PH regulation of amphotericin B channels activity in the bilayer lipid membrane

Background: Amphotericin B (AmB) is a polyene antibiotic frequently applied in the treatment of systemic fungal infections in spite of its secondary effects. The pH plays a crucial role in modulating biophysical features of ion channels in the bilayer lipid membranes. Aim: In this study, the role of pH in the regulation of AmB channel was assessed by single channel recording of ion channel incorporated in the artificial membrane. Materials and Methods: Bilayer lipid membrane was formed by phosphatidylcholine in a 350 m diameter aperture between two chambers, cis and trans contained 200/50 mMKCl solutions, respectively; then AmB was incorporated into the bilayer lipid membrane. Single channel recordings were used to indicate the effects of pH changes on AmB channels activity. The records were analyzed by Clamp fit 10 software. Results: A kinetic analysis of single channel currents indicated a cation ion channel with 500 pS conductance and voltage-dependence of the open probability of the AmB channel (Po ). A reduction of cis pH to 6 decreased Po and conductance. This effect was also voltage-dependent, being greater at a more positive above -40. The pH changes in the range of 6-8 had no effect on the reversal potential and ion selectivity. Conclusion: Our data indicated that extracellular acidity can reduce AmB activity. © 2016 Journal of Natural Science, Biology and Medicine | Published by Wolters Kluwer - Medknow

Examen de l'effet de potentialisation des médicaments antipsychotiques par les inhibiteurs de la recapture de la sérotonine pour traiter les symptômes négatifs de la schizophrénie : approche méta-analytique

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

An Investigation of Phytochemical, Total Phenolic and Flavonoid Contents and Antioxidant Activity in Aerial Parts of Two Species of Salvia and the Effect of Environmental Factors on their Distribution in Behshahr Hezarjarib Area

The purpose of this study was an investigation of phytochemical and antioxidant characteristics in aerial parts of Salvia multicaulis Vahl and Salvia Sclarea L. and the effect of ecological factors on their distribution in Behshahr Hezarjarib area. Salvia grows wildly in the north of Iran. Literature review has shown that there is no report on phytochemical investigation about aerial parts of Salvia in north of Iran. In order to understand the relationship between vegetation and environmental factors, the PCA (Principle Component Analysis) method has been adopted. Essential oil of the aerial part of Salvia was analyzed by GC/MS. Antioxidant activities were evaluated by DPPH test. Thirteen and five components were identified representing 94.01% and 99.9% of the oils, respectively. The main compounds of Salvia multicaulis Vahl were α-Pinene (29.82), 1,8-Cineole (23.84) and Camphor (19.93) while 1,6-Cyclodecadiene (41.95) and β-Caryophyllene (36.19) were the major ingredients of Salvia Sclarea L

Sur la première ligne : sondage pour un partage. Les omnipraticiens et la schizophrénie

Contexte : Les omnipraticiens (MFs) jouent un rôle prépondérant dans le traitement des patients atteints de schizophrénie. Buts : Découvrir le nombre de patients atteints de schizophrénie qui sont traités par les MFs ; les besoins et attitudes des MFs, leurs connaissances en matière de diagnostic, et le traitement qu’ils prodiguent. Méthodologie : Un sondage postal a été conduit auprès de MFs du Québec choisis de façon aléatoire. Résultats : Un total de 1 003 MFs ont répondu au sondage. Parmi eux, un faible pourcentage a à rencontrer une schizophrénie débutante et les MFs désirent être plus informés sur l’accessibilité aux services des spécialistes. Les résultats objectivés aux questions portant sur les diagnostics et les connaissances sur les traitements sont inconsistants. La majorité des MFs traite les premiers épisodes psychotiques avec des antipsychotiques. Seulement un tiers d’entre eux proposent de maintenir le traitement après un premier épisode psychotique, conformément aux recommandations internationales et au récent guide de pratique canadien qui préconisent au moins de 6 à 12 mois de traitement après la réponse clinique partielle ou complète. Le temps consacré par les MFs masculins à un premier contact s’étale entre 10 et 20 minutes, tandis que 80 % des MFs femmes y consacrent au moins 20 minutes Les effets secondaires des antipsychotiques les plus préoccupants sont les gains de poids avant les signes neurologiques. Conclusion : un certain nombre de données de ce sondage devraient être reprises par les différentes associations professionnelles et gouvernementales, afin de bonifier la place des MFs dans un plan de santé à l’égard de la schizophrénie.Context: General practitioners (GP) play a preponderant role in the treatment of patients suffering of schizophrenia. Objectives: Discovering the number of patients with schizophrenia who are treated by GPs ; the needs and attitudes of GPs, their knowledge concerning diagnosis, and the treatment they provide. Methodology: A postal survey was conducted with Quebec GPs who were randomly chosen. Results: A total of 1 003 GPs have participated in the survey. Among them, a small percentage have to treat an early onset schizophrenia and the GPs have expressed their wish to be more informed on the accessibility of specialized services. Results pertaining to questions on diagnoses and knowledge on treatments are inconsistent. The majority of GPs treat the first psychotic episodes with antipsychotic medication. Only a third of GPs surveyed propose maintaining the treatment after a first psychotic episode, in accordance with international recommendations and the recent Canadian guidelines on practices that recommends at least 6 to 12 months of treatment after a partial or complete clinical response. Time given by male GPs to a first contact varies between 10 and 20 minutes, while 80 % of female GPs spend at least 20 minutes. The adverse effects of antipsychotic medication that raise most concern is weight gain before neurological signs. Conclusion: some of this survey’s data should be considered by various professional and governmental associations, in order to improve the place of GPs in a health plan destined to treat schizophrenia.Contexto: Los médicos familiares (MFs) desempeñan un papel preponderante en el tratamiento de pacientes que sufren de esquizofrenia. Objetivos: Descubrir el número de pacientes que sufren de esquizofrenia y que son tratados por los MFs; las necesidades y actitudes de los MFs, sus conocimientos en materia de diagnóstico y el tratamiento que ofrecen. Metodología: Se realizó una encuesta por correo con los MFs de Quebec elegidos de modo aleatorio. Resultados: Un total de 1,003 MFs respondieron a la encuesta. Entre ellos, un porcentaje bajo han encontrado una esquizofrenia inicial y los MFs desean estar más informados sobre la accesibilidad a los servicios de los especialistas. Los resultados asociados a las preguntas sobre los diagnósticos y los conocimientos acerca de los tratamientos son inconsistentes. La mayoría de los MFs tratan los primeros episodios psicóticos con antipsicóticos. Solamente un tercio de ellos propone mantener el tratamiento después de un primer episodio psicótico, conforme a las recomendaciones internacionales y a la reciente guía de práctica canadiense que preconiza al menos de 6 a 12 meses de tratamiento después de la respuesta clínica parcial o completa. El tiempo consagrado por los MFs masculinos en un primer contacto se extiende de 10 a 20 minutos, mientras que el 80% de los MFs femeninas consagran al menos 20 minutos. Los efectos secundarios de los antipsicóticos más preocupantes son el aumento de peso antes que los signos neurológicos. Conclusión: un cierto número de datos de esta encuesta deberían ser retomados por las diferentes asociaciones profesionales y gubernamentales a fin de bonificar el lugar de los MFs en un plan de salud con respecto a la esquizofrenia.Contexto: os clínicos gerais (médicos de família - MFs) representam um papel preponderante no tratamento dos pacientes que sofrem de esquizofrenia. Objetivos: descobrir o número de pacientes que sofrem de esquizofrenia que são tratados por MFs, as necessidades e atitudes dos MFs, seus conhecimentos em matéria de diagnóstico, e o tratamento que prescrevem. Metodologia: uma sondagem postal foi realizada com MFs do Quebec, escolhidos de maneira aleatória. Resultados: um total de 1.003 MFs responderam à sondagem. Dentre eles, uma pequena porcentagem encontrou uma esquizofrenia inicial e os MFs desejam ser melhor informados sobre a acessibilidade aos serviços de especialistas. Os resultados obtidos com as questões sobre os diagnósticos e os conhecimentos sobre os tratamentos são inconsistentes. A maioria dos MFs trata os primeiros episódios psicóticos com antipsicóticos. Apenas um terço dentre eles propõe manter o tratamento após um primeiro episódio psicótico, conforme as recomendações internacionais e o recente guia de prática canadense, que preconiza pelo menos 6 a 12 meses de tratamento após a resposta clínica parcial ou completa. O tempo dedicado pelos MFs masculinos a um primeiro contato dura entre 10 e 20 minutos, ao passo que 80% das MFs femininas consagram, pelo menos, 20 minutos. O efeito colateral dos antipsicóticos mais inquietante é o aumento de peso antes dos sinais neurológicos. Conclusão: um certo número de dados desta sondagem deverão ser retomados por diferentes associações profissionais e governamentais, a fim de melhorar a importância dos MFs em um plano de saúde com respeito à esquizofrenia

Diabetes Mellitus and Depression as Risk Factors for Dementia: SADEM Study

Aim: 3Evidence indicates that the comorbidity of dementia with diabetes and depression may affect most cognitive functions. Our chief interest was to examine the patterns of cognitive functioning in individuals diagnosed with dementia, diabetes, and depression as compared with dementia plus diabetes (DDM), or dementia plus depression (DD) and healthy controls

Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial

Background Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions. Objective To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia. Design A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up Setting Adult psychiatric services, treating people with schizophrenia. Participants Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity. Interventions Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study. Main Outcome Measures The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich’s Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale. Results No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference –1.3, 95% confidence interval–2.5 to–0.09). There were no statistically significant differences between the two treatment arms over 48-week follow-up in either the health economics outcomes or costs, and no differences in the frequency or severity of adverse effects, including corrected QT interval prolongation. Limitations The trial under-recruited, partly because cardiac safety concerns about citalopram were raised, with the 62 participants recruited falling well short of the target recruitment of 358. Although this was the largest sample randomised to citalopram in a randomised controlled trial of antidepressant augmentation for negative symptoms of schizophrenia and had the longest follow-up, the power of statistical analysis to detect significant differences between the active and placebo groups was limited. Conclusion Although adjunctive citalopram did not improve negative symptoms overall, there was evidence of some positive effect on avolition/amotivation, recognised as a critical barrier to psychosocial rehabilitation and achieving better social and community functional outcomes. Comprehensive assessment of side-effect burden did not identify any serious safety or tolerability issues. The addition of citalopram as a long-term prescribing strategy for the treatment of negative symptoms may merit further investigation in larger studies. Future Work Further studies of the viability of adjunctive antidepressant treatment for negative symptoms in schizophrenia should include appropriate safety monitoring and use rating scales that allow for evaluation of avolition/amotivation as a discrete negative symptom domain. Overcoming the barriers to recruiting an adequate sample size will remain a challenge.</p

Pain and the risk for falls in community-dwelling older adults: systematic review and meta-analysis

Objective: To conduct a systematic review and meta-analysis to establish the association between pain and falls in community dwelling older adults. Data Sources: Electronic databases from inception until 1st March 2013 including Cochrane Library, CINAHL, EBSCO, EMBASE, PubMed and PsycINFO. Study Selection: Two reviewers independently conducted the searches and completed methodological assessment of all included studies. Studies were included that (a) focussed on older adults over 60 years old, (b) recorded falls over 6 or more months, (c) identified a group with and without pain. Studies were excluded that (d) included participants with dementia, a neurological condition (e.g. stroke), (e) participants whose pain was caused by a previous fall, (f) individuals with surgery/ fractures in the past 6 months. Data extraction: One author extracted all data and this was independently validated by another author. Data synthesis: 1,334 articles were screened and 21 studies met the eligibility criteria. 50.5% of older adults with pain reported one or more fall over 12 months compared to 25.7% of controls (p<0.001). A global meta-analysis with 14 studies (n=17,926) demonstrated that pain was associated with an increased odds of falling (OR: 1.56, 95% Confidence Interval (CI): 1.36 to 1.79, I2=53%). A subgroup meta-analysis incorporating studies that monitored falls prospectively established that the odds of falling was significantly higher in those with pain (n=4,674; OR: 1.71, CI: 1.48 to 1.98, I2=0%). Foot pain was strongly associated with falls (n=691; OR: 2.38, CI: 1.62 to 3.48, I2=8%) as was chronic pain (n= 5,367; OR 1.80, CI: 1.56 to 2.09, I2=0%). Conclusion: Community dwelling older adults with pain were more likely to have fallen in the past 12 months and fall again in the future. Foot and chronic pain were particularly strong risk factors for falls and clinicians should routinely enquire about these when completing falls risk assessments