Studies on the antihypertensive and antidyslipidemic activities of Viola odorata leaves extract

<p>Abstract</p> <p>Background</p> <p>This study was undertaken to provide pharmacological basis for the medicinal use of <it>Viola odorata </it>Linn. in hypertension and dyslipidemia using the <it>in vivo </it>and <it>in vitro </it>assays.</p> <p>Results</p> <p><it>Viola odorata </it>leaves extract (Vo.Cr), which tested positive for alkaloids, saponins, tannins, phenolics, coumarins and flavonoids, caused a dose-dependent (0.1-1.0 mg/kg) decrease in mean arterial blood pressure in anaesthetized rats. In isolated guinea-pig atria, Vo.Cr equally inhibited force and rate of spontaneous atrial contractions. On the baseline of rat thoracic aortae (endothelium-intact and denuded), the plant extract caused phentolamine-sensitive vasoconstriction. When tested on phenylephrine (PE, 1 μM) and K⁺(80 mM)-induced vasoconstriction, Vo.Cr caused a concentration-dependent relaxation and also caused a rightward shift of Ca⁺⁺concentration-response curves as well as suppression of PE (1 μM) control peaks in Ca⁺⁺-free medium, similar to that caused by verapamil. In the presence of L-NAME, the relaxation curve of Vo.Cr was partially inhibited showing involvement of Nitric oxide (NO) mediated pathway. In Tyloxapol-induced dyslipidemia, Vo.Cr caused reduction in total cholesterol and triglyceride levels. In high-fat diet-induced dyslipidemia model, the plant extract caused a significant decrease in total cholesterol, LDL-C, atherogenic index and prevented the increase in average body weights, while it increased HDL-C.</p> <p>Conclusions</p> <p>These data indicate that the vasodilator effect of the plant extract is mediated through multiple pathways like inhibition of Ca⁺⁺influx via membranous Ca⁺⁺channels, its release from intracellular stores and NO-mediated pathways, which possibly explain the fall in BP. The plant also showed reduction in body weight and antidyslipidemic effect which may be due to the inhibition of synthesis and absorption of lipids and antioxidant activities. Thus, this study provides a pharmacologic rationale to the medicinal use of <it>Viola odorata </it>in hypertension and dyslipidemia.</p

Genome-wide analysis of the maternal-to-zygotic transition in Drosophila primordial germ cells

Background: During the maternal-to-zygotic transition (MZT) vast changes in the embryonic transcriptome are produced by a combination of two processes: elimination of maternally provided mRNAs and synthesis of new transcripts from the zygotic genome. Previous genome-wide analyses of the MZT have been restricted to whole embryos. Here we report the first such analysis for primordial germ cells (PGCs), the progenitors of the germ-line stem cells. Results: We purified PGCs from Drosophila embryos, defined their proteome and transcriptome, and assessed the content, scale and dynamics of their MZT. Transcripts encoding proteins that implement particular types of biological functions group into nine distinct expression profiles, reflecting coordinate control at the transcriptional and posttranscriptional levels. mRNAs encoding germ-plasm components and cell-cell signaling molecules are rapidly degraded while new transcription produces mRNAs encoding the core transcriptional and protein synthetic machineries. The RNA-binding protein Smaug is essential for the PGC MZT, clearing transcripts encoding proteins that regulate stem cell behavior, transcriptional and posttranscriptional processes. Computational analyses suggest that Smaug and AU-rich element binding proteins function independently to control transcript elimination. Conclusions: The scale of the MZT is similar in the soma and PGCs. However, the timing and content of their MZTs differ, reflecting the distinct developmental imperatives of these cell types. The PGC MZT is delayed relative to that in the soma, likely because relief of PGC-specific transcriptional silencing is required for zygotic genome activation as well as for efficient maternal transcript clearance.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000305391700004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biotechnology &amp; Applied MicrobiologyGenetics &amp; HereditySCI(E)20ARTICLE2null1

Docosahexaenoic acid reduces microglia phagocytic activity via miR-124 and induces neuroprotection in rodent models of spinal cord contusion injury

Microglia are activated after spinal cord injury (SCI), but their phagocytic mechanisms and link to neuroprotection remain incompletely characterized. Docosahexaenoic acid (DHA) has been shown to have significant neuroprotective effects after hemisection and compression SCI and can directly affect microglia in these injury models. In rodent contusion SCI, we demonstrate that DHA (500 nmol/kg) administered acutely post-injury confers neuroprotection and enhances locomotor recovery, and also exerts a complex modulation of the microglial response to injury. In rodents, at 7 days after SCI, the level of phagocytosed myelin within Iba1-positive or P2Y12-positive cells was significantly lower after DHA treatment, and this occurred in parallel with an increase in intracellular miR-124 expression. Furthermore, intraspinal administration of a miR-124 inhibitor significantly reduced the DHA-induced decrease in myelin phagocytosis in mice at 7 days post-SCI. In rat spinal primary microglia cultures, DHA reduced the phagocytic response to myelin, which was associated with an increase in miR-124, but not miR-155. A similar response was observed in a microglia cell line (BV2) treated with DHA, and the effect was blocked by a miR-124 inhibitor. Furthermore, the phagocytic response of BV2 cells to stressed neurones was also reduced in the presence of DHA. In peripheral monocyte-derived macrophages, the expression of the M1, but not the M0 or M2 phenotype, was reduced by DHA, but the phagocytic activation was not altered. These findings show that DHA induces neuroprotection in contusion injury. Furthermore, the improved outcome is via a miR-124-dependent reduction in the phagocytic response of microglia.US Department of Defence CDMRP/SCIRP award (W81XWH-10-1-1040 to P.K.Y., T.B. and A.M.T.); The Barts and London Charity (to P.K.Y. and A.M.T.); Rod Flower Vacation Scholarship (to A.L.B.); International Spinal Research Trust (to J.H. and P.G.P.); Ray W. Poppleton Endowment (to P.G.P.); Chang Gung Memorial Hospital, Taiwan (CMRPG3A1051–1054 to Z.-H.L.). M.A.B. is funded by the Spanish Ministry of Economy and Competitivity (Programa Ramón y Cajal: RYC-2017-21804)

Building local capacities in the operation and management of an integrated solid waste management programme; Experience of Ampara District, Eastern Sri Lanka

Open dumping and burning of wastes in the environmental sensitive areas were common practices in almost all the local authorities in Ampara district. It had become a big threat to public health, the beautiful natural environment and to the local economy. The Local Authorities of the District often faced severe difficulties in the management of solid waste in an environmentally, socially and economically feasible manner. The lack of technical and financial capacities to apply and practice the newly developed waste management guidelines and policies further aggravated this situation.Having identified the gravity  and the importance of this serious environmental issue, the Department of Assistant Commissioner of Local Government of Ampara District, with the financial assistance of the European Union and the technical assistance of the United Nations Office for Project Services (UNOPS), is currently implementing an Integrated Solid Waste Management Programme (ISWMP) in 12 local authorities of the District. This ISWMP is completely being operated with the full coordination of the District Office of the Central Environmental Authority, Ampara. The UNOPS, as part of its technical assistance, has constructed solid waste management facilities such as 7 engineered landfills, one Waste Transfer Station, 4 Recycling Centers, 5 compost yards, well developed collection systems  as well as provided with capability building/training assistance aiming to establish an effective and efficient solid waste management system for the District. These  facilities are now completed,  already in use and operational. With these facilities in place, and with the continued support from UNOPS in providing institutional and capacity building assistance to the LA officers and staff, haphazard dumping and littering of waste in certain areas of the LAs have now been stopped. Thus 45,000 urban households or 58% of the total urban population are benefitted under thisprogramme with a total collection of 137tonnes of wastes per day through this programme. Out of this 137tonnes of waste, 59 tonnes are collected from cluster systems involving five local authorities while the balance from the other non-clustered Local Authorities.The paper will also present the processes and methodologies to improve the landfill practices from the open dumping practices to controlled tipping and then to engineered landfills  among the implementing local authorities. It will also highlight interventions/strategies to ensure sustainability of the operation and their management through the introduction of a User Fee system/Service Charge which is currently being implemented in 04  Local Authorities. This collected User Fee covers about 80% of cost of collection of waste which would otherwise been spent through their normal budget.Key words: Integrated Solid Waste Management, Ampara, haphazard dumping, controlled tipping, engineered landfill

Wheat (Triticum aestivum l.) production under drought and heat stress – adverse effects, mechanisms and mitigation: A review

Heat and drought stresses are the most important abiotic factors that reduce crops productivity by affecting various physiological and biochemical processes. Thus, selecting cultivars with better drought or heat stress tolerance or breeding for stress tolerance will be helpful in enhancing crop productivity under harsh environments. This review elaborates the physiological basis of high temperature and drought stress tolerance in wheat which can be used as selection criteria in wheat breeding program. In addition, some agronomic selection criteria which are valid and useful in selecting stress tolerant wheat species and cultivars. The review also discussed the valid usage of stress tolerance indices (such as mean productivity (MP), geometric mean productivity (GMP), yield index (YI), yield stability index (YSI), relative productivity (RP%), stress susceptibility index (SSI), and the tolerance index (TOL)) to scan the genotypes against drought and heat stress. Beside these, exogenous application of stress signaling compounds, osmolytes, or certain inorganic salts play a vital role for alleviating adverse effects of abiotic stresses for sustainable wheat production. In addition, applications for soil amendments will also helpful in increasing wheat crop productivity under stressful conditions. All these strategies may be helpful to meet the food demands of the increasing population.Fil: El Sabagh, A.. University of Kafrelsheikh; EgiptoFil: Hossain, A.. Bangladesh Agricultural Research Institute; BangladeshFil: Barutçular, C.. University of Çukurova; TurquíaFil: Islam, Mohammad Sirajul. Hajee Mohammad Danesh Science and Technology University; BangladeshFil: Awan, S. I.. University of the Poonch; PakistánFil: Galal, A.. University of Kafrelsheikh; EgiptoFil: Iqbal, M. A.. University of the Poonch; PakistánFil: Sytar, O.. Slovak University of Agriculture; EslovaquiaFil: Yildirim, M.. Dicle University; TurquíaFil: Meena, R. S.. Inistitute of Agricultural Sciences; IndiaFil: Fahad, S.. The University of Swabi; PakistánFil: Najeeb, U.. The University of Queensland; AustraliaFil: Konuskan, O.. Mustafa Kemal University; TurquíaFil: Habib, R. A.. Bahauddin Zakariya University; PakistánFil: Llanes, Analia Susana. Universidad Nacional de Rio Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones Agrobiotecnológicas - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Agrobiotecnológicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Ciencias Naturales; ArgentinaFil: Hussain, S.. University of Agriculture; PakistánFil: Farooq, M.. Sultan Qaboos University; OmánFil: Hasanuzzaman, M.. Sher-e-Bangla Agricultural University; BangladeshFil: Abdelaal, K. H.. Kafrelsheikh University; EgiptoFil: Hafez, Y.. Kafrelsheikh University; EgiptoFil: Cig, F.. Siirt University; TurquíaFil: Saneoka, H.. Hiroshima University; Japó

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS).

BACKGROUND: Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin-gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. METHODS: In BARNARDS, consenting mother-neonates aged 0-60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic-pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. FINDINGS: Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin-gentamicin, ceftazidime-amikacin, piperacillin-tazobactam-amikacin, and amoxicillin clavulanate-amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime-amikacin than for neonates treated with ampicillin-gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14-0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin-gentamicin; 286 (73·3%) to amoxicillin clavulanate-amikacin; 301 (77·2%) to ceftazidime-amikacin; and 312 (80·0%) to piperacillin-tazobactam-amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin-gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate-amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime-amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin-tazobactam-amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis. INTERPRETATION: Our data raise questions about the empirical use of combined ampicillin-gentamicin for neonatal sepsis in LMICs because of its high resistance and high rates of frequency of resistance and low probability of target attainment. Accessibility and affordability need to be considered when advocating antibiotic treatments with variance in economic health structures across LMICs. FUNDING: The Bill & Melinda Gates Foundation

Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study

Background Neonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs. Methods The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Data for sepsis-associated factors in the four domains of health care, maternal, birth and neonatal, and living environment were collected for all mothers and neonates enrolled. Primary outcomes were clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality in neonates during the first 60 days of life. Incidence proportion of livebirths for clinically suspected sepsis and laboratory-confirmed sepsis and incidence rate per 1000 neonate-days for all-cause mortality were calculated. Modified Poisson regression was used to investigate factors associated with neonatal sepsis and parametric survival models for factors associated with all-cause mortality. Findings Between Nov 12, 2015 and Feb 1, 2018, 29 483 mothers and 30 557 neonates were enrolled. The incidence of clinically suspected sepsis was 166·0 (95% CI 97·69–234·24) per 1000 livebirths, laboratory-confirmed sepsis was 46·9 (19·04–74·79) per 1000 livebirths, and all-cause mortality was 0·83 (0·37–2·00) per 1000 neonate-days. Maternal hypertension, previous maternal hospitalisation within 12 months, average or higher monthly household income, ward size (>11 beds), ward type (neonatal), living in a rural environment, preterm birth, perinatal asphyxia, and multiple births were associated with an increased risk of clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality. The majority (881 [72·5%] of 1215) of laboratory-confirmed sepsis cases occurred within the first 3 days of life. Interpretation Findings from this study highlight the substantial proportion of neonates who develop neonatal sepsis, and the high mortality rates among neonates with sepsis in LMICs. More efficient and effective identification of neonatal sepsis is needed to target interventions to reduce its incidence and subsequent mortality in LMICs. Funding Bill & Melinda Gates Foundation

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

Sesame

Sesame (Sesamum indicum L.) is one of the oldest domesticated oilseed crops. Due to the presence of high oil, protein and other nutritional elements, its seed has become an important ingredient of food and feed. However, lack of information about sesame yield structure has restricted the process of crop improvement through breeding. Sesame breeding methods vary from plant selection and hybridization to molecular breeding. Genetic variability in a species is the basic requirement of any breeding program. Available genetic diversity is either directly used for evaluation and selection or desired traits are combined into a single plant via hybridization and backcrossing. Sesame germplasm evaluation and selection for high-yielding varieties are based on genetic heritability estimates of yield-related traits including higher number of capsules, branches and plant biomass, etc. Mutational techniques are employed for broadening genetic diversity of sesame breeding material. Concentrations and application time of any mutagen were found critical for mutation-breeding program. Large number of sesame varieties possessing desirable traits for higher yield and better quality has been developed through mutagenesis. Application of innovative breeding methods helps to reduce our dependence on existence of genetic variability within a species and overcome the limitations of conventional breeding. For this purpose biotechnological techniques have been introduced to sesame breeding programs. Protocols for sesame in vitro culturing and genetic transformation are optimized by using appropriate concentration of hormones and nutrients. Various marker-assisted selection (MAS) techniques such as isozymes, random amplified polymorphic DNA (RAPD) and inter-simple sequence repeats (ISSR), etc. are also used in sesame breeding to study genetic variability of sesame to increase selection efficiency