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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women associated with cardiovascular disease and obesity. The possible benefits of omega-3 supplementation in this syndrome have been discussed much. This study is aimed to verify, based on the scientific data published, if there are any benefits in the omega-3 supplementation in the treatment of PCOS and to indicate its possible dosages for the treatment of polycystic ovary. The work consists of a systematic review of clinical trials and cohort of the MEDLINE/PubMed database from 2009 to October 2019. All studies that analyzed the omega-3 supplementation in women with PCOS were included. Cross-sectional studies, review articles, systematic reviews, meta-analysis, duplicates, studies in animals or cell culture, studies with omega-3 supplementation via food or associated with other supplementations were not included, except those involving vitamin E. In total, 21 articles were selected. Despite the heterogeneity of the studies selected, indirect benefits were observed mainly regarding the glycemic profile, such as insulin resistance reduction, lipid profile modulation (i.e. decrease in total cholesterol, triglycerides, and elevation of high-density lipoprotein), and the regulation of the androgenic profile. As for the anthropometric profile, the studies were scarce and most of them had no significant meaning. Regarding the antioxidant profile and inflammatory biomarkers, the findings differ among studies, but promising results were observed with different doses over 12 weeks of use, such as C-reactive protein (CRP) reduction. Thus, omega-3 fatty acids promote indirect benefits in the treating of women with PCOS. However, to reveal well-defined standards for dosage and supplementation time, further studies are needed.

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5-Nitro-furan nitrones (1) and 5-nitro-thiophene nitrones (2) were synthesized in one step. Compounds 1a-c had the most potent leishmanicidal activity against intracellular amastigote forms of Leishmania amazonensis and L. infantum (from 0.019 to 2.76 µM), with excellent selectivity (from 39 to 5673). The comparison of the leishmanicidal activity in promastigotes of wild type L. donovani with those overexpressing nitroreductases NRT1 or NRT2 shows that 1a,b are activated by both, which could slow the development of resistance. Their redox potential (E redox) obtained by cyclic voltammetry (-0.67 and -0.62 V) shows that the reduction of the nitro group is modulated by the nitrone group. Oral administration of 1b to mice infected by L. infantum reduced the parasite load on the spleen by 76.6 and 95.0% with doses of 50 and 100 mg/kg, respectively, administered twice a day, for 5 days. In the liver, the parasite load suppression was above 75% with either treatment.

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BACKGROUND: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, and the modification at their redox center is an interesting strategy to overcome such harmful activity. OBJECTIVE: In this study, four novel semisynthetic hydrazones, derived from the isomers α- and ß- lapachones (α and ß, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. METHODS: The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. RESULTS: The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, compounds 3 and 4 being the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than ß-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90-12.40 µM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. CONCLUSION: These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.

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Chagas disease is caused by the hemoflagellate protozoa Trypanosoma cruzi and is one of the most important neglected tropical diseases, especially in Latin American countries, where there is an association between low-income populations and mortality. The nitroderivatives used in current chemotherapy are far from ideal and present severe limitations, justifying the continuous search for alternative drugs. Since the1990s, our group has been investigating the trypanocidal activity of natural naphthoquinones and their derivatives, and three naphthoimidazoles (N1, N2 and N3) derived from ß-lapachone were found to be most effective in vitro. Analysis of their mechanism of action via cellular, molecular and proteomic approaches indicates that the parasite mitochondrion contains one of the primary targets of these compounds, trypanothione synthetase (involved in trypanothione production), which is overexpressed after treatment with these compounds. Here, we further evaluated the participation of the mitochondria and reactive oxygen species (ROS) in the anti-T. cruzi action of naphthoimidazoles. Preincubation of epimastigotes and trypomastigotes with antioxidants (α-tocopherol and urate) strongly protected the parasites from the trypanocidal effect of naphthoimidazoles, decreasing the ROS levels produced and reverting the mitochondrial swelling phenotype. The addition of pro-oxidants (menadione and H2O2) before the treatment induced an increase in parasite lysis. Despite the O2 uptake and mitochondrial complex activity being strongly reduced by N1, N2 and N3, urate partially restored the mitochondrial metabolism only in N1-treated parasites. In parallel, MitoTEMPO, a mitochondrial-targeted antioxidant, protected the functionality of the mitochondria in N2- and N3-treated parasites. In addition, the trypanothione reductase activity was remarkably increased after treatment with N1 and N3, and molecular docking demonstrated that these two compounds were positioned in pockets of this enzyme. Based on our findings, the direct impairment of the mitochondrial electron transport chain by N2 and N3 led to an oxidative misbalance, which exacerbated ROS generation and led to parasite death. Although other mechanisms cannot be discounted, mainly in N1-treated parasites, further investigations are required.

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INTRODUÇÃO: A síndrome de Burnout é uma condição que envolve basicamente três dimensões: a exaustão emocional, a despersonalização e a redução da realização profissional. Apresenta-se hoje, como um dos grandes problemas psicossociais no Brasil, sendo recordista em afastamento e incapacidades para o trabalho. OBJETIVO: estimar a frequência de Síndrome de Burnout em uma amostra de fisioterapeutas intensivistas na cidade de Salvador, Bahia, Brasil. Método: estudo transversal, utilizando-se o Maslach Burnout Inventory para avaliar a síndrome e suas dimensões e o Inventário de Sintomas para avaliar a frequência com que alguns sintomas são sentidos no cotidiano dos fisioterapeutas intensivistas. RESULTADOS: foram incluídos dados de 45 fisioterapeutas intensivistas, sendo que nove (20%) apresentaram alto nível de exaustão emocional, 1 (2,2%) alto nível para despersonalização e 6 (13,3%) com alta reduzida realização profissional. A frequência da síndrome de Burmout apresentou um percentual relevante: 31,1% (14 participantes). CONCLUSÃO: o número de pacientes, assim como o número de atendimento destes, por plantão contribui para uma sobrecarga física e mental do profissional, caracterizando o trabalho da fisioterapia como fator de risco para a incidência da SB. [AU]

INTRODUCTION: Burnout syndrome is a condition that basically involves three dimensions: emotional exhaustion, depersonalization and reduction of professional achievement. He presents himself today as one of the great psychosocial problems in Brazil, being a record holder in his absence and incapacities for work. OBJECTIVE: To estimate the frequency of burnout syndrome in a sample of intensive physical therapists in the city of Salvador, Bahia, Brazil. METHODS: Cross-sectional, descriptive study using the Maslach Burnout Inventory to assess the syndrome and its dimensions and Symptoms Inventory to assess the frequency with which some symptoms are felt in the daily lives of intensive physical therapists. RESULTS: were included in the survey data for 45 intensive physical therapists, and 20% had high levels of emotional exhaustion, 1 (2.2%) high level to depersonalization and 6 (13.3%) with high reduced professional accomplishment. The frequency of the Burnout syndrome showed a significant percentage 31.1% (14 participants). CONCLUSION: The number of patients, as well as the number of these services, per shift contributes to physical and mental overload professional, featuring the work of physical therapy as a risk factor for the incidence of SB. [AU]

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We report a sequential C-H iodination/organoyl-thiolation of naphthoquinones and their relevant trypanocidal activity. Under a combination of AgSR with a copper source, sulfur-substituted benzenoid quinones were prepared in high yields (generally >90%). This provides an efficient and general method for preparing A-ring modified naphthoquinoidal systems, recognized as a challenge in quinone chemistry.

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Thirty four halogen and selenium-containing quinones, synthesized by rhodium-catalyzed C-H bond activation and palladium-catalyzed cross-coupling reactions, were evaluated against bloodstream trypomastigotes of T. cruzi. We have identified fifteen compounds with IC50/24 h values of less than 2 µM. Electrochemical studies on A-ring functionalized naphthoquinones were also performed aiming to correlate redox properties with trypanocidal activity. For instance, (E)-5-styryl-1,4-naphthoquinone 59 and 5,8-diiodo-1,4-naphthoquinone 3, which are around fifty fold more active than the standard drug benznidazole, are potential derivatives for further investigation. These compounds represent powerful new agents useful in Chagas disease therapy.

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For the first time, a fluorescent lapachone-based BODIPY was synthesised and characterised by NMR and mass spectrometry. Computational and electrochemical aspects, as well as cytotoxic activity and subcellular localisation, were studied. Confocal microscopy experiments indicated that the probe was a specific mitochondria-staining agent. These in-detail analyses were useful in understanding the cytotoxic effects and mechanism of action of this novel hybrid compound. This molecule constitutes a promising prototype owing to its potential biological activities and the new strategies aimed at mechanistic investigations in cells and in vivo, and opens up an interesting avenue of research.

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This study reports on the design, synthesis and antiparasitic activity of three new semi-synthetic naphthoquinones structurally related to the naturally-occurring lapachol and lapachone. Of the compounds tested, 3-(3-methylbut-1-en-1-yl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl acetate (1) was the most active against Plasmodium falciparum among both natural and semi-synthetic naphthoquinones, showing potent and selective activity. Compound 1 was able to reduce the in vitro parasite burden, in vitro parasite cell cycle, as well as the blood parasitemia in Plasmodium berghei-infected mice. More importantly, infection reduction under compound 1-treatment was achieved without exhibiting mouse genotoxicity. Regarding the molecular mechanism of action, this compound inhibited the hemozoin crystal formation in P. falciparum treated cells, and this was further confirmed by observing that it inhibits the ß-hematin polymerization process similarly to chloroquine. Interestingly, this compound did not affect either mitochondria structure or cause DNA fragmentation in parasite treated cells. In conclusion, we identified a semi-synthetic antimalarial naphthoquinone closely related to isolapachol, which had stronger antimalarial activity than lapachol.

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