Objective: To compare plasma concentrations of cannabidiol (CBD) following oral administration of two formulations of the drug (powder and dissolved in oil), and to evaluate the effects of these distinct formulations on responses to emotional stimuli in healthy human volunteers. Methods: In a randomized, double-blind, placebo-controlled, parallel-group design, 45 healthy male volunteers were randomly assigned to three groups of 15 subjects that received either 150 mg of CBD powder; 150 mg of CBD dissolved in corn oil; or placebo. Blood samples were collected at different times after administration, and a facial emotion recognition task was completed after 150 min. Results: There were no significant differences across groups in the subjective and physiological measures, nor in the facial emotion recognition task. However, groups that received the drug showed statistically significant differences in baseline measures of plasma CBD, with a significantly greater difference in favor of the oil formulation. Conclusion: When administered as a single 150-mg dose, neither formulation of oral CBD altered responses to emotional stimuli in healthy subjects. The oil-based CBD formulation resulted in more rapid achievement of peak plasma level, with an approximate fourfold increase in oral bioavailability.

Current pharmacotherapy of Parkinson’s disease (PD) is palliative and unable to modify the progression of neurodegeneration. Treatments that can improve patients’ quality of life with fewer side effects are needed, but not yet available. Cannabidiol (CBD), the major non-psychotomimetic constituent of cannabis, has received considerable research attention in the last decade. In this context, we aimed to critically review the literature on potential therapeutic effects of CBD in PD and discuss clinical and preclinical evidence supporting the putative neuroprotective mechanisms of CBD. We searched MEDLINE (via PubMed) for indexed articles published in English from inception to 2019. The following keywords were used: cannabis; cannabidiol and neuroprotection; endocannabinoids and basal ganglia; Parkinson’s animal models; Parkinson’s history; Parkinson’s and cannabidiol. Few studies addressed the biological bases for the purported effects of CBD on PD. Six preclinical studies showed neuroprotective effects, while three targeted the antidyskinetic effects of CBD. Three human studies have tested CBD in patients with PD: an open-label study, a case series, and a randomized controlled trial. These studies reported therapeutic effects of CBD on non-motor symptoms. Additional research is needed to elucidate the potential effectiveness of CBD in PD and the underlying mechanisms involved.

The oral microbiota of humans and animals is made up of a wide variety of yeasts and bacteria, but microbiota of dogs is not totally described. Although such identification is an important step to establish the etiopathogenesis and adequate therapy for the periodontal disease The aim of this study was to evaluate and correlate oral alterations with the presence of yeasts in oral cavity of female dogs. After clinical evaluation samples from healthy and from dogs with oral diseases were obtained from three different oral sites by swabs, curettes, millimeter periodontal probes and HA membrane tip in cellulose ester. Yeast identification was performed through macroscopic and microscopic colony features and biochemical tests. Dental calculus was the most prevalent occurrence in the oral cavity of 59 females. However, the isolation of yeasts was significantly higher (p < 0.05) in animals suffering from halitosis. Eleven yeast species were identified, namely: Malassezia pachydermatis, Rhodotorula spp., Candida albicans, C. catenulata, C. famata, C. guilliermondii, C. parapsilosis, C. intermedia, Trichosporon asahii, T. mucoides and Cryptococcus albidus. It could be concluded that the yeasts are part of the microbiota from the different sites of the oral cavity of the female canines studied without causing any significant alterations except halitosis.

Com o objetivo de descrever o uso de medicamentos prescritos e não prescritos, realizou-se um estudo descritivo em gestantes em pré-natal no Sistema Único de Saúde (SUS) no município de Santa Rosa, Estado do Rio Grande do Sul. Os dados sobre o uso de medicamentos foram coletados através de entrevista estruturada e consulta aos prontuários das gestantes. A prevalência do uso de medicamentos foi de 90%, correspondendo a uma média de uso de 4,1 medicamentos por gestante, dos quais 83,6% foram prescritos e 16,4% foram utilizados por automedicação. Do total de medicamentos, 17,5% estão incluídos na categoria C de risco ao feto. O uso de medicamentos é frequente, e a maioria das gestantes utilizou um ou mais fármacos prescritos ou não prescritos. Esses dados sugerem a necessidade de medidas de intervenção para promover o uso racional de medicamentos durante a gestação.

In order to ascertain the use of prescribed and unprescribed drugs among pregnant patients of the Unified Health System (SUS), a descriptive study comprised of a sample of pregnant women was carried out in the city of Santa Rosa, State of Rio Grande do Sul, Brazil. Data were collected by means of structured interviews and consultation of patient records of pregnant women in the prenatal period. The prevalence of drug use was 90%, corresponding to an average of 4.1 drugs per pregnant woman, of which 83.6% were prescribed and 16.4% were self-medicated. Of this total, 17.5% of the drugs were included in fetal risk category C. The use of drugs during pregnancy is frequent and the majority of the pregnant women used one or more prescribed and unprescribed drugs during pregnancy. These data suggest the need for preventive measures to promote rational drug use during pregnancy.

Com o objetivo de descrever o uso de medicamentos prescritos e não prescritos, realizou-se um estudo descritivo em gestantes em pré-natal no Sistema Único de Saúde (SUS) no município de Santa Rosa, Estado do Rio Grande do Sul. Os dados sobre o uso de medicamentos foram coletados através de entrevista estruturada e consulta aos prontuários das gestantes. A prevalência do uso de medicamentos foi de 90%, correspondendo a uma média de uso de 4,1 medicamentos por gestante, dos quais 83,6% foram prescritos e 16,4% foram utilizados por automedicação. Do total de medicamentos, 17,5% estão incluídos na categoria C de risco ao feto. O uso de medicamentos é frequente, e a maioria das gestantes utilizou um ou mais fármacos prescritos ou não prescritos. Esses dados sugerem a necessidade de medidas de intervenção para promover o uso racional de medicamentos durante a gestação.

In order to ascertain the use of prescribed and unprescribed drugs among pregnant patients of the Unified Health System (SUS), a descriptive study comprised of a sample of pregnant women was carried out in the city of Santa Rosa, State of Rio Grande do Sul, Brazil. Data were collected by means of structured interviews and consultation of patient records of pregnant women in the prenatal period. The prevalence of drug use was 90%, corresponding to an average of 4.1 drugs per pregnant woman, of which 83.6% were prescribed and 16.4% were self-medicated. Of this total, 17.5% of the drugs were included in fetal risk category C. The use of drugs during pregnancy is frequent and the majority of the pregnant women used one or more prescribed and unprescribed drugs during pregnancy. These data suggest the need for preventive measures to promote rational drug use during pregnancy.

FUNDAMENTO: Estudos recentes demonstram que a expressão de mediadores inflamatórios, como as citocinas, é um importante fator de desenvolvimento e progressão da insuficiência cardíaca (IC), principalmente na presença de disfunção ventricular esquerda. Essas alterações têm sido demonstradas tanto no plasma como no músculo cardíaco e, mais recentemente, no músculo esquelético de ratos e pacientes com IC. OBJETIVO: Investigar a produção e expressão do fator de necrose tumoral-α (TNF-α) e interleucina-10 (IL-10) no músculo sóleo e extensor digital longo (EDL) em animais com disfunção ventricular pós-infarto do miocárdio (IM). MÉTODOS: Utilizaram-se ratos Wistar machos que foram submetidos à ligadura da artéria coronária esquerda sem posterior reperfusão. Quatro semanas após esse procedimento, os animais foram submetidos à análise ecocardiográfica e divididos nos seguintes grupos experimentais: falso operado (Sham) e IM. Mantiveram-se em observação por um período adicional de 8 semanas. RESULTADOS: O nível da citocina TNF-α aumentou 26,5% (p < 0,05), e sua expressão gênica, 3 vezes (p < 0,01). O nível de IL-10 apresentou diminuição de 38,2% (p < 0,05). Ambas as alterações ocorreram apenas no músculo sóleo, sem alterações no EDL. A diminuição (36,5%, p < 0,05) na razão IL-10/ TNF-α deveu-se tanto ao aumento dos níveis teciduais do TNF-α quanto à diminuição da IL-10 dos níveis teciduais. CONCLUSÃO: Nossos resultados demonstraram alterações relevantes na razão IL-10/ TNF-α, o que pode ter um papel aditivo na avaliação da deterioração e progressão do quadro da disfunção ventricular esquerda pós-IM. Além disso, nosso estudo sugere que essas alterações parecem estar relacionadas ao tipo de fibra muscular.

BACKGROUND: Recent studies show that the expression of inflammatory mediators, such as cytokines, is an important factor for the development and progression of heart failure (HF), especially in the presence of left ventricular dysfunction. These changes have been demonstrated both in the plasma and heart muscle and, more recently, in skeletal muscle of rats and in patients with HF. OBJECTIVE: To investigate the production and expression of tumor necrosis factor-α (TNF) and interleukin-10 (IL-10) in the soleus and the extensor digitorum longus (EDL) muscles of animals with left ventricular dysfunction after myocardial infarction (MI). METHODS: We used male Wistar rats that underwent ligation of the left coronary artery without reperfusion. Four weeks after this procedure, the animals underwent echocardiography and were divided into the following experimental groups: sham operated (sham) and IM. They remained under observation for a further period of 8 weeks. RESULTS: The level of the cytokine TNF-α increased by 26.5% (p <0.05), and its gene expression increased 3 times (p <0.01). The level of IL-10 decreased by 38.2% (p <0.05). Both changes occurred only in the soleus muscle, with no change in the EDL. The decrease (36.5%, p <0.05) in the IL-10/TNF-α ratio was due to both increased tissue levels of TNF-α and decreased tissue levels of IL-10. CONCLUSION: Our results showed significant changes in the IL-10/TNF-α ratio, which may have an additive role in the assessment of deterioration and progression of left ventricular dysfunction post-MI. Furthermore, our study suggests that these changes seem to be related to the muscle fiber type. (Arq Bras Cardiol 2010; 94(3):293-300)

O aumento da atividade nervosa simpática e a taquicardia em repouso ou durante esforços físicos estão associados ao aumento da morbimortalidade, mesmo na ausência de sinais clínicos de doença cardíaca. Sabendo-se da importância dos receptores α2A/α2C-adrenérgicos na modulação da atividade nervosa e frequência cardíaca (FC), o presente trabalho utiliza um modelo genético de cardiomiopatia induzida por excesso de catecolaminas circulantes baseado na inativação gênica dos receptores α2A/α2C-adrenérgicos em camundongos (α2A/α2CKO) para verificar a resposta da FC ao exercício físico (EF), assim como o controle simpatovagal da FC ao EF. Testou-se a hipótese de que haveria resposta taquicárdica exacerbada durante o EF nos camundongos α2A/α2CKO mesmo quando a função cardíaca ainda estivesse preservada em repouso, sendo o receptor α2A-adrenérgico o principal responsável por essa resposta. Camundongos machos da linhagem C57Bl6J, controle (CO) e com inativação gênica para os receptores α2A (α2AKO), α2C α2CKO) e α2A/α2CKO foram submetidos a um teste de tolerância ao esforço físico. Outros dois grupos de camundongos, CO e α2A/α2CKO, foram submetidos ao bloqueio farmacológico dos receptores muscarínicos e β-adrenérgicos e ao EF progressivo para se avaliar a contribuição simpatovagal para a taquicardia de EF. Observou-se intolerância ao esforço físico (1.220 ± 18 e 1.460 ± 34 vs. 2.630 ± 42m, respectivamente) e maior taquicardia ao EF (765 ± 16 e 792 ± 13 vs. 603 ± 18bpm, respectivamente) nos camundongos α2AKO e α2A/α2CKO vs. CO. Além disso, o balanço autonômico estava alterado nos camundongos α2A/α2CKO pela hiperatividade simpática e menor efeito vagal cardíaco. Esses resultados demonstram a importância dos receptores α2A/α2C-adrenérgicos no controle autonômico não só no repouso, mas também durante o EF, sendo o receptor α2A-adrenérgico o responsável pela hiperatividade simpática e menor efeito vagal observados. Essa resposta taquicárdica exacerbada nos camundongos α2A/α2CKO está presente mesmo quando ainda não se observa disfunção cardíaca.

Increase of sympathetic nervous activity and tachycardia at rest or during physical exertions are associated with increase of morbimortality, even in the absence of clinical signs of cardiac disease. Considering the importance of the α2A/α2C-adrenergic receptors in the modulation of the nervous activity and heart rate (HR), the present study uses a genetic model of cardiomyopathy induced by excess of circulating catecholamine in the gene inactivation of the α2A/α2 -adrenergic receptors in mice (α2A/α2CKO) to verify the HR response to physical exercise (PE), as well as the sympathetic-vagal control of the HR to PE. The hypothesis is that there would be exacerbated tachycardic response during PE in α2A/α2CKO mice even when the cardiac function was still preserved at rest, being the α2A-adrenergic receptor the main reason for this response. Male mice of the C57Bl6J lineage, control (CO) and with gene inactivation for the a2A (α2AKO), α2C α2CKO) and α2A/α2CKO receptors were submitted to tolerance to a physical exercise test. Two other groups of mice, CO and α2A/α2CKO, were submitted to pharmacological blocking of the muscarinic and β-adrenergic receptors as well as to progressive PE to assess the sympathetic-vagal contribution to PE tachycardia. Intolerance to physical exercise (1.220 ± 18 and 1.460 ± 34 vs. 2.630 ± 42m, respectively) and higher tachycardia to PE (765 ± 16 e 792 ± 13 vs. 603 ± 18 bpm, respectively) in the α2AKO and α2A/α2CKO vs. CO mice was observed. Moreover, the autonomic balance was altered in the α2A/α2CKO mice by the sympathetic hyperactivity and lower cardiac vagal effect. These outcomes demonstrated the importance of the α2A/α2C-adrenergic receptors in autonomic control not only at rest, but also during PE, being theα2A-adrenergic receptor responsible for the sympathetic hyperactivity and lower vagal effect observed. This exacerbated tachycardic response in α2A/α2CKO mice is present even when cardiac dysfunction is not observed.

A insuficiência cardíaca (IC) é a via final comum da maioria das doenças cardiovasculares e uma das maiores causas de morbi-mortalidade. O desenvolvimento do estágio final da IC freqüentemente envolve um insulto inicial do miocárdio, reduzindo o débito cardíaco e levando ao aumento compensatório da atividade do sistema nervoso simpático (SNS). Existem evidências de que apesar da exposição aguda ser benéfica, exposições crônicas a elevadas concentrações de catecolaminas, liberadas pelo terminal nervoso simpático e pela glândula adrenal, são tóxicas ao tecido cardíaco e levam a deterioração da função cardíaca. Em nível molecular observa-se que a hiperatividade do SNS está associada a alterações na sinalização intracelular mediada pelos receptores beta-adrenérgicos. Sabe-se que tanto a densidade como a função dos receptores beta-adrenérgicos estão diminuídas na IC, assim como outros mecanismos intracelulares subjacentes à estimulação da via receptores beta-adrenérgicos. Nesta revisão, apresentaremos uma breve descrição da via de sinalização dos receptores beta-adrenérgicos no coração normal e as conseqüências da hiperatividade do SNS na IC. Daremos ênfase ao potencial miopático de diversos componentes da cascata de sinalização dos receptores beta-adrenérgicos discutindo estudos realizados com animais geneticamente modificados. Finalmente, discorreremos sobre o impacto clínico do conhecimento dos polimorfismos para o gene do receptor beta-adrenérgico para um melhor entendimento da progressão da IC.

Heart failure (HF) is a common endpoint for many forms of cardiovascular disease and a significant cause of morbidity and mortality. The development of end-stage HF often involves an initial insult to the myocardium that reduces cardiac output and leads to a compensatory increase in sympathetic nervous system activity. Acutely, the sympathetic hyperactivity through the activation of beta-adrenergic receptors increases heart rate and cardiac contractility, which compensate for decreased cardiac output. However, chronic exposure of the heart to elevated levels of catecholamines released from sympathetic nerve terminals and the adrenal gland may lead to further pathologic changes in the heart, resulting in continued elevation of sympathetic tone and a progressive deterioration in cardiac function. On a molecular level, altered beta-adrenergic receptor signaling plays a pivotal role in the genesis and progression of HF. beta-adrenergic receptor number and function are decreased, and downstream mechanisms are altered. In this review we will present an overview of the normal beta-adrenergic receptor pathway in the heart and the consequences of sustained adrenergic activation in HF. The myopathic potential of individual components of the adrenergic signaling will be discussed through the results of research performed in genetic modified animals. Finally, we will discuss the potential clinical impact of beta-adrenergic receptor gene polymorphisms for better understanding the progression of HF.

As leveduras são organismos comensais da pele, trato genital e gastrointestinal, e de outras mucosas de mamíferos. O gênero Candida vem sendo isolado freqüentemente de animais domésticos e silvestres. O isolamento de Candida spp da mucosa vaginal de mulheres é freqüente, porém na espécie canina são escassos os estudos referentes à microbiota fúngica vaginal, especialmente do gênero candida, não se tendo conhecimento de sua relação com o ciclo reprodutivo. O presente trabalho teve como objetivo isolar leveduras do gênero Candida em fêmeas caninas hígidas e identificar as espécies isoladas, relacionando-as com as diferentes fases do ciclo estral. Foram analisadas 224 amostras obtidas da mucosa vaginal de 14 fêmeas caninas. Candida spp foi observada em 83 (37%) amostras, destas, nove (42,9%) foram obtidas no proestro, 14 (43,8%) no estro, 31 (62%) no diestro, 24 (21,1%) no anestro e cinco (71,4%) de gestantes. Nas amostras caracterizadas, C. parapsilosis foi a espécie isolada com maior freqüência (21,7%), seguida de C. guillermondii (8,4%), C. kefir (6%) e C. albicans (4,8%). Com base neste estudo pode-se concluir que Candida spp faz parte da microbiota vaginal de fêmeas caninas hígidas, e que o isolamento é influenciado pelo ciclo reprodutivo.

Yeasts are commensal organisms found in the skin, genital and gastrointestinal tracts, and other mucosa in mammalians. Candida spp has been frequently isolated from domestic and sylvan animals. Yeast isolation from vaginal mucus is frequent in women, especially of Candida genus. In canine females, however, studies about vaginal fungal microbiota are rare and the connection with estrous cycle is unknown. The purpose of this study was to isolate yeast 5 of Candida genus from healthy canine females and identify the isolated species, establishing their connection with estrous cycle phases. Two hundred twenty-four samples taken from vaginal mucus of 14 canine females were analyzed in this study. Candida spp was observed in 83 (37%) from these samples; nine samples were taken in proestrus, 14 in oestrus, 31 in dioestrus, 24 in anoestrus and five samples were obtained during pregnancy. Candida parapsilosis the most frequently isolated specie (21.7%), followed by C. guillermondii (8.4%), C. kefir (6%) and C. albicans (4.8%). We concluded that Candida spp is a commion component of healthy canine females' vaginal microbiota, and isolation varies according to the estrous cycle phase.