Method Dvelopment and Validation for the Simultaneous Estimation of Clidinium Bromide and Chlordizepoxide in Bulk and Tablet Dosage form by a RPHPLC.

The modern form of column chromatography has been called high performance, high pressure, and high-resolution and high-speed liquid chromatography. High-Performance Liquid Chromatography (HPLC) is a special branch of column chromatography in which the mobile phase is forced through the column at high speed. As a result the analysis time is reduced by 1-2 orders of magnitude relative to classical column chromatography and the use of much smaller particles of the adsorbent or support becomes possible increasing the column efficiency substantially. In the present study, new RP-HPLC method for simultaneous estimation of Clidinium bromide and Chlordiazepoxide in bulk and pharmaceutical dosage form was developed. The developed method was validation for various parameters such as accuracy, precision, ruggedness, linearity, robustness, system suitability, specificity, limit of detection and limit of quantification as per ICH guidelines. The developed RP-HPLC method has been successfully applied for the simultaneous determination of Clidinium bromide and Chlordiazepoxide in pure drug and marketed formulation. The methods are found to be rapid, simple, accurate and convenient to adopt. The developed methods are completely validated with all validation parameters.The results indicate that this method are precise, accurate further more it is easy and convenient for routine drug analysis

Nano-composite single grain YBa2Cu3O 7-δ/Y2Ba4CuBiOy bulk superconductors

We have succeeded recently in synthesizing a chemically stable, inert family of materials of composition Y2Ba4CuMOy (Y-2411 where M Nb, Ta, Mo, W, Zr, Hf) within the superconducting YBa 2Cu3O7-δ (Y-123) phase matrix that forms effective flux pinning centers of nano-scale dimensions. In this paper we report the synthesis of the Y2Ba4CuBiOy phase with nano-scale dimensions that is similarly compatible with the Y-123 matrix and which does not impair the properties of the bulk superconductor. YBa 2Cu3O7-δ/Y2BaCuO5 (Y-123/Y-211) precursor powders enriched with various amounts of Bi 2O3 and Y2Ba4CuBiOy have been fabricated successfully in the form of large, single grains by the top seeded melt growth (TSMG) process. Microstructural studies of these composites reveal the presence of nanometer-sized Y2Ba4CuBiO y and much larger Y-211 phase particles (∼1 νm) embedded in the Y-123 phase matrix. The critical current density of the nano-composites is observed to increase significantly compared to undoped YBCO. © 2006 IOP Publishing Ltd

Ethnobotanical study of Penchalakona forest area of Nellore District, Andhra Pradesh, India.

An ethno botanical survey was undertaken to collect information from yanadi tribe of penchalakona forest area, Rapur mandal, Nellore district, Andhra Pradesh, India.  The indigenous knowledge of traditional healers of this ethnic group has been disappearing due to lack of ancestors as well as followers. Only few people are practicing with little knowledge which was transmitted orally from their elders. The native plants used for medicinal purposes by few people were collected through questionnaire and personally interviewed during field trips. An aboriginal tribe called “Yanadi”, of this area has authentic information on medicinal values of different plant species.  Yanadi tribal community being drifted from their natural way of life due to agro rural development activities, a few aged persons are still able to furnish very little traditional ethno botanical data and continue to depend on medicinal plants atleast for the treatment of primary healthcare.  Because the area is located near the forest and 70 Kms from Nellore town.The study revealed that, the Yanadi tribe used 20 plants species belonging to 20 families to treat various diseases like worm infestations, scorpion stinge, headache, body pains, fevers, swelling of foots, skin diseases, heart diseases, stomach ulcers, diuretic, dysentery, snake bites, nerve disorders, rheumatic pains, antiseptic, helmentic disease, diabetes, cold and dental problems.These plants represents the major source for the pharmaceutical industries in view of their raw material. The information requires validation for further clinical usage

Evaluation of clinical outcomes in neuropathic pain with combinations of anti-neuropathic drugs

Background: Much of the pharmacological treatment modalities especially individual drugs for treating neuropathic pain have unwanted side effects, multiple day to day dosing, modest efficacy of topical treatments, and their local side effects. Combination drug regimen has the advantage of offering relatively better pain relief at lower drug doses and lesser side effects.Methods: The study was conducted in the Department of Neurology at NRI General Hospital, Guntur. The patients who met the inclusion and exclusion criteria were enrolled and assigned into 3 groups of the study drug combinations. The baseline characteristics and post interventional scores of Toronto Clinical Scoring System (TCSS), visual analogue scale (VAS), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D) and Medical outcome of sleep scale (MOS) and were analyzed using t test and mean difference.Results: A statistically significant reduction in neuropathic pain in all the three groups was found. The mean difference between the baseline and post interventional scores of TCSS and VAS of group I, II and III were 2.97, 2.75, and 1.97; 2.32, 1.12, and 0.95 respectively. There was a statistically significant improvement of HAM-A in all the three groups, HAM-D and MOS sleep scale were found significant only in group II.Conclusions: The study findings revealed that all the three drug combinations were effective in the management of neuropathic pain with pregabalin and oxcarbazepine combination being better with respect to efficacy and tolerability. Regarding the treatment of depression and sleep disturbances associated with NP pregabalin and duloxetine was more effective

Barcoding life to conserve biological diversity: Beyond the taxonomic imperative

Barcoding scientists aspire to adhere to the objectives of the Convention on Biological Diversity by promoting conservation, sustainability, and the equitable sharing of benefits arising from use of genetic resources. (Image: Juan Manuel Escalante, wwww.realitat.com

Molecular Characterization of the Gene of Vertically Transmitted HIV-1 Strains in Children with Virological Failure.

HIV-1 gene sequences were analyzed from 77 HIV-1 positive children infected perinatally and exhibiting virological failure (VF). Viral subtyping, phylogenetic analysis, and genotypic drug resistance analysis were carried out on samples collected before start of anti retroviral treatment (ART) (baseline, BL), and at 12 months post-ART initiation (M12). Subtype C was found to be most predominant, seen in 75 of the 77 (97.4%) children. The level of pretreatment drug resistance (PDR) was 14% among these children. At BL, K103N (5), E138A/G (4), and M184V (3) were the most common mutations. At M12 the prevalence of any resistance-associated mutation (RAM) (acquired drug resistance/ADR) was 81.8% (63/77). Dual class resistance mutations were seen in 64% (49/77) of children. M184V/I, K103N/S, and Y181C were the most commonly occurring mutations, seen in 76%, 51%, and 36% children. RAMs to the second-generation non-nucleoside reverse transcriptase inhibitors (NNRTI), etravirine (ETR) and rilpivirine (RPV), were seen in 40.2% (31/77) and 48.05% (37/77) of the children, respectively. Our findings reveal similar prevalence rates of PDR and ADR in children with VF as reported in other studies. Occurrence of ETR and RPV resistance associated mutations (RAMs) is of concern and highlights the need for timely switch of regimens guided by genotypic resistance testing in perinatally infected children from India

Expression of SDF-1α and nuclear CXCR4 predicts lymph node metastasis in colorectal cancer

Although stromal cell-derived factor (SDF)-1α and its receptor CXCR4 are experimentally suggested to be involved in tumorigenicity, the clinicopathological significance of their expression in human disease is not fully understood. We examined SDF-1α and CXCR4 expression in colorectal cancers (CRCs) and their related lymph nodes (LNs), and investigated its relationship to clinicopathological features. Specimens of 60 primary CRCs and 27 related LNs were examined immunohistochemically for not only positivity but also immunostaining patterns for SDF-1α and CXCR4. The relationships between clinicopathological features and SDF-1α or CXCR4 expression were then analysed. Stromal cell-derived factor-1α and CXCR4 expression were significantly associated with LN metastasis, tumour stage, and survival of CRC patients. Twenty-nine of 47 CXCR4-positive CRCs (61.7%) showed clear CXCR4 immunoreactivity in the nucleus and a weak signal in the cytoplasm (nuclear type), whereas others showed no nuclear immunoreactivity but a diffuse signal in the cytoplasm and at the plasma membrane (cytomembrane type). Colorectal cancer patients with nuclear CXCR4 expression showed significantly more frequent LN metastasis than did those with cytomembrane expression. Colorectal cancer patients with nuclear CXCR4 expression in the primary lesion frequently had cytomembrane CXCR4-positive tumours in their LNs. In conclusion, expression of SDF-1α and nuclear CXCR4 predicts LN metastasis in CRCs

A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening.

The unparalleled global effort to combat the continuing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic over the last year has resulted in promising prophylactic measures. However, a need still exists for cheap, effective therapeutics, and targeting multiple points in the viral life cycle could help tackle the current, as well as future, coronaviruses. Here, we leverage our recently developed, ultra-large-scale in silico screening platform, VirtualFlow, to search for inhibitors that target SARS-CoV-2. In this unprecedented structure-based virtual campaign, we screened roughly 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets. In addition to targeting the active sites of viral enzymes, we also targeted critical auxiliary sites such as functionally important protein-protein interactions

HGF-Induced PKCζ Activation Increases Functional CXCR4 Expression in Human Breast Cancer Cells

The chemokine receptor CXCR4 and its ligand CXCL12 have been shown to mediate the metastasis of many malignant tumors including breast carcinoma. Interaction between hepatocyte growth factor (HGF) and the Met receptor tyrosine kinase mediates development and progression of cancers. HGF is able to induce CXCR4 expression and contributes to tumor cell invasiveness in breast carcinoma. However, the mechanism of the CXCR4 expression modulated by c-Met-HGF axis to enhance the metastatic behavior of breast cancer cells is still unclear. In this study, we found that HGF induced functional CXCR4 receptor expression in breast cancer cells. The effect of HGF was specifically mediated by PKCζ activity. After transfection with PKCζ-siRNA, the phosphorylation of PKCζ and CXCR4 was abrogated in breast cancer cells. Interference with the activation of Rac1, a downstream target of HGF, prevented the HGF-induced increase in PKCζ activity and CXCR4 levels. The HGF-induced, LY294002-sensitive translocation of PKCζ from cytosol to plasma membrane indicated that HGF was capable of activating PKCζ, probably via phosphoinositide (PI) 3-kinases. HGF treatment also increased MT1-MMP secretion. Inhibition of PKCζ, Rac-1 and phosphatidylinositol 3-kinase may attenuate MT1-MMP expression in cells exposed to HGF. Functional manifestation of the effects of HGF revealed an increased ability for migration, chemotaxis and metastasis in MDA-MB-436 cells in vitro and in vivo. Our findings thus provided evidence that the process of HGF-induced functional CXCR4 expression may involve PI 3-kinase and atypical PKCζ. Moreover, HGF may promote the invasiveness and metastasis of breast tumor xenografts in BALB/c-nu mice via the PKCζ-mediated pathway, while suppression of PKCζ by RNA interference may abrogate cancer cell spreading