Subacute exposure to Roundup® changes steroidogenesis and gene expression of the glutathione-glutaredoxin system in rat ovaries: Implications for ovarian toxicity of this glyphosate-based herbicide.

Studies have indicated that glyphosate induces endocrine disruption and may adversely affect the male reproductive system. However, evidence of its effects on ovarian function is poorly understood so far, making further studies necessary on the mechanisms of the glyphosate toxicity in the female reproductive system. The aim of this work was to evaluate the effect of a subacute exposure (28 days) to the glyphosate-based formulation Roundup® (1.05, 10.5 and 105 µg/kg b.w. of glyphosate) on steroidogenesis, oxidative stress, systems involved in cell redox control and histopathological parameters in rat ovaries. Hence we quantify plasma estradiol and progesterone by chemiluminescence; non-protein thiol levels, TBARS, superoxide dismutase and catalase activity by spectrophotometry; gene expression of steroidogenic enzymes and redox systems by real-time PCR; and ovarian follicles by optical microscopy. Our results demonstrated that oral exposure increased progesterone levels and the mRNA expression of 3ß-hydroxysteroid dehydrogenase. Histopathological analysis revealed a decrease in the number of primary follicles and an increase in the number of corpus luteum in rats exposed to Roundup®. An imbalance of the oxidative status was also evidenced by decreasing the catalase activity at all groups exposed to the herbicide. Increased lipid peroxidation and gene expression of glutarredoxin and decreased of glutathione reductase were also observed. Our results indicate that Roundup® causes endocrine disruption of hormones related to female fertility and reproduction and changes the oxidative status by altering antioxidant activity, inducing lipid peroxidation, as well as changing the gene expression of the glutathione-glutarredoxin system in rat ovaries.

Análise do consumo de psicofármacos por usuários da Atenção Primária à Saúde / Analysis of the consumption of psychotropic drugs by users of Primary Health Care

O elevado consumo de psicofármacos na Atenção Primária à Saúde tem sido motivo de preocupação. O objetivo deste estudo foi investigar o perfil desses usuários e analisar a correlação sociodemográfica e individual de cada medicamento consumido. Trata-se de pesquisa quantitativa, envolvendo 603 usuários que retiraram psicofármacos na farmácia de uma Unidade Básica de Saúde. Realizou-se a coleta dos dados em 2020 no sistema da farmácia e dos cadastros dos usuários. Analisou-se a correlação sociodemográfica e individual de cada psicofármaco, além das interações medicamentosas entre as combinações farmacológicas identificadas. A idade média dos participantes foi de 55 anos, com prevalência de mulheres (65,8%), casadas (72,5%) e aposentadas (44,3%); foram utilizados 11 diferentes psicofármacos e identificaram-se 38 associações entre eles, e todas geram interação. Prevaleceu o consumo de antidepressivos e benzodiazepínicos. Concluiu-se que, ao longo do período estudado, aumentou o número de usuários de psicofármacos e também o quantitativo dispensado dessas medicações.

High consumption of psychotropic drugs in Primary Health Care has been a matter of concern. This study aimed to investigate the profile of users of psychotropic drugs in Primary Health Care, as well as analyzed the sociodemographic and individual correlation of each psychotropic drug consumed. Quantitative research, involving 603 users of psychotropic drugs that withdrew these psychotropic drugs in the Primary Care Unit drugstore. Data collection took place in 2020 through the pharmacy's computerized system and user records. Sociodemographic and individual correlation analysis of each psychotropic drug was performed, as well as the analysis of drug interactions between identified pharmacological combinations. Age mean of participants was of 55 years old, with prevalence of married (72,5%) and retired (44,3%) women (65,8); 11 different psychotropic drugs were used and 38 different association between these drugs were identified, of them, all generate a level of interaction. There was a prevalence of consumption of antidepressants and benzodiazepines. It was concluded that over the period studied, there was an increase in the number of users of psychotropic drugs and also in the quantity dispensed with these medications.

Fluxograma multiprofissional para atendimento de intoxicações agudas por agrotóxicos na atenção primária à saúde / Diagrama de flujo multiprofesional para la atención del envenenamiento agudo por agrotoxicos en la atención primaria de salud / Multiprofessional flowchart for care of acute intoxications by agrotoxic in primary health care

Resumo Objetivo construir e validar um fluxograma de atendimento multiprofissional para casos de intoxicações agudas por agrotóxicos na Atenção Primária à Saúde. Método estudo metodológico, realizado em duas etapas: produção-construção e validação do conteúdo. A construção do fluxograma foi realizada com base na literatura, abordando a temática agrotóxicos, e entrevista coletiva envolvendo 19 profissionais da Atenção Primária à Saúde de um município catarinense, em dezembro de 2018. O processo de validação foi realizado por meio de questionário do Google Forms, por sete juízes. Utilizou-se o Percentual de Concordância e o Índice de Validade de Conteúdo. Resultados o fluxograma apresentou validade de conteúdo global igual a 0,97, tendo os oito primeiros itens apresentado valor máximo e aprovação pelo Conselho Municipal de Saúde. Conclusão o fluxograma passou a ser utilizado como instrumento tecnológico que orienta e qualifica os atendimentos dos casos de intoxicações agudas por agrotóxicos. Implicações para a prática a utilização do fluxograma na assistência ao paciente, suspeito ou intoxicado por agrotóxico, constitui-se como ferramenta de gestão do cuidado, permitindo que a equipe de saúde atue de forma harmônica, além de que as ações da assistência sejam sistematizadas e, consequentemente, se obtenha qualidade do serviço prestado.

Resumen Objetivo construir y validar un diagrama de flujo de atención multiprofesional para casos de intoxicación aguda por plaguicidas en Atención Primaria de Salud. Método estudio metodológico, realizado en dos etapas: producción-construcción y validación de contenido. La construcción del diagrama de flujo se llevó a cabo a partir de la literatura que aborda el tema plaguicidas, y una entrevista colectiva a 19 profesionales de Atención Primaria de Salud de un municipio de Santa Catarina, en diciembre de 2018. El proceso de validación se realizó a través de un cuestionario de Google Forms, por siete jueces. Se utilizaron el porcentaje de acuerdo y el índice de validez de contenido. Resultados el diagrama de flujo tuvo una validez de contenido global de 0.97, mostrando los primeros ocho ítems el valor máximo y la aprobación del Consejo Municipal de Salud. Conclusión el diagrama de flujo pasó a ser utilizado como un instrumento tecnológico que orienta y califica la atención en casos de intoxicación aguda por plaguicidas. Implicaciones para la Practica el uso del diagrama de flujo en el cuidado de pacientes sospechosos o intoxicados por pesticidas es una herramienta de gestión de la atención, permitir que el equipo de salud actúe en armonía, que se sistematicen las acciones asistenciales y consecuentemente se obtiene calidad de servicio.

Abstract Objective To construct and validate a multiprofessional care flowchart for acute pesticide intoxication cases in Primary Health Care. Method This is a methodological study, carried out in two stages: production-construction and content validation. The flowchart construction was carried out based on scientific literature, addressing the topic of pesticides, and a press conference involving 19 Primary Health Care professionals in a municipality in Santa Catarina, in December 2018. The validation process was carried out through a Google Forms questionnaire, by seven judges. The Percentage of Agreement and the Content Validity Index were used. Results The flowchart had a global content validity of 0.97, with the first eight items having a maximum value and approval by the Municipal Health Council. Conclusion The flowchart started to be used as a technological tool that guides and qualifies the care of acute pesticide intoxications cases. Implications for practice The flowchart use in care for patients suspected or intoxicated by pesticides is a care management tool, allowing the health team to act harmoniously, in addition to assistance actions systematized and, consequently, obtain the quality of the service provided.

Strategies for changing the nursing preceptorship activity in Primary Health Care.

OBJECTIVES: to present actions to qualify preceptorship and teaching-health service integration to strengthen nursing training in PHC internship. METHODS: qualitative research, developed through the Appreciative Inquiry Research carried out with eight nurses, both from the fields of teaching and health service, within Primary Health Care. The production and documentation of information took place between April and June 2019, through five meetings that characterized the four phases that make up the "4D cycle": Discovery, Dream, Design, and Destiny. Ethical issues were respected. RESULTS: the participants dreamed of the best scenario for preceptorship and built a schedule of actions related to the qualification of preceptorship in Nursing and the strengthening of teaching-health service integration. FINAL CONSIDERATIONS: it is possible, through effective participation of the actors involved in teaching and practice, the collective development of goals and actions, aiming at the qualification of nursing education.

Estradiol and 1α,25(OH)2 vitamin D3 share plasma membrane downstream signal transduction through calcium influx and genomic activation in immature rat testis.

The aim of this study was to investigate the rapid response pathway and gene and protein expression profiles of the rat testis in response to estradiol (E2) and 1α,25(OH)2 vitamin D3 (1,25-D3), to understand how they mediate their effects on the first spermatogenic wave. To do this, we compared the effects of 1,25-D3 and E2 on 45calcium(Ca2+) uptake and the involvement of estrogen receptors (ESR) in their rapid responses. Additionally, we studied the downstream signal transduction effects of 1,25-D3 and E2 on cyclin A1/B1 and cellular cycle protein expression. As previously observed for 1,25-D3, E2 also increased 45Ca2+ uptake in immature rat testes via voltage-dependent Ca2+ channels, Ca2+-dependent chloride channels and via the activation of protein kinase C, protein kinase A and mitogen-activated protein kinase kinase (MEK). Elevated aromatase expression by testes was observed in the presence of 1,25-D3 and both hormones decreased ESR mRNA expression. Furthermore, 1,25-D3 and E2 diminished cyclin A1 mRNA expression, but E2 did not affect cyclin B1 mRNA levels. Consistent with these findings, the immunocontent of cyclin A1 and B1 in the testes was also increased by 1,25-D3 and E2. 1,25-D3 increased expressions of the p16 and p53 proteins, supporting the anti-proliferative and pro-apoptotic properties of 1,25-D3, while E2 also augmented p16. Data indicate that both hormones trigger rapid responses at the plasma membrane that may control the expression of gene and proteins related to cell cycle regulation, and thereby modulate spermatogenesis.

Characterization of the chemical profile and the effects of ethanolic extracts of Maytenus ilicifolia Mart. ex Reissek on glucose metabolism in normal hyperglycemic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus ilicifolia Mart. ex Reissek, Celastraceae, is popularly known as "espinheira-santa" and used to treat pathologies related to the stomach. However, in popular culture, this species has also been used to treat other disorders such as diabetes, but without scientific evidence, requiring more phytochemical and pharmacological studies on the plant. AIM OF THE STUDY: This work aims to investigate the anti-hyperglycemic potential of ethanolic extracts obtained from leaves from two different accessions of Maytenus ilicifolia (MIA and MIB) in normal hyperglycemic rats. MATERIALS AND METHODS: The animals were divided into different experimental groups: normal hyperglycemic (negative control); MIA (treatment of Maytenus ilicifolia extract from access 116); MIB (treatment with Maytenus ilicifolia extract from access 122; and glipizide (positive control). At 30 min after treatment, all animals received glucose overload orally. Blood collection occurred at different periods for the assessment of blood glucose (0, 60, 90 and 210 min after treatment) and at the end of the experiment blood was collected through cardiac puncture and the liver, muscle, pancreas and intestine were dissected for further analysis. RESULTS: Chromatographic analysis identified oleic and palmitic acid as the most common constituents, and both extracts of Maytenus ilicifolia caused a reduction in blood glucose levels within 60 min after administration of glucose overload when compared to the normal hyperglycemic group. No significant changes were observed in hepatic and muscular glycogen levels, plasma insulin concentration and disaccharidases activity with none of the extracts in the model employed. However, hyperglycemic rats treated with the extracts showed a marked increase in triglyceride and HDL cholesterol levels. CONCLUSIONS: Our data suggest that Maytenus ilicifolia extracts from different locations showed differences in chemical composition which did not reflect significant differences in the results of biological tests. In addition, it was possible to conclude that the treatment with Maytenus ilicifolia had a discreet anti-hyperglycemic effect; however, it was not possible to identify the responsible mechanism, being necessary, therefore, new studies using different technologies in order to determine the possible mechanisms of action of the extract.

Strategies for changing the nursing preceptorship activity in Primary Health Care / Estrategias para el cambio en la actividad de preceptoría en enfermería en la Atención Primaria de Salud / Estratégias para a mudança na atividade de preceptoria em enfermagem na Atenção Primária à Saúde

ABSTRACT Objectives: to present actions to qualify preceptorship and teaching-health service integration to strengthen nursing training in PHC internship. Methods: qualitative research, developed through the Appreciative Inquiry Research carried out with eight nurses, both from the fields of teaching and health service, within Primary Health Care. The production and documentation of information took place between April and June 2019, through five meetings that characterized the four phases that make up the "4D cycle": Discovery, Dream, Design, and Destiny. Ethical issues were respected. Results: the participants dreamed of the best scenario for preceptorship and built a schedule of actions related to the qualification of preceptorship in Nursing and the strengthening of teaching-health service integration. Final Considerations: it is possible, through effective participation of the actors involved in teaching and practice, the collective development of goals and actions, aiming at the qualification of nursing education.

RESUMEN Objetivos: presentar acciones para calificar la preceptoría e integración enseñanza-servicio, con vistas al fortalecimiento de la formación en Enfermería con prácticas en Atención Primaria de Salud. Métodos: estudio cualitativo, desarrollado por medio de Investigación Apreciativa realizada con ocho enfermeras, procedentes de la enseñanza y servicio, en ámbito de Atención Primaria de Salud. Producción y registro de informaciones ocurrieron entre abril y junio de 2019, mediante cinco encuentros que caracterizaron las cuatro fases que constituyen el "ciclo 4D": Discovery, Dream, Design y Destiny. Cuestiones éticas fueron respetadas. Resultados: las participantes soñaron con el mejor escenario para la preceptoría y construyeron un cronograma de acciones relacionadas a calificación de la preceptoría en Enfermería y fortalecimiento de la integración enseñanza-servicio. Consideraciones Finales: es posible, basado en la participación efectiva de los actores envueltos en la enseñanza y servicio, el desarrollo colectivo de metas y acciones, visando a calificación de la formación en Enfermería.

RESUMO Objetivos: apresentar ações para qualificar a preceptoria e a integração ensino-serviço, com vistas ao fortalecimento da formação em Enfermagem com estágio na Atenção Primária à Saúde. Métodos: estudo qualitativo, desenvolvido por meio da Pesquisa Apreciativa realizada com oito enfermeiras, procedentes do ensino e do serviço, no âmbito da Atenção Primária à Saúde. A produção e o registro das informações ocorreram entre abril e junho de 2019, mediante cinco encontros que caracterizaram as quatro fases que constituem o "ciclo 4D": Discovery, Dream, Design e Destiny. As questões éticas foram respeitadas. Resultados: as participantes sonharam com o melhor cenário para a preceptoria e construíram um cronograma de ações relacionadas à qualificação da preceptoria em Enfermagem e fortalecimento da integração ensino-serviço. Considerações Finais: é possível, com base na participação efetiva dos atores envolvidos no ensino e no serviço, o desenvolvimento coletivo de metas e ações, visando à qualificação da formação em Enfermagem.

Análise das interações medicamentosas e perfil epidemiológico de indivíduos com diabetes mellitus na atenção primária / Análisis de interacciones farmacológicas y perfil epidemiológico de individuos con diabetes mellitus en atención primaria / Analysis of drug interactions and epidemiological profile of individuals with diabetes mellitus in primary care

Objetivo: analisar as interações medicamentosas e o perfil epidemiológico de indivíduos com diabetes mellitus (DM). Método: estudo quantitativo com aplicação de questionário a 42 pacientes com DM pertencentes a um Centro de Saúde da Família (CSF). Os dados foram coletados em 2018, em três etapas: encontro no CSF, visitas domiciliares e busca em prontuário eletrônico; seguido de análise das interações medicamentosas nas bases Drug Interactions Checker Drug Information e DrugBank. Resultados: a idade média dos pacientes foi de 68,36 anos. O número total de associações entre fármacos foi de 1355 (média de 32,26/paciente). O total de medicações que interagem foi de 479 (11,40 interações/paciente). Em 65% as combinações não interagiram, 4% foram interações leves, 26,05% moderadas e 1,70% graves. Conclusão: a quantidade de interações medicamentosas é expressiva, predominando as de grau moderado. A idade dos pacientes e presença de comorbidades podem estar associadas à

Objetivo: analizar como interacciones medicamentosas y el perfil epidemiológico de individuos con diabetes mellitus (DM). Método: estudio cuantitativo con aplicación de cuestionario a 42 pacientes con DM pertencentes en el Centro de Salud de la Familia (CSF). Os dados foram coletados em 2018, em três etapas: encontro no CSF, visitas domiciliares e busca em prontuário eletrônico; seguido de análise das interações medicamentosas nas bases Comprobador de interacciones de medicamentos Información sobre medicamentos e DrugBank. Resultados: una idade media dos pacientes fe de 68,36 años. Número total de asociaciones entre religiones de 1355 (medios de 32.26/paciente). O total de medicamentos que interagencian la fe de 479 (11.40 interacciones/paciente). Em 65% como combinações não interagiram, 4% foram interações leves, 26.05% moderadas y 1.70% grave. Conclusión: una cantidad de interacõs medicamentosas é expressiva, predominando como de grau moderado. A idade dos pacientes y presença de comorbidades podem estar asociado a polimedicação, contribindo para ocorrência dessas interações.

Aim: to analyze drug interactions and the epidemiological profile of individuals with diabetes mellitus (DM). Method: quantitative study with the application of a questionnaire to 42 patients with DM belonging to a Family Health Center (FHC). Data were collected in 2018, in three stages: meeting at the CSF, home visits and searching electronic medical records; followed by analysis of drug interactions in the Drug Interactions Checker Drug Information and DrugBank databases. Results: the mean age of the patients was 68.36 years. The total number of associations between drugs was 1355 (mean 32.26 / patient). The total number of medications that interact was 479 (11.40 interactions /patient). In 65% the combinations did not interact, 4% were mild interactions, 26.05% moderate and 1.70% severe. Conclusion: the number of drug interactions is significant, with a moderate degree predominating. The age of patients and the presence of comorbidities can be associated with polymedication, contributing to the occurrence of these interactions.

Iron and manganese present in underground water promote biochemical, genotoxic, and behavioral alterations in zebrafish (Danio rerio).

Iron (Fe) and manganese (Mn) are metals commonly found at high concentrations in underground water. These metals are essential for the good functioning of living organisms, but high concentrations lead to imbalance, potentiating the appearance of pathologies. This study aimed to evaluate the effect of exposure to naturally occurring metals in groundwater, using zebrafish (Danio rerio) as an experimental model. Thus, zebrafish were exposed to Fe (0.8 and 1.3 mg/L), Mn (0.2 and 0.4 mg/L), and groundwater collected from deep tube wells with Fe and Mn (Fe 0.8/Mn 0.2 mg/L and Fe 1.3/Mn 0.4 mg/L) for 30 days. Bioaccumulation of these metals has been demonstrated in the livers and muscles of zebrafish. Acetylcholinesterase activity changed only in zebrafish muscles in all groups. Sulfhydryl levels changed mainly in the group Mn 0.4. SOD/CAT ratio decreased in the groups Fe 0.8 and 1.3, Mn 0.4, and Fe 0.8/Mn 0.4. An increase in the frequency of micronucleus in all groups was shown as a consequence of these changes. Behavioral parameters (time and distance traveled, mean speed, turn angle, latency, and number of crossings between compartments) have also changed, mainly in the groups Fe 1.3, Mn 0.4, and Fe 1.3/Mn 0.4. Therefore, long-term exposure to Fe and Mn, even at not so high concentrations, may cause biochemical, genotoxic, and behavioral changes in zebrafish.

Body composition and nutritional and metabolic parameters in postmenopausal women sufficient, insufficient and deficient in vitamin D

ABSTRACT Objective We investigated changes in body composition and nutritional and metabolic parameters in a group of postmenopausal women who were classified as sufficient, insufficient and deficient in vitamin D. Subjects and methods A total of 106 postmenopausal women were included in this cross-sectional study and classified according to their serum levels of 25-OH-vitamin D as sufficient (≥ 30 ng/mL; group S), insufficient (20.1 and 29.9 ng/mL; group I) or deficient (≤ 20 ng/mL; group D) in vitamin D. Body composition was measured by dual-energy X-ray absorptiometry (DXA); dietary recall questionnaires were completed; and blood samples were analysed to compare the metabolic and nutritional status of the study groups. Results Eleven (10.4%) of the women were classified in group S, 50 (47.2%) in group I and 45 (42.4%) in group D, with a mean serum level for 25-OH-D of 21.1 ± 7.0 ng/mL in all participants. Body composition did not differ among the groups. Serum levels of 25-OH-D were negatively correlated with serum levels of triglycerides, total cholesterol and LDL cholesterol. Conclusions Vitamin D insufficiency and deficiency were highly prevalent in our group of postmenopausal women, showing an association with an unfavourable lipid profile.

Body composition and nutritional and metabolic parameters in postmenopausal women sufficient, insufficient and deficient in vitamin D.

OBJECTIVE: We investigated changes in body composition and nutritional and metabolic parameters in a group of postmenopausal women who were classified as sufficient, insufficient and deficient in vitamin D. SUBJECTS AND METHODS: A total of 106 postmenopausal women were included in this cross-sectional study and classified according to their serum levels of 25-OH-vitamin D as sufficient (≥ 30 ng/mL; group S), insufficient (20.1 and 29.9 ng/mL; group I) or deficient (≤ 20 ng/mL; group D) in vitamin D. Body composition was measured by dual-energy X-ray absorptiometry (DXA); dietary recall questionnaires were completed; and blood samples were analysed to compare the metabolic and nutritional status of the study groups. RESULTS: Eleven (10.4%) of the women were classified in group S, 50 (47.2%) in group I and 45 (42.4%) in group D, with a mean serum level for 25-OH-D of 21.1 ± 7.0 ng/mL in all participants. Body composition did not differ among the groups. Serum levels of 25-OH-D were negatively correlated with serum levels of triglycerides, total cholesterol and LDL cholesterol. CONCLUSIONS: Vitamin D insufficiency and deficiency were highly prevalent in our group of postmenopausal women, showing an association with an unfavourable lipid profile.

New ionic targets of 3,3',5'-triiodothyronine at the plasma membrane of rat Sertoli cells.

The functions of Sertoli cells, which structurally and functionally support ongoing spermatogenesis, are effectively modulated by thyroid hormones, amongst other molecules. We investigated the mechanism of action of rT3 on calcium (45Ca2+) uptake in Sertoli cells by means of in vitro acute incubation. In addition, we performed electrophysiological recordings of potassium efflux in order to understand the cell repolarization, coupled to the calcium uptake triggered by rT3. Our results indicate that rT3 induces nongenomic responses, as a rapid activation of whole-cell potassium currents in response to rT3 occurred in <5 min in Sertoli cells. In addition, the rT3 metabolite, T2, also exerted a rapid effect on calcium uptake in immature rat testis and in Sertoli cells. rT3 also modulated calcium uptake, which occurred within seconds via the action of selective ionic channels and the Na+/K+ ATPase pump. The rapid response of rT3 is essentially triggered by calcium uptake and cell repolarization, which appear to mediate the secretory functions of Sertoli cells.

Association between undercarboxylated osteocalcin, bone mineral density, and metabolic parameters in postmenopausal women.

OBJECTIVE: Osteocalcin has been associated with several effects on energy and glucose metabolism. However, the physiological role of undercarboxylated osteocalcin (U-osc; the hormonally active isoform of osteocalcin) is still controversial. To correlate the serum levels of U-osc with bone mineral density (BMD) values and metabolic parameters in postmenopausal women. SUBJECTS AND METHODS: Cross-sectional study including 105 postmenopausal women (age 56.5 ± 6.1 years, body mass index [BMI] 28.2 ± 4.9 kg/m2) grouped based on the presence of three or less, four, or five criteria of metabolic syndrome according to the International Diabetes Federation (IDF). The subjects underwent dualenergy x-ray absorptiometry (DXA) for the assessment of body composition and BMD and blood tests for the measurement of U-osc and bone-specific alkaline phosphatase (BSAP) levels. RESULTS: The mean U-osc level was 3.1 ± 3.4 ng/mL (median 2.3 ng/mL, range 0.0-18.4 ng/mL) and the mean BSAP level was 12.9 ± 4.0 ng/mL (median 12.1 ng/mL, range 73-24.4 ng/mL). There were no associations between U-osc and BSAP levels with serum metabolic parameters. Lower fasting glucose levels were observed in participants with increased values of U-osc/femoral BMD ratio (3.61 ± 4 ng/mL versus 10.2 ± 1.6 ng/mL, p = 0.036). When the participants were stratified into tertiles according to the U-osc/ femoral BMD and U-osc/lumbar BMD ratios, lower fasting glucose levels correlated with increased ratios (p = 0.029 and p = 0.042, respectively). CONCLUSION: Based on the ratio of U-osc to BMD, our study demonstrated an association between U-osc and glucose metabolism. However, no association was observed between U-osc and metabolic parameters.The U-osc/BMD ratio is an innovative way to correct the U-osc value for bone mass.

Association between undercarboxylated osteocalcin, bone mineral density, and metabolic parameters in postmenopausal women

ABSTRACT Objective: Osteocalcin has been associated with several effects on energy and glucose metabolism. However, the physiological role of undercarboxylated osteocalcin (U-osc; the hormonally active isoform of osteocalcin) is still controversial. To correlate the serum levels of U-osc with bone mineral density (BMD) values and metabolic parameters in postmenopausal women. Subjects and methods: Cross-sectional study including 105 postmenopausal women (age 56.5 ± 6.1 years, body mass index [BMI] 28.2 ± 4.9 kg/m2) grouped based on the presence of three or less, four, or five criteria of metabolic syndrome according to the International Diabetes Federation (IDF). The subjects underwent dualenergy x-ray absorptiometry (DXA) for the assessment of body composition and BMD and blood tests for the measurement of U-osc and bone-specific alkaline phosphatase (BSAP) levels. Results: The mean U-osc level was 3.1 ± 3.4 ng/mL (median 2.3 ng/mL, range 0.0-18.4 ng/mL) and the mean BSAP level was 12.9 ± 4.0 ng/mL (median 12.1 ng/mL, range 73-24.4 ng/mL). There were no associations between U-osc and BSAP levels with serum metabolic parameters. Lower fasting glucose levels were observed in participants with increased values of U-osc/femoral BMD ratio (3.61 ± 4 ng/mL versus 10.2 ± 1.6 ng/mL, p = 0.036). When the participants were stratified into tertiles according to the U-osc/ femoral BMD and U-osc/lumbar BMD ratios, lower fasting glucose levels correlated with increased ratios (p = 0.029 and p = 0.042, respectively). Conclusion: Based on the ratio of U-osc to BMD, our study demonstrated an association between U-osc and glucose metabolism. However, no association was observed between U-osc and metabolic parameters.The U-osc/BMD ratio is an innovative way to correct the U-osc value for bone mass.

Protective effect of Uncaria tomentosa extract against oxidative stress and genotoxicity induced by glyphosate-Roundup® using zebrafish (Danio rerio) as a model.

Oxidative stress and DNA damage are involved in the glyphosate-based herbicide toxicity. Uncaria tomentosa (UT; Rubiaceae) is a plant species from South America containing bioactive compounds with known beneficial properties. The objective of this work was to evaluate the antioxidant and antigenotoxic potential of UT extract in a model of acute exposure to glyphosate-Roundup® (GR) in zebrafish (Danio rerio). We showed that UT (1.0 mg/mL) prevented the decrease of brain total thiols, the increase of lipid peroxidation in both brain and liver, and the decrease of liver GPx activity caused after 96 h of GR (5.0 mg/L) exposure. In addition, UT partially protected against the increase of micronucleus frequency induced by GR exposure in fish brain. Overall, our results indicate that UT protects against damage induced by a glyphosate-based herbicide by providing antioxidant and antigenotoxic effects, which may be related to the phenolic compounds identified in the extract.

Effects of hydroalcoholic extract of Celtis iguanaea on markers of cardiovascular diseases and glucose metabolism in cholesterol-fed rats

ABSTRACT Celtis iguanaea (Jacq.) Sarg., Cannabaceae, is popularly used in the treatment of diabetes mellitus. However, chemical and pharmacological investigations are lacking. In this study, we investigated the effects of the hydroalcoholic extract from C. iguanaea on markers of cardiovascular diseases and the glucose metabolism in cholesterol-fed rats. Therefore, hypercholesterolemic rats (1% cholesterol) were orally treated with C. iguanaea extract (C-150, CI-300, or CI-600 mg/kg) or simvastatin (4 mg/kg) (n = 6) once a day (30 days) with a hypercholesterolemic diet. A control group (C) was given saline. C. iguanaea extract showed significant decreases in serum levels of total cholesterol, LDL-cholesterol, HMG-CoA-reductase, interleukin-1 and 6, TNF-α and IFN-γ when compared to group C (p < 0.001). Hypoglycemic effects were observed along with a decrease of the activity of sucrase (CI-600), maltase (CI-150, CI-300), and an increase in muscle glycogen levels (CI-300). Antioxidant effects were observed in plasma by the decrease of TBARS and increase of nonprotein thiols levels (CI-600). The histopathological analysis showed a significant decrease in the liver fat area for C. iguanaea extract compared to group C (p < 0.001). Our results suggest that the biological effects of C. iguanaea extract could be related to the flavonoids that possibly exert antioxidant, enzymatic inhibitory, and insulin-mimetic effects.

Use of pamidronate for osteoporosis treatment in public health care in Brazil / Uso de pamidronato para o tratamento da osteoporose no sistema público de saúde no Brasil

Abstract Purpose: The use of bisphosphonates for osteoporosis is effective in reducing the risk of fractures. However, oral formulations are sometimes not well tolerated or are contraindicated. Due to its availability in Brazilian public health system, pamidronate is frequently prescribed for osteoporosis, despite the lack of studies demonstrating its anti-fracture efficacy and the absence of FDA or EMEA approval for this purpose. The aim of this study was to evaluate the bone mineral density (BMD) response to pamidronate in a group of women with osteoporosis in a tertiary care hospital. Patients and methods: The medical records of women with osteoporosis who received pamidronate for up to two years of treatment were reviewed. Patients were stratified at high or intermediate risk of fracture. Results: A total of 70 women were in treatment with pamidronate. Among them, 74% were at high risk of fracture. A significant gain in spine BMD after 24 months of treatment was observed (p = 0.012). There was no difference between the groups of high and not high risk of fracture. At the femur, no significant increase in BMD was present, though, a strong negative correlation with high PTH levels (r = −0.61; p = 0.003) was seen. In the multivariate analysis BMI at 12 months had impact in the response to the treatment. Conclusion The intravenous pamidronate in a group of postmenopausal women with predominant high risk of fracture promoted an isolated gain in the spine BMD, even though, clinical randomized trials are needed to confirm its anti-fracture efficacy.

Resumo Justificativa: O uso de bisfosfonatos para a osteoporose é eficaz na redução do risco de fraturas. No entanto, as formulações orais às vezes não são bem toleradas ou são contraindicadas. Em razão da sua disponibilidade no sistema público de saúde brasileiro, o pamidronato é frequentemente prescrito para a osteoporose, apesar da falta de estudos que demonstrem a sua eficácia antifratura e da ausência de aprovação da Food and Drug Administration (FDA) ou da European Medicine Agency (Emea) para essa finalidade. O objetivo deste estudo foi avaliar a resposta da densidade mineral óssea (DMO) ao pamidronato em um grupo de mulheres com osteoporose em um hospital terciário. Pacientes e métodos: Revisaram-se os prontuários médicos de mulheres com osteoporose que receberam pamidronato por até dois anos de tratamento. As pacientes foram estratificadas em risco alto ou intermediário de fratura. Resultados: Estavam em tratamento com pamidronato 70 mulheres. Entre elas, 74% tinham alto risco de fratura. Observou-se um ganho significativo na DMO da coluna vertebral após 24 meses de tratamento (p = 0,012). Não houve diferença entre os grupos de risco de fratura alto e não alto. No fêmur, não foi encontrado aumento significativo na massa óssea; contudo, observou-se uma forte correlação negativa com altos níveis de PTH (r = −0,61; p = 0,003). Na análise multivariada, o IMC aos 12 meses tinha impacto na resposta ao tratamento. Conclusão O pamidronato intravenoso em um grupo de mulheres na pós-menopausa predominantemente com alto risco de fratura promoveu um ganho isolado na DMO da coluna vertebral, embora sejam necessários ensaios clínicos randomizados para confirmar sua eficácia antifratura.

Use of pamidronate for osteoporosis treatment in public health care in Brazil.

PURPOSE: The use of bisphosphonates for osteoporosis is effective in reducing the risk of fractures. However, oral formulations are sometimes not well tolerated or are contraindicated. Due to its availability in Brazilian public health system, pamidronate is frequently prescribed for osteoporosis, despite the lack of studies demonstrating its anti-fracture efficacy and the absence of FDA or EMEA approval for this purpose. The aim of this study was to evaluate the bone mineral density (BMD) response to pamidronate in a group of women with osteoporosis in a tertiary care hospital. PATIENTS AND METHODS: The medical records of women with osteoporosis who received pamidronate for up to two years of treatment were reviewed. Patients were stratified at high or intermediate risk of fracture. RESULTS: A total of 70 women were in treatment with pamidronate. Among them, 74% were at high risk of fracture. A significant gain in spine BMD after 24 months of treatment was observed (p=0.012). There was no difference between the groups of high and not high risk of fracture. At the femur, no significant increase in BMD was present, though, a strong negative correlation with high PTH levels (r=-0.61; p=0.003) was seen. In the multivariate analysis BMI at 12 months had impact in the response to the treatment. CONCLUSION: The intravenous pamidronate in a group of postmenopausal women with predominant high risk of fracture promoted an isolated gain in the spine BMD, even though, clinical randomized trials are needed to confirm its anti-fracture efficacy.

1,25(OH)2 vitamin D3 signalling on immature rat Sertoli cells: gamma-glutamyl transpeptidase and glucose metabolism.

1α,25-Dihydroxyvitamin D3 (1,25-D3) is critical for the maintenance of normal male reproduction since reduced fertility is observed in vitamin D-deficient rats. Gamma-glutamyl transpeptidase (GGT) is a membrane-bound enzyme that is localized on Sertoli cells and catalyses the transfer of the gamma-glutamyl residues to an amino acid or peptide acceptor. Sertoli cells are also responsible for providing nutrients, as lactate, to the development of germ cells. The aim of this study was to investigate the effect and the mechanism of action of 1,25-D3 on GGT on Sertoli cell functions from 30-day-old immature rat testis. Results demonstrated that 1,25-D3 stimulates GGT activity at Sertoli cells plasma membrane through a PKA-dependent mechanism of action, which was not dependent of active de novo protein synthesis. The hormone increases glucose uptake, as well as lactate production and release by Sertoli cells without altering the reactive oxygen species (ROS) generation. In addition, 1,25-D3 did not change reduced glutathione (GSH) amount or oxygen consumption, and diminished Sertoli cell death. These findings demonstrate that 1,25-D3 stimulatory effect on GGT activity, glucose uptake, LDH activity and lactate production seem to be an important contribution of Sertoli cells for germ cells nutrition and for a full and active ongoing spermatogenesis.

Prevention of unpredictable chronic stress-related phenomena in zebrafish exposed to bromazepam, fluoxetine and nortriptyline.

RATIONALE: Several model organisms have been employed to study the impacts of stress on biological systems. Different models of unpredictable chronic stress (UCS) have been established in rodents; however, these protocols are expensive, long-lasting, and require a large physical structure. Our group has recently reported an UCS protocol in zebrafish with several advantages compared to rodent models. We observed that UCS induced behavioral, biochemical, and molecular changes similar to those observed in depressed patients, supporting the translational relevance of the protocol. OBJECTIVES: Considering that a pharmacological assessment is lacking in this zebrafish model, our aim was to evaluate the effects of anxiolytic (bromazepam) and antidepressant drugs (fluoxetine and nortriptyline) on behavioral (novel tank test), biochemical (whole-body cortisol), and molecular parameters (cox-2, tnf-α, il-6, and il-10 gene expression) in zebrafish subjected to UCS. RESULTS: We replicated previous data showing that UCS induces behavioral and neuroendocrine alterations in zebrafish, and we show for the first time that anxiolytic and antidepressant drugs are able to prevent such effects. Furthermore, we extended the molecular characterization of the model, revealing that UCS increases expression of the pro-inflammatory markers cox-2 and il-6, which was also prevented by the drugs tested. CONCLUSIONS: This study reinforces the use of zebrafish as a model organism to study the behavioral and physiological effects of stress. The UCS protocol may also serve as a screening tool for evaluating new drugs that can be used to treat psychiatric disorders with stress-related etiologies.