Geissoschizoline, a promising alkaloid for Alzheimer's disease: Inhibition of human cholinesterases, anti-inflammatory effects and molecular docking.

Due to the lack of effective pharmacotherapy options to treats Alzheimer's disease, new strategies have been approached in the search for multi-target molecules as therapeutic options. In this work, four indole alkaloids, geissoschizoline, geissoschizone, geissospermine, and 3',4',5',6'-tetradehydrogeissospermine were isolated from Geissospermum vellosii (Pao pereira) and evaluated for their anticholinesterase activities. While geissospermine inhibited only butyrylcholinesterase (BChE), the other alkaloids behaved as non-selective inhibitors of acetylcholinesterase (AChE) and BChE. In cell viability tests, only geissoschizoline was not cytotoxic. Therefore, geissoschizoline actions were also evaluated in human cholinesterases, where it was twice as potent inhibitor of hBChE (IC50 = 10.21 ± 0.01 µM) than hAChE (IC50 = 20.40 ± 0.93 µM). On enzyme kinetic studies, geissoschizoline presented a mixed-type inhibition mechanism for both enzymes. Molecular docking studies pointed interactions of geissoschizoline with active site and peripheral anionic site of hAChE and hBChE, indicating a dual site inhibitor profile. Moreover, geissoschizoline also played a promising anti-inflammatory role, reducing microglial release of NO and TNF-α at a concentration (1 µM) ten and twenty times lower than the IC50 values of hBChE and hAChE inhibition, respectively. These actions give geissoschizoline a strong neuroprotective character. In addition, the ability to inhibit hAChE and hBChE, with approximate inhibitory potencies, accredits this alkaloid for therapeutic use in the moderate to severe phase of AD. Thus, geissoschizoline emerges as a possible multi-target prototype that can be very useful in preventing neurodegeneration and restore neurotransmission.

NK1 receptor mediates cerebral cellular and extracellular morphological changes during the LPS-induced febrile response.

Fever elicited by bacterial lypopolyssacharide (LPS) is mediated by pro-inflammatory cytokines, which activate central mediators and regulate the hypothalamic temperature setpoint. This response is often accompanied by morphological changes involving the extracellular matrix, neurons and glial cells, with significant health impacts. The NK1 receptor is involved in the febrile response induced by LPS but its effects over the extracellular matrix in the context of neuroinflammation remain unknown. The present work aims to clarify the extracellular changes associated with NK1 signaling in LPS-induced fever. Male Wistar rats were exposed to LPS intraperitoneally. Experimental groups were pre-treated intracerebroventricularly with the NK1 selective inhibitor SR140333B or saline. Histological changes involving the brain extracellular matrix were evaluated using hematoxylin and eosin, Mason's trichrome, picrosirius, alcian blue, periodic acid Schiff's stains. The expression of matrix metalloproteinase 9 (MMP9) was studied using confocal microscopy. Fever was accompanied by edema, perivascular lymphoplamacytic and neutrophylic infiltration, spongiosis and MMP9 overexpression. SR140333B significantly reduced LPS-induced fever (p < 0.0001), MMP9 overexpression (p < 0.01) and associated histological changes. These results contribute to characterize cerebral extracellular matrix changes associated with LPS-induced fever. Overall, the present work supports a role for NK1 receptor in these neuroinflammatory changes, involving MMP9 overexpression, edema and leukocytic infiltration.

Effects of babassu nut oil on ischemia/reperfusion-induced leukocyte adhesion and macromolecular leakage in the microcirculation: observation in the hamster cheek pouch.

BACKGROUND: The babassu palm tree is native to Brazil and is most densely distributed in the Cocais region of the state of Maranhão, in northeastern Brazil. In addition to the industrial use of refined babassu oil, the milk, the unrefined oil and the nuts in natura are used by families from several communities of African descendants as one of the principal sources of food energy. The objective of this study was to evaluate the effects of babassu oil on microvascular permeability and leukocyte-endothelial interactions induced by ischemia/reperfusion using the hamster cheek pouch microcirculation as experimental model. METHODS: Twice a day for 14 days, male hamsters received unrefined babassu oil (0.02 ml/dose [BO-2 group], 0.06 ml/dose [BO-6 group], 0.18 ml/dose [BO-18 group]) or mineral oil (0.18 ml/dose [MO group]). Observations were made in the cheek pouch and macromolecular permeability increase induced by ischemia/reperfusion (I/R) or topical application of histamine, as well as leukocyte-endothelial interaction after I/R were evaluated. RESULTS: The mean value of I/R-induced microvascular leakage, determined during reperfusion, was significantly lower in the BO-6 and BO-18 groups than in the MO one (P < 0.001). In addition, histamine-induced increase of microvascular permeability was significantly less pronounced in BO groups compared to MO one. No significant differences among groups in terms of leukocyte adhesion, concentrations of tumor necrosis factor alpha, interleukin 1, and interleukin 6 were found. CONCLUSIONS: Our findings suggest that unrefined babassu oil reduced microvascular leakage and protected against histamine-induced effects in postcapillary venules and highlights that these almost unexploited nut and its oil might be secure sources of food energy.

Elevated leptin levels in healthy climacteric women from Northeastern Brazil: an effect of age or adiposity?

OBJECTIVE: Climacterium is associated with elevated leptin levels and increased risk of cardiovascular disorders. Conflicting data diverge on whether high leptin levels in climacterium reflect increasing adipose mass or, at least partially, age-related hormonal changes. This study addresses this issue in women from a Brazilian state with a low human development index. SUBJECTS AND METHODS: A case-control study was conducted, enrolling 136 women from the state of Maranhão, 52 (38.2%) climacteric and 84 (61.8%) non-climacteric. Biometric, biochemical, hormonal and immunological parameters were analyzed. RESULTS: Climacteric women showed a moderately increased waist/hip ratio (0.894 versus 0.834, p < 0.05), sustained body mass index (27.46 versus 28.68, p > 0.05) increased leptin levels (9.59 versus 7.13, p < 0.05) and no evidence of metabolic syndrome. No other parameters were altered. The climacteric cohort didn't show significant body fat gains but displayed a typical age-related redistribution of adipose tissue. Even so, leptin levels were significantly elevated compared with non-climacteric women. CONCLUSIONS: Altogether, these data support the hypothesis that leptin is elevated, at least partially, as a function of age and climacterium and is not necessarily correlated with metabolic dysfunction and systemic inflammation. Further studies are needed to evaluate the impact of higher leptin levels on postmenopausal women. Arch Endocrinol Metab. 2020;64(3):276-81.

Association between pacifier use and bottle-feeding and unfavorable behaviors during breastfeeding.

OBJECTIVE: To investigate the association between pacifier use and bottle-feeding and unfavorable behaviors during breastfeeding. METHOD: A cross-sectional study was conducted with 427 babies/mothers. Socio-demographic, perinatal data, and information about the use of artificial nipples (pacifier and/or bottle) were collected through a questionnaire. The breastfeeding aspects regarding position, affectivity, sucking behavior, baby responses, and breast anatomy were evaluated through observation during breastfeeding. The chi-squared test and the multiple linear regression analysis were used to investigate the association between the variables. RESULTS: The aspects of breastfeeding that showed higher percentages of the category "poor" were sucking behavior (22.5%) and position (22.2%). The group of infants who used pacifiers and/or bottle showed higher percentages in the poor and fair categories when compared with the good category for all five breastfeeding aspects evaluated (p<0.001). The linear regression analysis revealed that the increase in the number of unfavorable behaviors regarding position, affectivity, sucking behavior, and baby responses were independently associated with both pacifier and bottle use (ß positive, p<0.05), while breast anatomy was independently associated only with bottle use. CONCLUSION: The findings suggest that the use of pacifiers and/or bottle-feeding may be associated with unfavorable behaviors during breastfeeding, especially the use of bottle-feeding.

Human papillomavirus genotypes 68 and 58 are the most prevalent genotypes in women from quilombo communities in the state of Maranhão, Brazil.

OBJECTIVES: To determine the frequency of human papillomavirus (HPV) types and behavioral characteristics related to cytological abnormalities in women descendants of slaves, who live in isolated communities known as quilombos in the state of Maranhão, Brazil. METHODS: Cervicovaginal specimens of 353 women were analyzed by conventional cytology and genotyping. HPV detection and genotyping was performed using a linear array HPV genotyping test kit. Behavioral factors and their association with cytological abnormalities were analyzed, as well as the association between cytological abnormalities and HPV infection. RESULTS: The frequency of HPV infection was 13%, and infection with high-risk HPV types was more frequent than with low-risk types (10.2% vs. 2.8%). The most prevalent genotypes were HPV 68 (3.1%) and HPV 58 (2.6%). HPV-positive women were 6.5 times more likely than HPV-negative women to be diagnosed with cytological abnormalities. There was a significant association between HPV infection and the presence of cytological abnormalities in women 31-40 years of age and in women 51-60 years of age. CONCLUSIONS: A distinct profile of high-risk HPV genotypes was detected, with predominance of types 68 and 58. It is possible that the results of the present study are due to specific characteristics of the population, which is geographically isolated and maintains conservative sexual habits.

Cytotoxic analysis and chemical characterization of fractions of the hydroalcoholic extract of the Euterpe oleracea Mart. seed in the MCF-7 cell line.

OBJECTIVES: To analyse the antineoplastic activity of fractions derived from the hydroalcoholic extract of Euterpe oleracea Mart. seed in the MCF-7 cell line and to identify the compounds responsible for the antineoplastic action. METHODS: Cells were treated with 10, 20, 40 and 60 µg/ml with the hexane, chloroform and ethyl acetate fraction (EAF) of the hydroalcoholic extract of açaí seed, for 24 and 48 h. After treatment, cell viability was measured using MTT assay and cell death was assessed using the Annexin-Pi assay. The most cytotoxic fraction under study was analysed by mass spectrometry using an electrospray ionization source and a cyclotron analyser coupled to a Fourier transform. Data were analysed statistically by analysis of variance (ANOVA) or by Student's t-test, where appropriate. KEY FINDINGS: All fractions caused significant reduction in the cell viability, but the EAF was the most cytotoxic (P < 0.001). It was observed the absence of significant annexin staining but increase Pi staining (P < 0.001). The EAF is composed of epicatechin, proanthocyanidin A2 and trimeric and tetrameric procyanidins. CONCLUSIONS: In this study, we demonstrated that EAF was the most effective fraction in reducing cell viability and causing necroptosis in the MCF-7 cell.

Elevated leptin levels in healthy climacteric women from Northeastern Brazil: an effect of age or adiposity?

ABSTRACT Objective Climacterium is associated with elevated leptin levels and increased risk of cardiovascular disorders. Conflicting data diverge on whether high leptin levels in climacterium reflect increasing adipose mass or, at least partially, age-related hormonal changes. This study addresses this issue in women from a Brazilian state with a low human development index. Subjects and methods A case-control study was conducted, enrolling 136 women from the state of Maranhão, 52 (38.2%) climacteric and 84 (61.8%) non-climacteric. Biometric, biochemical, hormonal and immunological parameters were analyzed. Results Climacteric women showed a moderately increased waist/hip ratio (0.894 versus 0.834, p < 0.05), sustained body mass index (27.46 versus 28.68, p > 0.05) increased leptin levels (9.59 versus 7.13, p < 0.05) and no evidence of metabolic syndrome. No other parameters were altered. The climacteric cohort didn't show significant body fat gains but displayed a typical age-related redistribution of adipose tissue. Even so, leptin levels were significantly elevated compared with non-climacteric women. Conclusions Altogether, these data support the hypothesis that leptin is elevated, at least partially, as a function of age and climacterium and is not necessarily correlated with metabolic dysfunction and systemic inflammation. Further studies are needed to evaluate the impact of higher leptin levels on postmenopausal women. Arch Endocrinol Metab. 2020;64(3):276-81

Association between pacifier use and bottle-feeding and unfavorable behaviors during breastfeeding / Associação entre uso de chupeta e mamadeira e comportamentos desfavoráveis à amamentação durante as mamadas

Abstract Objective: To investigate the association between pacifier use and bottle-feeding and unfavorable behaviors during breastfeeding. Method: A cross-sectional study was conducted with 427 babies/mothers. Socio-demographic, perinatal data, and information about the use of artificial nipples (pacifier and/or bottle) were collected through a questionnaire. The breastfeeding aspects regarding position, affectivity, sucking behavior, baby responses, and breast anatomy were evaluated through observation during breastfeeding. The chi-squared test and the multiple linear regression analysis were used to investigate the association between the variables. Results: The aspects of breastfeeding that showed higher percentages of the category "poor" were sucking behavior (22.5%) and position (22.2%). The group of infants who used pacifiers and/or bottle showed higher percentages in the poor and fair categories when compared with the good category for all five breastfeeding aspects evaluated (p < 0.001). The linear regression analysis revealed that the increase in the number of unfavorable behaviors regarding position, affectivity, sucking behavior, and baby responses were independently associated with both pacifier and bottle use (β positive, p < 0.05), while breast anatomy was independently associated only with bottle use. Conclusion: The findings suggest that the use of pacifiers and/or bottle-feeding may be associated with unfavorable behaviors during breastfeeding, especially the use of bottle-feeding.

Resumo Objetivo: Investigar a associação entre uso de chupeta e mamadeira e comportamentos desfavoráveis à amamentação durante as mamadas. Métodos: Um estudo transversal foi conduzido com 427 bebês/mães. Foram coletados dados sociodemográficos, perinatais e sobre o uso de bicos artificiais (chupeta e/ou mamadeira) através de questionário. Os aspectos de amamentação referentes à posição, afetividade, adequação da sucção, respostas do bebê e anatomia das mamas foram avaliados através da observação durante a mamada. O teste qui-quadrado e a análise de regressão linear múltipla foram usados para investigar associação entre as variáveis. Resultados: Os aspectos de amamentação que apresentaram percentuais mais elevados da categoria ruim foram a adequação da sucção (22,5%) e posição (22,2%). O grupo de bebês que usavam chupeta e/ou mamadeira apresentou percentuais mais elevados nas categorias ruim e regular quando comparados com a categoria bom para todos os cinco aspectos da amamentação avaliados (p < 0,001). A análise de regressão linear revelou que o incremento do número de comportamentos desfavoráveis referentes à posição, afetividade, adequação da sucção e respostas do bebê estavam associados de forma independente tanto ao uso de chupeta quanto ao uso de mamadeira (β positivo, p < 0,05), enquanto que anatomia das mamas estava associado de forma independente apenas com o uso de mamadeira. Conclusão: Os achados sugerem que o uso de chupeta e/ou mamadeira pode estar associado a comportamentos desfavoráveis durante amamentação, em especial o uso de mamadeira.

Doença de Chagas Congênita em Goiânia-Go, Brasil / Congenit Chagas'disease

Trata-se de relato de caso de Doença de Chagas congênita constatado em criança de 4 meses de idade, sexo masculino, procedente de Goiânia-Go, nascimento - parto prematuro que evoluiu para o óbito, tendo sido esclarecido o diagnóstico através de dados de necrópsia

Inquérito sorológico sobre Doença de Chagas e Leishmaniose em adultos residentes na Ilha de Säo Luís-MA - Brasil / Serologic evaluation of Chagas'disease and Leishmaniosis in adult population of Säo Luís-MA - Brazil

De 373 indivíduos de faixa etária entre 17 e 56 anos, residentes na Ilha de Säo Luís - Maranhäo, Brasil foram coletadas amostras de soros aleatoriamente, onde evidenciou-se 17 (4,5 pôr cento reagentes para Doenças de Chagas e 17 (4,5 pôr cento) e 4 (1 pôr cento) reagentes respectivamente para Doenças de Chagas e Leishmaniose pela reaçäo de imunofluorescência indireta (IFI). Discute-se a importância epidemiológica dos resultados obtidos

Toxoplasmose na Ilha de Säo Luís - Estado do Maranhäo - Brasil / Toxoplasmosis in Säo Luís - Maranhäo State. Brazil

Realizou-se estudo da produçäo de anticorpos para toxoplasmose em 373 amostras de soro coletadas aleatoriamente de doadores de sangue de um Banco de Sangue localizado na Ilha de Säo Luís - Maranhäo, através da reaçäo de imunofluorescência indireta. Verificou-se 118 (31,6 pôr cento) amostras com títulos positivos ò 1:32, para toxoplasmose. Discute-se aspectos imunodiagnósticos, epidemiológicos e sanitários com ênfase à realizaçäo de inquérito regional

Aspectos epidemiológicos determinantes na manutençäo da leishmaniose visceral no estado do Maranhäo - Brasil / The epidemiological determinant aspects in the maintenance of visceral leishmaniasis in the state of Maranhäo, Brazil

Analisou-se o comportamento da leishmaniose visceral (LV) no Estado do Maranhao-Brasil, no período de 1982 a 1993. A enfermidade vem ocorrendo predominantemente na Ilha de Sao Luís-MA em áreas periurbanas, destacando, no período epidêmico, a capital Sao Luís como principal área endêmica. A maior freqüênciade casos ocorreu em 1993, apesar do uso de inseticidas e controle dos caes. Houve predomínio na faixa etária de 0 a 4 anos de idade com 58,4 por cento dos casos. Nem a doença humana nem o índice pluviométrico apresentaram variaçoes sazonais significativas entretanto estiveram moderadamente correlacionados, havendo quase sempre elevaçao do número de casos após o período de maior precipitaçao chuvosa. A partir deste estudo, poderao ser levantadas questoes para o controle mais eficaz, consoante à urbanizaçao da doença, aliada aos fatores da dinâmica de trasmissao em áreas endêmicas do Estado.