Rational-Based Discovery of Novel ß-Carboline Derivatives as Potential Antimalarials: From In Silico Identification of Novel Targets to Inhibition of Experimental Cerebral Malaria.

Malaria is an infectious disease widespread in underdeveloped tropical regions. The most severe form of infection is caused by Plasmodium falciparum, which can lead to development of cerebral malaria (CM) and is responsible for deaths and significant neurocognitive sequelae throughout life. In this context and considering the emergence and spread of drug-resistant P. falciparum isolates, the search for new antimalarial candidates becomes urgent. ß-carbolines alkaloids are good candidates since a wide range of biological activity for these compounds has been reported. Herein, we designed 20 chemical entities and performed an in silico virtual screening against a pool of P. falciparum molecular targets, the Brazilian Malaria Molecular Targets (BRAMMT). Seven structures showed potential to interact with PfFNR, PfPK7, PfGrx1, and PfATP6, being synthesized and evaluated for in vitro antiplasmodial activity. Among them, compounds 3−6 and 10 inhibited the growth of the W2 strain at µM concentrations, with low cytotoxicity against the human cell line. In silico physicochemical and pharmacokinetic properties were found to be favorable for oral administration. The compound 10 provided the best results against CM, with important values of parasite growth inhibition on the 5th day post-infection for both curative (67.9%) and suppressive (82%) assays. Furthermore, this compound was able to elongate mice survival and protect them against the development of the experimental model of CM (>65%). Compound 10 also induced reduction of the NO level, possibly by interaction with iNOS. Therefore, this alkaloid showed promising activity for the treatment of malaria and was able to prevent the development of experimental cerebral malaria (ECM), probably by reducing NO synthesis.

Impact on health and well-being of working at home during the SARS-CoV-2 pandemic.

Introduction: After the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, many workers were forced to start working from home, creating a new dynamic that could potentially affect their health in several ways. Objectives: To study the impact of working at home during the SARS-CoV-2 pandemic on a sample of Brazilian workers. Methods: This study used a cross-sectional methodology with an online survey conducted by a Brazilian human resources website from June 1 to August 15, 2020, with a sample of employees working at home during the SARS-CoV-2 pandemic. Results: The sample of 653 valid responses revealed that 87.7% of the survey respondents reported that the change to home working started because of the situation caused by the pandemic. However, 550 (84.2%) people from this group stated that their employer did not conduct any health and safety evaluation of their workstation in the domestic environment. Regarding physical symptoms, there were high prevalence rates of symptoms related to musculoskeletal conditions, sleeping problems, feelings of fatigue, headaches, and migraines. The study also used the World Health Organization-5 Well-Being Index instrument and there were statistically significant associations between low scores and physical symptoms of musculoskeletal conditions, feelings of fatigue, headache or migraine, heartburn and indigestion, and leg pain. Conclusions: The findings of this research confirm the importance of developing strategies and programs to preserve the health and well-being of workers who start working at home, with participation of and supervision by companies' occupational physicians. Future investigations should continue to capture data about health, well-being, and productivity and share best practices to plan support for the occupational health of those working from home.

Evaluation of antiplasmodial activity in silico and in vitro of N-acylhydrazone derivatives.

N-acylhydrazones are considered privileged structures in medicinal chemistry, being part of antimicrobial compounds (for example). In this study we show the activity of N-acylhydrazone compounds, namely AH1, AH2, AH4, AH5 in in vitro tests against the chloroquine-resistant strain of Plasmodium falciparum (W2) and against WI26 VA-4 human cell lines. All compounds showed low cytotoxicity (LC50 > 100 µM). The AH5 compound was the most active against Plasmodium falciparum, with an IC50 value of 0.07 µM. AH4 and AH5 were selected among the tested compounds for molecular docking calculations to elucidate possible targets involved in their mechanism of action and the SwissADME analysis to predict their pharmacokinetic profile. The AH5 compound showed affinity for 12 targets with low selectivity, while the AH4 compound had greater affinity for only one target (3PHC). These compounds met Lipinski's standards in the ADME in silico tests, indicating good bioavailability results. These results demonstrate that these N-acylhydrazone compounds are good candidates for future preclinical studies against malaria.

Potent and selective antiplasmodial activity of marine sponges from Bahia state, Brazil.

This study evaluated the in vitro antiplasmodial and cytotoxic effects of 26 extracts from nine marine sponges collected in Salvador, Bahia state, Brazil. All assayed extracts were found to be potently active against Plasmodium falciparum W2 strain, with IC50 values ranging from 0.28 to 22.34 µg mL-1, and weakly cytotoxic against the human cell line WI-26-VA4 with CC50 values > 89 µg mL-1, thus displaying selectivity indices (SI) equal or higher than 17. Interestingly, some SI values exceeded 1,000. The highly potent and selective antiplasmodial activity of the assessed marine sponges is reported for the first time in this study.

Synthesis of Novel 1,2,3-Triazole Derivatives of Isocoumarins and 3,4-Dihydroisocoumarin with Potential Antiplasmodial Activity In Vitro.

BACKGROUND: Malaria greatly affects the world health, having caused more than 228 million cases only in 2018. The emergence of drug resistance is one of the main problems in its treatment, demonstrating the need for the development of new antimalarial drugs. OBJECTIVE: Synthesis and in vitro antiplasmodial evaluation of triazole compounds derived from isocoumarins and a 3,4-dihydroisocoumarin. METHODS: The compounds were synthesized in 4 to 6-step reactions with the formation of the triazole ring via the Copper(I)-catalyzed 1,3-dipolar cycloaddition between isocoumarin or 3,4- dihydroisocoumarin azides and terminal alkynes. This key reaction provided compounds with an unprecedented connection of isocoumarin or 3,4-dihydroisocoumarin and the 1,2,3-triazole ring. The products were tested for their antiplasmodial activity against a Plasmodium falciparum chloroquine resistant and sensitive strains (W2 and 3D7, respectively). RESULTS: Thirty-one substances were efficiently obtained by the proposed routes with an overall yield of 25-53%. The active substances in the antiplasmodial test displayed IC50 values ranging from 0.68-2.89 µM and 0.85-2.07 µM against W2 and 3D7 strains, respectively. CONCLUSION: This study demonstrated the great potential of isocoumarin or 3,4-dihydroisocoumarin derivatives because practically all the tested substances were active against Plasmodium falciparum.

Curcumin-loaded nanocapsules: Influence of surface characteristics on technological parameters and potential antimalarial activity.

The present study aimed to develop nanocapsules (NCs) loaded with curcumin (CCM) using different coatings, comparing the effect of these coatings on physicochemical properties of NCs. NCs were prepared by interfacial deposition of performed polymer, using different polymers as coatings (P80, PEG, Chitosan and Eudragit RS100®) and then, characterized in detail by different techniques (AFM, FTIR, DSC, XRD, among others). In vitro studies were performed, evaluating the release profile, cytotoxicity and antimalarial activity of CCM-loaded NCs. Overall, all CCM-loaded NCs samples exhibited typical characteristics as nanometric size, coating-dependent zeta potential, acidic pH value, span values below 2, homogeneous morphology and CCM-distribution in pseudophases of type VI (for all of coatings). Experimental results showed that CCM remains stable in lipid-core of NCs, maintaining its physicochemical and biological properties after nanoencapsulation process. In vitro release assays showed that nanoencapsulation was an efficient strategy to controlled release of CCM and P80-coated NCs presented slowest CCM-release considering all nanoformulations tested. Still, CCM-loaded NCs presented no cytotoxic effect. Also, all CCM-loaded NCs showed a perceptible antimalarial activity independently of their coatings (anionic and cationic), with more expressive results for CS-coated NCs. In conclusion, findings for CCM-loaded NCs and their different coatings seem to be a promising strategy to improve your biological activity.

Mindfulness interventions during pregnancy: A narrative review.

Pregnancy is a period of major transformations in a woman's life; increased stress, and mood and sleep disorders are frequent. This review evaluates mindfulness interventions during pregnancy and their ability to help manage stress, anxiety, depression, emotional regulation, level of mindfulness and sleep quality. A search of English language scientific literature relevant to mindfulness interventions for pregnant women was conducted using PubMed, Scopus and Web of Science, without restriction on publication date. Inclusion criteria were randomized clinical trials with pregnant women, using mindfulness as an intervention for at least three weeks, in one of our main areas of interest, and using only validated scales to measure outcomes. Two hundred and thirty studies were identified in our searches of research databases, and thirteen were included in our analysis. We found a large diversity of mindfulness programs, heterogeneity among the instruments used to evaluate outcomes, and inconsistency in the gestational periods used in the studies. Mindfulness interventions were beneficial for stress, anxiety and depression. Mindfulness was also effective when applied in pregnant women with a history of depression or experiencing depression. Considering emotional regulation and the level of mindfulness, there were signs of improvement, but more studies are needed. None of the studies evaluated sleep quality. Our review provides information about current mindfulness programs, an overview of the effects of mindfulness interventions, a description of the measurements used so far, and recommendations for developing high-quality mindfulness protocols for pregnant women.

Brazilian malaria molecular targets (BraMMT): selected receptors for virtual high-throughput screening experiments.

BACKGROUND: Owing to increased spending on pharmaceuticals since 2010, discussions about rising costs for the development of new medical technologies have been focused on the pharmaceutical industry. Computational techniques have been developed to reduce costs associated with new drug development. Among these techniques, virtual high-throughput screening (vHTS) can contribute to the drug discovery process by providing tools to search for new drugs with the ability to bind a specific molecular target. OBJECTIVES: In this context, Brazilian malaria molecular targets (BraMMT) was generated to execute vHTS experiments on selected molecular targets of Plasmodium falciparum. METHODS: In this study, 35 molecular targets of P. falciparum were built and evaluated against known antimalarial compounds. FINDINGS: As a result, it could predict the correct molecular target of market drugs, such as artemisinin. In addition, our findings suggested a new pharmacological mechanism for quinine, which includes inhibition of falcipain-II and a potential new antimalarial candidate, clioquinol. MAIN CONCLUSIONS: The BraMMT is available to perform vHTS experiments using OCTOPUS or Raccoon software to improve the search for new antimalarial compounds. It can be retrieved from www.drugdiscovery.com.br or download of Supplementary data.

Brazilian malaria molecular targets (BraMMT): selected receptors for virtual high-throughput screening experiments

BACKGROUND Owing to increased spending on pharmaceuticals since 2010, discussions about rising costs for the development of new medical technologies have been focused on the pharmaceutical industry. Computational techniques have been developed to reduce costs associated with new drug development. Among these techniques, virtual high-throughput screening (vHTS) can contribute to the drug discovery process by providing tools to search for new drugs with the ability to bind a specific molecular target. OBJECTIVES In this context, Brazilian malaria molecular targets (BraMMT) was generated to execute vHTS experiments on selected molecular targets of Plasmodium falciparum. METHODS In this study, 35 molecular targets of P. falciparum were built and evaluated against known antimalarial compounds. FINDINGS As a result, it could predict the correct molecular target of market drugs, such as artemisinin. In addition, our findings suggested a new pharmacological mechanism for quinine, which includes inhibition of falcipain-II and a potential new antimalarial candidate, clioquinol. MAIN CONCLUSIONS The BraMMT is available to perform vHTS experiments using OCTOPUS or Raccoon software to improve the search for new antimalarial compounds. It can be retrieved from www.drugdiscovery.com.br or download of Supplementary data.

Funcionalidade e qualidade de vida em pacientes com osteoartrose submetidos a artroplastia total do joelho / Functionality and quality of life in patients with osteoarthritis submitted to total knee arthroplasty

A osteoartrose do joelho é uma condição clínica degenerativa e crónica que se manifesta pela presença de dor, rigidez articular, limitação dos movimentos e deformidade. A incapacidade provocada pela doença tem um impacto negativo sobre as atividades de vida diária dos pacientes, podendo diminuir a sua qualidade de vida. As consequências da osteoartrose faz com que, muitas vezes, seja necessário recorrer ao tratamento cirúrgico através da artroplastia. Objetivo: Avaliar a incapacidade gerada por problemas no joelho e a qualidade de vida em pacientes com osteoartrose do joelho submetidos a artroplastia total. Metodologia: Estudo de natureza quantitativa e de carater longitudinal prospetivo. Resultados: A amostra estudada apresentou uma média de idades próxima dos 72 anos (71,6±8,1 anos e IMC 27,2 ±3,9) constituiu-se maioritariamente por elementos do sexo feminino (62.5%). A maioria dos participantes proveio dos concelhos do distrito de Bragança. Os resultados da avaliação da qualidade de vida relacionada com a saúde, estudada através do Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF­36 v2), revelam que relativamente à perceção do estado de saúde existiu uma tendência de respostas mais favorável no segundo momento de avaliação, que correspondeu a seis semanas após artroplastia total do joelho (ATJ). No que diz respeito à saúde física verificou-se melhoria no segundo momento de avaliação (p<0,05) de todas as suas dimensões (função física, desempenho físico, dor corporal e saúde em geral). Na saúde mental verificou-se também uma melhoria significativa (p<0,05) da qualidade de vida em todas as dimensões (função social, desempenho emocional e saúde menta), à exceção da vitalidade (p=0,062). A avaliação da perceção da funcionalidade/problemas no joelho, avaliada através do Knee injury and osteoarthritis outome score (KOOS), revelou melhoria nas dimensões sintomas (p=0,015), dor (p<0,001) e qualidade de vida (p<0,001). Conclusão: Os resultados obtidos no estudo mostram que houve melhoria na perceção de saúde após ATJ. Verificou-se ainda melhoria na qualidade de vida com melhoria do desempenho físico e diminuição da dor nesse período de tempo.

The knee osteoarthrosis is a degenerative and chronic clinical condition which manifests by the presence of pain, articular rigidity, movement limitation and deformity. The incapacity caused by the disease has a negative impact on the patients daily activities, reducing their life quality. The consequences of the osteoarthrosis frequently leads to a surgical treatment through arthroplasty. Objective: To evaluate the incapacity caused by knee problems and the quality of life in patients with knee osteoarthrosis submitted to total arthroplasty. Methodology: A quantitative study with an exploratory longitudinal character. Results: The studied sample was 72 years old (71,6±8,1 years and BMI 27,2 ±3,9), majorly constituted by female elements (67.5%). Most of the participants came from countries belonging to the district of Bragança. The results of the health-related quality of life assessment, studied through the Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF-36 v2), reveal that regarding the perception of health status there was a tendency for more responses favourable at the second moment of evaluation, which corresponded to six weeks after total knee arthroplasty (TKA). With regard to physical health, improvement in the second moment of evaluation (p <0.05) of all its dimensions (physical function, physical performance, body pain and general health) was observed. Mental health also showed a significant (p <0.05) improvement in quality of life in all dimensions (social function, emotional performance and mental health), with the exception of vitality (p = 0.062). Knee injury and osteoarthritis outome score (KOOS) showed improvement in symptoms (p = 0.015), pain (p <0.001) and quality of life (p <0.001) .Conclusions: The results obtained in this study show that there were improvements on the perception of health after TKA. It was also observed an improvement on the quality of life with improvement of the physical performance and pain decrease during that period of time.

Virtual rehabilitation via Nintendo Wii® and conventional physical therapy effectively treat post-stroke hemiparetic patients.

BACKGROUND: The Nintendo® Wii is a simple and affordable virtual therapy alternative. It may be used at home, and it is a motivating recreational activity that provides continuous feedback. However, studies comparing the use of the Nintendo® Wii to conventional physical therapy are needed. OBJECTIVE: To compare the effect of a rehabilitation treatment using the Nintendo® Wii (NW) with conventional physical therapy (CPT) to improve the sensorimotor function and quality of life for post-stroke hemiparetic patients. METHODS: The present study applied a randomized, blind, and controlled clinical trial. In total, 30 patients with post-stroke hemiparesis were evaluated. A total of 15 patients were randomly assigned to each group. The SF-36 quality of life and Fugl-Meyer scales were used to evaluate the patients. RESULTS: After treatment, the only variable that differed between the groups was the physical functioning domain of the SF-36 in the group that received conventional physical therapy. A significant difference was observed between both groups before and after treatment in terms of the following Fugl-Meyer scale items: passive movement and pain, motor function of the upper limbs (ULs), and balance. The CPT group also showed a significant difference with regard to their UL and lower limb (LL) coordination. The SF-36 scale analysis revealed a significant difference within both groups with regard to the following domains: physical functioning, role limitation due to physical aspects, vitality, and role limitation due to emotional aspects. The NW group also exhibited a significant difference in the mental health domain. The results indicate that both approaches improved the patients' performance in a similar manner. CONCLUSION: Virtual rehabilitation using the Nintendo Wii® and CPT both effectively treat post-stroke hemiparetic patients by improving passive movement and pain scores, motor function of the upper limb, balance, physical functioning, vitality, and the physical and emotional aspects of role functioning.

A experiência da Terapia Ocupacional com contação de histórias em uma instituição educacional / The experience of Occupational Therapy with storytelling in an educational institution

As histórias são recursos importantes no processo educacional e no cotidiano das crianças, já que elas contribuem para a prática docente na educação infantil e para o desenvolvimento da criança em vários aspectos, principalmente na aprendizagem. O objetivo deste relato é apresentar a experiência de um grupo de contação de histórias realizado em uma instituição filantrópica no município de Uberaba-MG, no decorrer de Estágio Supervisionado I do Curso de Terapia Ocupacional da Universidade Federal do Triângulo Mineiro (UFTM). O referido grupo desenvolve estratégias para aprimorar aspectos psicomotores, cognitivos e habilidades expressivas dos educandos ali inseridos. Foram realizados 12 encontros grupais, semanais, denominados "Vivendo a história", com educandos entre 6 e 12 anos que permaneciam na instituição em contraturno escolar. No decorrer dos grupos foram desenvolvidas ações voltadas à criação, expressão gráfica, oral e escrita, e confecção de recursos vinculados às histórias infantis tradicionais e às relatadas pelos educandos. As ações se basearam nos pressupostos teóricos da Psicomotricidade Funcional e Relacional. Como resultado dos grupos foi possível observar melhoras em habilidades cognitivas, de regulação emocional, de atenção/concentração, resolução de problemas e aspectos psicomotores em geral, como grafomotores, coordenação global, esquema corporal, entre outros. A partir dos registros semanais, pôde-se perceber a influência das histórias, tanto tradicionais como pessoais, no processo de aprendizagem, aprimorando-se as habilidades cognitivas, o processo de leitura e escrita, e, principalmente, a expressão e comunicação infantil.

Stories are important tools in the educational process and daily lives of children, because they contribute to the teaching practice in early education and to child development in many aspects, especially in learning. The purpose of this report is to present the experience of a storytelling group in an educational institution in the municipality of Uberaba, Minas Gerais state, during an internship supervised by the Occupational Therapy Course - Federal University of Triângulo Mineiro. The group developed strategies to improve psychomotor and cognitive aspects and expressive abilities of the students. Twelve one-hour weekly meetings were held during the morning, and the public were students aged 6 to 12 years old that stayed in school the whole day. In the workshop, entitled "Living the Story", the group developed actions aimed at the creation and telling of stories, the confection of resources that were linked to the stories, and the concepts of experiences related to psychomotor aspects. As a result, it was possible to observe improvements in cognitive skills, emotional regulation, attention and concentration, problem solving, and general psychomotor aspects. Therefore, it is possible to point out that creating and listening to stories stimulate the imagination, educate, instruct, develop cognitive skills, facilitate the process of reading and writing, and enhance children's communication skills.

Projeto de extensão de Yoga: auxiliando na formação profissional e acadêmica do estudante de graduação em Educação Física / Yoga Project: Contributing to academic and professional formation of student of Physical Education

O programa de extensão de Yoga realizado na UNESP ? Rio Claro teve início em 2006 e é constituído por três grupos. As aulas são de 60 minutos de duração duas vezes por semana, focadas em trabalhar o corpo físico, com base nas posturas psicofísicas do Yoga, aliadas a exercícios respiratórios e de relaxamento. Procura através deste método proporcionar bem estar físico e mental favorecendo a manutenção e melhora de aspectos psicológicos dos alunos, que são predominantemente pessoas da universidade e da comunidade de Rio Claro. Resultados positivos foram obtidos nos estudos sobre motivação e estados de ânimo feitos com esses grupos. O programa possibilita ainda uma vivência pedagógica dos alunos do curso de Educação Física interessados nessa área e o desenvolvimento de projetos de pesquisa auxiliando na formação profissional e acadêmica do estudante de graduação.

The extension program of Yoga at UNESP ? Rio Claro began in 2006 and constitutes of 3 classes that are 60 minutes long twice a week, focus in a physical work out, through Yoga psychophysical postures, along with breathing exercises and relaxation and seeks through this method to provide physical and mental well-being, favoring the maintenance and improvement of students? psychological aspects, which are predominantly people from the university and the community of Rio Claro. Positive results were obtained in studies on motivation and moods made with these groups. The program also allows an experience teaching students of Physical Education who are interesting in this area of study. It also allows the educational experience for students of physical education and the development of a lot research projects.

Experimental Chagas' disease in orchiectomized Calomys callosus infected with the CM strain of Trypanosoma cruzi.

The incidence and progression of disorders associated with an unbalanced immune response has among many factors the gender as a contributory factor. The aims of this work were to evaluate the effects of orchiectomy and the immune response during the experimental Trypanosoma cruzi infection. Young adult, male Calomys callous were i.p. inoculated with 1 x 10(5) blood trypomastigotes of the CM strain of T. cruzi and divided in groups: Control, Sham and Castrated. Castrated group displayed significantly lower values for prostate and seminal vesicle weights indicating a drastic drop of testosterone plasmatic levels. Orchiectomized animals also displayed lesser number of blood parasites, enhanced lytic antibody percentage, splenocyte proliferation and NO concentration when compared to its sham and control counterparts, indicating that steroid gonadal ablation actually influences immune response triggering a more efficient cellular and humoral response which led animals to become more resistant against T. cruzi infection.

Alterations triggered by steroid gonadal hormones in triglycerides and the cellular immune response of Calomys callosus infected with the Y strain of Trypanosoma cruzi.

Calomys callosus is a wild rodent found naturally infected with different Trypanosoma cruzi strains. In the work described here, groups of male and female C. callosus were subjected to orchiectomy, ovariectomy and sham operation. One month after surgery, animals were inoculated intraperitoneally (i.p.) with 4x10(4) blood trypomastigotes of the "Y" strain of T. cruzi. Parasitemia, triglycerides, nitric oxide (NO) and concanavalin A (ConA)-induced proliferation were evaluated. Parasitemia during the course of infection was significantly higher in infected and sham operated animals as compared to infected orchiectomized animals. The opposite was observed in the ovariectomized and infected group. Orchiectomized and infected animals displayed elevated triglyceride levels, as well as a more vigorous immune response, with higher splenocyte proliferation and elevated concentrations of NO. Ovariectomy resulted in an impaired immune response, as observed by a reduction of splenocyte proliferation and NO concentration. The results suggest a pivotal role for gonadal hormones in the modulation of triglyceride levels and the magnitude of the immune response during the acute phase of T. cruzi infection.

Mechanism of the endothelium-dependent vasodilation and the antihypertensive effect of Brazilian red wine.

The mechanisms involved in the cardioprotector effect of red wine have not yet been completely elucidated but probably an endothelium-dependent vasodilator action may play a significant role in this effect. Experiments were undertaken to determine whether a Brazilian red wine (BRW) induces vasodilation in the mesenteric vascular bed (MVB) and an antihypertensive effect was also assessed in rats with NO-deficient hypertension. In MVB precontracted with norepinephrine, BRW (alcohol-free lyophilized) induces a long-lasting endothelium-dependent vasodilation that is not reduced by indomethacin. Inhibition of NO-synthase by NG-nitro-L-arginine methyl ester (L-NAME) and guanylyl cyclase by 1H-[1,2,3] oxadiazolo [4,4-a]quinoxalin-1-one (ODQ) reduces the vasodilator effect of BRW. In vessels precontracted with norepinephrine and depolarized with KCl (25 Mm) or treated with Ca-dependent K channel blockers charybdotoxin (ChTx) plus apamin, the effect of BRW was significantly reduced. However, this effect is not affected by ATP-dependent K (KATP) channel blocker (glibenclamide). The residual vasodilator effect of BRW observed in vessels pretreated with ChTx plus apamin is completely abolished by ChTx plus apamin plus L-NAME. Concentrations of atropine, pyrilamine, yohimbine, and HOE 140 that significantly reduced the vasodilator effect of acetylcholine, histamine, clonidine, and bradykinin, respectively did not change the vasodilator effect of BRW. Chronic oral administration of BRW induced a significant reduction in systolic, mean and diastolic arterial pressure in rats with L-NAME hypertension. The present results demonstrated that vasodilator effect of BRW is dependent on endothelium-derived hyperpolarizing factor (EDHF) in combination with nitric oxide (NO). The antihypertensive effect of red wine demonstrated in the present study may play a significant role on the cardioprotective action of chronic red wine consumption.

Glicocorticóides e hormönio de crescimento (GH): efeito da administraçäo aguda de dexametasona e do hipocortisolismo sobre a resposta do GH ao GHRP-6 ("GH-releasing peptide") / Acute administration of glucocorticoids stimulates GH secretion probably by a decrease in hypothalamic somatostatin release

Estudo 1- Nosso estudo demonstrou que a administração oral de dexametasona na dose de 4 mg, 3 1/2horas antes, aumenta a resposta do GH ao GHRP-6. Isto pode sugerir que a dexametasona e o GHRP-6 atuam em locais distintos nos mecanismos de liberação de GH. No entanto, outros estudos são necessários para elucidar estes achados. Estudo 2 - Nossos dados demonstram que a deprivação aguda de glicocorticóide aparentemente não altera a resposta do GH ao GHRP-6 em indivíduos normais. Pacientes com insuficiência adrenal apresentam uma resposta normal de GH ao GHRP-6. Entretanto, após a interrupção do glicocorticóide, a resposta do GH ao GHRP-6 nestes pacientes é menor que àquela observada em indivíduos normais previamente tratados com metopirona. Em conclusão, a deprivação de glicocorticóide por curto período não causa alterações importantes nos mecanismos de liberação de GH dependentes de GHRP-6. Entretanto, o hipocortisolismo de longa duração poderia afetar, de modo sutil, as vias de liberação de GH utilizadas pelo GHRP-6 nos somatotrofos

Sindrome de Klinefelter associada a prolactinoma: descriçäo de um caso / Klinefelter's syndrome associated with prolactinoma: a case report

Descrevemos o caso de um indivíduo portador de síndrome de Klinefelter associada a um tumor hipofisário produtor de prolactina. O paciente apresentou quadro de hipogonadismo na vigência de terapêutica substitutiva adequada com testosterona, sendo entäo aventada a hipótese diagnóstica de hiperprolactinemia, que se confirmou após disagem sérica de prolactina. Foi iniciado tratamento com bromocriptina oral, sendo posteriormente utilizada bromocriptina injetável (Parlodel-LAR Sandoz) devido à intolerancia à forma oral. Houve resposta terapêutica satisfatória com diminuiçäo dos níveis de prolactina e reduçäo do volume tumoral. Ainda que algumas neoplasia como carcinoma de mama e tumores de células germinativas, ocorram mais frequentemente em pacientes com síndrome de Klinefelter, a associaçäo com adenoma hipofisário produtor de prolactina ainda näo foi relatada. Em conclusäo, a presença de hipogonadismo em pacientes com síndrome de Klinefelter recebendo terapêutica substitutiva adequada com testosterona, pode indicar a presença de hiperprolactinemia