Behavioral Pharmacology of Five Uncommon Passiflora Species Indicates Sedative and Anxiolytic-like Potential.

BACKGROUND: There are over 500 species in the Passiflora genus, and while some of them are very well known in folk medicine for their anxiolytic effects, very little is known for the other genus representants, which could also present medicinal effects. OBJECTIVE: In this study, we performed an interspecific pharmacological comparison of five investigated Passiflora species, all native to Brazil, namely P. bahiensis, P. coccinea, P. quadrangularis, P. sidaefolia, and P. vitifolia. METHODS: Extracts were administered to mice before behavioral testing, including a general pharmacological screening and anxiolytic-like effect investigation. RESULTS: Three of the species (P. coccinea, P. quadrangularis, and P. sidaefolia) induced a decrease in locomotor activity of mice; P. coccinea also reduced the latency to sleep. Importantly, none of the species interfered with motor coordination. Oral administration evoked no severe signs of toxicity, even at higher doses. Regarding the anxiolytic-like profile, P. sidaefolia reduced the anxious-like behavior in the Holeboard test in a similar way to the positive control, Passiflora incarnata, while not affecting total motricity. CONCLUSION: These results indicated that P. coccinea, P. quadrangularis, and P. sidaefolia reduced the general activity of mice and conferred a calmative/sedative potential to these three species, which must be further elucidated by future investigations.

Partial protective effects of cannabidiol against PTZ-induced acute seizures in female rats during the proestrus-estrus transition.

Approximately 70% of women with epilepsy experience additional challenges in seizure exacerbation due to hormonal changes, particularly during fluctuations of estrogen-progesterone levels in the menstrual cycle, which is known as catamenial epilepsy. In animal models of epilepsy, a sustained increase in seizure frequency has been observed in female rats during the proestrus-estrus transition when estrogen levels are high and progesterone levels are low resembling catamenial epilepsy. Cannabidiol (CBD) has been proposed to have anticonvulsant and anti-inflammatory effects, able to decrease seizure duration and increase seizure threshold in rats with epilepsy. However, most studies have used males to investigate the pharmacological effects of CBD on seizures, and the neuroprotective effects of CBD against seizures exacerbated by hormonal fluctuations in females are still little explored. Given this scenario, the aim of the present study was to investigate whether CBD would protect against acute seizures induced by pentylenetetrazole (PTZ) in female rats during a pro-convulsant hormonal phase. Therefore, CBD (50 mg/kg) or saline was administered during the proestrus-estrus transition phase, 1 h prior to induction of seizures with PTZ (60 mg/kg), and the following parameters were recorded: duration, latency to first seizure, as well as percentage of convulsing animals (incidence), mortality, and severity of seizures. Brains were processed for immunohistochemistry for microglial cells (Iba-1), and blood was collected for the analysis of cytokines (IL-1ß, IL-6, IL-10, and TNF-α). Cannabidiol pre-treated rats showed a significant reduction in duration and severity of seizures, and IL-1ß levels, although the latency, incidence of seizures, and mortality rate remained unchanged as well the quantification of microglia in the selected areas. Therefore, acute administration of CBD in a single dose prior to seizure induction showed a partial neuroprotective effect against seizure severity and inflammation, suggesting that female rats in the proconvulsant phase of proestrus-estrus have a low seizure threshold and are more resistant to the anticonvulsant effects of CBD. It appears that other doses or administration windows of CBD may be required to achieve a full protective effect against seizures, suggesting that CBD could be used as an adjunctive therapy during fluctuations of estrogen-progesterone levels. In this sense, considering the hormonal fluctuation as a seizure-potentiating factor, our study contributes to understand the anticonvulsant activity of CBD in females in a pro-convulsant hormonal phase, similar to catamenial seizures in humans.

Phytochemistry profile of rosella and jambolan extracts and the therapeutic effects on obesity.

Hibiscus sabdariffa extract (HSE) and Syzygium cumini extract (SCE) have been used in traditional medicine due to their hypoglycemic, antidiabetic, anti-obesity and antioxidant activities. This study aimed to evaluate the anti-obesity effects of these extracts, as well as to evaluate their toxicities. The phytochemical profiles were obtained by HPLC-DAD-ESI-MS/MS analyses. Pharmacological screening, motor activity, motor coordination and acute toxicity were evaluated by administering HSE or SCE (oral or intraperitoneal routes) at different doses to mice. The anti-obesity effects were examined by assessing the decrease in food intake and body weight loss in Wistar albino rats and by gastrointestinal transit in Swiss albino mice. Sibutramine was used as the positive control. Both extracts showed no toxic effects. At the end of 7 days of treatment, we observed that SCE and HSE reduced the weight gain and food intake of the treated rats in relation to the controls. Sub-chronic treatment revealed that HSE, SCE and sibutramine had the best effect 7 and 14 days after starting treatment. After 28 days, the SCE group showed less weight gain and reduced food consumption compared to the HSE group and controls. In addition, intestinal transit was increased in the HSE group, which is probably due to the high fiber content of the extract and may explain its anti-obesity properties. Myricetin glycosides were found in high levels in SCE and low levels in HSE, which may be the main compounds associated with the anti-obesity effect found in SCE. It is not possible to suggest an effective dose without conducting a preclinical toxicology study. We recommend clinical studies that evaluate the efficacy and safety, as well as the effect of discontinuing the extracts.

Ayahuasca blocks ethanol preference in an animal model of dependence and shows no acute toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Ayahuasca, a psychoactive beverage prepared from Banisteriopsis caapi and Psychotria viridis, is originally used by Amazon-based indigenous and mestizo groups for medicinal and ritualistic purposes. Nowadays, ayahuasca is used in religious and shamanic contexts worldwide, and preliminary evidence from preclinical and observational studies suggests therapeutic effects of ayahuasca for the treatment of substance (including alcohol) use disorders. AIM OF THE STUDY: To investigate the initial pharmacological profile of ayahuasca and its effects on ethanol rewarding effect using the conditioned place preference (CPP) paradigm in mice. MATERIALS AND METHODS: Ayahuasca beverage was prepared using extracts of B. caapi and P. viridis, and the concentration of active compounds was assessed through high performance liquid chromatography (HPLC). The following behavioral tests were performed after ayahuasca administration: general pharmacological screening (13, 130, or 1300 mg/kg - intraperitoneally - i.p., and 65, 130, 1300, or 2600 mg/kg - via oral - v.o.); acute toxicity test with elevated doses (2600 mg/kg - i.p., and 5000 mg/kg - v.o.); motor activity, motor coordination, and hexobarbital-induced sleeping time potentiation (250, 500, or 750 mg/kg ayahuasca or vehicle - v.o.). For the CPP test, the animals received ayahuasca (500 mg/kg - v.o.) prior to ethanol (1.8 g/kg - i.p.) or vehicle (control group - i.p.) during conditioning sessions. RESULTS: Ayahuasca treatment presented no significant effect on motor activity, motor coordination, hexobarbital-induced sleeping latency or total sleeping time, and did not evoke signs of severe acute toxicity at elevated oral doses. Ayahuasca pre-treatment successfully inhibited the ethanol-induced CPP and induced CPP when administered alone. CONCLUSIONS: Our results indicate that ayahuasca presents a low-risk acute toxicological profile when administered orally, and presents potential pharmacological properties that could contribute to the treatment of alcohol use disorders.

Green coffee extract attenuates Parkinson's-related behaviors in animal models.

Epidemiological studies have shown an inverse association between coffee consumption and the development of Parkinson's disease (PD). The effects of the oral treatment with green (non-roasted) coffee extracts (CE, 100 or 400 mg/kg) and caffeine (31.2 mg/kg) were evaluated on catalepsy induced by haloperidol in mice, and unilateral 6-OHDA lesion of medial forebrain bundle (MFB) or striatum in rats. Also, the in vitro antioxidant activity and the monoamine levels in the striatum were investigated. CE presented a mild antioxidant activity in vitro and its administration decreased the catalepsy index. CE at the dose of 400 mg/kg induced ipsilateral rotations 14 days after lesion; however, chronic 30-day CE and caffeine treatments did not interfere with the animals' rotation after apomorphine or methamphetamine challenges in animals with MFB lesion, nor on monoamines levels. Furthermore, CE and caffeine were effective in inhibiting the asymmetry between ipsilateral and contralateral rotations induced by methamphetamine and apomorphine in animals with lesion in the striatum but did not avoid the monoamines depletion. These results indicate that CE components indirectly modulate dopaminergic transmission, suggesting a pro-dopaminergic action of CE, and further investigation must be conducted to elucidate the mechanisms of action and the possible neuroprotective role in PD.

From an Alternative Medicine to a New Treatment for Refractory Epilepsies: Can Cannabidiol Follow the Same Path to Treat Neuropsychiatric Disorders?

Although cannabis has been known for ages as an "alternative medicine" to provide relief from seizures, pain, anxiety, and inflammation, there had always been a limited scientific review to prove and establish its use in clinics. Early studies carried out by Carlini's group in Brazil suggested that cannabidiol (CBD), a non-psychotropic phytocannabinoid present in Cannabis sativa, has anticonvulsant properties in animal models and reduced seizure frequency in limited human trials. Over the past few years, the potential use of cannabis extract in refractory epilepsy, including childhood epilepsies such as Dravet's syndrome and Lennox-Gastaut Syndrome, has opened a new era of treating epileptic patients. Thus, a considerable number of pre-clinical and clinical studies have provided strong evidence that phytocannabinoids has anticonvulsant properties, as well as being promising in the treatment of different neuropsychiatric disorders, such as depression, anxiety, post-traumatic stress disorder (PTSD), addiction, neurodegenerative disorders and autism spectrum disorder (ASD). Given the advances of cannabinoids, especially CBD, in the treatment of epilepsy, would the same expectation regarding the treatment of other neuropsychiatric disorders be possible? The present review highlights some contributions from Brazilian researchers and other studies reported elsewhere on the history, pre-clinical and clinical data underlying the use of cannabinoids for the already widespread treatment of refractory epilepsies and the possibility of use in the treatment of some neuropsychiatric disorders.

Impact of the Training of Professionals from São Paulo Public Health System in Phytotherapy Practice / Impacto da Capacitação de Profissionais da Rede Pública de Saúde de São Paulo na Prática da Fitoterapia

Abstract: Introduction: Following the introduction in 2006 of the National Policy on Integrative and Complementary Practices, and The National Policy on Medicinal Plants and Herbal Medicines, the Municipal Secretariat for the Environment of the City Hall of Sao Paulo initiated the Medicinal Plants Course, later expanded to The Medicinal Plants and Herbal Medicines Course for the training of health professionals. This study aimed to evaluate the impact of the 2014 and 2015 edition of the course "Medicinal Plants and Herbal Medicines" on health professional practices. Methods: An exploratory and descriptive study was conducted with a qualitative-quantitative approach. The quantitative process (Phase I) consisted of a questionnaire being emailed to health professionals who were involved in the course, divided into seven categories: biomedical professional, dental surgeon, nurse, pharmacist, physiotherapist, physician and nutritionist; and, out of 165 questionnaires, 114 responses were received (69.1%). The Qualitative and Quantitative process (Phase II), comprised semi-structured, in-person individual interviews to obtain detailed information on Phytotherapy practices, with 73 health professionals being interviewed, before and after the training, comparing their practices afterwards. Results: The course had a positive impact on the acceptance and application of Phytotherapy by health professionals with a significant increase (p<0.001) in the expansion of activities related to Phytotherapy (herbal tea "meetings", medicinal herb gardens and capacity training), regarding the use of herbal products, such as Matricaria chamomilla (chamomile), Maytenus ilicifolia (espinheira-santa), Valeriana officinalis (valeriana). An increase in the knowledge of Phytotherapy risks was also observed, although there was no increase in the reporting of adverse reactions. The study confirmed the importance of the inclusion of Medicinal Plants and Herbal Medicines Courses as part of undergraduate and postgraduate school, as well as the technical training and continuing education for SUS health professionals. Conclusion: The positive impact found out in almost all evaluated aspects, such as the increase in the knowledge and in the prescription of herbal medicines, confirms the importance of such courses. The results suggest the training promoted a positive impact on the Phytotherapy practice of the Public Health System professionals in São Paulo.

Resumo: Introdução: Após a aprovação da Política Nacional de Práticas Integrativas e Complementares e da Política Nacional de Plantas Medicinais e Fitoterápicos em 2006, a Secretaria Municipal do Verde e do Meio Ambiente de São Paulo iniciou o curso "Plantas Medicinais" que posteriormente foi ampliado para curso "Plantas Medicinais e Fitoterapia", com o propósito de capacitar profissionais de saúde. Este estudo teve como objetivo avaliar o impacto das edições de 2014 e 2015 do curso "Plantas Medicinais e Fitoterapia" nas práticas profissionais. Métodos: Realizou-se estudo exploratório, descritivo, com abordagem quali-quantitativa. No processo quantitativo (fase I), enviou-se um questionário via e-mail para profissionais de saúde egressos do curso, divididos em sete categorias: biomédico, cirurgião-dentista, enfermeiro, farmacêutico, fisioterapeuta, médico e nutricionista. Do total de 165 questionários, 114 foram respondidos (69,1%). No processo qualitativo e quantitativo (fase II), realizaram-se entrevistas semiestruturadas, presenciais e individuais visando obter informações detalhadas da prática fitoterápica. Entrevistaram-se 73 profissionais de saúde a fim de comparar as práticas deles antes e depois da capacitação. Resultados: O curso impactou positivamente a aceitação e a aplicação da fitoterapia pelos profissionais de saúde, com um aumento significativo (p < 0,001) na ampliação de atividades relacionadas à fitoterapia (rodas de "chás", "hortas medicinais" e capacitação). Houve ainda impacto na aplicação de produtos à base de plantas como Matricaria chamomilla (camomila), Maytenus ilicifolia (espinheira-santa) e Valeriana officinalis (valeriana). Verificou-se também aumento no conhecimento dos riscos da fitoterapia, embora sem o respectivo aumento na notificação de reações adversas. O estudo confirmou a importância da inclusão dos cursos em "Plantas Medicinais e Fitoterapia" na graduação e na pós-graduação, bem como da capacitação técnica e educação permanente para profissionais de saúde do SUS. Conclusão: O impacto positivo na quase totalidade dos aspectos avaliados, como o aumento do conhecimento e a prescrição de fitoterápicos, confirma a importância de tais cursos. Os resultados sugerem que a capacitação promoveu impacto positivo na prática fitoterápica dos profissionais da rede pública de saúde de São Paulo.

Percepciones y experiencias de usuarios de benzodiazepinas en la atención primaria de salud en Cuba / Perceptions and experiences of benzodiazepine users in primary health care in Cuba

Resumen A pesar de que son ampliamente conocidos los perfiles de utilización de las benzodiazepinas (BZD) y los riesgos asociados, este conocimiento no ha conducido a visibles transformaciones que mejoren la seguridad de los tratamientos y la salud de los pacientes. Por tanto, es necesaria una mejor compresión del contexto de su utilización, con el fin de implementar acciones educativas eficaces, tomar decisiones clínicas pertinentes y perfeccionar su regulación en los servicios de salud. Este artículo se propone caracterizar el perfil de utilización de benzodiazepinas en un área de salud de Santiago de Cuba y analizar el contexto de consumo a partir de los sentidos construidos por usuarios crónicos. Se realiza un estudio de caso, que describe el perfil de consumo a partir de las recetas dispensadas en la Farmacia Principal Municipal, y se realizan entrevistas a profundidad a los usuarios crónicos. El contenido de las entrevistas fue realizado temáticamente. Los resultados revelan los siguientes temas: poca concientización sobre el beneficio-riesgo del tratamiento, sufrimiento con la dependencia y tolerancia, autonomía en el tratamiento y limitada credibilidad en las terapias alternativas. La proporción de adultos mayores que reciben las BZD es mayor que la identificada en otros estudios. Se concluye que los usuarios perciben aspectos negativos del uso, pero están presos en la dependencia. Se evidencia la importancia de estudiar estrategias para el tratamiento del insomnio y la ansiedad en la atención primaria de salud, así como valorizar las políticas de implementación de terapias naturales y otros abordajes para contribuir al uso racional de las BZD.

Abstract The profiles for the use of benzodiazepines and associated risks are well known. However, this knowledge has not led to visible transformations that improve the safety of treatments and the health of patients. It is therefore necessary to better understand the context of use of these medications in order to implement effective educational actions, make relevant clinical decisions and improve their regulation in health services, especially in primary care. To characterize the profile of use of benzodiazepines in a health area of Santiago de Cuba and to analyze the context of consumption from the senses built by chronic users. Methods: A case study was carried out on the consumption patterns and interviews with chronic users was performed. The content of the interviews was thematically analyzed. The themes revealed were: little awareness of the benefit-risk of treatment; suffering with dependence and tolerance; autonomy in treatment; and limited credibility in alternative therapies. The proportion of older adults receiving benzodiazepines is greater than that identified in other studies. The users perceive negative aspects of use, but they are tied to the dependence. It is evident the importance of studying strategies for the treatment of insomnia and anxiety in primary health care, as well as valuing the policies of implementation of natural therapies and other approaches to contribute to the rational use of benzodiazepines.

[Use and abuse of benzodiazepines in primary healthcare: professional practices in Brazil and Cuba]. / Uso e abuso de benzodiazepínicos na atenção primária à saúde: práticas profissionais no Brasil e em Cuba.

The current study aimed to grasp the healthcare aspects present at the basis of the indiscriminate use of benzodiazepines. Based on a partnership between a Brazilian university and a Cuban university, the study aimed to understand the practices related to the use of these drugs in primary care and the meanings healthcare workers assign to them. The research was part of a multiple case study in the cities of São Paulo and Diadema (Brasil), and Santiago de Cuba (Cuba). The fieldwork data collection strategy was based on individual interviews and focus groups. Data were analyzed thematically and yielded five themes: (i) no man's land: lack of management of benzodiazepine use by primary care workers; (ii) inadequate indications: the benzodiazepine prescribed for unjustifiable situations; (iii) salvation and perdition: the medicine as attenuating the difficulty of acting in mental health by primary care professionals; (iv) limited empowerment to work in mental health; and (v) fragmented care: dissociation of the psychosocial care network. Limited grasp of mental health issues by primary care workers, fragmented care, work overload with what are considered other priorities, deficiencies in the availability of therapeutic resources, and limited investment in specific training contribute to the inadequate use of benzodiazepines. Independently of the health contexts, the challenges are similar for the health systems and can only be confronted if they become a priority for the organizations' management and the health workers as a whole.

O presente estudo buscou compreender aspectos assistenciais presentes na base da utilização indiscriminada de benzodiazepínicos. Com base numa parceria entre uma universidade brasileira e uma cubana, buscou-se o entendimento das práticas relacionadas ao uso desses medicamentos na atenção primária e dos sentidos que profissionais de saúde atribuem a elas. A investigação integrou um estudo de casos múltiplos realizado nos municípios de São Paulo e Diadema (Brasil) e Santiago de Cuba (Cuba). O trabalho de campo adotou como estratégias de coleta de dados entrevistas individuais e grupos focais. Os dados, analisados tematicamente, revelaram cinco temas: (i) terra de ninguém: a ausência de gestão sobre o uso dos benzodiazepínicos pelos profissionais da atenção básica; (ii) indicação inadequada: o benzodiazepínico prescrito psra situações injustificáveis; (iii) salvação e perdição: o medicamento como atenuante da dificuldade de atuação na saúde mental pelos profissionais da atenção primária; (iv) pouco empoderamento dos profissionais da atenção primária para atuação na saúde mental; e (v) cuidado fragmentado: a desarticulação da rede de atenção psicossocial. A pouca apropriação das questões da saúde mental pelos profissionais da atenção primária, a fragmentação do cuidado, a sobrecarga de trabalho com temas considerados prioritários, as deficiências na disponibilidade de recursos terapêuticos e o pouco investimento em formação específica contribuem para o uso não adequado de benzodiazepínicos. Independentemente dos contextos sanitários estudados, os desafios são semelhantes para os sistemas de saúde e só podem ser enfrentados se convertidos em prioridade para a gestão das organizações e para o conjunto dos profissionais.

El presente estudio tuvo como meta comprender aspectos asistenciales existentes en relación con la utilización indiscriminada de benzodiacepinas. A partir de la colaboración entre una universidad brasileña y una cubana, se procuró el entendimiento mutuo de las prácticas relacionadas con el uso de esos medicamentos en la atención primaria, así como el sentido que los profesionales de la salud les atribuyen. La investigación integró un estudio de casos múltiples, realizado en los municipios de Sao Paulo y Diadema (Brasil) y Santiago de Cuba (Cuba). El trabajo de campo adoptó como estrategias de recogida de datos entrevistas individuales y grupos focales. Los datos, analizados temáticamente, revelaron cinco temas que detallamos a continuación. (i) tierra de nadie: la ausencia de gestión sobre el uso de las benzodiacepinas por parte de los profesionales de la atención básica; (ii) indicación inadecuada: las benzodiacepinas para situaciones injustificables; (iii) salvación y perdición: la medicación como atenuación de la dificultad de actuar en la salud mental por los profesionales de la atención primaria; (iv) poco empoderamiento para trabajar en el ámbito de la salud mental y (v) cuidado fragmentado: la desarticulación de la red de atención psicosocial. La escasa asunción de las cuestiones de salud mental por parte de los profesionales de atención primaria, la fragmentación del cuidado, la sobrecarga de trabajo con temas considerados prioritarios, las deficiencias en la disponibilidad de recursos terapéuticos y la poca inversión en formación específica contribuyen al uso no adecuado de benzodiacepinas. Independientemente de los contextos sanitarios estudiados, los desafíos son semejantes en todos los sistemas de salud y sólo pueden enfrentarse si se convierten en prioridad para quienes gestionan instituciones, así como para el conjunto de profesionales.

Enkephalin related peptides are released from jejunum wall by orally ingested bromelain.

Stem bromelain [EC 3.4.22.32] is a thiol-endopeptidase and orally recommended in traditional medicine due to its analgesic activity, but the mechanisms are not known. Proenkephalin is expressed in the nervous system, but also in the gastrointestinal tract, where it can be assessed by ingested stem bromelain. Here we demonstrated that stem bromelain hydrolyses synthetic proenkephalin fragments after basic amino acid residues flanking the enkephalin sequences. We also observed with in vivo studies that oral administration of bromelain reduced jejunum proenkephalin levels and increased the serum enkephalin in mice. Effective anti-nociceptive effects in mice were observed 3 h after oral administration of 3 mg/kg stem bromelain by the acetic acid-induced writhing test. However, with higher doses this effect is reduced due to hydrolysis of enkephalin that possibly occurs by the presence of ananain in commercial pineapple stem bromelain preparations, that is also a thiol-protease with broad specificity. The analgesic effects were also evaluated by hot-plate and formalin tests and the obtained results indicated that enkephalin generated in intestine acts in periphery where it also can have anti-inflammatory activity.

Uso e abuso de benzodiazepínicos na atenção primária à saúde: práticas profissionais no Brasil e em Cuba / Use and abuse of benzodiazepines in primary healthcare: professional practices in Brazil and Cuba / Uso y abuso de benzodiacepinas en la atención primaria de salud: prácticas profesionales en Brasil y Cuba

O presente estudo buscou compreender aspectos assistenciais presentes na base da utilização indiscriminada de benzodiazepínicos. Com base numa parceria entre uma universidade brasileira e uma cubana, buscou-se o entendimento das práticas relacionadas ao uso desses medicamentos na atenção primária e dos sentidos que profissionais de saúde atribuem a elas. A investigação integrou um estudo de casos múltiplos realizado nos municípios de São Paulo e Diadema (Brasil) e Santiago de Cuba (Cuba). O trabalho de campo adotou como estratégias de coleta de dados entrevistas individuais e grupos focais. Os dados, analisados tematicamente, revelaram cinco temas: (i) terra de ninguém: a ausência de gestão sobre o uso dos benzodiazepínicos pelos profissionais da atenção básica; (ii) indicação inadequada: o benzodiazepínico prescrito psra situações injustificáveis; (iii) salvação e perdição: o medicamento como atenuante da dificuldade de atuação na saúde mental pelos profissionais da atenção primária; (iv) pouco empoderamento dos profissionais da atenção primária para atuação na saúde mental; e (v) cuidado fragmentado: a desarticulação da rede de atenção psicossocial. A pouca apropriação das questões da saúde mental pelos profissionais da atenção primária, a fragmentação do cuidado, a sobrecarga de trabalho com temas considerados prioritários, as deficiências na disponibilidade de recursos terapêuticos e o pouco investimento em formação específica contribuem para o uso não adequado de benzodiazepínicos. Independentemente dos contextos sanitários estudados, os desafios são semelhantes para os sistemas de saúde e só podem ser enfrentados se convertidos em prioridade para a gestão das organizações e para o conjunto dos profissionais.

The current study aimed to grasp the healthcare aspects present at the basis of the indiscriminate use of benzodiazepines. Based on a partnership between a Brazilian university and a Cuban university, the study aimed to understand the practices related to the use of these drugs in primary care and the meanings healthcare workers assign to them. The research was part of a multiple case study in the cities of São Paulo and Diadema (Brasil), and Santiago de Cuba (Cuba). The fieldwork data collection strategy was based on individual interviews and focus groups. Data were analyzed thematically and yielded five themes: (i) no man's land: lack of management of benzodiazepine use by primary care workers; (ii) inadequate indications: the benzodiazepine prescribed for unjustifiable situations; (iii) salvation and perdition: the medicine as attenuating the difficulty of acting in mental health by primary care professionals; (iv) limited empowerment to work in mental health; and (v) fragmented care: dissociation of the psychosocial care network. Limited grasp of mental health issues by primary care workers, fragmented care, work overload with what are considered other priorities, deficiencies in the availability of therapeutic resources, and limited investment in specific training contribute to the inadequate use of benzodiazepines. Independently of the health contexts, the challenges are similar for the health systems and can only be confronted if they become a priority for the organizations' management and the health workers as a whole.

El presente estudio tuvo como meta comprender aspectos asistenciales existentes en relación con la utilización indiscriminada de benzodiacepinas. A partir de la colaboración entre una universidad brasileña y una cubana, se procuró el entendimiento mutuo de las prácticas relacionadas con el uso de esos medicamentos en la atención primaria, así como el sentido que los profesionales de la salud les atribuyen. La investigación integró un estudio de casos múltiples, realizado en los municipios de Sao Paulo y Diadema (Brasil) y Santiago de Cuba (Cuba). El trabajo de campo adoptó como estrategias de recogida de datos entrevistas individuales y grupos focales. Los datos, analizados temáticamente, revelaron cinco temas que detallamos a continuación. (i) tierra de nadie: la ausencia de gestión sobre el uso de las benzodiacepinas por parte de los profesionales de la atención básica; (ii) indicación inadecuada: las benzodiacepinas para situaciones injustificables; (iii) salvación y perdición: la medicación como atenuación de la dificultad de actuar en la salud mental por los profesionales de la atención primaria; (iv) poco empoderamiento para trabajar en el ámbito de la salud mental y (v) cuidado fragmentado: la desarticulación de la red de atención psicosocial. La escasa asunción de las cuestiones de salud mental por parte de los profesionales de atención primaria, la fragmentación del cuidado, la sobrecarga de trabajo con temas considerados prioritarios, las deficiencias en la disponibilidad de recursos terapéuticos y la poca inversión en formación específica contribuyen al uso no adecuado de benzodiacepinas. Independientemente de los contextos sanitarios estudiados, los desafíos son semejantes en todos los sistemas de salud y sólo pueden enfrentarse si se convierten en prioridad para quienes gestionan instituciones, así como para el conjunto de profesionales.

Factors affecting the use of medicinal plants by migrants from rural areas of Brazilian Northeast after moving to a metropolitan region in Southeast of Brazil.

BACKGROUND: Ethnopharmacological studies about migrants reveal a dynamic process of knowledge and use of medicinal plants. In this study, we sought to elucidate quantitative and qualitatively the main factors influencing the use of medicinal plants by migrants from rural areas to an urban region in Brazil with traces of remnant natural vegetation. METHODS: Seven Northeastern individuals who migrated to the Southeastern Region of Brazil (Bororé Peninsula, in the city of São Paulo) were selected to participate in semi-structured interviews regarding the use of medicinal plants throughout their lives, and indicated an inhabitant in their hometown that would be able to accompany the field collections in each area. Socioeconomic, educational, family structure, and use of Western medicine data were provided during interviews with the individuals from their hometowns. Plant samples cited by the interviewees were collected both at the current place of residence and in their hometowns. RESULTS: The participants cited 131 plants and 315 recipes, being the main indications related to the gastrointestinal system, respiratory problems, and pain and inflammatory processes. We observed that most plant uses were maintained after migration. Higher percentages of maintenances and incorporations in plant uses occurred to exotic species, while replacements happen mainly to native plants. The introduction of new species into the migrants' therapeutics occurred mainly by observations of organoleptic similarities between the substituted plant and the incorporated species, conversations with neighbors, and contact with the television and print media. In addition, the public health system allowed the interviewees access to prophylactic drugs, leading to the discontinuation of certain recipes used in endemic diseases. CONCLUSION: Migrants were exposed to information about new plants and their uses, new diseases, and socioeconomic and cultural differences that impacted their use of medicinal plants. Although migration to a more developed city facilitated access to public health and education, on the other hand, it made access to fresh medicinal plants difficult, causing some medicinal plants to be replaced or ceased to be used.

Antioxidant, anticholinesterase and antifatigue effects of Trichilia catigua (catuaba).

BACKGROUND: Trichilia catigua A. Juss. (Meliaceae) is a species known as catuaba and used in folk medicine for the treatment of fatigue, stress, impotence and memory deficit. The main phytochemical compounds identified in the barks of T. catigua are flavalignans, flavan-3-ols and flavonoids which are associated with its antioxidant activity. Pre-clinical studies with T. catigua extracts have identified many pharmacological properties, such as anti-inflammatory, antidepressant, antinociceptive, pro-memory and neuroprotective against ischemia and oxidative stress. This study was designed in order to compare the chemical composition and in vitro antioxidant and anticholinesterase activity of four different polarity extracts and selected the one most active for in vivo studies in rodent models of stress, fatigue and memory. METHODS: Hexane, chloroform, hydroalcoholic and aqueous extracts from bark of Trichilia catigua were analyzed by RPHPLC-DAD-ESI-MS/MS. Antioxidant activity was assessed by 2,2-diphenyl-1-picryl hydrazyl (DPPH) assay and acetylcholinesterase inhibition by Ellman's modified method. In vivo studies (stress, fatigue and memory) were carried out with adult male mice and rats treated with hydroalcoholic extract in doses of 25-300 mg/kg (p.o.). RESULTS: We confirmed the presence of cinchonain IIa, Ia and Ib, as main constituents in the four extracts, while procyanidins were detected only in hydroalcoholic extract. Antioxidant and anticholinesterase activity were observed for all extracts, with most potent activity found on the hydroalcoholic extract (EC50 = 43 µg/mL and IC50 = 142 µg/mL for DPPH scavenger and acetylcholinesterase inhibition, respectively). The treatment of laboratory animals with hydroalcoholic extract did not protect rats from cold immobilization stress and did not prevent the scopolamine-induced amnesia in mice. However, the treatment of mice with the hydroalcoholic extract partially reduced the fatigue induced by treadmill, since the highest dose increased the spontaneous locomotor activity and reduced the deficit on grip strength after the forced exercise (p < 0.05), in some observation times. CONCLUSIONS: These data suggest the hydroalcoholic extract as the most suitable for plant extraction and partially support the folk use of T. catigua as antifatigue drug. . Trichilia catigua hydroalcoholic extract exhibits antioxidant and anticholinesterase activity in vitro and reduces the fatigue induced by forced exercise.

Pre-clinical interaction of ayahuasca, a brew used in spiritual movements, with morphine and propofol

ABSTRACT Ayahuasca is a beverage with psychoactive properties used in religious and ceremonial rituals by some religious groups. The main active components of ayahuasca are dimethyltryptamine and the harmala alkaloids with ß-carboline structure acting as monoamine oxidase A inhibitors. This combination produces a pronounced activation of serotonergic pathways and presents potential interaction with other psychotropics. The objective of this study was to investigate the possible interactions between ayahuasca and agents employed in general anesthesia. The pharmacological interactions between ayahuasca and morphine or propofol were evaluated in mice using doses of 12, 120 and 1200 mg/kg (0.1 to 10 times the average dose consumed by humans in religious rituals). Ayahuasca alone showed an antinociceptive effect in the writhing and formalin tests, and intensified the analgesic effect of morphine in the hot plate test. Concerning the pharmacological interactions between ayahuasca and propofol, the results were opposite; ayahuasca intensified the depressant effect of propofol in the rotarod test, but decreased the sleeping time induced by propofol. These set of results showed the occurrence of some interactions between ayahuasca and the drugs morphine and propofol, possibly by both pharmacokinetics and pharmacodynamics mechanisms

Pharmacological and Toxicological Study of Maytenus ilicifolia Leaf Extract. Part I - Preclinical Studies.

One of the Brazilians medicinal plants most cited in ethnopharmacological surveys for the treatment of ulcers and gastric diseases was evaluated for its efficacy and toxicity. Maytenus ilicifolia leaf extract (MIE) was acutely and chronically (180 days) administered to rats, mice, and dogs. Acute tests were antiulcer effect and toxicological trials (observational pharmacological screening, LD50, motor coordination, sleeping time and motor activity). Chronic tests were the following: weight gain/loss and behavioral parameters in rats and mice; estrus cycle, effects on fertility, and teratogenic studies in rats and mutagenic features in mice, in addition to the Ames and micronucleus test. The following parameters were assessed in dogs: weight gain/loss, general physical conditions, water/food consumption, and anatomopathological examination of the organs subsequent to the 180-day treatment. The results showed a clear antiulcer activity for MIE from 70 mg/kg and an absence of toxicological effects in the three animal species, even if given in high doses or over a long period. The present results confirm the antiulcer property and absence of toxicological effects in three animal species of MIE, which is in line with its current popular medicinal use. Copyright © 2017 John Wiley & Sons, Ltd.

The association of psychiatric symptomatology with patterns of alcohol, tobacco, and marijuana use among Brazilian high school students.

BACKGROUND AND OBJECTIVES: Studies have highlighted psychosocial factors associated with drug use among adolescents. Association of specific psychiatric comorbidity with substance use has not been properly established in Brazil. This study aimed to investigate alcohol, tobacco, and marijuana use by 15-18-year-old high school Brazilian students and to estimate associations with psychiatric symptoms. METHODS: A cross-sectional survey of 4,034 students from 128 public and private schools in São Paulo State was carried out using a two-step probability sample. Data were collected through self-report standardized questionnaires including questions on substance use patterns and the Strengths and Difficulties Questionnaire (SDQ). Key outcome variables were past-month use and past-month frequent use of alcohol, tobacco and marijuana. Questionnaires with missing information were excluded, resulting in a final sample of 2,532 adolescents. Weighted data was analyzed through logistic regressions, adjusted by gender and by socio-economic status (SES). RESULTS: Regarding SDQ total score, 43.6% of students had no psychiatric symptoms, 7.9% had subclinical symptoms and 48.5% presented clinically significant symptoms. Respondents with a clinically significant SDQ score were more likely to be past month alcohol (aOR = 1.51; 95%CI 1.22-1.88), tobacco (aOR = 1.82; 95%CI 1.25-2.66), and marijuana (aOR = 1.79; 95%CI 1.21-2.64) users as compared to those with no symptomatology. DISCUSSION AND CONCLUSIONS: Psychopathological symptoms were associated with alcohol, tobacco and marijuana use by 15-18-year-old adolescents. These associations should also be considered when planning public policies of mental health promotion. SCIENTIFIC SIGNIFICANCE: This study discusses the importance of the association between psychopathological symptoms and substance use in a middle-income country, with high level of social inequalities, in a state representative sample. (Am J Addict 2016;25:416-425).

Phytochemical analysis of hydroethanolic extract of Turnera diffusa Willd and evaluation of its effects on astrocyte cell death.

OBJECTIVE: To evaluate the phytochemical composition of hydroethanolic extracts from powdered aerial parts of Turnera diffusa Willd (Turneraceae; T. diffusa), as well as its toxicity in astrocytes. METHODS: Chemical analyses of hydroethanolic extract from powdered aerial parts ofT. diffusa were carried out using HPLC-DAD-ESI-MS/MS.In vitro assays using astrocytes culture were performed to evaluate cell death. RESULTS: Flavone-C, O-diglycosides, such as, luteolin-8-C-[6-deoxy-2-O-rhamnosyl]-xylo-hexos-3-uloside, apigenin-8-C-[6-deoxy-2-O-rhamnosyl]-xylo-hexos-3-uloside and apigenin-7-O-6"-p-coumaroylglucoside were the main compounds found in this hydroethanolic extract. Concentration time-effect demonstrated the toxicity of this extract at a concentration of 1,000µg/mL in astrocyte culture, after 6 and 24 hours of incubation. CONCLUSION: In phytochemical analyses, important antioxidants (mainly flavonoids) were observed. T. diffusa extracts presented cytotoxic effect in high concentrations, leading to increased cell death in astrocyte culture.

Phytochemical analysis of hydroethanolic extract of Turnera diffusa Willd and evaluation of its effects on astrocyte cell death / Análise fitoquímica do extrato hidroetanólico de Turnera diffusa Willd e avaliação de seus efeitos na morte de astrócitos

ABSTRACT Objective To evaluate the phytochemical composition of hydroethanolic extracts from powdered aerial parts of Turnera diffusa Willd (Turneraceae; T. diffusa), as well as its toxicity in astrocytes. Methods Chemical analyses of hydroethanolic extract from powdered aerial parts ofT. diffusa were carried out using HPLC-DAD-ESI-MS/MS.In vitro assays using astrocytes culture were performed to evaluate cell death. Results Flavone-C, O-diglycosides, such as, luteolin-8-C-[6-deoxy-2-O-rhamnosyl]-xylo-hexos-3-uloside, apigenin-8-C-[6-deoxy-2-O-rhamnosyl]-xylo-hexos-3-uloside and apigenin-7-O-6”-p-coumaroylglucoside were the main compounds found in this hydroethanolic extract. Concentration time-effect demonstrated the toxicity of this extract at a concentration of 1,000µg/mL in astrocyte culture, after 6 and 24 hours of incubation. Conclusion In phytochemical analyses, important antioxidants (mainly flavonoids) were observed. T. diffusa extracts presented cytotoxic effect in high concentrations, leading to increased cell death in astrocyte culture.

RESUMO Objetivo Avaliar a composição fitoquímica do extrato hidroetanólico das partes aéreas de Turnera diffusa Willd (Turneraceae; T. diffusa) e sua toxicidade em astrócitos. Métodos Análises químicas do extrato hidroetanólico de partes aéreas de T. diffusa foram feitas por HPLC-DAD-ESI-MS/MS. Os ensaiosin vitro utilizaram culturas de astrócitos para avaliar morte celular. Resultados Flavonas-C, O-diglicosídeos, como, luteolina-8-C-[6-deoxi-2-O-raminosil]-xilo-hexos-3-ulosideo, apigenina-8-C-[6-deoxi-2-O-raminosil]-xilo-hexos-3-ulosideo e apigenina-7-O-6”-p-cumaroilglucosídeo foram os principais constituintes encontrados neste extrato hidroetanólico. Uma curva tempo-concentração demonstrou toxicidade desse extrato na concentração de 1.000µg/mL, na cultura de astrócitos após 6 e 24 horas de incubação. Conclusão Nas análises fitoquímicas, importantes antioxidantes, sobretudo flavonoides, foram observados. Extratos de T. diffusa apresentaram efeitos citotóxicos em altas concentrações, ocasionando aumento de morte celular em cultura de astrócitos.

Ocimum gratissimum Essential Oil and Its Isolated Compounds (Eugenol and Myrcene) Reduce Neuropathic Pain in Mice.

Ocimum gratissimum is used in popular medicine to treat painful diseases. The antihypernociceptive properties of O. gratissimum essential oil and two of its active components (eugenol and myrcene) were tested in a model of neuropathic pain induced by a chronic constriction injury of the sciatic nerve. In tests to determine chronic antinociception, adult male C57BL/6 J mice were treated orally with corn oil (control group), O. gratissimum essential oil at doses of 10, 20, or 40 mg/kg or eugenol or myrcene at doses of 1, 5, or 10 mg/kg for 14 days after surgery. Pregabalin (20 mg/kg) was used as a standard in this study. The treatment with 20 and 40 mg/kg of O. gratissimum essential oil and at doses of 5 and 10 mg/kg of the active components were able to promote antihypernociception in both mechanical (von Frey) and thermal (hot plate) tests. The treatment with the essential oil of the plant or eugenol was effective in reducing the levels of interleukin-1ß in the sciatic nerve. Our findings demonstrate that O. gratissimum essential oil and its isolated active components possess antihypernociceptive activity in neuropathic pain models.

Chemical Analysis of Suspected Unrecorded Alcoholic Beverages from the States of São Paulo and Minas Gerais, Brazil.

Our study analyzed 152 samples of alcoholic beverages collected from the states of São Paulo and Minas Gerais, Brazil, using gas chromatography with flame ionization detection (GC-FID) and mass spectrometry (GC-MS), Fourier transform infrared spectroscopy (FT-IR), and inductively coupled plasma atomic emission spectrometry (ICP-AES). The methanol content varied from 20 to 180 ppm in 28 samples, and the limit of the accepted level of 200 ppm was exceeded in only one sample. High content of cyanide derivatives and ethyl carbamate, above the accepted level of 150 ppb, was observed in 109 samples. Carbonyl compounds were also observed in 111 samples, showing hydroxy 2-propanone, 4-methyl-4-hepten-3-one, furfural, and 2-hydroxyethylcarbamate as main constituents. Copper was found at concentrations above 5 ppm in 26 samples; the maximum value observed was 28 ppm. This work evaluated the human health risk associated with the poor quality of suspected unrecorded alcohols beverages.