease

There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. Targeting drugs selectively to the inflamed intestine may improve therapeutic outcomes and minimize systemic toxicity. We report the development of an inflammation-targeting hydrogel (IT-hydrogel) that acts as a drug delivery system to the inflamed colon. Hydrogel microfibers were generated from ascorbyl palmitate, an amphiphile that is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. IT-hydrogel microfibers loaded with the anti-inflammatory corticosteroid dexamethasone (Dex) were stable, released drug only upon enzymatic digestion, and demonstrated preferential adhesion to inflamed epithelial surfaces in vitro and in two mouse colitis models in vivo. Dex-loaded IT-hydrogel enemas, but not free Dex enemas, administered every other day to mice with colitis resulted in a significant reduction in inflammation and were associated with lower Dex peak serum concentrations and, thus, less systemic drug exposure. Ex vivo analysis of colon tissue samples from patients with ulcerative colitis demonstrated that IT-hydrogel microfibers adhered preferentially to mucosa from inflamed lesions compared with histologically normal sites. The IT-hydrogel drug delivery platform represents a promising approach for targeted enema-based therapies in patients with colonic IBD

Analysis of multi-location data of hybrid rice trials reveals complex genotype by environment interaction

The All India Coordinated Rice Improvement Project of ICAR-Indian Institute of Rice Research, Hyderabad organizes multi-location testing of elite lines and hybrids to test and identify new rice cultivars for the release of commercial cultivation in India. Data obtained from Initial Hybrid Rice Trials of three years were utilized to understand the genotype × environment interaction (GEI) patterns among the test locations of five different agro-ecological regions of India using GGE and AMMI biplot analysis. The combined analysis of variance and AMMI ANOVA for a yield of rice hybrids were highly significant for GEI. The GGE biplots first two PC explained 54.71%, 51.54% and 59.95% of total G + GEI variation during 2010, 2011 and 2012, respectively, whereas AMMI biplot PC1 and PC2 explained 46.62% in 2010, 36.07% in 2011 and 38.33% in 2012 of the total GEI variation. Crossover interactions, i.e. genotype rank changes across locations were observed. GGE biplot identified hybrids, viz. PAN1919, TNRH193, DRH005, VRH639, 26P29, Signet5051, KPH385, VRH667, NIPH101, SPH497, RH664 Plus and TNRH222 as stable rice hybrids. The discriminative locations identified in different test years were Coimbatore, Maruteru, VNR, Jammu, Raipur, Ludhiana, Karjat and Dabhoi. The AMMI1 biplot identified the adaptable rice hybrids viz., CNRH102, DRH005, NK6303, NK6320, DRRH78, NIPH101, Signet5050, BPH115, Bio452, NPSH2003, and DRRH83. The present study demonstrated that AMMI and GGE biplots analyses were successful in assessing genotype by environment interaction in hybrid rice trials and aided in the identification of stable and adaptable rice hybrids with higher mean and stable yields