Larvicidal activity of coumarin derivatives on Toxocara canis larvae, cytotoxicity analysis, and in silico bioavailability studies.

Human toxocariasis is a neglected anthropozoonosis with global distribution. Treatment is based on the administration of anthelmintics; however, their effectiveness at the tissue level is low to moderate, necessitating the discovery of new drug candidates. Several groups of synthetic compounds, including coumarin derivatives, have demonstrated bioactivity against fungi, bacteria, and even parasites, such as Dactylogyrus intermedius, Leishmania major, and Plasmodium falciparum. The aim of this study was to evaluate the effect of ten coumarin-derived compounds against Toxocara canis larvae using in vitro, cytotoxicity, and in silico tests for selecting new drug candidates for preclinical tests aimed at evaluating the treatment of visceral toxocariasis. The compounds were tested in vitro in duplicate at a concentration of 1 mg/mL, and compounds with larvicidal activity were serially diluted to obtain concentrations of 0.5 mg/mL; 0.25 mg/mL; 0.125 mg/mL; and 0.05 mg/mL. The tests were performed in a microculture plate containing 100 T. canis larvae in RPMI-1640 medium. One compound (COU 9) was selected for cytotoxicity analysis using J774.A1 murine macrophages and it was found to be non-cytotoxic at any concentration tested. The in silico analysis was performed using computational models; the compound presented adequate results of oral bioavailability. To confirm the non-viability of the larvae, the contents of the microplate wells of COU 9 were inoculated intraperitoneally (IP) into female Swiss mice at 7-8 weeks of age. This confirmed the larvicidal activity of this compound. These results show that COU 9 exhibited larvicidal activity against T. canis larvae, which, after exposure to the compound, were non-viable, and that COU 9 inhibited infection in a murine model. In addition, COU 9 did not exhibit cytotoxicity and presented adequate bioavailability in silico, similar to albendazole, an anthelmintic, which is the first choice for treatment of human toxocariasis, supporting the potential for future investigations and preclinical tests on COU 9.

Pleiotropic antifibrotic actions of aspirin-triggered resolvin D1 in the lungs.

Introduction: Pulmonary fibrosis is a destructive, progressive disease that dramatically reduces life quality of patients, ultimately leading to death. Therapeutic regimens for pulmonary fibrosis have shown limited benefits, hence justifying the efforts to evaluate the outcome of alternative treatments. Methods: Using a mouse model of bleomycin (BLM)-induced lung fibrosis, in the current work we asked whether treatment with pro-resolution molecules, such as pro-resolving lipid mediators (SPMs) could ameliorate pulmonary fibrosis. To this end, we injected aspirin-triggered resolvin D1 (7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E19Z-docosahexaenoic acid; ATRvD1; i.v.) 7 and 10 days after BLM (intratracheal) challenge and samples were two weeks later. Results and discussion: Assessment of outcome in the lung tissues revealed that ATRvD1 partially restored lung architecture, reduced leukocyte infiltration, and inhibited formation of interstitial edema. In addition, lung tissues from BLM-induced mice treated with ATRvD1 displayed reduced levels of TNF-α, MCP-1, IL-1-ß, and TGF-ß. Of further interest, ATRvD1 decreased lung tissue expression of MMP-9, without affecting TIMP-1. Highlighting the beneficial effects of ATRvD1, we found reduced deposition of collagen and fibronectin in the lung tissues. Congruent with the anti-fibrotic effects that ATRvD1 exerted in lung tissues, α-SMA expression was decreased, suggesting that myofibroblast differentiation was inhibited by ATRvD1. Turning to culture systems, we next showed that ATRvD1 impaired TGF-ß-induced fibroblast differentiation into myofibroblast. After showing that ATRvD1 hampered extracellular vesicles (EVs) release in the supernatants from TGF-ß-stimulated cultures of mouse macrophages, we verified that ATRvD1 also inhibited the release of EVs in the bronco-alveolar lavage (BAL) fluid of BLM-induced mice. Motivated by studies showing that BLM-induced lung fibrosis is linked to angiogenesis, we asked whether ATRvD1 could blunt BLM-induced angiogenesis in the hamster cheek pouch model (HCP). Indeed, our intravital microscopy studies confirmed that ATRvD1 abrogates BLM-induced angiogenesis. Collectively, our findings suggest that treatment of pulmonary fibrosis patients with ATRvD1 deserves to be explored as a therapeutic option in the clinical setting.

The Amazonian kambô frog Phyllomedusa bicolor (Amphibia: Phyllomedusidae): Current knowledge on biology, phylogeography, toxinology, ethnopharmacology and medical aspects.

Phyllomedusa bicolor (Phyllomedusidae), popularly known as the kambô in Brazil, is a tree frog that is widely distributed in South American countries and is known for producing a skin secretion that is rich in bioactive peptides, which are often used in indigenous rituals. The biological effects of the skin secretion were observed in the first studies with indigenous communities. Over the last six decades, researchers have been studying the chemical composition in detail, as well as the potential pharmacological applications of its constituents. For this reason, indigenous communities and health agents fear the misuse of the kambô, or the inappropriate use of the species, which can result in health complications or even death of users. This article seeks to provide a transdisciplinary review that integrates knowledge regarding the biology of P. bicolor, ethnoknowledge about the ritual of the kambô, and the chemistry and pharmacology of the skin secretion of this species, in addition to medical aspects of the indiscriminate use of the kambô. Furthermore, this review seeks to shed light on perspectives on the future of research related to the kambô.

Retalho de avanço formato A-T para reconstrução malar / A-T flap for cheek reconstruction

A região malar é a maior unidade anatômica da face. Nessa área, o tratamento cirúrgico do câncer de pele deve objetivar, além de sua erradicação completa, o melhor resultado estético-funcional possível. Paciente do sexo feminino, 69 anos, com tumoração de 3,5cm na região malar esquerda há três anos, teve evidenciado, por biópsia, carcinoma espinocelular moderadamente diferenciado. Realizaram-se exérese do tumor e reconstrução por meio do retalho A-T, em que o defeito cirúrgico correspondeu ao "A" e o encontro dos sulcos do rebordo orbital inferior, nasofacial e nasogeniano, ao teto do "T". A paciente evoluiu sem recidiva e com excelente aspecto estético-funcional.

The cheek is the largest anatomical unit of the face. In this area, surgical skin cancer treatment must aim for its complete eradication and the best aesthetic-functional result. A 69-year-old woman presented with a 3.5 cm tumor in the left cheek for three years. Biopsy showed moderately differentiated squamous cell carcinoma. We performed an A-T flap, where the surgical defect corresponded to the "A" and the junction of the inferior orbital, nasofacial, and nasolabial grooves, to the top of the "T". The patient evolved without recurrence and had an excellent aesthetic-functional aspect.

Glycoinsulinemic parameters associated with vitamin D status in patients with chronic kidney disease undergoing dialysis therapy

ABSTRACT Evidence indicates that the physiological role of vitamin D goes beyond regulating classical domains of minerals and hormones. It is reported that the low status of Vitamin D may contribute to the occurrence of metabolic disorders, with emphasis on insulin resistance, atherosclerotic events and metabolic syndrome. In this sense, this study aimed to verify the association between metabolic and anthropometric parameters and vitamin D status in patients with chronic kidney disease undergoing hemodialysis. This was a cross-sectional study conducted with 95 patients with chronic kidney disease treated at clinics in Teresina, Piaui, Brazil. Lipid and inflammatory profile, glycemia, insulin and vitamin D status were determined. Data were analyzed using STATA software, adopting significance level of p<0.05. The results pointed to a significant association between vitamin D concentrations and adiposity of patients. It was observed that the high blood glucose and HOMA-IR values presented statistical association with vitamin D concentrations, and conditioned greater chances of their inadequacy. There was no correlation between nutrient concentrations and cytokines evaluated in the study. Therefore, it was concluded that the increase in levels of glycoinsulinemic parameters (insulin and HOMA-IR) seems to influence vitamin D status in patients with chronic kidney disease.

RESUMEN La evidencia indica que el papel fisiológico de la vitamina D va más allá de regular los dominios clásicos del eje mineral y hormonal. Hay trabajos que muestran que el bajo nivel de vitamina D puede contribuir a la aparición de trastornos metabólicos, con énfasis en la resistencia a la insulina, eventos ateroscleróticos y síndrome metabólico. En este sentido, el objetivo de este estudio fue verificar la asociación entre parámetros metabólicos y antropométricos y el estado de vitamina D en pacientes renales crónicos en hemodiálisis. Se trata de un estudio transversal realizado con 95 pacientes con enfermedad renal crónica atendidos en consultas externas de Teresina, Piauí, Brasil. Se determinó el perfil lipídico e inflamatorio, la glicemia, la insulina y el estado de vitamina D. Los datos se analizaron utilizando programa STATA , con un nivel de significancia de p<0,05. Los resultados apuntaron a una asociación significativa entre las concentraciones de vitamina D y la adiposidad de los pacientes. Se observó que los valores elevados de glucosa en sangre y HOMA-IR se asociaron estadísticamente con las concentraciones de vitamina D y condicionaron mayores posibilidades de su insuficiencia. No hubo correlación entre las concentraciones de nutrientes y las citocinas evaluadas en el estudio. Por tanto, se concluyó que el aumento de los niveles de parámetros glucoinsulinémicos (insulina y HOMA-IR) parece influir en el estado de la vitamina D en pacientes con enfermedad renal crónica.

Protein intake and its influence on the lipid and anthropometric profiles of patients with chronic kidney disease

ABSTRACT Introduction: Recent studies highlight Chronic Kidney Disease (CKD) as responsible for severe damage to clinical-nutritional status and for changes in the lipid profile of its patients, which, together, contribute to the increase in deaths and hospitalization time for these patients. Therefore, this study aimed to determine the protein intake and its association with the lipid and anthropometric profile of chronic renal patients. Methods: Data came from a cross-sectional survey conducted with 95 patients with CKD on dialysis treated at Renal Therapy Centers in the State of Piauí. Anthropometric variables were determined. Protein consumption was obtained by applying two 24hr dietary recalls. Lipid fractions were determined according to the calorimetric enzymatic method and specific calculations. Data were analyzed with Stata®, v.12 software (Statacorp, College Station, Texas, USA), with significance level set at p<0.05. The research received ethical approval, nº 2.527.329. Results: The final sample consisted of 95 patients, with a predominance of male participants (67.4%) and the average age of the total population was 40.8±10.7 years. There was no association between protein consumption and anthropometric variables. However, there was a significant, but negative, correlation between protein intake and total cholesterol concentrations (p= 0.017) and LDL-c (p= 0.025). Conclusion: The mean protein intake identified, 1.30±0.83 g/kg/day, despite meeting the recommendation for chronic renal patients did not appear to influence the anthropometric status, but had significant effects on specific lipid parameters of patients with CKD of this study.

RESUMEN Introducción: Estudios recientes destacan a la enfermedad renal crónica (ERC) como responsable del daño severo en el estado clínico-nutricional y de cambios en el perfil lipídico de sus pacientes, que, en conjunto, contribuyen al aumento del tiempo de hospitalización y mortalidad de estos pacientes. Por tanto, este estudio tuvo como objetivo determinar la ingesta proteica y su asociación con el perfil lipídico y antropométrico de pacientes renales crónicos. Métodos: Se analizaron los datos de la encuesta transversal realizada a 95 pacientes con ERC en diálisis tratados en Centros de Terapia Renal del Estado de Piauí. Se determinaron variables antropométricas. El consumo de proteínas se obtuvo aplicando dos encuestas de alimentación 24HR. Las fracciones lipídicas se determinaron según el método enzimático calorimétrico y cálculos específicos. Los datos se analizaron en Software Stata 12, y se adoptaron como nivel de significancia p<0.05. La investigación recibió la aprobación ética, bajo la opinión del número 2.527.329. Resultados: La muestra final estuvo conformada por 95 pacientes, con predominio de varones (67,4%) y la edad promedio de la población total fue de 40,8±10,7 años. No hubo asociación entre el consumo de proteínas y las variables antropométricas de los pacientes. Sin embargo, hubo una correlación significativa, pero negativa, entre la ingesta de proteínas y las concentraciones de CT (p= 0.017) y LDL-c (p= 0.025). Conclusión: Se concluyó que la ingesta media de proteínas identificada, 1,30±0,83 g/kg/día, a pesar de cumplir con la recomendación para pacientes renales crónicos, no pareció influir en el estado antropométrico, pero tuvo efectos significativos sobre parámetros lipídicos específicos de pacientes con ERC de este estudio.

Gut microbiota in colorectal cancer: Evidence from observational studies

ABSTRACT This study proposes to update knowledge about the relationship between microbiota and Colorectal Cancer (CRC). This is a review carried out using the methodology of the Preferred Report Item for Systematic Analysis and Meta-Analysis (PRISMA) and search for original articles, indexed in the Pubmed, Cochrane and Science Direct databases, published between 2011 and 2019, in English. Ten articles showed changes in bacterial composition and its influence on the development and progression of CRC, and only two addressed changes in the composition of fungi and their relationship with CRC. Most studies have shown that the increase in Fusobacterium nucleatum and bacteroides fragilis is strongly associated with the occurrence of CRC due to inflammatory mechanisms; and that Faecalibacterium prausnitzii is a protective factor through the production of butyrate. Additional research is recommended to assess the relationship of microorganisms with the development of CRC, with an emphasis on fungi.

RESUMEN Este estudio propone actualizar el conocimiento sobre la relación entre la microbiota y el Cancer Colorectal (CCR). Esta es una revisión realizada utilizando la metodología del Elemento de Informe Preferido para el Análisis Sistemático y el Meta-análises (PRISMA) y la búsqueda de artículos originales, indexados en las bases de datos Pubmed, Cochrane y Science Direct, publicados entre 2011 y 2019, en inglés. Diez artículos mostraron cambios en la composición bacteriana y su influencia en el desarrollo y la progresión del CCR, y solo dos abordaron los cambios en la composición de los hongos y su relación con el CCR. La mayoría de los estudios han demostrado que el aumento de Fusobacterium nucleatum y bacteroides fragilis está fuertemente asociado con la aparición de CCR debido a mecanismos inflamatorios; y que Faecalibacterium prausnitzii es un factor protector a través de la producción de butirato. Se recomienda investigación adicional para evaluar la relación de los microorganismos con el desarrollo de CCR, con énfasis en los hongos.

Association between matrix metalloproteinase-9 gene polymorphism and breast cancer in Brazilian women.

OBJECTIVE: This study aimed to determine the relationship between rs17576 (MMP-9) polymorphism and increased cancer risk in a Brazilian breast cancer cohort. METHODS: This study included 141 women (71 breast cancer patients and 70 controls without breast cancer) who donated 3 mL of their peripheral blood for genomic DNA extraction. This DNA was then genotyped using a real-time polymerase chain reaction. RESULTS: The AG (rs17576) genotype was identified in 26 (18.43%) participants in the case group and in 22 (15.60%) participants in the control group (p=0.274), while the GG genotype was identified in ten (7.09%) participants in the case group and in one (0.70%) participant in the control group (p<0.003 - OR (95% CI) 13.13 (1.73, 593.08). No significant difference in the incidence rates was observed for AG or GG rs17576 genotypes in premenopausal women, p=0.813 and p=0.556, respectively. However, in postmenopausal women, the AG genotype was shown to occur in 14 (22.5%) participants in the case group and in 4 (6.45%) participants in the control (p<0.043), while GG genotype occurred in eight (12.90%) of the individuals in the case group and in none of the individuals in the control group (p<0.006). CONCLUSION: In this study, the MMP-9 rs17576 GG polymorphic variant was shown to be significantly associated with breast cancer risk in premenopausal women, while the AG and GG genotypes were associated with increased cancer risk in postmenopausal women.

Feelings reported by adolescents after food ingestion: a comparative study / Sentimentos relatados por adolescentes após a ingestão alimentar: um estudo comparativo

INTRODUCTION: Food is closely linked with emotions in a complex relationship. The imaginary and symbolic meaning attributed to food has been little studied and the act of eating needs to be better understood. OBJECTIVE: To analyze the association of adolescents´ feelings to selected foods. METHODS: Cross-sectional study with 995 adolescents from public and private schools in Teresina, PI, Brazil. It was a Supplementary Project to the Brazilian national survey ERICA (Estudo de Riscos Cardiovasculares em Adolescentes). Adolescents had to choose one of the following feelings to selected food: well-being/satisfaction, malaise, no feeling, aversion. For the option aversion, the participant had to indicate if it was related to smell, color, appearance, or taste. Adolescents´ feelings to foods were analyzed by type of school, sex, and age range, using Pearson's chi-square (χ²) or Fisher's exact tests. RESULTS: There was significant differences regarding the type of school for the feeling to chocolate (p=0.015); vegetables (p=0.003); leafy greens (p=0.005); healthy sandwich/natural fruit juice (p≤0.001); high fat red meat (p=0.046); fruit/natural fruit juice (p≤0.001). For sex, there was significant difrerences for healthy sandwich/natural fruit juice (p=0.001); beans and rice (p=0.021) and high fat red meat (p=0.005). There was significant differences between age groups for sandwich, chips, soda and ice cream (p=0.018); pasta (p=0.047) and high fat red meat (p=0.021). Well-being predominated in almost all foods and aversion was poorly reported. CONCLUSION: The results suggest that adolescents' feelings are not directed to specific foods.

INTRODUÇÃO: O alimento está intimamente ligado com as emoções em uma relação complexa. O sentido imaginário e simbólico atribuído à alimentação tem sido pouco estudado e o ato de comer precisa ser melhor compreendido. OBJETIVO: Avaliar a associação de sentimentos dos adolescentes relacionados a alimentos selecionados. MÉTODO: Estudo transversal com 995 adolescentes de escolas públicas e privadas de Teresina, PI, Brasil. Os dados foram provenientes do Projeto Suplementar ao levantamento nacional brasileiro ERICA (Estudo de Riscos Cardiovasculares em Adolescentes). O adolescente teve que escolher um dos seguintes sentimentos para o alimento selecionado: bem-estar/satisfação, desconforto, nenhum sentimento ou aversão. Para a opção aversão, o participante deveria indicar se ela estava relacionada ao cheiro, cor, aparência ou sabor. Os sentimentos dos adolescentes em relação aos alimentos foram analisados ​​por tipo de escola, sexo e faixa etária, por meio do teste qui-quadrado de Pearson (c²) ou teste exato de Fisher. RESULTADOS: Houve diferenças significativas entre os tipos de escola para o sentimento em relação ao chocolate (p=0,015); legumes/verduras (p=0,003); folhosos (p=0,005); sanduiche/suco natural (p≤0,001); carne vermelha gordurosa (p=0,046); fruta/suco natural (p≤0,001). Para o sexo, houve diferença significativa para sanduiche/suco natural (p=0,001); arroz com feijão (p=0,021) e carne vermelha gordurosa (p=0,005). Para a faixa etária, houve diferença significativa para sanduíche, batata frita, refrigerante e sorvete (p=0,018); macarrão (p=0,047) e carne vermelha gordurosa (p=0,021). O bem-estar predominou em quase todos os alimentos e a aversão foi pouco relatada. CONCLUSÃO: Os resultados sugerem que os sentimentos dos adolescentes não estão direcionados a um alimento específico.

Antiparasitic activity of furanyl N-acylhydrazone derivatives against Trichomonas vaginalis: in vitro and in silico analyses.

BACKGROUND: Trichomonas vaginalis is the causative agent of trichomoniasis, which is one of the most common sexually transmitted diseases worldwide. Trichomoniasis has a high incidence and prevalence and is associated with serious complications such as HIV transmission and acquisition, pelvic inflammatory disease and preterm birth. Although trichomoniasis is treated with oral metronidazole (MTZ), the number of strains resistant to this drug is increasing (2.5-9.6%), leading to treatment failure. Therefore, there is an urgent need to find alternative drugs to combat this disease. METHODS: Herein, we report the in vitro and in silico analysis of 12 furanyl N-acylhydrazone derivatives (PFUR 4, a-k) against Trichomonas vaginalis. Trichomonas vaginalis ATCC 30236 isolate was treated with seven concentrations of these compounds to determine the minimum inhibitory concentration (MIC) and 50% inhibitory concentration (IC50). In addition, compounds that displayed anti-T. vaginalis activity were analyzed using thiobarbituric acid reactive substances (TBARS) assay and molecular docking. Cytotoxicity analysis was also performed in CHO-K1 cells. RESULTS: The compounds PFUR 4a and 4b, at 6.25 µM, induced complete parasite death after 24 h of exposure with IC50 of 1.69 µM and 1.98 µM, respectively. The results showed that lipid peroxidation is not involved in parasite death. Molecular docking studies predicted strong interactions of PFUR 4a and 4b with T. vaginalis enzymes, purine nucleoside phosphorylase, and lactate dehydrogenase, while only PFUR 4b interacted in silico with thioredoxin reductase and methionine gamma-lyase. PFUR 4a and 4b led to a growth inhibition (< 20%) in CHO-K1 cells that was comparable to the drug of choice, with a promising selectivity index (> 7.4). CONCLUSIONS: Our results showed that PFUR 4a and 4b are promising molecules that can be used for the development of new trichomonacidal agents for T. vaginalis.

Response of preantral follicles exposed to quinoxaline: A new compound with anticancer potential.

The culture of preantral follicles as an in vitro model to evaluate the toxicity of new anticancer drug has being established. Therefore, the aim of this study was to evaluate the effect of quinoxaline derivative the 2 2- (XYZC 6H 3 -CH=N-NH)-quinoxaline, 1 (QX) on caprine preantral follicles. We evaluate the follicular morphology and activation, proliferation and apoptosis of granulosa cells and finally the protein (ABCB1) and genes expression (cyclin/Cdks), respectively involved in multidrug resistance and cell cycle progression. Ovarian fragments containing primordial and developing follicles were exposed (in vitro culture) to different concentrations of QX (QX1.5, QX3.0 or QX6.0 µM/mL) during 6 days. To evaluate the effect of QX, the ovarian tissue was exposed to Paclitaxel 0.1 µg/mL (PTX - negative control) or in culture media without QX (MEM). At the end of exposure time, we realized that the QX (all concentrations) increased (P < .05) the normal morphology of preantral follicles compared to control (not treated ovarian tissue) or MEM. However, QX6.0 showed a enhanced (P < .05) on follicular activation (burnout) and apoptosis than QX1.5 and QX3.0. Expression of ABCB1 was similar between QX1.5 and QX6.0 and both were lower than control, MEM and PTX. Interestingly, the apoptosis rate in QX3.0 was similar to control and MEM and lower then QX1.5; QX6.0 and PTX. We conclude that quinoxaline may be a promising chemotherapeutic agent, however, other concentrations within a defined range (2-5.5 µM) could be widely investigated.

Synthesis of PJOV56, a new quinoxalinyl-hydrazone derivative able to induce autophagy and apoptosis in colorectal cancer cells, and related compounds.

Quinoxaline derivatives are reported as antineoplastic agents against a variety of human cancer cell lines, with some compounds being submitted to clinical trials. In this work, we report the synthesis, characterization and cytotoxicity potential of a new series of quinoxalinyl-hydrazones. The most cytotoxic compound was (E)-2-[2-(2-pyridin-2-ylmethylene)hydrazinyl]quinoxaline (PJOV56) that presented a time-dependent effect against HCT-116 cells. After 48 h of incubation, PJOV56 was able to induce autophagy and apoptosis of HCT-116 cells, mediated by upregulation of Beclin 1, upregulation of LC3A/B II and activation of caspase 7. Apoptosis was induced along with G0/G1 cell cycle arrest at the highest concentration of PJOV56 (6.0 µM). Thus, PJOV56 showed a dose-dependent mode of action related to induction of autophagy and apoptosis in HCT-116 cells.

Association between matrix metalloproteinase-9 gene polymorphism and breast cancer in Brazilian women

OBJECTIVE: This study aimed to determine the relationship between rs17576 (MMP-9) polymorphism and increased cancer risk in a Brazilian breast cancer cohort. METHODS: This study included 141 women (71 breast cancer patients and 70 controls without breast cancer) who donated 3 mL of their peripheral blood for genomic DNA extraction. This DNA was then genotyped using a real-time polymerase chain reaction. RESULTS: The AG (rs17576) genotype was identified in 26 (18.43%) participants in the case group and in 22 (15.60%) participants in the control group (p=0.274), while the GG genotype was identified in ten (7.09%) participants in the case group and in one (0.70%) participant in the control group (p<0.003 - OR (95% CI) 13.13 (1.73, 593.08). No significant difference in the incidence rates was observed for AG or GG rs17576 genotypes in premenopausal women, p=0.813 and p=0.556, respectively. However, in postmenopausal women, the AG genotype was shown to occur in 14 (22.5%) participants in the case group and in 4 (6.45%) participants in the control (p<0.043), while GG genotype occurred in eight (12.90%) of the individuals in the case group and in none of the individuals in the control group (p<0.006). CONCLUSION: In this study, the MMP-9 rs17576 GG polymorphic variant was shown to be significantly associated with breast cancer risk in premenopausal women, while the AG and GG genotypes were associated with increased cancer risk in postmenopausal women.

4H-1,3-Benzothiazin-4-one a Promising Class Against MDR/XDR-TB.

Nowadays, tuberculosis (TB) is an important global public health problem, being responsible for millions of TB-related deaths worldwide. Due to the increased number of cases and resistance of Mycobacterium tuberculosis to all drugs used for the treatment of this disease, we desperately need new drugs and strategies that could reduce treatment time with fewer side effects, reduced cost and highly active drugs against resistant strains and latent disease. Considering that, 4H-1,3-benzothiazin-4-one is a promising class of antimycobacterial agents in special against TB-resistant strains being the aim of this review the discussion of different aspects of this chemical class such as synthesis, mechanism of action, medicinal chemistry and combination with other drugs.

Análise das características de indivíduos com sequelas de traumatismo cranioencefálico (TCE) em um centro de referência em reabilitação (características de TCE) / Analysis of the characteristics of individuals with traumatic brain injury (TBI) in a rehabilitation reference center (TBI characteristics)

INTRODUÇÃO: O Traumatismo Cranioencefálico (TCE)é definido como uma alteração na função encefálica, devido a uma causa externa, ou seja, algum trauma físico de origem externa e que leva à morbimortalidade e incapacidades em todo o mundo. OBJETIVO: Analisar as características (aspectos sociodemográficos, causa do TCE; custos com saúde) de indivíduos com sequelas de traumatismo cranioencefálico em um centro de referência em reabilitação. METODOLOGIA: Estudo de natureza descritiva,retrospectiva e quantitativa no período de janeiro de 2009 a dezembro de 2013, por meio de análise documental, resultando em uma amostra final de 88 prontuários analisados. Foram incluídos indivíduos de ambos os sexos, com idade igual ou superior a dois anos de vida. RESULTADOS: Dos indivíduos com sequelas de TCE, 86,36% eram do sexo masculino, com idade entre 18 e 59 anos (80,68%), apresentando ensino médio completo (26,14%), de cor parda (52,27%) e com renda familiar entre um e cinco salários mínimos (60,23%). A causa mais frequente de TCE foi o acidente motociclístico (68,18%). Não houve diferença estatística entre tipos de causa de TCE e custos com saúde. CONCLUSÃO: O presente estudo demonstrou que grande parte dos indivíduos eram homens jovens e vítimas de acidente motociclístico.(AU)

INTRODUCTION: traumatic brain injury (TBI) is defined as a change in brain function due to an external cause, that is, some external physical trauma that leads to morbidity and mortality, disabilities and mortality worldwide. OBJECTIVE: To analyze the characteristics (Socio-demographic aspects; causes of TBI; Health costs) of individuals with traumatic brain injury sequelae in a referral center for rehabilitation. METHODOLOGY: descriptive, retrospective and quantitative study from January 2009 to December 2013, Through documentary analysis, resulting in a final sample of 88 analyzed medical records. Individuals of both sexes, aged 2 years or more, were included. RESULTS: Of the individuals with TBI sequelae, 86.36% were male, aged between 18 and 59 years (80.68%), with completed secondary education (26.14%), mulatto (52.27 %) and family income between 1 and 5 minimum wages (60.23%). The most frequent cause of TBI were motorcycle accidents (68.18%). There was no statistical difference between types of cause of TBI and health care costs. CONCLUSION: This study showed that most individuals were young men, motorcycle accident victims and who lost work capacity. (AU)

Synthesis, Biological Activity, and Mechanism of Action of 2-Pyrazyl and Pyridylhydrazone Derivatives, New Classes of Antileishmanial Agents.

In this work, we report the antileishmanial activity of 23 compounds based on 2-pyrazyl and 2-pyridylhydrazone derivatives. The compounds were tested against the promastigotes of Leishmania amazonensis and L. braziliensis, murine macrophages, and intracellular L. amazonensis amastigotes. The most potent antileishmanial compound was selected for investigation into its mechanism of action. Among the evaluated compounds, five derivatives [(E)-3-((2-(pyridin-2-yl)hydrazono)methyl)benzene-1,2-diol (2 b), (E)-4-((2-(pyridin-2-yl)hydrazono)methyl)benzene-1,3-diol (2 c), (E)-4-nitro-2-((2-(pyrazin-2-yl)hydrazono)methyl)phenol (2 s), (E)-2-(2-(pyridin-2-ylmethylene)hydrazinyl)pyrazine (2 u), and (E)-2-(2-((5-nitrofuran-2-yl)methylene)hydrazinyl)pyrazine (2 v)] exhibited significant activity against L. amazonensis amastigote forms, with IC50 values below 20 µm. The majority of the compounds did not show any toxic effect on murine macrophages. Preliminary studies on the mode of action of members of this hydrazine-derived series indicate that the accumulation of reactive oxygen species (ROS) and disruption of parasite mitochondrial function are important for the pharmacological effect on L. amazonensis promastigotes.

UNESCO, mulheres e biopoder no Brasil: alguns apontamentos / UNESCO, notes about women and biopower in Brazil

RESUMO O texto interroga as práticas da Organização das Nações Unidas para a Educação, a Ciência e a Cultura (UNESCO) frente às mulheres brasileiras e opera uma analítica dos discursos racistas e utilitaristas que promovem disciplina e regulações securitárias com base na educação e cultura. A preocupação com os direitos violados nos países chamados em desenvolvimento pela UNESCO, e seus designados parceiros se, de um lado, constitui um importante anteparo às violências, de outro, cria condições para práticas disciplinares e securitárias de base neoliberal e mundializada que devem ser problematizadas. As mulheres entram na agenda da UNESCO sob o ângulo da segurança ameaçada e da segurança a realizar traduzido em políticas públicas dirigidas a elas e a seus filhos.(AU)

ABSTRACT This article interrogates the practices of the United Nations Educational, Scientific and Cultural Organization (UNESCO) towards brazilian women. Elaborates the Foucault´s analytics of racists and utilitarian discourses that promote discipline and securitarian regulations through education and culture. The concern with the violated rights in developing countries named by UNESCO and its designated partners, constitutes an important bulkhead to violence. However, guidelines and practices recommended by this multilateral Organization although potencially capable of producing specific improvements in the lives of some women, update neoliberal biopolitics justified by humanitarian and universalizing principles. Women are on UNESCO's agenda from the perspective of threatened security and security, translated into public policies aimed at them and their children.(AU)

Práticas de esporte, lazer e cultura do UNICEF / Practice of sport, leisure and culture as UNICEF

Resumo O artigo presente visa problematizar as práticas do Fundo das Nações Unidas para a Infância (UNICEF), em especial, as dirigidas às crianças e adolescentes pobres por meio de atividades de esportes, lazer e cultura como maneira de forjar segurança, saúde e prevenir situações de violência Esta agência atribui a este grupo social supostas situações de riscos, vulnerabilidades, carências e privações derivadas do pertencimento desta infância e adolescência às famílias pobres, não escolarizadas e pela moradia em comunidades na periferia das cidades. Os modos de vida deste segmento da população são desqualificados e o UNICEF se apresenta como uma agência transformadora destas condições. Os projetos deste organismo multilateral oscilam entre o adestramento disciplinar produtor de docilidade e utilidade ao governo da vida para criar liberdade com segurança por meio de políticas compensatórias, recomendadas como receitas e oferecidas como favores, deixando de lado o campo dos direitos em detrimento da economia política neoliberal.(AU)

Abstract The present article aimes to discuss the practices of the United Nations Fund for Children (UNICEF), in particular those targeted at poor children and adolescents through sports activities, leisure and culture as a way of forging safety, health and prevent this avency situations of violence attributed to this social group alleged situations of risks, vulnerabilities, needs and deprivation derived from this childhood and adolescence belonging to poor families, illiterate and living in communities on the outskirts of towns. The way of life of this population segment are disqualified and UNICEF presents itself as an agency transformins these conditions. Projects of this multilateral organization oscillate between the dressage discipline producer of docility and usefulness to the government to create freedom of life safely through compensatory policies, as recommended recipes and offered as favors, dropping the field to the detriment of the rights of political economy neoliberal.(AU)