In vitro inhibitory activities of the extract of Hibiscus sabdariffa L. (family malvaceae) on selected cytochrome p450 isoforms

Literature is scanty on the interaction potential of Hibiscus sabdariffa L., plant extract with other drugs and the affected targets. This study was conducted to investigate the cytochrome P450 (CYP) isoforms that are inhibited by the extract of Hibiscus sabdariffa L. in vitro. The inhibition towards the major drug metabolizing CYP isoforms by the plantextract were estimated in human liver microsomal incubations, by monitoring the CYP-specific model reactions through previously validated N-in-one assay method. The ethanolic extract of Hibiscus sabdariffa showed inhibitory activities against nine selected CYP isoforms: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 andCYP3A4. The concentrations of the extract which produced 50% inhibition of the CYP isoforms ranged from 306 ìg/ml to 1660 ìg/ml, and the degree of inhibition based on the IC50 values for each CYP isoform was in the following order: CYP1A2 > CYP2C8 > CYP2D6 > CYP2B6 > CYP2E1 > CYP2C19 > CYP3A4 >> CYP2C9 >> CYP2A6. Ethanolic extract of Hibiscus sabdariffa caused inhibition of CYP isoforms in vitro. These observed inhibitions may not cause clinically significant herb-drug interactions; however, caution may need to be taken in co-administering the water extract of Hibiscus sabdariffa with other drugs until clinical studies are available to further clarify these findings.Key words: Cytochrome P450, Hibiscus sabdariffa, Herb-drug interaction, Anthocyanin, N-in-one assay

Performance Comparisons of Jet and Mesh Nebulizers Using Different Interfaces in Simulated Spontaneously Breathing Adults and Children

Background: Different types of nebulizers and interfaces are used for the treatment of adults and children with pulmonary diseases. The purpose of this study was to determine the efficiency of a mesh nebulizer (MN) with a proprietary adapter and a jet nebulizer (JN) under different configurations in adult and pediatric models of spontaneous breathing. We hypothesize that delivery efficiency of JN and MN will differ depending on the interface used during aerosol therapy in simulated spontaneously breathing adult and pediatric models. While we expect that aerosol delivery with JN will be less efficient than MN, we also hypothesize that lung deposition obtained with the adult lung model will be more than that with the pediatric lung model in all conditions tested in this study. Methods: A lung model using a teaching manikin connected to a sinusoidal pump via a collecting filter at the level of the bronchi simulating a spontaneously breathing adult (Vt 500 mL, RR 15 bpm, I:E ratio 1:2) or pediatric patient (Vt 150 mL, RR 25 bpm, I:E ratio 1:2). Albuterol sulfate (2.5 mg/3 mL) was aerosolized with JN (Mistymax 10, Airlife) or MN (Aerogen Solo®, Aerogen) with the Adapter (Aerogen Solo® Adapter, Aerogen Ltd, Galway, Ireland) using mouthpiece, aerosol mask, and valved-mask in adults and the dragon mask, aerosol mask, and valved-mask in pediatrics (n=3). The Adapter, specifically designed for MN, was attached to all the interfaces used in this study with supplemental oxygen of 2 lpm, and in addition, the MP was tested with no additional flow in the adult model. The JN was driven with 10 lpm based on the manufacturer\u27s label. Drug was eluted from the filter and analyzed via spectrophotometry. Descriptive statistics, dependent t-test and one-way analysis of variance were used for data analysis. Significant level was set at 0.05. Results: In adults, delivery efficiency of JN with the valved mask was significantly greater than that with the aerosol mask (p=0.01). Aerosol delivery of JN with the mouthpiece was not statistically significant from the valved mask (p=0.123) and the aerosol mask (p=0.193). Drug delivery with MN with mouthpiece (15.42±1.4%) and valved-mask (15.15±1.1%) was greater than the open aerosol mask (7.54±0.39%; p=0.0001) in the adult lung model. With no flow mouthpiece delivery increased\u3e2 fold (34.9±3.1%; p=.0001) compared to use of 2 lpm of flow. Using the JN with the pediatric model deposition with valved-mask (5.3±0.8%), dragon mask (4.7±0.9%), and aerosol mask (4.1±0.3%) were similar (p\u3e0.05); while drug delivery with MN via valved-mask (11.1±0.7%) was greater than the dragon mask (6.44±0.3%; p=0.002) and aerosol mask (4.6±0.4%; p=0.002), and the dragon mask was more efficient than the open aerosol mask (p=0.009) Conclusion: The type of nebulizer and interface used for aerosol therapy affects delivery efficiency in these simulated spontaneously breathing adult and pediatric models. Drug delivery was greatest with the valved-mouthpiece and mask with JN and MN, while the standard aerosol mask was least efficient in these simulated spontaneously breathing adult and pediatric lung models. Delivery efficiency of JN was less than MN in all conditions tested in this study except in the aerosol mask. Lung deposition obtained with the adult lung model was more than that with the pediatric lung model

Forest Conservation: A Potential Nutrition-Sensitive Intervention in Low- and Middle-Income Countries

Rasolofoson, Ricketts, Jacob, Johnson, Pappinen and Fisher. Childhood undernutrition yearly kills 3.1 million children worldwide. For those who survive early life undernutrition, it can cause motor and cognitive development problems that translate into poor educational performance and limited work productivity later in life. It has been suggested that nutrition-specific interventions (e.g., micronutrient supplementation) that directly address the immediate determinants of undernutrition (e.g., nutrient intake) need to be complemented by nutrition-sensitive interventions that more broadly address the underlying determinants of undernutrition (e.g., food insecurity). Here, we argue that forest conservation represents a potentially important but overlooked nutrition-sensitive intervention. Forests can address a number of underlying determinants of undernutrition, including the supply of forest food products, income, habitat for pollinators, women\u27s time allocation, diarrheal disease, and dietary diversity. We examine the effects of forests on stunting—a debilitating outcome of undernutrition—using a database of household surveys and environmental variables across 25 low- and middle-income countries. Our result indicates that exposure to forest significantly reduces child stunting (at least 7.11% points average reduction). The average magnitude of the reduction is at least near the median of the impacts of other known nutrition interventions. Forest conservation interventions typically cover large areas and are often implemented where people are vulnerable, and thus could be used to reach a large number of the world\u27s undernourished communities that may have difficult access to traditional nutrition programs. Forest conservation is therefore a potentially effective nutrition-sensitive intervention. Efforts are needed to integrate specific nutrition goals and actions into forest conservation interventions in order to unleash their potential to deliver nutritional benefits

Ekiden: A Platform for Confidentiality-Preserving, Trustworthy, and Performant Smart Contract Execution

Smart contracts are applications that execute on blockchains. Today they manage billions of dollars in value and motivate visionary plans for pervasive blockchain deployment. While smart contracts inherit the availability and other security assurances of blockchains, however, they are impeded by blockchains' lack of confidentiality and poor performance. We present Ekiden, a system that addresses these critical gaps by combining blockchains with Trusted Execution Environments (TEEs). Ekiden leverages a novel architecture that separates consensus from execution, enabling efficient TEE-backed confidentiality-preserving smart-contracts and high scalability. Our prototype (with Tendermint as the consensus layer) achieves example performance of 600x more throughput and 400x less latency at 1000x less cost than the Ethereum mainnet. Another contribution of this paper is that we systematically identify and treat the pitfalls arising from harmonizing TEEs and blockchains. Treated separately, both TEEs and blockchains provide powerful guarantees, but hybridized, though, they engender new attacks. For example, in naive designs, privacy in TEE-backed contracts can be jeopardized by forgery of blocks, a seemingly unrelated attack vector. We believe the insights learned from Ekiden will prove to be of broad importance in hybridized TEE-blockchain systems

Proactive case detection of common childhood illnesses by community health workers: a systematic review.

INTRODUCTION: Identifying design features and implementation strategies to optimise community health worker (CHW) programmes is important in the context of mixed results at scale. We systematically reviewed evidence of the effects of proactive case detection by CHWs in low-income and middle-income countries (LMICs) on mortality, morbidity and access to care for common childhood illnesses. METHODS: Published studies were identified via electronic databases from 1978 to 2017. We included randomised and non-randomised controlled trials, controlled before-after studies and interrupted time series studies, and assessed their quality for risk of bias. We reported measures of effect as study investigators reported them, and synthesised by outcomes of mortality, disease prevalence, hospitalisation and access to treatment. We calculated risk ratios (RRs) as a principal summary measure, with CIs adjusted for cluster design effect. RESULTS: We identified 14 studies of 11 interventions from nine LMICs that met inclusion criteria. They showed considerable diversity in intervention design and implementation, comparison, outcomes and study quality, which precluded meta-analysis. Proactive case detection may reduce infant mortality (RR: 0.52-0.94) and increase access to effective treatment (RR: 1.59-4.64) compared with conventional community-based healthcare delivery (low certainty evidence). It is uncertain whether proactive case detection reduces mortality among children under 5 years (RR: 0.04-0.80), prevalence of infectious diseases (RR: 0.06-1.02), hospitalisation (RR: 0.38-1.26) or increases access to prompt treatment (RR: 1.00-2.39) because the certainty of this evidence is very low. CONCLUSION: Proactive case detection may provide promising benefits for child health, but evidence is insufficient to draw conclusions. More research is needed on proactive case detection with rigorous study designs that use standardised outcomes and measurement methods, and report more detail on complex intervention design and implementation. PROSPERO REGISTRATION NUMBER: CRD42017074621

Molecular epidemiological analysis of Escherichia coli sequence type ST131 (O25:H4) and bla CTX-M-15among extended-spectrum-β- lactamase-producing E. coli from the United States, 2000 to 2009

Escherichia coli sequence type ST131 (from phylogenetic group B2), often carrying the extended-spectrum-β-lactamase (ESBL) gene bla , is an emerging globally disseminated pathogen that has received comparatively little attention in the United States. Accordingly, a convenience sample of 351 ESBL-producing E. coli isolates from 15 U.S. centers (collected in 2000 to 2009) underwent PCR-based phylotyping and detection of ST131 and bla . A total of 200 isolates, comprising 4 groups of 50 isolates each that were (i) bla negative non-ST131, (ii) bla positive non-ST131, (iii) bla negative ST131, or (iv) bla positive ST131, also underwent virulence genotyping, antimicrobial susceptibility testing, and pulsed-field gel electrophoresis (PFGE). Overall, 201 (57%) isolates exhibited bla , whereas 165 (47%) were ST131. ST131 accounted for 56% of bla -positive-versus 35% of bla -negative isolates (

IN VITRO INHIBITORY ACTIVITIES OF THE EXTRACT OF HIBISCUS SABDARIFFA L. (FAMILY MALVACEAE) ON SELECTED CYTOCHROME P450 ISOFORMS.

Literature is scanty on the interaction potential of Hibiscus sabdariffa L., plant extract with other drugs and the affected targets. This study was conducted to investigate the cytochrome P450 (CYP) isoforms that are inhibited by the extract of Hibiscus sabdariffa L. in vitro. The inhibition towards the major drug metabolizing CYP isoforms by the plant extract were estimated in human liver microsomal incubations, by monitoring the CYP-specific model reactions through previously validated N-in-one assay method. The ethanolic extract of Hibiscus sabdariffa showed inhibitory activities against nine selected CYP isoforms: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. The concentrations of the extract which produced 50% inhibition of the CYP isoforms ranged from 306 µg/ml to 1660 µg/ml, and the degree of inhibition based on the IC50 values for each CYP isoform was in the following order: CYP1A2 > CYP2C8 > CYP2D6 > CYP2B6 > CYP2E1 > CYP2C19 > CYP3A4 >> CYP2C9 >> CYP2A6. Ethanolic extract of Hibiscus sabdariffa caused inhibition of CYP isoforms in vitro. These observed inhibitions may not cause clinically significant herb-drug interactions; however, caution may need to be taken in co-administering the water extract of Hibiscus sabdariffa with other drugs until clinical studies are available to further clarify these findings