In vitro effects of the organophosphorus pesticide malathion on the reactivity of rat aorta.

BACKGROUND AND PURPOSE: There is a remarkable paucity of studies analyzing the role of the endothelium-derived relaxing factors on the vascular effects of organophosphates. This study was carried out to evaluate the vascular effects of malathion and the role of nitric oxide (NO) and prostacyclin (PGI2). METHODS: Vascular reactivity measuring isometric forces in vitro ('organ chambers') and flow cytometry (cells loaded with DAF-FM DA) were used. RESULTS: In rat thoracic aorta segments contracted with phenylephrine (Phe) (10(-7) mol/l), malathion (10(-10) to 10(-5) mol/l) induced concentration-dependent relaxation in arteries with intact endothelium (n = 7; p < 0.05). Malathion-mediated relaxation was blocked by N-nitro-L-arginine methyl ester (L-NAME; 10(-4) mol/l), a nonspecific NO synthase inhibitor, and/or indomethacin (10(-5) mol/l), a nonspecific cyclooxygenase inhibitor (n = 10, p < 0.05). In thoracic aorta rings, with and without endothelium, Phe (10(-10) to 10(-5) mol/l) evoked concentration-dependent contraction, which was reduced in the presence of malathion. In rings with or without endothelium, incubated with malathion, L-NAME and indomethacin, the Phe-induced contraction was restored. The role of NO was confirmed using flow cytometry. Malathion evokes endothelium-dependent relaxation through the M1 muscarinic receptor, since this relaxation was clearly blocked by atropine (M1 and M2 blocker) and pirenzepine (M1 blocker), but was less blocked by gallamine (M2 blocker) or 4-DAMP (M3 blocker). CONCLUSIONS: These findings suggest that the organophosphate compound effects on vascular reactivity depend of NO and PGI2.

The lignan (-)-cubebin inhibits vascular contraction and induces relaxation via nitric oxide activation in isolated rat aorta.

Cubebin, the most abundant lignan in Piper cubeba, has been described as having several effects as trypanocidal, antimycobacterial, antispasmodic, antimicrobial, anti-inflammatory, and analgesic. This study investigated the vasorelaxant effect produced by (-)-cubebin in isolated rat aortic rings pre-contracted with phenylephrine (Phe), and the possible mechanism involved in this event was evaluated. Endothelium-dependent relaxation was evoked by acetylcholine and (-)-cubebin in intact aortic rings, while endothelium-independent vasorelaxation was elicited by sodium nitroprusside and (-)-cubebin in denuded rings. Cumulative concentration-response curves for Phe (10(-10) -10(-5) M) were determined for endothelium-intact and endothelium-denuded aortic rings in either the presence or absence of (-)-cubebin. Dose-response curves were also constructed for pre-incubation of vascular rings with Nω-nitro-L-arginine methyl ester (L-NAME) (a non-specific nitric oxide synthase inhibitor), indomethacin (an unspecific cyclooxygenase inhibitor), and 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) (a guanylyl cyclase inhibitor). (-)-Cubebin was found to exert a vasorelaxant effect irrespective of the presence of endothelium, which was abolished by pretreatment with L-NAME and ODQ, but not with indomethacin. In addition, (-)-cubebin was able to reduce Phe contraction in the case of intact rings. These results suggest that (-)-cubebin promotes vasorelaxation via NO/cGMP pathway in rat aorta, without prostacyclin involvement.

Brazilian Copaifera Species: Antifungal Activity against Clinically Relevant Candida Species, Cellular Target, and In Vivo Toxicity.

Plants belonging to the genus Copaifera are widely used in Brazil due to their antimicrobial properties, among others. The re-emergence of classic fungal diseases as a consequence of antifungal resistance to available drugs has stimulated the search for plant-based compounds with antifungal activity, especially against Candida. The Candida-infected Caenorhabditis elegans model was used to evaluate the in vitro antifungal potential of Copaifera leaf extracts and trunk oleoresins against Candida species. The Copaifera leaf extracts exhibited good antifungal activity against all Candida species, with MIC values ranging from 5.86 to 93.75 µg/mL. Both the Copaifera paupera and Copaifera reticulata leaf extracts at 46.87 µg/mL inhibited Candida glabrata biofilm formation and showed no toxicity to C. elegans. The survival of C. glabrata-infected nematodes increased at all the tested extract concentrations. Exposure to Copaifera leaf extracts markedly increased C. glabrata cell vacuolization and cell membrane damage. Therefore, Copaifera leaf extracts are potential candidates for the development of new and safe antifungal agents.

In Vitro and In Vivo Anti-Candida spp. Activity of Plant-Derived Products.

Candidiasis therapy, especially for candidiasis caused by Candida non-albicans species, is limited by the relatively reduced number of antifungal drugs and the emergence of antifungal tolerance. This study evaluates the anticandidal activity of 41 plant-derived products against Candida species, in both planktonic and biofilm cells. This study also evaluates the toxicity and the therapeutic action of the most active compounds by using the Caenorhabditis elegans-Candida model. The planktonic cells were cultured with various concentrations of the tested agents. The Cupressus sempervirens, Citrus limon, and Litsea cubeba essential oils as well as gallic acid were the most active anticandidal compounds. Candida cell re-growth after treatment with these agents for 48 h demonstrated that the L. cubeba essential oil and gallic acid displayed fungistatic activity, whereas the C. limon and C. sempervirens essential oils exhibited fungicidal activity. The C. sempervirens essential oil was not toxic and increased the survival of C. elegans worms infected with C. glabrata or C. orthopsilosis. All the plant-derived products assayed at 250 µg/mL affected C. krusei biofilms. The tested plant-derived products proved to be potential therapeutic agents against Candida, especially Candida non-albicans species, and should be considered when developing new anticandidal agents.

Effect of rosmarinic acid on the arterial blood pressure in normotensive and hypertensive rats: Role of ACE.

BACKGROUND: In recent years, it has been demonstrated the inhibitory effect of some plant species on the angiotensin-converting enzyme and rosmarinic acid is a prominent constituent of these species. HYPOTHESIS/PURPOSE: This study was carried out to verify the effect of rosmarinic acid on blood pressure through inhibitory activity on angiotensin-converting enzyme in rats. STUDY DESIGN: The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The potential inhibitory rosmarinic acid effect on angiotensin-converting enzyme activity was compared with captopril actions by analyzing in vivo blood pressure dose-response curves to angiotensin I and bradykinin. The in vitro plasma angiotensin-converting enzyme activity was measured by fluorimetry using the substrate Abz-FRK(Dnp)P-OH substrate. In addition, dosages of nitrite/nítrate analysis were carried out. RESULTS: (1) rosmarinic acid caused systolic blood pressure dose-dependent decrease in hypertensive rats; (2) The angiotensin I dose-response curves demonstrated that rosmarinic acid promotes minor changes in systolic blood pressure only in the hypertensive group; (3) The bradykinin dose-response curves showed that both rosmarinic acid and captopril promoted a systolic blood pressure reduction, but only the captopril effect was significant; (4) The angiotensin-converting enzyme activity in rat lung tissue was inhibited by the rosmarinic acid in a dose dependent manner; (5) The analysis of nitrite/nítrate plasma concentrations showed no significant difference among the experimental groups. CONCLUSION: The rosmarinic acid is effective in reducing blood pressure, selectively, only in hypertensive animals. The rosmarinic acid (173µM) promoted almost a 98.96% reduction on angiotensin-converting enzyme activity.

In vitro reactivity ("organ chamber") of guinea pig tracheal rings-methodology considerations.

The present text was motivated by the difficulties faced by our postgraduate students when using airways studies protocols and will take into consideration the three mechanisms of relaxation: (I) guanosine 3,5-cyclic monophosphate (cGMP)/NO-dependent; (II) adenosine 3,5-cyclic monophosphate (cAMP)/PGI2-dependent, and (III) hyperpolarization-dependent. Tracheal rings are studied in an organ bath containing a gassed physiological salt solution, usually at a temperature of 37 °C. An agent or procedure that causes contraction [acetylcholine (Ach) or metacholine] of the smooth muscle is needed before study airway dilator drugs. The presented airways studies protocols are useful to study the bronchial epithelial-dependent reactivity.

Ensino de ressuscitação cardiopulmonar por meio de videoaula / Cardiopulmonary resuscitation teaching by video class

Objetivo: levantar o conhecimento sobre a ressuscitação cardiopulmonar no adulto em Suporte Básico de Vida, com o uso do desfibrilador externo automático, em profissionais de enfermagem que atuam em uma Unidade de Pronto Atendimento antes e após um programa de capacitação, utilizando a estratégia da videoaula. Método: trata-se de um estudo quantitativo, descritivo, quase-experimental, com 40 profissionais de enfermagem de uma Unidade de Pronto Atendimento. Realizou-se a coleta de dados por meio de um questionário específico sobre o tema, previamente validado, com 12 questões de múltipla escolha. Analisaram-se os dados por meio da estatística descritiva simples. Resultados: observou-se que 51,6% dos entrevistados responderam corretamente ao questionário antes da capacitação e, após a capacitação, evidenciou-se um acerto de 59,3%. Conclusão: percebeu-se a insuficiência do conhecimento sobre a ressuscitação cardiopulmonar pelos participantes e que a estratégia da videoaula não pode ser considerada efetiva para o ensino desse procedimento para os profissionais de enfermagem que atuam em Unidades de Pronto Atendimento. Aponta-se que estes dados também demonstram a importância de se dar continuidade à capacitação com outras estratégias, a fim de se obter melhores resultados na assistência ao paciente.(AU)

Objective: to raise knowledge about cardiopulmonary resuscitation in adults in Basic Life Support, with the use of automatic external defibrillator, in Nursing professionals who work in a Emergency Care Unit before and after a training program, using the video class strategy. Method: this is a quantitative, descriptive, quasi-experimental study conducted with 40 Nursing professionals from a Emergency Care Unit. Data was collected through a previously validated specific questionnaire with 12 multiple choice questions. Data were analyzed using simple descriptive statistics. Results: It was observed that 51.6% of respondents correctly answered the questionnaire before the training and after training, it was found a correctness of 59.3%. Conclusion: it was noticed the insufficient knowledge about cardiopulmonary resuscitation by the participants and that the strategy of the video lesson cannot be considered effective for teaching this procedure to Nursing professionals working in Emergency Care Units. It is pointed out that these data also demonstrate the importance of continuing training with other strategies in order to obtain better results in patient care.(AU)

Objetivo: aumentar el conocimiento sobre la reanimación cardiopulmonar en adultos en Soporte Vital Básico, utilizando el desfibrilador externo automático, en profesionales de Enfermería que trabajan en una Unidad de Atención de Emergencia antes y después de un programa de capacitación, utilizando la estrategia de videoclase. Método: este es un estudio cuantitativo, descriptivo, cuasi experimental realizado con 40 profesionales de Enfermería de una Unidad de Atención de Emergencia. Los datos fueron recolectados a través de un cuestionario específico previamente validado con 12 preguntas de opción múltiple. Los datos se analizaron mediante estadísticas descriptivas simples. Resultados: se observó que el 51.6% de los encuestados respondieron el cuestionario correctamente antes del entrenamiento y después del entrenamiento, se evidenció una precisión del 59.3%. Conclusión: los participantes notaron un conocimiento insuficiente sobre la reanimación cardiopulmonar y que la estrategia de la lección en video no puede considerarse efectiva para enseñar este procedimiento a los profesionales de Enfermería que trabajan en las Unidades de Atención de Emergencia. Se señala que estos datos también demuestran la importancia de continuar el entrenamiento con otras estrategias, a fin de obtener mejores resultados en la atención al paciente.(AU)

Construção e validação de simulação em vídeo para ensino da ressuscitação cardiopulmonar / Construcción y evaluación de una simulación en video para la enseñanza de resucitación cardiopulmonar / Construction and validation of a video simulation for teaching cardiopulmonary resuscitation

RESUMO Objetivo: desenvolver Tecnologia Educacional Digital (vídeo de simulação) sobre Ressuscitação Cardiopulmonar no adulto em Suporte Básico de Vida com o uso do Desfibrilador Externo Automático no ambiente hospitalar. Metodologia: trata-se de uma pesquisa de produção tecnológica, aplicada. Desenvolvida na Universidade de São Paulo, Escola de Enfermagem de Ribeirão Preto, no período de janeiro de 2017 a março de 2018. Expertises na área de Urgência e Emergência, 16 enfermeiros, participaram do estudo. Estatística AC1 foi utilizada para avaliar a concordância inter-avaliadores. Resultados: o roteiro/script e storyboard foi validado e alcançado 100% da avaliação em "concordo" ou "concordo fortemente". Classificados em "concordância considerável", com AC1 0,70 e p<0,0001, na concordância inter-avaliadores geral. Conclusão: este estudo proporciona contribuição exponencial no processo ensino-aprendizagem sobre o ensino de Ressuscitação Cardiopulmonar no adulto em Suporte Básico de Vida com o uso do Desfibrilador Externo Automático no ambiente hospitalar, pelo desenvolvimento do vídeo de simulação validado.

RESUMEN: Objetivo: desarrollar Tecnología Educativa Digital (video de simulación) sobre Resucitación Cardiopulmonar en adultos en Soporte Vital Básico con el uso del Desfibrilador Externo Automático en el entorno hospitalario. Metodología: se trata de una investigación de producción tecnológica aplicada que se desarrolló en la Universidad de San Pablo, Facultad de Enfermería de Ribeirão Preto, durante el período de enero de 2017 a marzo de 2018. Los participantes del estudio fueron especialistas en el área de Urgencia y Emergencia, específicamente 16 profesionales de Enfermería. Se utilizó la estadística AC1 para evaluar la concordancia entre los evaluadores. Resultados: se validaron el guion y el desarrollo secuencial (storyboard) con un 100% de las evaluaciones calificadas como "De acuerdo" o "Plenamente de acuerdo", clasificadas como "Concordancia considerable", con valores de AC1=0,70 y p<0,0001 en la concordancia general entre evaluadores. Conclusión: este estudio proporciona un aporte exponencial en el proceso de enseñanza-aprendizaje sobre la enseñanza de Resucitación Cardiopulmonar en adultos en Soporte Vital Básico con el uso del Desfibrilador Externo Automático en el entorno hospitalario, mediante el desarrollo del video de simulación validado.

ABSTRACT Objective: to develop Digital Educational Technology (simulation video) on Cardiopulmonary Resuscitation in adults in Basic Life Support with the use of the External Automated Defibrillator in the hospital environment. Methodology: this is an applied technological production research study developed at the University of São Paulo, Ribeirão Preto College of Nursing, from January 2017 to March 2018. Experts in the area of Urgency and Emergency, namely 16 nurses, participated in the study. The AC1 statistics was used to assess inter-rater agreement. Results: the script and storyboard were validated and reached 100% of the evaluation in "I agree" or "I strongly agree", classified as "Considerable agreement", with AC1=0.70 and p<0.0001, in general inter-rater agreement. Conclusion: this study provides an exponential contribution to the teaching-learning process on the teaching of Cardiopulmonary Resuscitation in adults in Basic Life Support with the use of the Automatic External Defibrillator in the hospital environment, through the development of the validated simulation video.

Construção e validação de Exame Clínico Objetivo Estruturado (OSCE) sobre ressuscitação cardiopulmonar / Construction and validation of Objective Structured Clinical Examination (OSCE) on cardiopulmonary resuscitation / Construcción y validación de un Examen Clínico Objetivo Estructurado (OSCE) sobre reanimación cardiopulmonar

OBJETIVO: desenvolver e validar um instrumento de exame clínico objetivo estruturado para o cenário de simulação sobre ressuscitação cardiopulmonar no adulto em suporte básico de vida com o uso do desfibrilador externo automático no ambiente hospitalar. MÉTODO: pesquisa aplicada, de produção tecnológica, desenvolvida na Escola de Enfermagem de Ribeirão Preto da Universidade de São Paulo, no período de janeiro de 2017 a março de 2018 com 16 profissionais experts da área de urgência e emergência para validação do exame clínico objetivo estruturado. O instrumento abordou 40 itens de intervenção relacionados ao elo da cadeia da sobrevivência da American Heart Association (2015) para realizar a avaliação clínica no cenário de simulação em ressuscitação cardiopulmonar. RESULTADOS: dos experts, 62,5% obtiveram pontuação superior ou igual a 10 nos critérios de Fehring e destaca-se que 93,75% possuem prática clínica em urgência e emergência no adulto. O exame clínico objetivo estruturado alcançou concordância de 97,34% em organização; 96,09% em objetividade; 93,75% em clareza, e na categorização da concordância interavaliador proposta por Landis e Kock evidenciou "concordância quase perfeita", com p<0,0001. CONCLUSÃO: no processo de validação pelos experts foram identificadas e acatadas as oportunidades de melhorias e o exame clínico objetivo estruturado apresentado demonstrou-se um objeto contemporâneo e adequado para aplicação no processo de ensino-aprendizagem sobre ressuscitação cardiopulmonar no adulto em suporte básico de vida com o uso do desfibrilador externo automático no ambiente hospitalar.(AU)

Objective: to develop and validate an objective structured clinical examination instrument for a simulation scenario on cardiopulmonary resuscitation in adults in basic life support, using automatic external defibrillator in the hospital environment. Method: applied research of technological production, developed at the Escola de Enfermagem in Ribeirão Preto of Universidade de São Paulo, from January 2017 to March 2018 with 16 expert professionals in the area of urgency and emergency for validation the structured objective clinical examination. The instrument addressed 40 intervention items related to the link in the chain of survival of American Heart Association (2015) to perform clinical evaluation in the cardiopulmonary resuscitation simulation scenario. Results: of the experts, 62.5% obtained a score higher than or equal to 10 in Fehring criteria and it is noteworthy that 93.75% have clinical practice in adults' urgency and emergence. The objective structured clinical examination reached agreement of 97.34% in organization; 96.09% in objectivity; 93.75% in clarity, and in the categorization of the inter-evaluator agreement proposed by Landis and Kock showed "almost perfect agreement", with p<0.0001. Conclusion: in the validation process by the experts, opportunities for improvement were identified and accepted and the objective structured clinical examination is a contemporary object and adequate for application in the teachinglearning process on cardiopulmonary resuscitation in adults on basic life support with...(AU)

Objetivo: desarrollar y validar un instrumento de examen clínico objetivo estructurado para el escenario simulado de reanimación cardiopulmonar en adultos con soporte vital básico mediante desfibrilador externo automático en el entorno hospitalario. Método: investigación aplicada de producción tecnológica, desarrollada en la Facultad de Enfermería de Ribeirão Preto de la Universidad de São Paulo, entre enero de 2017 y marzo de 2018 con 16 expertos de urgencias y emergencias para validar el examen clínico objetivo estructurado. El instrumento enfocó 40 aspectos de intervención relacionados con el eslabón de la cadena de supervivencia del American Heart Association (2015) para realizar una evaluación clínica en el escenario de reanimación cardiopulmonar simulada. Resultados: el 62.5% de los expertos obtuvo puntuación mayor o igual a 10 en los criterios de Fehring; se realza que el 93,75% tiene práctica clínica en urgencias y emergencias de adultos. El examen clínico objetivo estructurado alcanzó acuerdo de 97,34% en organización; 96,09% en objetividad; 93.75% en claridad, y la categorización acuerdo entre evaluadores propuesta por Landis y Kock mostró un "acuerdo casi perfecto", con p <0.0001. Conclusión: en el proceso de validación por parte de los expertos, se identificaron y aceptaron las oportunidades de mejora. El examen clínico objetivo estructurado resultó ser un objeto contemporáneo y apropiado para su aplicación en el proceso de enseñanza-aprendizaje de la reanimación cardiopulmonar adulta en soporte vital básico con el uso de desfibrilador externo automático en el entorno hospitalario.(AU)

Metabolic acidosis treatment as part of a strategy to curb inflammation.

Abnormalities in systemic acid-base balance may induce significant changes in the immune response, and they may play a significant role in the development or maintenance of immune dysfunction. Different forms of acidosis (metabolic and respiratory) and even different types of metabolic acidosis (hyperchloremic and lactic) may produce different effects on immune function. If alkalization has, or not, some effect on inflammation control is still a matter of speculation. Studies concerning these subjects are limited justifying this paper.

Is rosmarinic acid underestimated as an experimental cardiovascular drug?

PURPOSE: The rationale of the present review is to analize the activity of Rosmarinus officinalis in the the cardiovascular system METHODS: A MEDLINE database search (from January 1970 to December 2011) using only rosmarinic acid as searched term. RESULTS: The references search revealed 509 references about rosmarinic acid in 40 years (the first reference is from 1970). There is a powerful prevalence of antioxidant and cancer studies. Other diseases are few cited, as inflammation, brain (Alzheimer and Parkinson disease) and, memory; allergy; diabetes; atherosclerosis, and; hypertension. It is necessary to consider the complete absence of studies on coronary artery disease, myocardial ischemia, heart failure or ischemia/reperfusion injury. CONCLUSION: Rosmarinic acid is underestimated as an experimental cardiovascular drug and deserves more attention.

Does rosmarinic acid underestimate as an experimental cardiovascular drug? / Seria o ácido rosmarínico subestimado como droga cardiovascular experimental?

PURPOSE: The rationale of the present review is to analize the activity of Rosmarinus officinalis in the the cardiovascular system METHODS: A MEDLINE database search (from January 1970 to December 2011) using only rosmarinic acid as searched term. RESULTS: The references search revealed 509 references about rosmarinic acid in 40 years (the first reference is from 1970). There is a powerful prevalence of antioxidant and cancer studies. Other diseases are few cited, as inflammation, brain (Alzheimer and Parkinson disease) and, memory; allergy; diabetes; atherosclerosis, and; hypertension. It is necessary to consider the complete absence of studies on coronary artery disease, myocardial ischemia, heart failure or ischemia/reperfusion injury. CONCLUSION: Rosmarinic acid is underestimated as an experimental cardiovascular drug and deserves more attention.

OBJETIVO: A justificativa da revisão é analisar a atividade de Rosmarinus officinalis no sistema cardiovascular MÉTODOS: Uma busca de banco de dados MEDLINE (de janeiro de 1970 a dezembro de 2011), utilizando apenas o ácido rosmarínico como termo pesquisado. RESULTADOS: A busca referências revelou 509 referências sobre o ácido rosmarínico em 40 anos (a primeira referência é de 1970). Há uma prevalência poderoso antioxidante e estudos do câncer. Outras doenças são citados alguns, como o cérebro, inflamação (de Alzheimer e doença de Parkinson) e, a memória, hipertensão, alergia, diabetes, aterosclerose, e. É necessário ter em conta a ausência completa de estudos sobre a doença de artéria coronária, isquemia do miocárdio, insuficiência cardíaca ou isquemia / lesão de reperfusão. CONCLUSÃO: O ácido rosmarínico é subestimado como uma droga experimental cardiovascular e merece mais atenção.