New ent-kaurene-type nor-diterpene and other compounds isolated from Annona vepretorum Mart. (Annonaceae).

A new nor-ent-kaurene diterpene and ten other compounds were isolated from Annona vepretorum stems, including four kaurene diterpenes, three alkamides, one sesquiterpene and two steroids. Their chemical structures were elucidated using spectroscopic methods, including 1D-, 2D-NMR, and HRESIMS. The absolute configuration of compounds 1, 5, 8, 9 and 10 was confirmed by CD experiments. Compounds 1-5 and 8-10 were evaluated for cytotoxic activity using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT method, against three human carcinoma cell lines: human colon (HCT-116), glioblastoma (SF295) and prostate (PC3). However, all isolated compounds exhibited low cytotoxic activity.

Zeaxanthin from Porphyridium purpureum induces apoptosis in human melanoma cells expressing the oncogenic BRAF V600E mutation and sensitizes them to the BRAF inhibitor vemurafenib

Abstract Zeaxanthin, an abundant carotenoid present in fruits, vegetables and algae was reported to exert antiproliferative activity and induce apoptosis in human uveal melanoma cells. It also inhibited uveal melanoma tumor growth and cell migration in nude mice xenograft models. Here we report that zeaxanthin purified from the rhodophyte Porphyridium purpureum (Bory) K.M.Drew & R.Ross, Porphyridiaceae, promotes apoptosis in the A2058 human melanoma cell line expressing the oncogenic BRAF V600E mutation. Zeaxanthin 40 µM (IC50) induced chromatin condensation, nuclear blebbing, hypodiploidy, accumulation of cells in sub-G1 phase, DNA internucleosomal fragmentation and activation of caspase-3. Western blot analysis revealed that zeaxanthin induced up-regulation of the pro-apoptotic factors Bim and Bid and inhibition of NF-κB transactivation. Additionally, zeaxanthin sensitized A2058 melanoma cells in vitro to the cytotoxic activity of vemurafenib, a BRAF inhibitor widely used for the clinical management of melanoma, suggesting its potential interest as dietary adjuvant increasing melanoma cells sensitivity to chemotherapy.

LASSBio-1586, an N-acylhydrazone derivative, attenuates nociceptive behavior and the inflammatory response in mice.

Pain and inflammation are complex clinical conditions that are present in a wide variety of disorders. Most drugs used to treat pain and inflammation have potential side effects, which makes it necessary to search for new sources of bioactive molecules. In this paper, we describe the ability of LASSBio-1586, an N-acylhydrazone derivative, to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In these experimental models, LASSBio-1586 significantly (p<0.05) reduced nociceptive behavior. Several methods of acute and chronic inflammation induced by different chemical (carrageenan, histamine, croton oil, arachidonic acid) and physical (cotton pellet) agents were used to evaluate the anti-inflammatory effect of LASSBio-1586. LASSBio-1586 exhibited potent anti-inflammatory activity in all tests (p<0.05). Study of the mechanism of action demonstrated the possible involvement of the nitrergic, serotonergic and histamine signaling pathways. In addition, a molecular docking study was performed, indicating that LASSBio-1586 is able to block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. In summary, LASSBio-1586 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.

Neuropharmacological effects of essential oil from the leaves of Croton conduplicatus Kunth and possible mechanisms of action involved.

ETHNOPHARMACOLOGICAL RELEVANCE: Croton conduplicatus Kunth (Euphorbiaceae) is a Brazilian aromatic medicinal plant, widely known as "quebra-faca". In folk medicine, its leaves and stem-barks are used as a natural analgesic for the treatment of headaches. AIM OF THE STUDY: In this study, we describe for the first time the neuropharmacological potential of the essential oil obtained from the leaves of Croton conduplicatus (EO) in experimental models of pain, anxiety and insomnia. The mechanisms of action involved in these activities were also investigated. MATERIAL AND METHODS: Different experimental models were used to evaluate the antinociceptive (acetic acid, formalin-induced nociception and hot plate tests), anxiolytic (elevated plus maze and hole board tests) and sedative (thiopental-induced sleeping time) effects of EO in mice. EO was evaluated in three different doses (25, 50 and 100 mg/kg, i.p.) and compared with positive and negative controls in all experimental protocols. When appropriate, animals were pretreated with pharmacological antagonists (naloxone, atropine and flumazenil) in order to evaluate the mechanisms of action involved. A docking study also was performed to identify possible targets involved. RESULTS: EO (25, 50 and 100 mg/kg, i.p.) demonstrated a significant antinociceptive activity in all experimental models. Pretreatment with naloxone or atropine reversed the antinociceptive response (p < 0.05), suggesting the involvement of opioid and muscarinic receptors, respectively. A docking study was performed with the major components identified in EO (1,8 cineole - 21.42%, spathulenol - 15.47%, p-cymene - 12.41% and caryophyllene oxide - 12.15%), demonstrating favorable interaction profile with different subtypes of muscarinic (M2, M3 and M4) and opioids (delta and mu) receptors. EO also showed anxiolytic (mainly at doses of 25 and 50 mg/kg, i.p.) and sedative (only at the dose of 100 mg/kg, i.p.) effects in mice. These pharmacological responses were reversed by flumazenil (p < 0.05), indicating possible involvement of GABAA receptors. CONCLUSION: Our findings support the traditional use of this plant as a natural analgesic and suggest that EO is a multi-target natural product, presenting not only antinociceptive effect but also anxiolytic and sedative activities depending on the dose used.

Condições de trabalho das Equipes de Saúdeda Família do município de Petrolina-PE:percepção dos profissionais de saúde / Working conditions of Family Health Teams of the municipalityof Petrolina-PE: perceptions of health care professionals

O estudo objetiva traçar o perfil das Equipes de Saúde da Família (ESF) do município de Petrolina-PE, Brasil, quanto àscondições físico-estruturais nas quais se encontram e quanto à qualidade dos serviços de saúde prestados à população,analisando os principais problemas a serem enfrentados pelos profissionais de saúde em seu processo de trabalho. Foirealizado um estudo de caráter observacional descritivo, baseado na aplicação de um questionário semiestruturado, destinadoaos profissionais de saúde das mais diversas categorias que trabalham nas ESF do município de Petrolina. Entre osserviços disponibilizados pelo município nas ESF citados pelos profissionais, os considerados mais eficientes foram: vacinação,serviço de enfermagem e pré-natal, enquanto que a farmácia e odontologia foram consideradas os mais precários.A estrutura das unidades foi relatada como o principal problema que dificulta a execução dos serviços nas unidades (43%)e 27% dos profissionais entrevistados afirmaram que as unidades em que trabalham não conseguem atender à demanda.A escassez de profissionais, aliada à falta de equipamentos, materiais e medicamentos, acaba inviabilizando as práticasde trabalho, tornando o sistema de saúde vigente no país defasado, sobrecarregando os macrocomponentes dos níveis demédia e alta complexidade em saúde.

The study aims to evaluate the profile of ESF (Family Health Teams) in the city of Petrolina (Pernambuco, Brazil), concerningphysical and structural conditions of the ESF and concerning the quality of health services rendered to the population, byanalyzing the main problems to be faced by health professionals at work. An observational descriptive study was conductedbased on a semi-structured questionnaire intended to health professionals from several categories working at Petrolina’s ESF.Among the services provided by the municipality in the ESF, mentioned by the professionals, the ones considered as moreeffective were vaccination, nursing services and prenatal care, while pharmacy and dentistry were considered the most precarious.The units’ structure was reported by 43% of the professional as the main problem that hinders the implementation ofservices in the units and 27% said that the units in which they work cannot meet the demand. The shortage of professionalscoupled with lack of equipment, supplies and medicines preclude the working practices, lagging the current health system inthe country, overloading macrocomponents of medium and high levels of complexity in health.

Condições de trabalho das Equipes de Saúde da Família do município de Petrolina-PE:percepção dos profissionais de saúde / Working conditions of Family Health Teams of the municipality of Petrolina-PE: perceptions of health care professionals

O estudo objetiva traçar o perfil das Equipes de Saúde da Família (ESF) do município de Petrolina-PE, Brasil, quanto àscondições físico-estruturais nas quais se encontram e quanto à qualidade dos serviços de saúde prestados à população,analisando os principais problemas a serem enfrentados pelos profissionais de saúde em seu processo de trabalho. Foirealizado um estudo de caráter observacional descritivo, baseado na aplicação de um questionário semiestruturado, destinadoaos profissionais de saúde das mais diversas categorias que trabalham nas ESF do município de Petrolina. Entre osserviços disponibilizados pelo município nas ESF citados pelos profissionais, os considerados mais eficientes foram: vacinação,serviço de enfermagem e pré-natal, enquanto que a farmácia e odontologia foram consideradas os mais precários.A estrutura das unidades foi relatada como o principal problema que dificulta a execução dos serviços nas unidades (43%)e 27% dos profissionais entrevistados afirmaram que as unidades em que trabalham não conseguem atender à demanda.A escassez de profissionais, aliada à falta de equipamentos, materiais e medicamentos, acaba inviabilizando as práticasde trabalho, tornando o sistema de saúde vigente no país defasado, sobrecarregando os macrocomponentes dos níveis demédia e alta complexidade em saúde.(AU)

The study aims to evaluate the profile of ESF (Family Health Teams) in the city of Petrolina (Pernambuco, Brazil), concerningphysical and structural conditions of the ESF and concerning the quality of health services rendered to the population, byanalyzing the main problems to be faced by health professionals at work. An observational descriptive study was conductedbased on a semi-structured questionnaire intended to health professionals from several categories working at Petrolina’s ESF.Among the services provided by the municipality in the ESF, mentioned by the professionals, the ones considered as moreeffective were vaccination, nursing services and prenatal care, while pharmacy and dentistry were considered the most precarious.The units’ structure was reported by 43% of the professional as the main problem that hinders the implementation ofservices in the units and 27% said that the units in which they work cannot meet the demand. The shortage of professionalscoupled with lack of equipment, supplies and medicines preclude the working practices, lagging the current health system inthe country, overloading macrocomponents of medium and high levels of complexity in health.(AU)