Dayak onions ( Eleutherine bulbosa (Mill.) Urb. ) bulbs extracts reduces blood pressure of hypoestrogen model rats by controlling lipids profile / El extracto de bulbos de cebollas dayak ( Eleutherine bulbosa (Mill. ) Urb. ) reduce la presión sanguínea en un modelo hipoestrogénico en ratas controlando el perfil lipídico

To determine the effects of 70 % ethanolic extract of Eleutherine bulbosa (Mill.) L. bulbs contained naphtoquinone in blood pressure and lipids profile level of ovariectomized rats. Thin layer chromatography was performed to analyze the content of the Eleutherine bulbosa (Mill.) bulbs extracts using Chloroform : Methanol (7:1) as eluent. This study used white female Sprague-Dawley rats which were divided into 6 groups: SHAM and OVX, both given 0.5 % carboxymethyl cellulose; the positive control group that was given tamoxifen (0.36 mg/200 g B.W.); the three various of doses of extract namely dose 1, 2, and 3 that were given 8, 12, and 18 mg/200 g BW respectively on day 29 until 50. All groups were ovariectomized on day 1, except sham group. Measurement of blood pressure were performed on the day before ovariectomy using non-invasive tool CODA®; and on the second, third, and fourth weeks post-ovariectomy. Three weeks after treatment of hypoestrogen rats by the dose 18 mg/200 g B.W, Eleutherine bulbosa extracts could decrease the systolic blood pressure level to 28.06 %, the diastolic to 30.47 %. Lipid profile of Dose 3 also showed recovery of Triglyceride, LDL and also Total Cholesterol. Eleutherine bulbosa extracts could improve blood pressure of ovariectomized rats by controlling lipids profile level.

Para determinar los efectos del 70 % de extracto etanólico de Eleutherine bulbosa (Mill.) L. en bulbos que contenían naftoquinona, se analizó la presión arterial de ratas ovariectomizadas. Se realizó un estudio de cromatografía de capa fina para analizar el contenido de los extractos de bulbos de Eleutherine bulbosa (Mill.) usando cloroformo:metanol (7:1) como diluyente. En este estudio se utilizaron ratas blancas Sprague-Dawley hembras, que se dividieron en 6 grupos: SHAM y OVX, ambos grupos fueron administrados con carboximetilcelulosa al 0,5 %; grupo control positivo, recibió tamoxifeno (0,36 mg / 200 g de B.W.); y tres grupos restantes, que recibieron tres dosis diferentes de extracto, es decir, dosis 1, 2 y 3 a las que se les administró 8, 12 y 18 mg / 200 g de por peso, respectivamente el día 29 hasta el día 50. Todos los grupos fueron sometidos a ovariectomía en el día 1, excepto el grupo simulado. La medición de la presión arterial se realizó el día anterior a la ovariectomía con la herramienta no invasiva CODA®, y, posteriormente, en la segunda, tercera y cuarta semanas de realizada la ovariectomía. Tres semanas después del tratamiento aplicado a las ratas hipoestrógenas, con la dosis de 18 mg / 200 g por peso, los extractos de Eleutherine bulbosa podrían disminuir el nivel de presión arterial sistólica al 28,06 %, y la diastólica al 30,47 %. La dosis 3 del perfil lipídico mostró mejoría en los niveles de Triglicéridos, LDL y Colesterol Total. Los extractos de Eleutherine bulbosa podrían mejorar la presión sanguínea de ratas ovariectomizadas controlando el nivel del perfil lipídico.

A long-term estrogen deficiency in ovariectomized mice is associated with disturbances in fatty acid oxidation and oxidative stress / Deficiência de estrogênio em longo prazo em camundongas ovarietcomizadas está associada a distúrbios na oxidação de ácidos graxos e estresse oxidativo

Abstract Objective The aim of this work was to evaluate the changes caused by estrogen deficiency in lipid metabolism. Methods This study encompassed direct measurements of plasma biochemical analyses, liver lipid contents, and assessments of the mitochondrial β-oxidation capacity as well as an evaluation of the liver redox status in an animal model of estrogen deficiency. Results When compared with control mice, the livers of ovariectomized (OVX) mice presented considerable accretions in their lipid contents, which were accompanied by increased levels of lipid peroxidation in liver homogenates andmitochondria from OVX groups and decreased reduced glutathione (GSH) contents. In isolated mitochondria, estrogen deficiency inhibited mitochondrial β-oxidation of fatty acids irrespective of their chain length. The liver mitochondrial and peroxisomal H2O2 generations in OVX mice were increased. Additionally, the activities of all antioxidant enzymes assessed were decreased. Conclusion These data provide one potential explanation for the increased susceptibility to metabolic diseases observed after menopause.

Resumo Objetivo O objetivo desse trabalho foi avaliar as alterações causadas pela deficiência estrogênica no metabolismo de lipídeos. Métodos Este estudo abrangeu análises bioquímicas plasmáticas, verificação de conteúdo lipídico do fígado e avaliações da capacidade de β-oxidação mitocondrial e do estado redox do fígado em um modelo animal de deficiência estrogênica. Resultados Os fígados das camundongas ovariectomizadas (OVXs) apresentaram acréscimos consideráveis no conteúdo de lipídeos, que foram acompanhados por aumento de peroxidação lipídica em homogenatos e mitocôndrias de fígado e diminuição do conteúdo de glutationa reduzida (GSH) quando comparadas as camundongas do grupo controle. Nas mitocôndrias isoladas, a deficiência estrogênica causou a inibição da β-oxidação mitocondrial independentemente do comprimento da cadeia dos ácidos graxos. A geração mitocondrial e peroxissomal de H2O2 apresentou-se aumentada em camundongas OVXs. Além disso, as atividades de todas as enzimas antioxidantes avaliadas foram diminuídas. Conclusão Esses dados fornecem uma explicação potencial para o aumento da suscetibilidade às doenças metabólicas observadas após a menopausa.

Estudio comparativo de la absorción neta de calcio de dos formulaciones distintas de carbonato de calcio en mujeres posmenopáusicas / Comparative study of net calcium absorption of two different pharma¬ceutical formulations of calcium carbonate in posmenopausal women

La suplementación con calcio reduciría, sola o asociada a otra medicación para osteoporosis, la pérdida de masa ósea y el riesgo de fracturas. Sin embargo, su tasa de adherencia es baja debido a la poca tolerancia. Objetivo: comparar la tasa de absorción neta de calcio entre dos formulaciones distintas de carbonato de calcio (500 mg): comprimidos vs. mousse. Material y métodos: 11 pruebas fueron realizadas en mujeres posmenopáusicas de 58,9±3 años. El diseño fue exploratorio abierto, aleatorizado, prospectivo cruzado de fase 4. Intervención: las participantes fueron aleatorizadas en dos grupos para recibir las dos formulaciones previa suplementación con vitamina D3. La tasa de absorción neta de calcio fue estudiada por la prueba de inhibición de hormona paratiroidea (PTH). Se obtuvieron muestras de sangre: basal y en la 1a, 2a y 3a hora posadministración del calcio asignado, y de orina de 2 horas basal y al final de la prueba. Determinaciones bioquímicas: calcio, fósforo, albúmina, 25-hidroxivitamina D y hormona paratiroidea intacta y calciuria. Análisis estadístico: método de los trapecios para calcular el área bajo la curva (AUC) de la concentración de calcio en el tiempo (R Development Core Team (2008). http://www.Rp-project.org) y Anova con dos términos de error para evaluar el efecto secuencia, período y formulación. Resultados: la mayor inhibición de PTH se observó a dos horas de la toma de ambas formulaciones (comprimidos -39,2% vs. mousse -38,0%; p=ns), con similar AUC0-3 h (comprimidos 3,35; IC 95%: 3,32; 3,37 vs. mousse 3,36; IC 95%: 3,33; 3,38). Cuando analizamos tolerancia y preferencias no se observaron diferencias estadísticamente significativas entre ambas formulaciones. Conclusión: el carbonato de calcio en mousse mostró similar tasa de absorción intestinal, preferencia y tolerancia gastrointestinal que en comprimido. (AU)

Calcium supplementation, administered alone or in combination with a specific medication for osteoporosis, would reduce bone mass loss and fracture risk in postmenopausal women. However, the adherence rate to calcium supplements is low, mainly due to low tolerance. Objective: comparisson of net calcium absorption rate between two different pharmaceutical formulations of calcium carbonate (PFCa) in postmenopausal women. Materials and Methods: 11 tests were performed in postmenopausal women aged 58.9±3 yrs. Design: Comparative, randomized, prospective, open-label exploratory crossover study of calcium mousse versus calcium pills. Intervention: Participants were randomized in 2 groups to receive the 2 different PFCa (500mg): pills vs. mousse, with previous vitamin D3 supplementation. The parathyroid hormone (PTH) inhibition test and the area-under-thecurve (AUC) of calcium were analyzed. Blood samples were taken at baseline and 1, 2 and 3 hrs after intake of the assigned PFCa. Urine samples (2hs) were obtained at -baseline, after 2hs of PFCa intake and at the end of the test. Biochemical Determinations: Serum: calcium, phosphorus, albumin, 25-hydroxyvitamin D, and intact PTH. In urine: calcium. Statistical Analysis: The trapezoid rule was applied to assess AUC in time (R Development Core Team (2008). http://www.Rp-project.org). An ANOVA model with 2 error terms was used to assess the effect of sequence, period, and formulation. Results: The highest inhibition PTH rates were observed after 2 hrs of PFCa (pills -39.2% vs. mousse -38.0%; p=ns). The AUC0-3hrs for both PFCa was similar (pills 3.35; 95%CI: 3.32; 3.37 vs. mousse 3.36; 95%CI: 3.33; 3.38). No statistically significant differences were observed when we analyze tolerance and predilection. Conclusion: The calcium carbonate in mousse showed an adequate rate of intestinal absorption, similarly predilection and gastrointestinal tolerance than the pill presentation. (AU)

Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats / Tratamento com Resveratrol Normaliza a Função Endotelial e a Pressão Arterial em Ratas Ovariectomizadas

Abstract Background: Despite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure). Objective: To verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats. Methods: 3-month old female Wistar rats were used and distributed in 6 groups: intact groups with 60 or 90 days, ovariectomized groups with 60 or 90 days, and ovariectomized treated with resveratrol (10 mg/kg of body weight per day) for 60 or 90 days. The number of days in each group corresponds to the duration of the experimental period. Vascular reactivity study was performed in abdominal aortic rings, systolic blood pressure was measured and serum nitric oxide (NO) concentration was quantified. Results: Ovariectomy induced blood pressure increase 60 and 90 days after surgery, whereas the endothelial function decreased only 90 days after surgery, with no difference in NO concentration among the groups. Only longer treatment (90 days) with resveratrol was able to improve the endothelial function and normalize blood pressure. Conclusion: Our results suggest that 90 days of treatment with resveratrol is able to improve the endothelial function and decrease blood pressure in ovariectomized rats.

Resumo Fundamentos: Apesar de se saber que o resveratrol apresenta efeitos sobre a pressão arterial e os vasos sanguíneos, e que os fitoestrógenos podem melhorar o relaxamento/vasodilatação dependente do endotélio, não há relatos do efeito direto do resveratrol sobre a pressão arterial e a função endotelial em animais com deficiência de estrógeno (mimetizando a pressão arterial aumentada pós-menopausa). Objetivo: Verificar o efeito de dois diferentes períodos de tratamento preventivo com resveratrol sobre a pressão arterial e a função endotelial em ratas adultas jovens ovariectomizadas. Métodos: Foram utilizadas ratas Wistar com 3 meses de idade, distribuídas em 6 grupos: grupos intactas com 60 ou 90 dias, grupos ovariectomizadas com 60 ou 90 dias, grupos ovariectomizadas e tratadas com resveratrol na dose de 10mg/kg de massa corporal por dia, durante 60 ou 90 dias, sendo o número de dias em cada grupo relativo à duração do período experimental. Foi realizado um estudo de reatividade vascular em anéis da aorta abdominal, mensurada a pressão arterial sistólica e quantificada a concentração sérica de óxido nítrico (NO). Resultados: A ovariectomia induziu aumento da pressão arterial 60 e 90 dias após a cirurgia, enquanto a função endotelial decaiu apenas após 90 dias, e não houve diferença na concentração de NO entre os grupos. Apenas o tratamento prolongado com resveratrol (90 dias) foi capaz de melhorar a função endotelial e normalizar a pressão arterial. Conclusão: Nossos resultados sugerem que o tratamento por 90 dias com resveratrol é capaz de melhorar a função endotelial e diminuir a pressão sanguínea em ratas ovariectomizadas.

Estrogen deficiency in ovariectomized rats: can resistance training re-establish angiogenesis in visceral adipose tissue?

OBJECTIVE: The purpose of this study was to investigate the effects of resistance training on angiogenesis markers of visceral adipose tissue in ovariectomized rats. METHOD: Adult Sprague-Dawley female rats were divided into four groups (n=6 per group): sham-sedentary, ovariectomized sedentary, sham-resistance training and ovariectomized resistance training. The rats were allowed to climb a 1.1-m vertical ladder with weights attached to their tails and the weights were progressively increased. Sessions were performed three times per week for 10 weeks. Visceral adipose tissue angiogenesis and morphology were analyzed by histology. VEGF-A mRNA and protein levels were analyzed by real-time PCR and ELISA, respectively. RESULTS: Ovariectomy resulted in higher body mass (p=0.0003), adipocyte hypertrophy (p=0.0003), decreased VEGF-A mRNA (p=0.0004) and protein levels (p=0.0009), and decreased micro-vascular density (p=0.0181) in the visceral adipose tissue of the rats. Resistance training for 10 weeks was not able to attenuate the reduced angiogenesis in the visceral adipose tissue of the ovariectomized rats. CONCLUSION: Our findings indicate that the resistance training program used in this study could not ameliorate low angiogenesis in the visceral adipose tissue of ovariectomized rats.

Déficit de estrógeno e inmunidad, una aproximación sugerente a la mujer posmenopáusica / Shortage of estrogen and immunity, a suggestive approach to the postmenopausal woman

La reducción en la concentración de estrógenos producida durante la transición del estado reproductivo al estado posmenopáusico, como expresión del envejecimiento femenino, es responsable de las alteraciones metabólicas que se producen en diferentes sistemas, como el neurológico y el inmunológico, entre otros. La identificación oportuna de estas características clínicas constituye una necesidad para el tratamiento integral y personalizado de este grupo de mujeres, a nivel regional e internacional. Se verifica en la literatura científica la repercusión de la disminución de los niveles de estrógeno en el desempeño de los mecanismos inmunológicos de la mujer posmenopáusica. Para ello se realizó una revisión bibliográfica, a través del sitio web PubMed de la Biblioteca Médica Nacional de EUA, de las revistas especializadas más actualizadas y de libre acceso referentes al tema. Del total de 158 publicaciones encontradas, 42 fueron consultadas de manera íntegra y más del 50 por ciento de estas pertenecen a los últimos 5 años. Existen evidencias que reflejan la asociación existente entre la senectud ovárica y la inmunológica. La inmunosenescencia implica cambios en la inmunidad innata y la adquirida. Estas transformaciones han sido atribuidas a la deprivación estrogénica, ya que pueden ser reversibles con terapia hormonal sustitutiva. La contribución del déficit estrogénico al declive de la función inmunológica, no está bien dilucidada. Aún es insuficiente el nivel de conocimiento existente en este campo de las investigaciones biomédicas; el bajo índice de publicaciones científicas actualizadas así lo confirman. Escrutar con precisión los mecanismos patogénicos que desencadenan estos fenómenos permitiría un eficaz tratamiento integral, diagnóstico y terapéutico, de este grupo poblacional(AU)

Reduction in the estrogen concentration during the transition from the reproductive state to the postmenopausal condition, as an expression of female aging, accounts for the metabolic alterations occurring in different systems like the neurological and the immune ones among others. The timely detection of these clinical characteristics is a requirement for the comprehensive customized treatment of this group of women at regional and international levels. The impact of the decline in estrogen levels on the performance of the immune mechanisms of the postmenopausal woman was verified in the scientific literature. To this end, a literature review was made through the PubMed website of the National Medical Library of the United States to find the most updated open access specialized journals that dealt with the topic. Out of the 158 journals found, 42 were fully reviewed and over 50 percent of them were published in the last 5 years. There is some evidence that shows the association between ovarian senescence and the immune senescence. The immunosenescence means the changes occured in the innate immunity and the acquired immunity. These changes have been attributed to lack of estrogen because they may be reverted with the aid of an hormone replacement therapy. The estrogen shortage contribution to the decline in the immune function has not been yet solved. The level of knowledge in this field of biomedical research is still poor, which is confirmed by the low number of updated scientific publications. An accurate exploration of the pathogenic mechanisms triggering these phenomena would allow the comprehensive, effective diagnostic and therapeutic treatment of this population section(AU)

Etapas del climaterio y función endotelial en mujeres de edad mediana / Climacteric stages and endothelial function in middle-aged women

Introducción: La disminución de los estrógenos durante el climaterio repercute negativamente en el endotelio vascular, y origina disfunción endotelial, cuyo significado clínico está aún por definir. Objetivo: determinar la frecuencia de disfunción endotelial en las etapas del climaterio. Métodos: estudio descriptivo transversal, en 133 mujeres de 40-59 años, sin factores de riesgo cardiovascular, seleccionadas en centros de los 3 niveles de atención del Sistema Nacional de Salud, entre mayo de 2012 y mayo de 2013. Se evaluó la función endotelial mediante la prueba de dilatación mediada por el flujo de la arteria braquial, y su relación con etapas del climaterio. Se exploró la asociación entre variables utilizando pruebas no paramétricas (Kruskal-Wallis). Resultados: en el 38 por ciento de las mujeres se encontró disfunción endotelial, más frecuente en la etapa temprana de la posmenopausia respecto a la tardía y a la perimenopausia (45,0 vs. 27,5 vs. 27,5 por ciento respectivamente [p< 0,05]). Conclusiones: la disfunción endotelial es un evento frecuente en las mujeres de edad mediana aparentemente sanas, y al parecer, el descenso inicial de los estrógenos en los primeros años de la posmenopausia, tiene mayor impacto negativo en el endotelio vascular que el tiempo de exposición al hipoestrogenismo(AU)

Introduction: Estrogen reduction during the climacteric has a negative effect on the vascular endothelium and causes endothelial dysfunction, whose clinical significance is still to be defined.Objective: determine the frequency of endothelial dysfunction in the different stages of climacteric. Methods: a descriptive cross-sectional study was conducted of 133 women aged 40-59 with no cardiovascular risk factors, selected from institutions of the three health care levels within the National Health System from May 2012 to May 2013. Endothelial function was evaluated using the brachial artery flow-mediated dilation test and its association with climacteric stages. The relationship between variables was analyzed using non-parametric tests (Kruskal-Wallis). Results: 38 percent of the women had endothelial dysfunction, which was more common in the early stage of post-menopause than in the late stage and in perimenopause (45.0 vs. 27.5 vs. 27.5 percent, respectively [p< 0.05]). Conclusions: endothelial dysfunction is a common event among seemingly healthy middle-aged women. It seems that the initial reduction in estrogens in the first years of post-menopause has a greater negative impact on the vascular endothelium than the time of exposure to hypoestrogenism(AU)

Effects of estrogen deficiency combined with chronic alcohol consumption on rat mandibular condyle

Estrogen deficiency and chronic alcohol consumption may have a synergistic and deleterious effect on bone tissue. AIM: To investigate the effects of estrogen deficiency associated with chronic alcohol consumption on the mandibular condyle in rats. METHODS: Fifty-four female rats were first divided equally into two groups: ovariectomized Ovx and simulated ovariectomy Sham. One month after the surgeries, these groups were equally sub-divided according to their dietary treatment: G1: Sham/ad-libitum diet; G2: Sham/alcohol; G3: Sham/isocaloric; G4: Ovx/ad-libitum diet; G5: Ovx/alcohol, G6: Ovx/isocaloric. Eight weeks after starting the diets, all animals were anesthetized and sacrificed. The condyles were analyzed histologically, histomorphometrically, and immunohistochemically using the antibodies for bone sialoprotein BSP, osteocalcin OCC and receptor activator of nuclear factor kappa-B ligand RANKL. RESULTS: Histological analysis of the mandibular condyles showed that Ovx and Sham groups presented almost the same characteristics. The histomorphometric analysis showed that there was a statistically significant difference only between Ovx/isocaloric and Ovx/ad-libitum groups p=0.049. No difference was observed in the intensity of BSP, OCC, and RANKL antibody staining between the Ovx/alcohol and the other groups. CONCLUSIONS: It may be concluded that there was no histomorphometric, histological, or RANKL, BSP, and OCC staining differences between the Ovx/alcohol group and other experimental groups...

Immunolocalization of markers for bone formation during guided bone regeneration in osteopenic rats

Objective The aim of this paper was to evaluate the repair of onlay autogenous bone grafts covered or not covered by an expanded polytetrafluoroethylene (e-PTFE) membrane using immunohistochemistry in rats with induced estrogen deficiency. Material and Methods Eighty female rats were randomly divided into two groups: ovariectomized (OVX) and with a simulation of the surgical procedure (SHAM). Each of these groups was again divided into groups with either placement of an autogenous bone graft alone (BG) or an autogenous bone graft associated with an e-PTFE membrane (BGM). Animals were euthanized on days 0, 7, 21, 45, and 60. The specimens were subjected to immunohistochemistry for bone sialoprotein (BSP), osteonectin (ONC), and osteocalcin (OCC). Results All groups (OVX+BG, OVX+BMG, SHAM+BG, and SHAM+BMG) showed greater bone formation, observed between 7 and 21 days, when BSP and ONC staining were more intense. At the 45-day, the bone graft showed direct bonding to the recipient bed in all specimens. The ONC and OCC showed more expressed in granulation tissue, in the membrane groups, independently of estrogen deficiency. Conclusions The expression of bone forming markers was not negatively influenced by estrogen deficiency. However, the markers could be influenced by the presence of the e-PTFE membrane. .

An overview on the treatment of postmenopausal osteoporosis / Uma visão geral sobre o tratamento da osteoporose pós-menopausa

Osteoporosis is a worldwide health problem related to the aging of the population, and it is often underdiagnosed and undertreated. It is related to substantial morbidity, mortality and impairment of the quality of life. Estrogen deficiency is the major contributing factor to bone loss after menopause. The lifetime fracture risk at 50 years of age is about 50% in women. The aim of the treatment of osteoporosis is to prevent fractures. Non-pharmacological treatment involves a healthy diet, prevention of falls, and physical exercise programs. Pharmacological treatment includes calcium, vitamin D, and active medication for bone tissue such, as anti-resorptives (i.e., SERMs, hormonal replacement therapy, bisphosphonates, denosumab), bone formers (teriparatide), and mixed agents (strontium ranelate). Bisphosphonates (alendronate, risedronate, ibandronate, and zoledronate) are the most used anti-resorptive agents for the treatment of osteoporosis. Poor compliance, drug intolerance, and adverse effects can limit the benefits of the treatment. Based on the knowledge on bone cells signaling, novel drugs were developed and are being assessed in clinical trials.

A osteoporose é um problema de saúde mundial relacionada com o envelhecimento da população e muitas vezes é subdiagnosticada e subtratada. Relaciona-se à significativa morbidade, mortalidade e redução da qualidade de vida. A deficiência de estrogênio é o principal fator que contribui para a perda óssea após a menopausa. O risco de fratura a partir dos 50 anos de idade é de cerca de 50% em mulheres. O objetivo do tratamento da osteoporose é a prevenção de fraturas. O tratamento não farmacológico envolve uma dieta saudável, prevenção de quedas e de programas de exercícios físicos. O tratamento farmacológico inclui cálcio, vitamina D e medicação ativa em tecido ósseo, tais como antirreabsortivos (SERMs, terapia de substituição hormonal, bifosfonatos, denosumabe), formadores de osso (PTH e análogos) e agentes mistos (ranelato de estrôncio). Os bisfosfonatos (alendronato, risedronato, ibandronato e zoledronato) são os mais utilizados agentes antirreabsortivos para o tratamento da osteoporose. A baixa aderência, a intolerância medicamentosa e os efeitos adversos podem limitar os benefícios do tratamento. Com base no conhecimento da sinalização entre as células ósseas, novos medicamentos foram desenvolvidos e estão sendo avaliados em ensaios clínicos.

Effect of cyclic versus continous hormonal replacement therapy on the structure of dentate gyrus of ovarictomized adult albino rats: a histological and immunohistochemical study

Hormonal replacement has been implicated as a possible therapeutic agent for ameliorating age-related cognitive decline in postmenopausal women. Estrogen in particular enhanced learning and memory in many women by improving the function of hippocampus after menopause. However, there is lack of studies concerning the most effective way of replacement therapy. The aim of the study was to investigate the effect of hormonal replacement on the structure of dentate gyrus and to assess the most effective therapy regimen. Thirty six adult female albino rats were used in the study and were divided into four groups: the control group, the ovariectomized group, the ovariectomy and continuous estrogen+progesterone group, and the ovariectomy and cyclic estrogen+progesterone group. All rats were sacrificed after 5 months from the beginning of therapy. Coronal brain specimens were obtained, processed into paraffin blocks, and subjected to histological, immunohistochemical, histomorphometric, and statistical studies. Ovariectomy resulted in neurodegenerative changes in the dentate gyrus. These changes were partially reversed by continuous hormonal therapy; however, cyclic method of therapy was more effective. Cyclic hormonal therapy was proven to be more effective than continuous method after ovariectomy. Hence, it is recommended to use the cyclic method of hormonal therapy for after menopause

Calcium and caffeine interaction in increased calcium balance in ovariectomized rats / Interação cálcio e cafeína no aumento do balanço de cálcio em ratas ovariectomizadas

OBJECTIVE: This study investigated the effects of caffeine intake associated with inadequate or adequate calcium intake in laparotomized or ovariectomized rats by means of the calcium balance. Forty adults Wistar rats were ovariectomized or laparotomized. METHODS: The animals (n=40) were randomly placed in eight groups receiving the AIN-93 diet with 100% or 50% of the recommended calcium intake with or without added caffeine (6mg/kg/day). The animals were kept in individuals metabolic cages at a temperature of 24°±2ºC, light/dark cycles of 12/12 hours, and deionized water available ad libitum. On the 8th week of the experiment, food consumption was measured and 24-hour urine and 4-day feces were collected to determine calcium balance [Balance=Ca intake-(Urinary Ca+Fecal Ca)]. RESULTS: Animals with adequate calcium intake presented higher balances and rates of calcium absorption and retention (p<0.05) than those with inadequate calcium intake, regardless of caffeine intake (p<0.05). Caffeine intake did not affect urinary calcium excretion but increased balance (p<0.05) in the groups with adequate calcium intake. CONCLUSION: Adequate calcium intake attenuated the negative effects of estrogen deficiency and improved calcium balance even in the presence of caffeine.

OBJETIVO: Investigar a relação entre a ingestão de cafeína e a adequação de cálcio dietético em ratas ovariectomizadas ou inteiras, por meio do balanço de cálcio. Foram utilizadas 40 ratas Wistar adultas submetidas à cirurgia de ovariectomia ou laparotomia. MÉTODOS: Os animais foram alocados em grupos (n=5) e receberam dieta AIN-93M contendo 100 ou 50% da recomendação de cálcio com ou sem adição de cafeína (6mg/kg/dia). As fêmeas foram alojadas em gaiolas metabólicas individuais, à temperatura de 24±2ºC e ciclo de 12 horas claro/escuro e receberam água deionizada ad libitum. Na oitava semana de experimento, quantificou-se a ingestão da dieta e coletaram-se fezes de 4 dias e urina dos animais por 24 horas para determinação do balanço [Balanço=Ca Ingerido - (Ca Fecal+Ca Urinário)]. RESULTADOS: Por meio de interação entre fatores, foi observado que o consumo de 100% de cálcio elevou o balanço e os teores de cálcio absorvido e retido (p<0,05) quando comparados aos grupos 50%. As ratas com adequação no consumo de cálcio aumentaram o balanço (p<0,05), independentemente da suplementação de cafeína. A ingestão de cafeína não afetou a excreção urinária de cálcio e elevou (p<0,05) o balanço nas ratas com 100% de cálcio, mas não nas com 50%. CONCLUSÃO: A adequação no consumo de cálcio atenuou os efeitos deletérios da redução estrogênica e proporcionou maior balanço de cálcio mesmo com ingestão de cafeína.

Supervivencia en pacientes con cáncer de mama triple negativo / Superlife in patients with breast triple negative cancer

El cáncer de mama es una enfermedad heterogénea y multifactorial. Se estadifica en base al sistema TNM. En los últimos años la biología molecular y la inmunohistoquímica, nos permite una nueva perspectiva con una clasificación molecular que nos lleva a un abordaje terapéutico diferente; nos muestran un fenotipo triple negativo que se define por falta de expresión de receptores estrogénicos, progestágeno y her2/neu. Este subgrupo son bastantes agresivos y de mal pronóstico. En diferentes estudios, la sobrevida en 5 años oscila entre 3% - 15%. Este trabajo hace mención a la supervivencia de pacientes con cáncer de mama triple negativo. Estudio observacional, prospectivo no concurrente. Se evaluaron 472 pacientes con cáncer de mama entre enero 2004 y diciembre 2009. Solo en 269 pacientes se realizó la inmunohistoquímica, de estos 65 pacientes fueron clasificados como triple negativo, excluyendo 13 y quedando 52 pacientes. La incidencia fue del 11% y la sobrevida reportó un 11,5% a 5 años. El grupo etario predominante estuvo entre 60-69 años (34,6%). Los estadios tempranos y el grupo de edad de 40 a 49 años mostraron mayor sobrevida libre de enfermedad. El tipo histológico mixto y lobulillar presentaron menor sobrevida libre de enfermedad. Observamos que a mayor invasión ganglionar menor sobrevida libre de enfermedad, y al igual que en otros estudios, el tamaño tumoral y la metástasis ganglionares mantienen su valor pronóstico en la sobrevida libre de enfermedad

The cancer of the breast is a heterogeneous disease and considered depend of multiple factors. It was classified based on of the system TNM. In the last years the molecular biology and the immunohistochemestry, allows us a new perspective with a molecular classification that takes a therapeutic different boarding, where they show a triple negative phenotype that is defined for lack of expression of recipients estrogenic, progestagen and her2/ neu all negatives. This subgroup are aggressive enough and of badly forecasts. In different studies, the survival in 5 years ranged from 3 % to 15%. This work mentions patients survival with triple negative cancer classified of the breast. The study was observational, market not competing. We study and evaluated 472 patients by cancer of breast between the years January of 2004 to December 2009. Only 269 patients of them were immunohistochemestry study, of these we found 65 patients classified how triple negative breast cancer, we excluding 13 and leaving 52 patients. The incidence was 11% and we reported 11.5% survival at 5 years. The predominant age group was 60-69 years (34.6%). Early stages and the age group 40 to 49 years showed higher disease-free survival. We observed that to mayor ganglion invasion less disease free survival. The higher were to the lower node-free survival. Like other studies, tumor size and lymph node metastases maintain his value in the prognosis and in disease-free survival

Influence of estrogen deficiency and tibolone therapy on trabecular and cortical bone evaluated by computed radiography system in rats / Influência da deficiência estrogênica e do tratamento com tibolona no osso trabecular e cortical avaliada pelo sistema de radiografia computadorizada em ratas

PURPOSE: To verify the effects of tibolone administration on trabecular and cortical bone of ovariectomized female rats by computed radiography system (CRS). METHODS: The experiment was performed on two groups of rats previously ovariectomized, one received tibolone (OVX+T) while the other did not (OVX), those groups were compared to a control group (C) not ovariectomized. Tibolone administration (1mg/day) began thirty days after the ovariectomy and the treatment remained for five months. At last, the animals were euthanized and femurs and tibias collected. Computed radiographies of the bones were obtained and the digital images were used to determine the bone optical density and cortical thickness on every group. All results were statistically evaluated with significance set at P<0.05 percent. RESULTS: Tibolone administration was shown to be beneficial only in the densitometric analysis of the femoral head, performing higher optical density compared to OVX. No difference was found in cortical bone thickness. CONCLUSION: Ovariectomy caused bone loss in the analyzed regions and tibolone administered in high doses over a long period showed not to be fully beneficial, but preserved bone mass in the femoral head.

OBJETIVO: Verificar o efeito da administração de tibolona no tecido ósseo cortical e trabecular de ratas castradas através de radiografia computadorizada. MÉTODOS: O experimento foi realizado em dois grupos de ratas previamente ooforectomizadas, onde um grupo recebeu tibolona (OVX+T) e o outro não (OVX). Esses grupos foram comparados a um grupo controle (C) não ooforectomizado. A administração de tibolona (1mg/dia) começou trinta dias após a ooforectomia e o tratamento teve duração de cinco meses. No final, os animais foram mortos e fêmures e tibias coletados. As radiografias computadorizadas dos ossos foram obtidas e as imagens digitais usadas para determinar a densidade óssea e a espessura cortical em todos os grupos. Todos os resultados foram avaliados estatisticamente com significância estabelecida a 5 por cento. RESULTADOS: A administração de tibolona mostrou ser benéfica apenas para análise densitométrica da cabeça do fêmur, apresentando maiores valores de densidade comparada ao grupo OVX. Nenhuma diferença significativa foi encontrada para espessura óssea cortical. CONCLUSÃO: A ooforectomia ocasionou perda óssea nas regiões analisadas e a tibolona administrada, em dose elevada e durante um longo período, mostrou não ser totalmente benéfica, porém preservou a massa óssea na cabeça femoral.

Influence of different durations of estrogen deficiency on alveolar bone loss in rats

The purpose of this study was to morphometrically evaluate the influence of different durations of ovariectomy-induced estrogen deficiency on alveolar bone loss associated with ligature-induced bone loss in rats. Sixty female Wistar rats were randomly assigned to ovariectomy (OVX test group) or sham operation (SHAM control group). The OVX and SHAM groups were each distributed into three subgroups of ten rats each according to the duration of estrogen deficiency (30, 60 and 90 postoperative days). In all groups, for the last 30 days of the experimental period, cotton ligatures were placed around the cervix of the right upper second molar; the contralateral tooth was left unligated to serve as a control. The maxillary bones were removed, and the alveolar bone loss was analyzed by measuring the distance between the cementoenamel junction and the alveolar bone crest at the buccal site of the right upper second molar. A comparison between the ligated and unligated groups verified the presence of ligature-induced alveolar bone loss (p < 0.05). No significant differences were observed among the unligated groups (p > 0.05). A significant increase in bone loss was observed when ligation occurred 90 days after ovariectomy compared with the sham group (p < 0.05). These results demonstrate that long-term estrogen deficiency affects ligature-induced alveolar bone loss.

Efeito da deficiência de estrógeno no preenchimentode defeitos ósseos tratados ou não com biomaterial:um estudo radiográfico em ratas / The effect of estrogen deficiency on filling bone defects treated or not with biomaterial: a radiographic study on rats

Objetivos: O objetivo deste estudo foi avaliar radiograficamente o preenchimento ósseo de defeitos criados em tíbia de ratas ovariectomizadas e não ovariectomizadas, preenchidos por coágulo ou material substituto ósseo. Materiais e métodos: Foram utilizadas 30 ratas wistar, sendo que 15 foram ovariectomizadas(grupo OV) e 15 ratas não receberam ovariectomia (grupo NOV). Decorridos 60 dias da cirurgia de ovariectomia,ambos os grupos foram submetidos à cirurgia para confecção de defeitos ósseos nas tíbias. A tíbia direita foi preenchida por coágulo, e a esquerda, por biomaterial sintético (Bone Ceramic®), formando os seguintes grupos: grupos não ovariectomizados com defeitos preenchidos por coágulo (grupo NOV/C) ou por biomaterial (grupo NOV/B), e grupos ovariectomizados com defeitos preenchidos por coágulo (grupoOV/C) ou por biomaterial (grupo OV/B). Decorridos 60 dias da cirurgia de confecção dos defeitos e seus preenchimentos, as ratas foram mortas e suas tíbias removidas. A densidade óssea das tíbias foi avaliada em radiografias digitais e as imagens foram estudadas no programa de imagem ImageJ, por examinador único.Para a análise estatística, utilizou-se o teste Anova a dois critérios multifatoriais completos com α < 0,05.Resultados: A porcentagem média de preenchimento ósseo para cada grupo foi: grupo NOV/C, 71,55%;grupo NOV/B, 70,44%; grupo OV/C, 21,03% e grupo OV/B, 58,93%. Conclusão: Com base nos resultados par obtidos,pôde-se concluir que a deficiência de estrógeno interferiu no grau de preenchimento ósseo em defeitos cirurgicamente criados em tíbias de ratas, com ou sem o uso de um biomaterial.

Objectives: The aim of this study was to evaluate radiographically the bone filling of defects surgically createdin the tibiae of ovariectomized and non-ovariectomized rats. Defects were filled with coagulum or syntheticbone graft. Materials and methods: Thirty female Wistar rats were divided into two groups: 15 rats receivedovariectomy (group OVX) and 15 did not (group NOVX). Sixty days after ovariectomy surgery, both groups weresubmitted to ostectomy surgery for bone defect creation in the tibiae. The right tibiae were filled with coagulumand the left one with synthetic bone graft (Bone Ceramic®). The groups of study were: non--ovariectomizedgroup, with defects filled with coagulum (group NOV/C) or biomaterial (group NOV/B), and ovariectomizedgroup, with defects filled with coagulum (group OV/C) or biomaterial (group OV/B). After 120 days, the ratswere sacrificed and their tibiae removed. The bone density was evaluated by digital radiograph and the imageswere analyzed by ImageJ program. In order to carry out the statistical analysis, Anova test was applied α <0.05. Results: The mean percentages of bone filling for each group were: group NOV/C, 71.55%; group NOV/B,70.44%; group OV/C, 21.03% and group OV/B, 58.93%. Conclusion: Based on the results obtained, it was possibleto conclude that estrogen deficiency interfered on the level of bone filling of surgically created defects inrats tibiae, with or without the use of biomaterial.

La calidad de vida de las mujeres en edad media varía según el estado menopáusico / Quality of life in middle aged women varies with menopausal status

Objetivo: evaluar con la escala MRS (Menopause Rating Scale) la frecuencia y gravedad de los síntomas menopáusicos presentes en un conjunto de mujeres saludables en la edad media de la vida. Metodología: estudio transversal con aplicación de la escala MRS entre noviembre de 2006 y enero de 2009 a 1.215 mujeres saludables de 40-59 años de edad, originarias y residentes en distintas comunidades de la región Caribe colombiana. El grupo incluyó afrodescendientes, indígenas y mestizas (hispano-colombianas). Se las dividió en premenopáusicas, perimenopáusicas y postmenopáusicas. Resultados: las molestias musculares y articulares, oleadas de calor, cansancio físico y mental e irritabilidad se presentaron en más del 60% de las mujeres, pero el síntoma predominante fue diferente en cada estado menopáusico. El cansancio físico y mental predominó en la premenopausia (58,9%), las molestias musculares y articulares en la perimenopausia (78,9%) y las oleadas de calor en la postmenopausia (83,2%). Se evidenció un deterioro progresivo de la calidad de vida, en todos los ítems evaluados, al pasar del estado premenopáusico al posmenopáusico. También se halló deterioro de la calidad de vida con el paso del estado premenopáusico al perimenopáusico en todos los ítems (con excepción de los problemas vesicales); de la perimenopausia a la posmenopausia se observó deterioro a expensas de oleadas de calor, problemas sexuales y de vejiga, sequedad vaginal y molestias músculo-articulares, en tanto que los puntajes de molestias cardíacas, trastornos del sueño, estado de ánimo depresivo, irritabilidad, ansiedad, cansancio físico y mental se redujeron en la posmenopausia, aunque permanecieron por encima de los puntajes de la premenopausia. Conclusiones: Caracterizar los síntomas climatéricos y su comportamiento a lo largo de los estados menopáusicos permite establecer medidas de prevención y de intervención que mejoren la calidad de vida de la mujer en esta etapa.

Objective: To determine, by means of the MRS scale (Menopause Rating Scale), the frequency and severity of menopausal symptoms in a group of healthy middle-aged, Colombian women. Methods: A cross sectional study was carried out between November 2006 and January 2009. A survey form and the MRS were applied to 1.215 healthy women 40-59 years old, native and resident in different communities of the Colombian Caribbean coast, who were from African, indigenous or mestizo descent. According to their menopausal status they were divided into premenopausal, menopausal and postmenopausal. Results: Joint and muscular discomfort, hot flashes, physical and mental exhaustion, and irritability were present in more than 60% of the whole group. The predominant symptom, however, differed according to the menopausal status: physical and mental exhaustion in premenopausal women (58.9%), joint and muscular discomfort in the perimenopausal ones (78.9%) and hot flashes during the postmenopause (83.2%). A gradual decline in the quality of life (QOL) was evident from premenopause through perimenopause to postmenopause. Deterioration in the QOL was found from premenopause to perimenopause in all items (with the exception of bladder problems). Decline was also observed from perimenopause to postmenopause centered on hot flashes, sex and bladder problems, vaginal dryness and joint and muscular discomfort. In contrast, the scores of heart discomfort, sleep disturbances, depressed mood, irritability, anxiety and physical and mental exhaustion decreased in the postmenopause although they remained higher than those of the premenopausal women. Conclusions: Knowledge of the profile of climacteric symptoms and of their behavior through the menopausal statuses is the basis for preventive strategies and appropriate interventions that improve the quality of life of women.

Expression of TGF-β1 in the blood during fracture repair in an estrogen-deficient rat model

OBJECTIVES: Previous studies have reported that osteoporosis due to estrogen deficiency influences fracture healing. Transforming growth factor (TGF-b) has been found to be involved in fracture healing via the regulation of the differentiation and activation of osteoblasts and osteoclasts. The current study aimed to determine the effects of estrogen on the expression of TGF-β1 during fracture healing in ovariectomized rats. METHODS: Thirty female Sprague-Dawley rats weighing 200-250 g were assigned to: (i) a sham-operated group that was given a normal saline; (ii) an ovariectomized control group that was given a normal saline; or (iii) an ovariectomized + estrogen (100 mg/kg/day) group that was treated with conjugated equine estrogen. The right femur of all rats was fractured, and a Kirschner wire was inserted six weeks post-ovariectomy. Treatment with estrogen was given for another six weeks post-fracture. At the end of the study, blood samples were taken, and the right femur was harvested and subjected to biomechanical strength testing. RESULTS: The percentage change in the plasma TGF-β1 level before treatment was significantly lower in the ovariectomized control and estrogen groups when compared with the sham group (p<0.001). After six weeks of treatment, the percentage change in the plasma TGF-β1 level in the estrogen group was significantly higher compared with the level in the ovariectomized control group (p = 0.001). The mean ultimate force was significantly increased in the ovariectomized rats treated with estrogen when compared with the ovariectomized control group (p = 0.02). CONCLUSION: These data suggest that treatment with conjugated equine estrogen enhanced the strength of the healed bone in estrogen-deficient rats by most likely inducing the expression of TGF-β1.

Piper sarmentosum enhances fracture healing in ovariectomized osteoporotic rats: a radiological study

INTRODUCTION: Osteoporotic fractures are common during osteoporotic states. Piper sarmentosum extract is known to possess antioxidant and anti-inflammatory properties. OBJECTIVES: To observe the radiological changes in fracture calluses following administration of a Piper sarmentosum extract during an estrogen-deficient state. METHODS: A total of 24 female Sprague-Dawley rats (200-250 g) were randomly divided into 4 groups: (i) the sham-operated group; (ii) the ovariectomized-control group; (iii) the ovariectomized + estrogen-replacement therapy (ovariectomized-control + estrogen replacement therapy) group, which was supplemented with estrogen (100 μg/kg/day); and (iv) the ovariectomized + Piper sarmentosum (ovariectomized + Piper sarmentosum) group, which was supplemented with a water-based Piper sarmentosum extract (125 mg/kg). Six weeks after an ovariectomy, the right femora were fractured at the mid-diaphysis, and a K-wire was inserted. Each group of rats received their respective treatment for 6 weeks. Following sacrifice, the right femora were subjected to radiological assessment. RESULTS: The mean axial callus volume was significantly higher in the ovariectomized-control group (68.2 + 11.74 mm³) than in the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups (20.4 + 4.05, 22.4 + 4.14 and 17.5 + 3.68 mm³, respectively). The median callus scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups had median (range, minimum - maximum value) as 1.0 (0 - 2), 1.0 (1 - 2) and 1.0 (1 - 2), respectively, which were significantly lower than the ovariectomized-control group score of 2.0 (2 - 3). The median fracture scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups were 3.0 (3 - 4), 3.0 (2 - 3) and 3.0 (2 - 3), respectively, which were significantly higher than the ovariectomized-control group score of 2.0 (1 - 2) (p<0.05). CONCLUSION: The Piper sarmentosum extract improved fracture healing, as assessed by the reduced callus volumes and reduced callus scores. This extract is beneficial for fractures in osteoporotic states.