Hypolipidemic, Hypoglycemic and Anti-oxidant Activities of Flower Extracts of Allamanda Violacea A. DC (Apocynaceae)

Purpose: To investigate the anti-dyslipidemic, anti-oxidant and anti-diabetic activities of the aqueous extract and solvent fractions of A. violacea flowers.Methods: The aqueous extract was fractionated into petroleum ether, ether, chloroform, chloroformmethanol (4:1) and chloroform-methanol (3:2) fractions. Lipid lowering activity was evaluated in two models, viz, triton WR-1339 - induced hyperlipimea in rats as well as fructose-rich high fat diet. To assess anti-oxidant activity, in-vitro model of non-enzymic superoxide hydroxyl radicals and microsomal lipid peroxidation by non-enzymic inducer was adopted. Hypoglycemic activity was evaluated by sucrose-loaded rat model.Results: Amongst the fractions, ether and chloroform fractions caused marked decrease in the levels of total cholesterol (Tc), triglycerides (Tg), plasma lipids (Pl), and protein by 24, 23, 23 and 22 %, and 24, 22, 23 and 19 %, respectively. In rats fed with high fat diet (HFD), ether and chloroform fractions lowered Tc, Tg and, Pl by 26, 25 and 26 %, and 18, 19 and 20 %, respectively. Significant decrease in superoxide anions, hydroxyl radicals and microsomal lipid peroxidation by ether and chloroform fractions was also observed. Chloroform, chloroform-methanol (4:1) and chloroform-methanol (3:2) fractions showed antihyperglycaemic activity to the extent of 25.2, 21.6 and 23.2 %, respectively.Conclusion: The flowers of this plant, especially the ether and chloroform extracts, may be suitable as an anti-oxidant supplement for lipid management.Keywords: Allamanda violacea flowers, Anti-hyperlipidemic,  Anti-hyperglycemic, Anti-oxidant

Design and Development of Halogenated Chalcone Derivatives as Potential Anticancer Agents

Purpose: To design and develop halogenated chalcone derivatives and evaluate them as anticancer agents using different cancer cell lines.Methods: Based on in silico design and docking on known target, crystal structure of the complex of interleukin-1beta converting enzyme (ICE) with a peptide based inhibitor, (3S )-N-Methanesulfonyl-3- ({1-[N-(2-naphtoyl)-l-valyl]-l-prolyl}amino)-4-oxobutanamide (1BMQ), novel halogenated chalcone derivatives were designed (7a-h) employing LigandFit module of Accelrys (Discovery Studio, 2.1 version). Standard protocols for ligand and protein preparation were employed and their binding orientation validated using (3S)-N-Methanesulfonyl-3-({1-[N-(2-naphtoyl)-l-valyl]-l-prolyl}amino)-4-oxobutanamide (MNO 601), a caspase inhibitor as reference standard. Energy minimized conformers with best dock scores were considered for the identification of interacting amino acid residues with ligands. Selected derivatives were synthesized and analyzed by melting point, 1H NMR, IR and mass spectroscopy. Their evaluation for anticancer activity was carried out using adriamycin, paclitaxel and 5-fluorouracil as reference standards on prostrate (PC-3), colon (COLO-205), ovary (OVCAR-5), liver (HEP-2) and neuroblastoma (IMR-32) cancer cell lines, and % growth inhibition and half maximal inhibitory concentration (IC50) values were calculated.Results: Among synthesized compounds, 7b showed the most promising cytotoxic activity with an IC50 of 49.9 ìM on colon cancer cell lines (Colo-205), followed by 7d with an IC50 of 66.6 ìM against ovarian cancer cell lines (OVCAR-5).Conclusion: We report the successful synthesis, spectral characterization and in vitro anticancer evaluation of a series of novel halogenated chalcone derivatives against a number of human cancer cell lines. The findings indicate the emergence of new anticancer compounds.Keywords: Halogenated chalcones, Dock scores, Anticancer activity,  Interleukin-1beta converting enzyme

Immunosuppressive and anti-cancer potential of aqueous extract of Solanum Xanthocarpum

451-457In this study whole plant aqueous extract of Solanum Xanthocarpum (HAESX) was investigated to assess its effect on humoral immune response along with interleukin-2 (IL-2) production and its expression in Wistar albino rats splenocytes culture. Anticancer potential of HAESX was investigated using rat lever hepatoma (N1S1 cancerous cell line). The effect of HAESX over humoral immune response was studied using four groups of five animals each (Group-I as control, Group -II orally fed with 125 mg/kg body weight, Group -III orally fed with 250 mg/kg body weight and Group -IV orally fed with 500 mg/kg body weight of HAESX). Quantification of IL-2 was done by sandwich ELISA and its expression was detected by the real time PCR. SRB assay (Sulforhodamine B) was done for detecting the effect of HAESX on N1S1 cell line. Dose dependent decrease in antibody titer was observed and production of IL-2 was also decreased significantly. Suppression of IL-2 production at 250 µg/mL and 500 µg/mL dose was also confirmed by the Real time PCR. Relative fold change in the expression of IL-2 gene was 592.22 and 10.77 at 250, 500 μg/mL HAESX concentrations respectively with respect to control. Dose dependent suppression of percent growth of N1S1 cells with increasing concentrations (10, 20, 40 and 80 µg/mL) of HAESX was found. It was concluded that S. xanthocarpum have the immunosuppressive, and anti cancer activity that can be further explore in treatment of various inflammatory and autoimmune disease

Publisher Correction: Graphene overcoats for ultra-high storage density magnetic media.

Publisher Correction: Graphene overcoats for ultra-high storage density magnetic media

Evaluation of the impact of the voucher and accreditation approach on improving reproductive behaviors and RH status: Bangladesh

<p>Abstract</p> <p>Background</p> <p>Cost of delivering reproductive health services to low-income populations will always require total or partial subsidization by the government and/or development partners. Broadly termed "Demand-Side Financing" or "Output-Based Aid", includes a range of interventions that channel government or donor subsidies to the service user rather than the service provider. Initial findings from the few assessments of reproductive health voucher-and-accreditation programs suggest that, if implemented well, these programs have great potential for achieving the policy objectives of increasing access and use, reducing inequities and enhancing program efficiency and service quality. At this point in time, however, there is a paucity of evidence describing how the various voucher programs function in different settings, for various reproductive health services.</p> <p>Methods/Design</p> <p>Population Council-Nairobi, funded by the Bill and Melinda Gates Foundation, intends to address the lack of evidence around the pros and cons of 'voucher and accreditation' approaches to improving the reproductive health of low income women in five developing countries. In Bangladesh, the activities will be conducted in 11 accredited health facilities where Demand Side Financing program is being implemented and compared with populations drawn from areas served by similar non-accredited facilities. Facility inventories, client exit interviews and service provider interviews will be used to collect comparable data across each facility for assessing readiness and quality of care. In-depth interviews with key stakeholders will be conducted to gain a deeper understanding about the program. A population-based survey will also be carried out in two types of locations: areas where vouchers are distributed and similar locations where vouchers are not distributed.</p> <p>Discussion</p> <p>This is a quasi-experimental study which will investigate the impact of the voucher approach on improving maternal health behaviors and status and reducing inequities at the population level. We expect a significant increase in the utilization of maternal health care services by the accredited health facilities in the experimental areas compared to the control areas as a direct result of the interventions. If the voucher scheme in Bangladesh is found effective, it may help other countries to adopt this approach for improving utilization of maternity care services for reducing maternal mortality.</p

Assessment of the effect of phenytoin on cutaneous healing from excision of melanocytic nevi on the face and on the back

<p>Abstract</p> <p>Background</p> <p>Topical phenytoin is a powerful skin wounds healing and it may be useful in clinical practice. The purpose of this study was to evaluate the effect of topical phenytoin 0.5%, by comparing it with cream (control) in wounds resulting from excision of two melanocytic nevi in the same patient. Our purpose was also to assess if phenytoin had better therapeutic and cosmetic outcomes when compared with cream (control).</p> <p>Methods</p> <p>This study evaluated 100 patients with skin wounds from excision of melanocytic nevi. 50 patients with lesions on the face and 50 patients with lesions on the back, totalizing 200 lesions excised with modified punch. The resulting superficial skin wounds had the same diameter and depth, and second intention healing followed.</p> <p>Patients were followed for 60 days. Student's t-test, Mann Whitney nonparametric test, analysis of variance, LSD test, Shapiro-Wilks test and Fisher test were used to analyze the results, depending on the nature of the variables being studied.</p> <p>Results</p> <p>Phenytoin showed better therapeutic and cosmetic results, by healing faster, with more intense epithelization in wounds in comparison with cream (control). Phenytoin showed a statistically significant difference regarding the following parameters (p < 0.05): wounded area and healing time. Phenytoin application resulted in a smaller area and a shorter healing time. Also the intensity of exudates, bleeding, and the epithelization were more intense in phenytoin-treated wounds. Regarding the shape and thickness of the scar, injuries treated with phenytoin had round and flat shaped scars in most of the cases. Considering patient's gender and phototype, female patients presented smaller wounds and scar areas; and phototype I had the largest scar areas. Contact eczema was an adverse reaction in 7 injuries located on the back caused by cream (control) and hypoallergenic tape.</p> <p>Conclusions</p> <p>Phenytoin showed better therapeutic and cosmetic results compared with cream (control). Phenytoin is a low cost drug, which accelerates skin wounds healing in human patients. Trial registration: ISRCTN96539803</p

Functional neurological disorders in Parkinson disease

OBJECTIVE: To ascertain demographic and clinical features of Parkinson disease (PD) associated with functional neurological features. METHODS: A standardised form was used to extract data from electronic records of 53 PD patients with associated functional neurological disorders (PD-FND) across eight movement disorders centres in the USA, Canada and Europe. These subjects were matched for age, gender and disease duration to PD patients without functional features (PD-only). Logistic regression analysis was used to compare both groups after adjusting for clustering effect. RESULTS: Functional symptoms preceded or co-occurred with PD onset in 34% of cases, nearly always in the most affected body side. Compared with PD-only subjects, PD-FND were predominantly female (68%), had longer delay to PD diagnosis, greater prevalence of dyskinesia (42% vs 18%; P=0.023), worse depression and anxiety (P=0.033 and 0.025, respectively), higher levodopa-equivalent daily dose (972±701 vs 741±559 mg; P=0.029) and lower motor severity (P=0.019). These patients also exhibited greater healthcare resource utilisation, higher use of [(123)I]FP-CIT SPECT and were more likely to have had a pre-existing psychiatric disorder (P=0.008) and family history of PD (P=0.036). CONCLUSIONS: A subtype of PD with functional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor disability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients

Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place