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The reliable and timely detection of poliovirus cases through surveillance for acute flaccid paralysis (AFP), supplemented by environmental surveillance of sewage samples, is a critical component of the polio eradication program. Since 1988, the number of polio cases caused by wild poliovirus (WPV) has declined by >99.9%, and eradication of WPV serotypes 2 and 3 has been certified; only serotype 1 (WPV1) continues to circulate, and transmission remains endemic in Afghanistan and Pakistan. This surveillance update evaluated indicators from AFP surveillance, environmental surveillance for polioviruses, and Global Polio Laboratory Network performance data provided by 28 priority countries for the program during 2022-2023. No WPV1 cases have been detected outside of Afghanistan and Pakistan since August 2022, when an importation into Malawi and Mozambique resulted in an outbreak during 2021-2022. During 2022-2023, among 28 priority countries, 20 (71.4%) met national AFP surveillance indicator targets, and the number of environmental surveillance sites increased. However, low national rates of reported AFP cases in priority countries in 2023 might have resulted from surveillance reporting lags; substantial national and subnational AFP surveillance gaps persist. Maintaining high-quality surveillance is critical to achieving the goal of global polio eradication. Monitoring surveillance indicators is important to identifying gaps and guiding surveillance-strengthening activities, particularly in countries at high risk for poliovirus circulation.
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Enterovirus , Poliomielite , Poliovirus , Humanos , alfa-Fetoproteínas , Saúde Global , Vigilância da População/métodos , Erradicação de Doenças , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Poliomielite/diagnóstico , Programas de ImunizaçãoRESUMO
Since the Global Polio Eradication Initiative (GPEI) was established in 1988, the number of wild poliovirus (WPV) cases has declined by >99.9%, and WPV serotypes 2 and 3 have been declared eradicated (1). By the end of 2022, WPV type 1 (WPV1) transmission remained endemic only in Afghanistan and Pakistan (2,3). However, during 2021-2022, Malawi and Mozambique reported nine WPV1 cases that were genetically linked to Pakistan (4,5), and circulating vaccine-derived poliovirus (cVDPV) outbreaks were detected in 42 countries (6). cVDPVs are oral poliovirus vaccine-derived viruses that can emerge after prolonged circulation in populations with low immunity allowing reversion to neurovirulence and can cause paralysis. Polioviruses are detected primarily through surveillance for acute flaccid paralysis (AFP), and poliovirus is confirmed through stool specimen testing. Environmental surveillance, the systematic sampling of sewage and testing for the presence of poliovirus, supplements AFP surveillance. Both surveillance systems were affected by the COVID-19 pandemic's effects on public health activities during 2020 (7,8) but improved in 2021 (9). This report updates previous reports (7,9) to describe surveillance performance during 2021-2022 in 34 priority countries.* In 2022, a total of 26 (76.5%) priority countries met the two key AFP surveillance performance indicator targets nationally compared with 24 (70.6%) countries in 2021; however, substantial gaps remain in subnational areas. Environmental surveillance expanded to 725 sites in priority countries, a 31.1% increase from the 553 sites reported in 2021. High-quality surveillance is critical to rapidly detect poliovirus transmission and enable prompt poliovirus outbreak response to stop circulation. Frequent monitoring of surveillance guides improvements to achieve progress toward polio eradication.
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COVID-19 , Enterovirus , Poliomielite , Poliovirus , Humanos , Pandemias , alfa-Fetoproteínas , Erradicação de Doenças , Vigilância da População , Saúde Global , COVID-19/epidemiologia , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Poliomielite/diagnóstico , Poliovirus/genética , Vacina Antipólio Oral , Surtos de Doenças/prevenção & controle , Programas de ImunizaçãoRESUMO
Background: The utility of an implantable loop recorder (ILR) in the evaluation of unexplained syncope or palpitations in young patients in the absence of structural heart disease or ventricular dysfunction is limited. To compare the diagnostic yield of ILR with conventional extended Holter evaluation in the detection of arrhythmias among young patients with a structurally normal heart presenting with unexplained palpitations or syncope. Methods: Open-label randomised control trial was conducted in a tertiary cardiac care centre among young patients with recurrent unexplained palpitations (≥3 episodes/year) or syncope (≥2 episodes) with normal electrocardiogram and echocardiography, after excluding non-cardiac causes. Patients were block randomised to either ILR implantation or conventional extended Holter monitoring. Results: Fourteen patients in the ILR group and 16 patients in the conventional group completed the study. The mean age of the patients was 31.9 ± 5.5 and 31.2 ± 5.4 years. Males constituted 78.5% and 75% in the two groups, respectively. Diagnosis was established in 10 (71.5%) patients in the ILR group as compared to only 3 (18.7%) in the conventional group (p = 0.01), with an RR of 0.26 (95% CI 0.089-0.76, p = 0.01). The arrhythmias diagnosed with ILR were narrow complex tachycardia (30%), atrial fibrillation (20%), VPCs (20%), severe bradycardia with asystole due to sinus arrest (10%), VPCs with bigeminy (10%), and ventricular tachycardia (10%). Conclusion: In young patients with unexplained syncope or palpitations, ILR has a higher diagnostic yield in the accurate detection of arrhythmia compared with conventional Holter strategy, resulting in better management.
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Since the Global Polio Eradication Initiative (GPEI) was launched in 1988, the number of polio cases worldwide has declined approximately 99.99%; only two countries (Afghanistan and Pakistan) have never interrupted wild poliovirus (WPV) transmission (1). The primary means of detecting poliovirus circulation is through surveillance for acute flaccid paralysis (AFP) among children aged <15 years with testing of stool specimens for WPV and vaccine-derived polioviruses (VDPVs) (genetically reverted strains of the vaccine virus that regain neurovirulence) in World Health Organization (WHO)-accredited laboratories (2,3). In many locations, AFP surveillance is supplemented by environmental surveillance, the regular collection and testing of sewage to provide awareness of the extent and duration of poliovirus circulation (3). This report presents 2018-2019 poliovirus surveillance data, focusing on 40 priority countries* with WPV or VDPV outbreaks or at high risk for importation because of their proximity to a country with an outbreak. The number of priority countries rose from 31 in 2018 to 40 in 2019 because of a substantial increase in the number of VDPV outbreaks (2,4). In areas with low poliovirus immunity, VDPVs can circulate in the community and cause outbreaks of paralysis; these are known as circulating vaccine derived polioviruses (cVDPVs) (4). In 2019, only 25 (63%) of the 40 designated priority countries met AFP surveillance indicators nationally; subnational surveillance performance varied widely and indicated focal weaknesses. High quality, sensitive surveillance is important to ensure timely detection and response to cVDPV and WPV transmission.
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Erradicação de Doenças , Saúde Global/estatística & dados numéricos , Poliomielite/prevenção & controle , Vigilância da População , Monitoramento Ambiental , Humanos , Laboratórios , Paralisia/epidemiologia , Poliomielite/epidemiologia , Poliovirus/isolamento & purificaçãoRESUMO
BACKGROUND: In Madhya Pradesh, India, the government invited private obstetric hospitals for partnership to provide intrapartum care to poor women, paid for by the state. This statewide program, the Janani Sahayogi Yojana (JShY or maternal support scheme), ran from 2006 to 2012. The partnership was an uneasy one with many private obstetricians choosing to leave the partnership. This paper explores the motives of private obstetricians in the state for participating in the JShY, their experiences within the partnership, their interactions with the state and motives for withdrawal among those who withdrew from the scheme. This study sheds light on the dynamics of a public-private partnership for obstetric care from the perspective of private sector obstetricians. METHOD: Fifteen in-depth interviews were conducted with private obstetricians and hospital administrators from eight districts of Madhya Pradesh who had participated in the JShY. A Framework approach was used to analyze the data. RESULTS: Private obstetricians reported entering the JShY partnership for altruistic reasons but also as way of expanding their practices and reputations. They perceived that although their facilities provided better quality of care than state facilities, participation was risky because beneficiaries were often unbooked and seen as 'high risk' cases. The need to arrange for blood transfusions for these high risk women was perceived as particularly difficult. Cumbersome paper work and delays in receiving payments from the state also dissuaded participation. Some participants felt that there was inadequate engagement by the state, and better monitoring and supervision would have helped. The state changed the financial reimbursement arrangements due to a high proportion of Cesarean births in the early years of the partnership, as these were perversely incentivized. This change resulted in a large exodus of private obstetricians from the partnership. CONCLUSION: This study highlights the contribution of cumbersome processes, trust deficits and a lack of dialogue between public and private partners. Input from both public and private sectors into the design of a carefully thought through financial reimbursement package for private partners was highlighted as a necessary component for future success of such schemes.
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Atitude do Pessoal de Saúde , Parto Obstétrico , Acessibilidade aos Serviços de Saúde , Motivação , Médicos/psicologia , Parcerias Público-Privadas , Adulto , Parto Obstétrico/economia , Feminino , Acessibilidade aos Serviços de Saúde/economia , Humanos , Índia , Entrevistas como Assunto , Gravidez , Pesquisa QualitativaRESUMO
The iodination of chlorinated aromatic compounds using Ag(2)SO(4)/I(2), AgSbF(6)/I(2), AgBF(4)/I(2) and AgPF(6)/I(2) offers access to iodoarenes that are valuable intermediates in organic synthesis. Specifically, iodination of phenols, anisoles and anilines with a 3,5-dichloro substitution pattern preferentially yielded the ortho, para and para iodinated product, respectively. In the case of chlorobenzene and 3-chlorotoluene, AgSbF(6)/I(2), AgBF(4)/I(2) and AgPF(6)/I(2), but not Ag(2)SO(4)/I(2), selectively introduced the iodine in para position to the chlorine substituent.
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Assessing the cost of vaccine preventable diseases (VPD) surveillance is becoming more important in the context of the Global Polio Eradication Initiative (GPEI) funding transition, since GPEI support to polio surveillance helped the incremental building of VPD surveillance systems in many countries, including low income countries such as Nepal. However, there is limited knowledge on the cost of conducting VPD surveillance, especially the national cost for surveillance of multiple vaccine-preventable diseases. The current study sought to calculate the economic and financial costs of Nepal's comprehensive VPD surveillance systems from July 2016 to July 2017. At thecentral level, all surveillance units were included in the sample. At sub-national level, a purposive sampling strategy was used to select a representative sample from locations involved in conducting surveillance. The sub-national sample costs were extrapolated to the nationwide VPD surveillance system. Nepal's total annual economic cost of VPD surveillance was USD 4.81 million or USD 0.18 per capita, while the total financial cost was USD 4.38 million or USD 0.16 per capita. Government expenditures accounted for 56% of the total economic cost, and World Health Organization accounting for 44%. The biggest cost driver was personnel accounting for 51% of the total economic cost. WHO supported trained surveillance personnel through donor funding, mainly from Global Polio Eradication Initiative. As a polio transition priority country, Nepal will need to make strategic choices to fully self-finance or seek full donor support or a mixed-financing model as polio program funding diminishes.
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Poliomielite , Doenças Preveníveis por Vacina , Gastos em Saúde , Humanos , Nepal/epidemiologia , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Organização Mundial da SaúdeRESUMO
Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50 to 95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help us to understand the vaccine's effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern; and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results.
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COVID-19 , Vacinas , Vacinas contra COVID-19 , Humanos , SARS-CoV-2 , Organização Mundial da SaúdeRESUMO
In accordance with the end game strategies for polio eradication a synchronized switch plan from tOPV to bOPV was implemented globally in 2016. The National Committee for Polio Eradication (NCCPE) validated the switch activities in India. An expert group of 104 academics conducted field visits in 25 states and 2 Union territories for independent verification (after an initial round of verification by the National Polio Surveillance Project [NPSP]). The objectives were to validate withdrawal and disposal of tOPV by screening cold chain points in public and private sector health facilities in both rural and urban areas; additionally, availability of bOPV and IPV was also documented. 34 filled tOPV and 5 empty vials were detected inside cold chain equipment and 17 outside. The disposal mechanism was found to be reasonably adequate. The key strategies -- 'throttling' of vaccine supplies well ahead of the switch date while preventing stock outs at various immunization points, simultaneously working with the regulators to delicense the tOPV on the switch date and helping manufacturers to calibrate vaccine production according to national timelines, and strong and persistent advocacy with professional associations to align with national bOPV and IPV policy facilitated successful accomplishment of the switch process. Effective implementation of the switch strategy in India also bears testimony to the resilience of the health system operating under diverse and heterogeneous governance.
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Substituição de Medicamentos , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/imunologia , Vacina Antipólio Oral/imunologia , Análise Fatorial , Geografia Médica , Humanos , Programas de Imunização , Índia/epidemiologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagem , Vacinação/métodosRESUMO
Background: Health care-associated infections (HAIs) result in treatment delays as well as failures and financial losses not only to patients but also to the treating hospital and overall health-care delivery system. Due to hospital-acquired infections, there are problems of increase in morbidity and mortality, additional diagnostic and therapeutic interventions and ultimately antimicrobial resistance. Proper understanding among health-care workers about the ill effects of HAIs is very important to address this issue. The present study is a qualitative exploration aimed at understanding various aspects of hospital environmental hygiene and Infection prevention control program, by exploring the staff perception regarding the challenges, facilitators and barriers as well as feasible measures towards improvement in a rural tertiary teaching hospital in central India. Method: A qualitative study was conducted using 10 focus group discussions (FGDs) among five different professional groups, which included hospital administrators, doctors, nurses, environmental cleaning staff, and undergraduate medical students. The FGD guide included the following topics: (1) opinion about the status of cleanliness, (2) concepts and actual practices prevailing of hospital environmental hygiene, (3) Barriers, constraints, and problems in maintaining hospital environmental hygiene, (4) Suggestions for improvements. The data were analyzed manually using the content (thematic) analysis method. Results: Two themes were identified: Theme 1: "Prevailing practices and problems related to hospital surface/object contamination and hospital infection control". Theme 2: "Measures suggested for improving hospital cleanliness within the existing constraints". The participants emphasized the influence of resource constraints and needed inputs. They brought up the consequent prevailing practices and problems related, on one hand, to various stakeholders (service consumers, hospital personnel including the management), on the other, to specific infection prevention and control processes. They also suggested various measures for improvement. Conclusions: The study has revealed prevailing practices, problems, and suggested measures related to hospital environmental hygiene, particularly hospital cleanliness and HAI prevention and control processes. These insights and assertions are important for developing future behavioral and structural interventions in resource-limited settings. This study recommends a nationwide reliable HAI surveillance system and a robust infection prevention and control program in each health-care institution.
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Infecção Hospitalar/prevenção & controle , Países em Desenvolvimento , Pessoal de Saúde/psicologia , Controle de Infecções , Saneamento , Adolescente , Adulto , Idoso , Atenção à Saúde/normas , Feminino , Grupos Focais , Recursos em Saúde , Hospitais de Ensino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , População Rural , Centros de Atenção Terciária , Adulto JovemRESUMO
INTRODUCTION: As part of national program, laboratory supported vaccine preventable diseases surveillance was initiated in Kerala in 2015. Mechanisms have been strengthened for case investigation, reporting, and data management. Specimens collected and sent to state and reference laboratories for confirmation and molecular surveillance. The major objective of this study is to understand the epidemiological information generated through surveillance system and its utilization for action. METHODS: Surveillance data captured from reporting register, case investigation forms, and laboratory reports was analyzed. Cases were allotted unique ID and no personal identifying information was used for analysis. Throat swabs were collected from investigated cases as part of surveillance system. All Corynebacterium diphtheriae isolates were confirmed with standard biochemical tests, ELEK's test, and real-time PCR. Isolates were characterized using whole genome-based multi locus sequence typing method. Case investigation forms and laboratory results were recorded electronically. Public health response by government was also reviewed. RESULTS: A total of 533 cases were identified in 11 districts of Kerala in 2016, of which 92% occurred in 3 districts of north Kerala; Malappuram, Kozhikode, and Kannur. Almost 79% cases occurred in >10 years age group. In <18 years age group, 62% were male while in ≥18 years, 69% were females. In <10 years age group, 31% children had received three doses of diphtheria vaccine, whereas in ≥10 years, 3% cases had received all doses. Fifteen toxigenic C. diphtheriae isolates represented 6 novel sequence types (STs) (ST-405, ST-408, ST-466, ST-468, ST-469, and ST-470). Other STs observed are ST-50, ST-295, and ST-377. CONCLUSION: Diphtheria being an emerging pathogen, establishing quality surveillance for providing real-time information on disease occurrence and mortality is imperative. The epidemiological data thus generated was used for targeted interventions and to formulate vaccine policies. The data on molecular surveillance have given an insight on strain variation and transmission patterns.
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AIM: To describe self-reported practices and assess knowledge and attitudes regarding hand hygiene among healthcare workers in a rural Indian teaching hospital. SETTING: A rural teaching hospital and its associated medical and nursing colleges in the district of Ujjain, India. METHOD: The study population consisted of physicians, nurses, teaching staff, clinical instructors and nursing students. Self-administered questionnaires based on the World Health Organization Guidelines on Hand Hygiene in Healthcare were used. RESULTS: Out of 489 healthcare workers, 259 participated in the study (response rate = 53%). The proportion of healthcare workers that reported to 'always' practice hand hygiene in the selected situations varied from 40-96% amongst categories. Reported barriers to maintaining good hand hygiene were mainly related to high workload, scarcity of resources, lack of scientific information and the perception that priority is not given to hand hygiene, either on an individual or institutional level. Previous training on the topic had a statistically significant association with self-reported practice (p = 0.001). Ninety three per cent of the respondents were willing to attend training on hand hygiene in the near future. CONCLUSION: Self-reported knowledge and adherence varied between situations, but hand hygiene practices have the potential to improve if the identified constraints could be reduced. Future training should focus on enhancing healthcare workers' knowledge and understanding regarding the importance of persistent practice in all situations.
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Higiene das Mãos/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , População Rural , Autorrelato , Adulto , Idoso , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Índia , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
We report here the draft genome sequences of five Corynebacterium diphtheriae isolates of Indian origin. The C. diphtheriae isolates TH1141, TH510, TH1526, TH1337, and TH2031 belong to sequence type ST-50, ST-295, ST-377, ST-405, and ST-405, with an average genome size of 2.5 Mbp.
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BACKGROUND: Health care or biomedical waste, if not managed properly, can be of high risk to the hospital staff, the patients, the community, public health and the environment, especially in low and middle income settings where proper disposal norms are often not followed. Our aim was to explore perceptions of staff of an Indian rural tertiary care teaching hospital on hospital waste management. METHOD: A qualitative study was conducted using 10 focus group discussions (FGDs), with different professional groups, cleaning staff, nurses, medical students, doctors and administrators. The FGD guide included the following topics: (i) role of Health Care Waste Management (HCWM) in prevention of health care associated infections, (ii) awareness of and views about HCWM-related guidelines/legislation, (iii) current HCWM practices, (iv) perception and preparedness related to improvements of the current practices, and (v) proper implementation of the available guidelines/legislation. The FGDs were recorded, transcribed verbatim, translated to English (when conducted in Hindi) and analysed using content analysis. RESULTS: Two themes were identified: Theme (A), 'Challenges in integration of HCWM in organizational practice,' with the categories (I) Awareness and views about HCWM, (II) Organizational practices regarding HCWM, and (III) Challenges in Implementation of HCWM; and Theme (B), 'Interventions to improve HCWM,' with three categories, (I) Educational and motivational interventions, (II) Organizational culture change, and (III) Policy-related interventions. CONCLUSION: A gap between knowledge and actual practice regarding HCWM was highlighted in the perception of the hospital staff. The participants suggested organizational changes, training and monitoring to address this. The information generated is relevant not merely to the microsystem studied but to other institutions in similar settings.
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Atitude do Pessoal de Saúde , Pessoal de Saúde , Eliminação de Resíduos de Serviços de Saúde , Resíduos de Serviços de Saúde , Serviços de Saúde Rural , Centros de Atenção Terciária , Adulto , Idoso , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-IdadeRESUMO
Non-dioxin like polychlorinated biphenyls (NDL-PCBs) are legacy environmental contaminants with contemporary unintentional sources. NDL-PCBs interact with ryanodine receptors (RyRs), Ca(2+) channels of sarcoplasmic/endoplasmic reticulum (SR/ER) that regulate excitation-contraction coupling (ECC) and Ca(2+)-dependent cell signaling in muscle. Activities of 4 chiral congeners PCB91, 95, 132, and 149 and their respective 4- and 5-hydroxy (-OH) derivatives toward rabbit skeletal muscle ryanodine receptor (RyR1) are investigated using [(3)H]ryanodine binding and SR Ca(2+) flux analyses. Although 5-OH metabolites have comparable activity to their respective parent in both assays, 4-OH derivatives are unable to trigger Ca(2+) release from SR microsomes in the presence of Ca(2+)-ATPase activity. PCB95 and derivatives are investigated using single channel voltage-clamp and primary murine embryonic muscle cells (myotubes). Like PCB95, 5-OH-PCB95 quickly and persistently increases channel open probability (p o > .9) by stabilizing the full-open channel state, whereas 4-OH-PCB95 transiently enhances p o. Ca(2+) imaging of myotubes loaded with Fluo-4 show that acute exposure to PCB95 (5 µM) potentiates ECC and caffeine responses and partially depletes SR Ca(2+) stores. Exposure to 5-OH-PCB95 (5 µM) increases cytoplasmic Ca(2+), leading to rapid ECC failure in 50% of myotubes with the remainder retaining negligible responses. 4-OH-PCB95 neither increases baseline Ca(2+) nor causes ECC failure but depresses ECC and caffeine responses by 50%. With longer (3h) exposure to 300 nM PCB95, 5-OH-PCB95, or 4-OH-PCB95 decreases the number of ECC responsive myotubes by 22%, 81%, and 51% compared with control by depleting SR Ca(2+) and/or uncoupling ECC. NDL-PCBs and their 5-OH and 4-OH metabolites differentially influence RyR1 channel activity and ECC in embryonic skeletal muscle.
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Músculo Esquelético/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Animais , Cálcio/metabolismo , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Contração Muscular/efeitos dos fármacos , Músculo Esquelético/enzimologia , Músculo Esquelético/fisiopatologia , Bifenilos Policlorados/química , Coelhos , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Relação Estrutura-AtividadeRESUMO
Tuberculosis caused by Mycobacterium tuberculosis remains a leading cause of mortality worldwide into 21st century. In continuation with our anti-tuberculosis research programme, in this work, we have prepared molecularly diverse coumarins clubbed with benzothiazepines as well as its aza-analogues-benzodiazepines by molecular hybridization. The resulting compounds were screened for their M. tuberculosis activity against H(37) Rv strains using microplate alamar blue assay. Among the designed diversity, the compounds 5k, 5n and 5o were found significantly active in primary anti-tuberculosis assay at minimum inhibitory concentration <6.25 µm. Moreover, the IC(50) values of 5k and 5o in level-2 screening were observed as >10 µg/mL and 3.63 µg/mL, respectively. Design and synthesis of more focused library and its three-dimensional quantitative structure activity relationship analysis are underway.
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Antituberculosos/química , Azepinas/química , Cumarínicos/química , Mycobacterium tuberculosis/efeitos dos fármacos , Tiazepinas/química , Antituberculosos/síntese química , Antituberculosos/farmacologia , Cumarínicos/síntese química , Cumarínicos/farmacologia , Testes de Sensibilidade Microbiana , Relação Quantitativa Estrutura-Atividade , Tiazepinas/síntese química , Tiazepinas/farmacologiaRESUMO
DB is a whitish to yellowish resin, characterized initially in terms of solubility, acid value, molecular weight (Mw), polydispersity index (Mw/Mn) and glass transition temperature (Tg). Neat plasticized films of DB (Damar Batu) are investigated for mechanical, water vapor transmission and moisture absorption properties. To improve the mechanical properties of the free films dibutyl sebacate, a hydrophobic plasticizer was added to film composition. The biomaterial was further investigated for sustaining the drug release from spherical units (multiparticulates). The core of pellet was prepared using Diclofenac sodium (10% w/w) as a model drug by extrusion and speronization. The drug containing pellets were coated using DB plasticized film-coating solutions. With 2% coat build-up, sustained drug release up to 10 h was achieved with coating solution containing 20% and 30% w/w (based on DB weight) plasticizers. Less than 3% drug was released in the first 2 h which may be explained in terms of the insolubility of DB and the drug in acidic milieu. The release from pellets coated using DB film coating solution containing 20% and 30% plasticizers followed first order release pattern. DB seems to be a promising film former for pharmaceutical coating due to its reasonably good mechanical properties, low water vapor transmission and sustained release capability.
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Two new series of cannabinoids were prepared and their affinities for the CB1 and CB2 receptors were determined. These series are the (2'R)- and (2'S)-1-methoxy- and 1-deoxy-3-(2'-methylalkyl)-delta8-tetrahydrocannabinols, with alkyl side chains of three to seven carbon atoms. These compounds were prepared by a route that employed the enantioselective synthesis of the resorcinol precursors to the cannabinoid ring system. All of these compounds have greater affinity for the CB2 receptor than the CB1 receptor and four of them, (2'R)-1-methoxy-3-(2'-methylbutyl)-delta8-THC (JWH-359), (2'S)-1-deoxy-3-(2'-methylbutyl)-delta8-THC (JWH-352), (2'S)-1-deoxy-3-(2'-methylpentyl)-delta8-THC (JWH-255), and (2'R)-1-deoxy-3-(2'-methylpentyl)-delta8-THC (JWH-255), have good affinity (K(i) = 13-47 nM) for the CB2 receptor and little affinity (K(i) = 1493 to >10,000 nM) for the CB1 receptor. In the 1-deoxy-3-(2'-methylalkyl)-delta8-THC series, the 2'S-methyl compounds in general have greater affinity for the CB2 receptor than the corresponding 2'R isomers.