Highly Oxygenated Flavonoids from the Leaves of Nicotiana plumbaginifolia (Solanaceae)

Nicotiana plumbaginifolia Viv. is an annual herb of the family Solanaceae, which grows abundantly in the weedy lands of Bangladesh. This plant possesses analgesic, antibacterial, anti-anxiety and hepatoprotective properties, and produces various phenolic compounds including flavonoids. The present study afforded determination of total phenolic and flavonoid contents, and for the first time, the isolation and characterization of highly oxygenated flavonoids, e.g., 3,3',5,6,7,8-hexamethoxy-4',5'-methylenedioxyflavone (1), 3,3',4',5',5,6,7,8-octamethoxyflavone (2, exoticin), 6,7,4',5'-dimethylenedioxy-3,5,3'-trimethoxyflavone (3) and (3,3',4',5,5',8-hexamethoxy-6,7-methylenedioxyflavone (4) from the leaves of N. plumbaginifolia. All these flavonoids are rather rare natural products, and only found in a few genera, e.g., Polygonum and Murraya. The structures of the isolated flavonoids were elucidated by comprehensive spectroscopic analyses, e.g., UV, 1H, 13C NMR, DEPT, HSQC, HMBC and MS

GC–MS analysis and pharmacological evaluations of Phoenix sylvestris (Roxb.) seeds provide new insights into the management of oxidative stress and hyperglycemia

Phoenix sylvestris Roxb. (Arecaceae) seeds are used in the treatment of diabetes in the traditional system of medicine. The present study evaluated antihyperglycemic and antioxidant activities as well as the total phenolic and flavonoid content of the methanol extract of P. sylvestris seeds (MEPS). The constituents of the extract were identified by GC–MS analysis. MEPS demonstrated strong antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 162.70 ± 14.99 μg) and nitric oxide (NO) (IC50 = 101.56 ± 9.46 μg/ml) free radicals. It also possesses a substantial amount of phenolics and flavonoids. It significantly (p < .05) reduced blood glucose levels in glucose-loaded and alloxan-induced diabetic mice at the doses of 150 and 300 mg/kg b.w., respectively. A total of 46 compounds were detected and identified by gas chromatography–mass spectroscopy (GC–MS) analysis, among which 8-methylisoquinoline N-oxide (32.82%) was predominant. The phytochemical study by GC–MS revealed that the MEPS possesses compounds which could be related to its antidiabetic and antioxidant activities. To recapitulate, P. sylvestris seeds can be a very good option for antidiabetic and antioxidant activity though further studies are still recommended to figure out the responsible phytochemicals and establish their exact mechanism of action

Birth preparedness and complication readiness (BPCR) among pregnant women in hard-to-reach areas in Bangladesh:BPCR in hard-to-reach areas of Bangladesh

Birth preparedness and complication readiness aims to reduce delays in care seeking, promote skilled birth attendance, and facility deliveries. Little is known about birth preparedness practices among populations living in hard-to-reach areas in Bangladesh.To describe levels of birth preparedness and complication readiness among recently delivered women, identify determinants of being better prepared for birth, and assess the impact of greater birth preparedness on maternal and neonatal health practices.A cross-sectional survey with 2,897 recently delivered women was undertaken in 2012 as part of an evaluation trial done in five hard-to-reach districts in rural Bangladesh. Mothers were considered well prepared for birth if they adopted two or more of the four birth preparedness components. Descriptive statistics and multivariable logistic regression were used for analysis.Less than a quarter (24.5%) of women were considered well prepared for birth. Predictors of being well-prepared included: husband's education (OR = 1.3; CI: 1.1-1.7), district of residence, exposure to media in the form of reading a newspaper (OR = 2.2; CI: 1.2-3.9), receiving home visit by a health worker during pregnancy (OR = 1.5; CI: 1.2-1.8), and receiving at least 3 antenatal care visits from a qualified provider (OR = 1.4; CI: 1.0-1.9). Well-prepared women were more likely to deliver at a health facility (OR = 2.4; CI: 1.9-3.1), use a skilled birth attendant (OR = 2.4, CI: 1.9-3.1), practice clean cord care (OR = 1.3, CI: 1.0-1.5), receive post-natal care from a trained provider within two days of birth for themselves (OR = 2.6, CI: 2.0-3.2) or their newborn (OR = 2.6, CI: 2.1-3.3), and seek care for delivery complications (OR = 1.8, CI: 1.3-2.6).Greater emphasis on BPCR interventions tailored for hard to reach areas is needed to improve skilled birth attendance, care seeking for complications and essential newborn care and facilitate reductions in maternal and neonatal mortality in low performing districts in Bangladesh

A retrospective analysis of clinical outcome of patients with chemo-refractory metastatic breast cancer treated in a single institution phase I unit

BACKGROUND AND METHODS: Novel approaches to treat chemo-refractory metastatic breast cancer (MBC) are currently under investigation. This retrospective series reviews the outcome of 70 MBC patients who have participated in 30 phase I trials at the Royal Marsden Hospital from 2002 to 2009. RESULTS: The median treatment lines before phase I trial entry for MBC was 5 (range: 1-12 lines). The overall response rate was 11.4% (95% CI: 4.0-18.9%) and the clinical benefit rate at 4 months was 20% (95% CI: 10.6-29.3). The median time to progression was 7.0 weeks (95% CI: 6.4-7.5) and median overall survival was 8.7 months (95% CI: 7.6-9.8) from start of first phase I treatment. No patients discontinued trial because of treatment-related toxicities. Abnormal lactate dehydrogenase, serum albumin <35 mg per 100 ml, >or=5 previous treatment lines, liver metastases and Eastern Cooperative Group performance status >or=2 at study entry were significantly associated with poor overall survival in multivariate analysis. CONCLUSION: This retrospective analysis provides evidence that patients with MBC tolerate phase I clinical trials and a significant proportion of patients with chemo-refractory disease, particularly those with triple-negative or Her2-positive breast cancer, may benefit from treatment

Antibacterial activity and mode of action of selected glucosinolate hydrolysis products against bacterial pathogens

Plants contain numerous components that are important sources of new bioactive molecules with antimicrobial properties. Isothiocyanates (ITCs) are plant secondary metabolites found in cruciferous vegetables that are arising as promising antimicrobial agents in food industry. The aim of this study was to assess the antibacterial activity of two isothiocyanates (ITCs), allylisothiocyanate (AITC) and 2-phenylethylisothiocyanate (PEITC) against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Listeria monocytogenes. The antibacterial mode of action was also characterized by the assessment of different physiological indices: membrane integrity, intracellular potassium release, physicochemical surface properties and surface charge. The minimum inhibitory concentration (MIC) of AITC and PEITC was 100 g/mL for all bacteria. The minimum bactericidal concentration (MBC) of the ITCs was at least 10 times higher than the MIC. Both AITC and PEITC changed the membrane properties of the bacteria decreasing their surface charge and compromising the integrity of the cytoplasmatic membrane with consequent potassium leakage and propidium iodide uptake. The surface hydrophobicity was also non-specifically altered (E. coli and L. monocytogenes become less hydrophilic; P. aeruginosa and S. aureus become more hydrophilic). This study shows that AITC and PEITC have strong antimicrobial potential against the bacteria tested, through the disruption of the bacterial cell membranes. Moreover, phytochemicals are highlighted as a valuable sustainable source of new bioactive products.This work was supported by the Operational Programme for Competitiveness Factors - COMPETE and by the Portuguese Foundation for Science and Technology through Project Phytodisinfectants - PTDC/DTP-SAP/1078/2012 (COMPETE: FCOMP-01-0124-FEDER-028765), the PhD grant awarded to Ana Abreu (SFRH/BD/84393/2012), and the post-doctoral grants awarded to Anabela Borges (SFRH/BPD/98684/2013) and Lucia C. Simoes (SFRH/BPD/81982/2011). Also, this work was undertaken as part of the European Research Project SUSCLEAN (Contract no FP7-KBBE-2011-5, project number: 287514) and the COST Action FA1202. The authors are solely responsible for this work. It does not represent the opinion of the European Community, and the Community is not responsible for any use that might be made of data appearing herein

Analysis of Interactions of Salmonella Type Three Secretion Mutants with 3-D Intestinal Epithelial Cells

The prevailing paradigm of Salmonella enteropathogenesis based on monolayers asserts that Salmonella pathogenicity island-1 Type Three Secretion System (SPI-1 T3SS) is required for bacterial invasion into intestinal epithelium. However, little is known about the role of SPI-1 in mediating gastrointestinal disease in humans. Recently, SPI-1 deficient nontyphoidal Salmonella strains were isolated from infected humans and animals, indicating that SPI-1 is not required to cause enteropathogenesis and demonstrating the need for more in vivo-like models. Here, we utilized a previously characterized 3-D organotypic model of human intestinal epithelium to elucidate the role of all characterized Salmonella enterica T3SSs. Similar to in vivo reports, the Salmonella SPI-1 T3SS was not required to invade 3-D intestinal cells. Additionally, Salmonella strains carrying single (SPI-1 or SPI-2), double (SPI-1/2) and complete T3SS knockout (SPI-1/SPI-2: flhDC) also invaded 3-D intestinal cells to wildtype levels. Invasion of wildtype and TTSS mutants was a Salmonella active process, whereas non-invasive bacterial strains, bacterial size beads, and heat-killed Salmonella did not invade 3-D cells. Wildtype and T3SS mutants did not preferentially target different cell types identified within the 3-D intestinal aggregates, including M-cells/M-like cells, enterocytes, or Paneth cells. Moreover, each T3SS was necessary for substantial intracellular bacterial replication within 3-D cells. Collectively, these results indicate that T3SSs are dispensable for Salmonella invasion into highly differentiated 3-D models of human intestinal epithelial cells, but are required for intracellular bacterial growth, paralleling in vivo infection observations and demonstrating the utility of these models in predicting in vivo-like pathogenic mechanisms

Molecular Characterization of Podoviral Bacteriophages Virulent for Clostridium perfringens and Their Comparison with Members of the Picovirinae

Clostridium perfringens is a Gram-positive, spore-forming anaerobic bacterium responsible for human food-borne disease as well as non-food-borne human, animal and poultry diseases. Because bacteriophages or their gene products could be applied to control bacterial diseases in a species-specific manner, they are potential important alternatives to antibiotics. Consequently, poultry intestinal material, soil, sewage and poultry processing drainage water were screened for virulent bacteriophages that lysed C. perfringens. Two bacteriophages, designated ΦCPV4 and ΦZP2, were isolated in the Moscow Region of the Russian Federation while another closely related virus, named ΦCP7R, was isolated in the southeastern USA. The viruses were identified as members of the order Caudovirales in the family Podoviridae with short, non-contractile tails of the C1 morphotype. The genomes of the three bacteriophages were 17.972, 18.078 and 18.397 kbp respectively; encoding twenty-six to twenty-eight ORF's with inverted terminal repeats and an average GC content of 34.6%. Structural proteins identified by mass spectrometry in the purified ΦCP7R virion included a pre-neck/appendage with putative lyase activity, major head, tail, connector/upper collar, lower collar and a structural protein with putative lysozyme-peptidase activity. All three podoviral bacteriophage genomes encoded a predicted N-acetylmuramoyl-L-alanine amidase and a putative stage V sporulation protein. Each putative amidase contained a predicted bacterial SH3 domain at the C-terminal end of the protein, presumably involved with binding the C. perfringens cell wall. The predicted DNA polymerase type B protein sequences were closely related to other members of the Podoviridae including Bacillus phage Φ29. Whole-genome comparisons supported this relationship, but also indicated that the Russian and USA viruses may be unique members of the sub-family Picovirinae

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study

BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future