<p>Generalni cilj ovog istraživanja je da se utvrdi da li postoji uticaj primenjenog<br />programa vežbanja na parametre ko&scaron;tane gustine i biohemijske markere ko&scaron;tanog<br />remodelovanja kod žena u periodu premenopauze i postmenopauze.<br />Uzorak ispitanica je činilo 26 žena starosti 45 do 55 godina, od kojih su 13 u periodu<br />premenopauze, a 13 u periodu postmenopauze. Ispitanice su učestvovale u programu vežbanja<br />u trajanju od 6 meseci, koji se realizovao u Novom Sadu, 4 puta nedeljno u trajanju od sat<br />vremena. Za utvrđivanje uticaja programa vežbanja na ko&scaron;tanu gustinu merena su 3<br />osteodenzitometrijska parametra na kičmi, vratu butne kosti i kuku i 5 parametara<br />biohemijskih markera ko&scaron;tanog remodelovanja.<br />Da bi se utvrdio uticaj vežbanja kod ispitanica, primenjena je multivarijatna analize<br />varijanse (MANOVA). Na celokupnom uzorku ispitanica nije utvrđena statistički značajna<br />razlika ni u jednom merenom parametru ko&scaron;tane gustine. U odnosu na biohemijske markere,<br />do&scaron;lo je do značajnog smanjenja nivoa ukupne alkalne fosfataze. Kod žena u periodu<br />premenopauze i kod žena u periodu postmenopauze, program vežbanja nije značajno uticao<br />na parametre ko&scaron;tane gustine merene na kičmi, vratu butne kosti i kuku (DXA, Lunar<br />Prodrigy), kao ni na parametre biohemijskih markera ko&scaron;tanog remodelovanja.<br />Primenom multivarijatne analize kovarijanse (MANCOVA) utvrđena je značajna<br />razlika u uticaju programa vežbanja između žena u pre- i postmenopauzi u mineralnoj<br />ko&scaron;tanoj gustini vrata butne kosti (BMD VF) i markera beta-crosslaps (CTX). Mineralna<br />ko&scaron;tana gustina je nakon programa vežbanja veća, a nivo beta-crosslapsa niži kod žena u<br />premenopauzi nego kod žena u periodu postmenopauze.<br />Na osnovu dobijenih rezultata, zaključujemo da je potreban duži vremenski period<br />realizacije programa vežbanja kako bi se mogla primetiti statistički značajna promena<br />merenih parametara. Ispitanicama se savetuje da nastave sa vežbanjem kako bi usporile<br />gubitak kosti</p> / <p>The genaral aim of this research is to determine is there an effects of the applied exercise<br />program on bone mineral density and and biochemical markers of bone turnover in the<br />premenopausal and postmenopausal period.<br />The sample was consisted of 26 women aged 45 to 55 years, of which 13 were in<br />premenopausal and 13 in postmenopausal period. Subjects were included (had performing) in 6-month<br />exercise program, which was implemented (maintained) in Novi Sad, 4 times a week in duration for an<br />hour. Three osteodensitometric parameters on lumbar spine, femoral neck and hip (DXA, Lunar<br />Prodrigy) and five parameters of biochemical markers of bone turnover were measured to assessed<br />(to determine) the effects of exercise program on bone density.<br />Multivariate analysis of variance (MANOVA) was used to determine the effect of exercise.<br />For the entire sample of subjects, there were no statistically significant difference in any measured<br />bone density parameter, but looking at biochemical markers, total alkaline phosphatase level were<br />significanly reduced. There were no significant changes in bone density parameters on the lumbar<br />spine, femoral neck and hip nor on the parameters of biochemical markers of bone turnover in women<br />in premenopausal and postmenopausal period.<br />Applying multivariate analyse of covariance it was found a significant difference in the<br />exercise program effect between pre- and postmenopausal women in bone mineral density of femoral<br />neck (BMD VF) and beta-crosslaps marker of turnover (CTX). Femoral neck BMD was higher, and<br />beta-crosslaps level was lower in premenopausal women than in postmenopausal women after<br />completion exercise program.<br />Based on obtained results, we conclude that is required a longer perod of exercise program<br />ralization in order to notice a statistically significant change in measured parameters. Subjects are<br />advised to continue their exercising in order to slow down the bone loss</p>

Homocystein (tHcy) gilt als unabhängiger kardiovaskulärer Risikofaktor und korreliert eng mit einer endothelialen Dysfunktion, welche nichtinvasiv mittels der flussinduzierten Vasodilatation (FMD) messbar ist. Experimentelle Hyperhomocysteinämie ist mit einer reduzierten Bioverfügbarkeit von endothelialen Stickstoffmonoxid (NO) bei gleichzeitig erhöhten Spiegeln des kompetetiven Inhibitors der NO-Biosynthese asymmetrisches Dimethylarginin (ADMA) assoziiert. In-vivo senkt eine Östrogenbehandlung neben tHcy auch die ADMA-Spiegel und verbessert signifikant die Endothelfunktion. Hinsichtlich ihrer Wirkung als selektive Östrogenrezeptormodulatoren wird angenommen, dass Phytoöstrogene, speziell Sojaisoflavone, ähnliche Effekte hervorrufen.<br><br> Innerhalb einer europäischen, multizentrischen, doppelblinden Interventionsstudie an 89 gesunden, postmenopausalen Frauen wurde der Einfluss von Sojaisoflavonen auf den Homocysteinmetabolismus, den Blutdruck und die in-vivo Endothelfunktion untersucht. Die cross-over Studie umfasste zwei achtwöchige Interventionsperioden, die von einer gleichlangen Wash-out-Phase unterbrochen waren. Die Zuteilung zum Isoflavon- (50 mg/d) oder Plazeboregime für die erste Interventionsphase erfolgte randomisiert. Endpunkterhebungen fanden jeweils in den Wochen 0 und 8 der Interventionsperioden statt.<br><br> Die renale Ausscheidung von Genistein, Daidzein und Equol war während der Isoflavonintervention signifikant erhöht (P>0,001). Die Phyoöstrogene hatten weder einen Effekt auf die tHcy-Konzentration (P=0,286), noch auf ADMA, Erythrozytenfolat und Vitamin B-12 (P>0,05) im Plasma. Während die Summe aus Nitrat und Nitrit (NOx), welche die NO-Bioverfügbarkeit reflektiert, im Verlaufe der Plazebobehandlung abfiel, wurde ein leichter Anstieg bei der Isoflavonsupplementation beobachtet (Delta Wo8-Wo0: -2,60 [-8,75; 2,25] vs. 1,00 [-6,65; 7,85] µmol/L P<0,001), was zu einem signifikanten Behandlungseffekt führte. Weiterhin wurde eine positive Korrelation zwischen ADMA und Vitamin B-12 gefunden (R=0,252; P=0,018). Die flussinduzierte Vasodilatation (P=0,716), ein Maß für die Endothelfunktion, blieb durch die Isoflavonbehandlung unbeeinflusst, obwohl sich diese über die Zeit insgesamt verbesserte (P>0,001). Bis auf einen marginalen Anstieg des systolischen Wertes (P=0,032) im Vergleich zur Plazebobehandlung blieb der Blutdruck während der Isoflavonintervention unverändert.<br><br> Im Gegensatz zu Östrogen übten Sojaisoflavone weder einen Einfluss auf die in-vivo Endothelfunktion noch auf die traditionellen und neuen kardiovaskulären Risikofaktoren den Blutdruck, tHcy und ADMA aus. Demzufolge ist der gesundheitliche Nutzen isolierter Isoflavone hinsichtlich einer Prävention hormonmangelbedingter Erkrankungen in gesunden postmenopausalen Frauen fraglich. / Homocysteine (tHcy) is a strong and independent risk factor for cardiovascular disease. Hyperhomocysteinemia contributes to endothelial dysfunction as assessed by flow-mediated vasodilation (FMD). The mechanisms by which homocysteine generates endothelial dysfunction remain incompletely understood although a growing body of data suggests that the bioavailability of nitric oxide (NO) is reduced. The principal competitive inhibitor of endothelial NO-synthase asymmetric dimethylarginine (ADMA) may play a central role in homocysteine related dysfunction as it is derived from homocysteine metabolism. Cardiovascular risk factor modification has suggested beneficial effects of estrogen on endothelial function by lowering homocysteine and ADMA levels. We hypothesize that phytoestrogens particular isoflavones act in a similar manner.<br><br> The effects of soy isoflavones on homocysteine metabolism and endothelial function were investigated within a multi-centre, double blind, cross-over intervention trial in 89 European postmenopausal women. Subjects consumed either fruit cereal bars with or without soy isoflavones (50 mg/d) for 8 weeks each with a 8 weeks washout period in between. Endpoint measurements were during both treatment phases at baseline and weeks 8, respectively. <br><br> Urinary phytoestrogens increased significantly after isoflavone intervention (P<0.001). Isoflavone supplementation did affect neither plasma total homocysteine (P=0.286) nor ADMA, vitamin B-12 or folate (P<0.05). Isoflavones had a favorable effect on NO-metabolism assessed by analysis of NO-metabolites (NOx) nitrite and nitrate. While NOx concentration significantly decreased during placebo there was a slight increase after isoflavone supplementation leading to a significant treatment difference (delta wk8-wk0: -2.60 [-8.75; 2.25] vs. 1.00 [-6.65; 7.85] µmol/L P<0.001). There was no association between total homocysteine and ADMA whereas a positive correlation was found for ADMA and vitamin B-12 (R=0.252; P=0.018). The endothelial function model did not demonstrate any difference between either treatment regime (P=0.716), although endothelial function assessed by flow-mediated vasodilation improved in general (P<0.001). A potential adverse effect was noted, with an elevation in systolic blood pressure (P=0.032) whereas diastolic blood pressure and mean arterial pressure remained unaffected.<br><br> Soy isoflavones did not have beneficial effects on endothelial function as well as on traditional and novel cardiovascular risk factors like plasma homocysteine, blood pressure and ADMA as observed for estrogen treatment. The health benefit of isolated isoflavones in healthy postmenopausal women is questionable.

Objectifs: Évaluer si un programme d’entraînement en résistance d’une durée d’un an prévient le regain de poids et majore l’amélioration du profil inflammatoire. Le second objectif de cette étude était de déterminer si la variation du tissu adipeux viscéral est associée aux changements dans les concentrations sanguines des marqueurs inflammatoires. Méthodes: Soixante-dix femmes post-ménopausées en surpoids ou obèses ont été randomisées dans un des deux groupes suivants : (1) Contrôle ou (2) Entraînement en résistance. La composition corporelle (absorptiométrie double à rayons X et tomographie axiale) et les marqueurs inflammatoires (protéine C-réactive, orosomucoïde, haptoglobine) ont été évalués avant et après la période de suivi d’une durée d’un an. Résultats: Suite à la période de suivi, un regain significatif de poids corporel et de masse grasse était observé dans le groupe contrôle et le groupe entraînement en résistance (p < 0,05). Une réduction des concentrations sériques de l’orosomucoïde et une hausse des niveaux sériques de l’haptoglobine étaient également notées dans les deux groupes (p < 0,05). La variation du tissu adipeux viscéral était seulement associée aux changements dans les concentrations sériques de la protéine C-réactive (r = 0,373, p < 0,05). Conclusion: Nos résultats suggèrent que l’entraînement en résistance ne prévient pas le regain de poids corporel et ne majore pas l’amélioration du profil inflammatoire chez des femmes post-ménopausées en surpoids ou obèses. De plus, nos résultats indiquent que la variation du tissu adipeux viscéral ne semble pas être un facteur clé impliqué dans les changements des concentrations sanguines des marqueurs inflammatoires. / Objectives: To evaluate if a 1-year resistance training program improved weight loss maintenance and the inflammatory profile in overweight and obese postmenopausal women. The second objective of this study was to determine if the variation in visceral adipose tissue was associated with the changes in inflammatory markers concentrations. Methods: Seventy overweight and obese postmenopausal women were randomized to a control group or a resistance training group. Body composition (dual energy X-ray absorptiometry and computed tomography) and inflammatory markers (C-reactive protein, orosomucoid, haptoglobin) were measured before and after the 1-year weight loss maintenance intervention. Results: Following the weight loss maintenance intervention, we observed a significant body weight and fat mass regain in the control group and the resistance training group (p < 0.05). Significant reductions in orosomucoid and increases in haptoglobin concentrations were noted in both groups (p < 0.05). The variation in visceral adipose tissue was only associated with the changes in C-reactive protein concentrations (r = 0,373, p < 0.05). Conclusion: Our results suggest that resistance training do not improve weight loss maintenance and the inflammatory profile in overweight and obese postmenopausal women. Moreover, our results indicate that the variation in visceral adipose tissue may not be a key factor implicated in the changes in inflammatory markers concentrations.

Glycemic intake influences the rise in blood glucose concentration following consumption of a carbohydrate containing meal, known as the postprandial glycemic response. The glycemic response is a result of both the type and amount of carbohydrate foods consumed and is commonly measured as the glycemic index (GI) or glycemic load (GL), where the GI is a ranking in comparison to glucose and the GL is an absolute value encompassing both the GI and amount of carbohydrate consumed. Evidence from controlled trials in rat models suggests that glycemic intake has a role in development of insulin resistance, however trials and observational studies of humans have produced conflicting results. As insulin resistance is a precursor to type 2 diabetes mellitus, lifestyle factors that could prevent development of this condition have important public health implications. Previous observational studies have used food frequency questionnaires to assess usual diet, which could have resulted in a lack of precision in assessment of individual serve sizes, and have been limited to daily measures of glycemic intake. Daily measures do not take fluctuations in glycemic intake on a per meal basis into account, which may be a more relevant measure for investigation in relation to disease outcomes. This PhD research was conducted in a group of Brisbane women aged 42 to 81 years participating in the multidisciplinary Brisbane Longitudinal Assessment of Ageing in Women (LAW study). Older women may be at particular risk of insulin resistance due to age, hormonal changes, and increases in abdominal obesity associated with menopause, and the LAW study provided an ideal opportunity to study the relationship between diet and insulin resistance. Using the diet history tool, we aimed to assess the glycemic intake of the population and hypothesised that daily GI and daily GL would be significantly positively associated with increased odds of insulin resistant status. We also hypothesised that a new glycemic measure representing peaks in GL at different meals would be a stronger predictor of insulin resistant status than daily measures, and that a specially designed questionnaire would be an accurate and repeatable dietary tool for assessment of glycemic intake. To address these hypotheses, we conducted a series of studies. To assess glycemic intake, information on usual diet was obtained by detailed diet history interview and analysed using Foodworks and the Australian Food and Nutrient (AUSNUT) database, combined with a customised GI database. Mean ± SD intakes were 55.6 ± 4.4% for daily GI and 115 ± 25 for daily GL (n=470), with intake higher amoung younger participants. Bread was the largest contributor to intakes of daily GI and GL (17.1% and 20.8%, respectively), followed by fruit (15.5% and 14.2%, respectively). To determine whether daily GI and GL were significantly associated with insulin resistance, the homeostasis model assessment of insulin resistance (HOMA) was used to assess insulin resistant status. Daily GL was significantly higher in subjects who were insulin resistant compared to those who were not (134 ± 33 versus 114 ± 24 respectively, P<0.001) (n=329); the odds of subjects in the highest tertile of GL intake being insulin resistant were 12.7 times higher when compared with the lowest tertile of GL (95% CI 1.6-100.1, P=0.02). Daily GI was not significantly different in subjects who were insulin resistant compared to those who were not (56.0 ± 3.3% versus 55.7 ± 4.5%, P=0.69). To evaluate whether a new glycemic measure representing fluctuations in daily glycemic intake would be a stronger predictor of insulin resistant status than other glycemic intake measures, the GL peak score was developed to express in a single value the magnitude of GL peaks during an average day. Although a significant relationship was seen between insulin resistant status and GL peak score (Nagelkerke’s R2=0.568, P=0.039), other glycemic intake measures of daily GL (R2=0.671, P<0.001) and daily GL per megajoule (R2=0.674, P<0.001) were stronger predictors of insulin resistant status. To develop an accurate and repeatable self-administered tool for assessment of glycemic intake, two sub-samples of women (n=44 for the validation study and n=52 for the reproducibility study) completed a semi-quantitative questionnaire that contained 23 food groupings selected to include the top 100 carbohydrate foods consumed by the study population. While there were significant correlations between the glycemic intake questionnaire and the diet history for GL (r=0.54, P<0.01), carbohydrate (r=0.57, P<0.01) and GI (r=0.40, P<0.01), Bland-Altman plots showed an unacceptable difference between individual intakes in 34% of subjects for daily GL and carbohydrate, and 41% for daily GI. Reproducibility results showed significant correlations for daily GL (r=0.73, P<0.001), carbohydrate (r=0.76, P<0.001) and daily GI (r=0.64, P<0.001), but an unacceptable difference between individual intakes in 25% of subjects for daily GL and carbohydrate, and 27% for daily GI. In summary, our findings show that a significant association was observed between daily glycemic load and insulin resistant status in a group of older women, using a diet history interview to obtain precise estimation of individual carbohydrate intake. Both the type and quantity of carbohydrate are important to consider when investigating relationships between diet and insulin resistance, although our results suggest the association is more closely related to overall daily glycemic intake than individual meal intake variations. A dietary tool that permits precise estimation of carbohydrate intake is essential when evaluating possible associations between glycemic intake and individual risk of chronic diseases such as insulin resistance. Our results also suggest that studies using questionnaires to estimate glycemic intake should state degree of agreement as well as correlation coefficients when evaluating validity, as imprecise estimates of carbohydrate at an individual level may have contributed to the conflicting findings reported in previous studies.

Made available in DSpace on 2016-12-23T13:49:03Z (GMT). No. of bitstreams: 1 Fernanda S Pimentel.pdf: 2000885 bytes, checksum: 1bf180bc2109c67426e7ca0264e6b4ae (MD5) Previous issue date: 2010-07-29 / The bone is a specialized form of connective tissue that provides support for metabolic and biomechanical throughout the body. Thus, the bone is very dynamic, with constantly renewing itself. His integrity therefore depends on the balance between the processes of formation and resorption. The loss of this balance alters both the structure of organic matrix as bone mineralization. Moreover, imbalances in bone remodeling process may result in the development of systemic skeletal diseases such as osteoporosis. The osteoporosis is a chronic progressive disease that affects millions of people around the world. Only in Brazil some 10 million people suffer from osteoporosis. The hormone estrogen deficiency induced by ovariectomy (OVX) rats, demonstrably stimulates increased bone resorption, especially in long bones and spine, mimicking what happens in postmenopausal osteoporosis. In this work we used OVX rats to investigate the interaction of alendronate (a drug widely used to treat osteoporosis) and vitamin K (VK) (recent investigations have pointed anabolic bone tissue of osteoporotic patients) in the metabolism osteomineral. This study revealed that administration of alendronate (ALE) and VK with ALE (ALE+VK) produced significant recovery in bone mineral density (BMD) in OVX rats. However, the use of VK alone did not appear to make any significant effect on BMD in OVX rats. We observed an increased excretion of urinary deoxypyridinoline (DPD), a marker of bone resorption, in OVX group, and statistically significant reduction of DPD when the animals were treated with VK, ALE, or both. There was no statistically significant difference in bone mineral content and body surface area. Was verified statistically significant difference in the thickness of compact bone in the different study groups. There was also a statistically significant reduction in wet weight and endometrium of OVX rats, demonstrating the effectiveness of ovariectomy. Therefore, the animal model used in this study efficiently mimicked estrogen deficiency induced by ovariectomy, resulting in increased bone resorption; treatment with ALE and VK+ALE increases BMD in OVX rats, while the VK alone does not produce this effect; treatment with ALE and VK reduces bone resorption in OVX rats, verified by the reduction in the excretion of DPD. / O osso é uma forma especializada de tecido conjuntivo que fornece suporte biomecânico e metabólico para todo o corpo. Para tanto, o tecido ósseo é muito dinâmico, apresentando-se em constante renovação. Sua integridade depende, portanto, do equilíbrio entre os processos de formação e reabsorção óssea. Ademais, desequilíbrios no processo de remodelamento ósseo podem resultar no desenvolvimento de doenças esqueléticas sistêmicas, como a osteoporose. A osteoporose é uma doença crônica e progressiva que afeta milhões de pessoas em todo o mundo. Somente no Brasil cerca de 10 milhões de pessoas sofrem de osteoporose. A deficiência hormonal estrogênica, induzida pela ovariectomia (OVX) em ratos, comprovadamente estimula o aumento da reabsorção óssea, principalmente em ossos longos e coluna vertebral, mimetizando o que acontece na osteoporose pós-menopausa. No presente trabalho foram utilizadas ratas OVX para se investigar a interação do alendronato (fármaco extensamente utilizado no tratamento da osteoporose) e da vitamina K (VK) (recentes investigações apontam possuir ação anabólica do tecido ósseo de pacientes osteoporóticas) no metabolismo osteomineral. Este estudo revelou que a administração de alendronato (ALE) e de VK juntamente com ALE (VK+ALE) produziu significante recuperação na densidade mineral óssea (DMO) de ratas OVX. No entanto, a utilização da VK isoladamente não pareceu exercer nenhum efeito significante na DMO de ratas OVX. Observou-se uma maior excreção de deoxipiridinolinas urinárias (DPD), marcador de reabsorção óssea no grupo OVX, e redução estatisticamente significante da DPD quando os animais foram tratados com VK, ALE ou ambas. Não houve diferença estatisticamente significante do conteúdo mineral ósseo e da área corporal. Também não foi verificada diferença estatisticamente significante na espessura do osso compacto nos diferentes grupos de estudo. Verificou-se ainda redução estatisticamente significante do peso úmido e do endométrio de ratas OVX, comprovando a eficiência da ovariectomia. Portanto, o modelo animal utilizado neste estudo mimetizou eficientemente a deficiência estrogênica induzida pela ovariectomia, resultando em aumento da reabsorção óssea; o tratamento com ALE e VK+ALE aumenta a DMO de ratas OVX, embora a VK isoladamente não apresente esse efeito; o tratamento com ALE e VK reduz a reabsorção óssea de ratas OVX, verificada pela redução na excreção de DPD.

Made available in DSpace on 2016-12-23T13:49:04Z (GMT). No. of bitstreams: 1 Dissertacao de Fernanda Scarpatti Pimentel.pdf: 2000878 bytes, checksum: cdfb57d1ceb94c6e6c0b410060dcfbfb (MD5) Previous issue date: 2010-07-29 / The bone is a specialized form of connective tissue that provides support for metabolic and biomechanical throughout the body. Thus, the bone is very dynamic, with constantly renewing itself. His integrity therefore depends on the balance between the processes of formation and resorption. The loss of this balance alters both the structure of organic matrix as bone mineralization. Moreover, imbalances in bone remodeling process may result in the development of systemic skeletal diseases such as osteoporosis. The osteoporosis is a chronic progressive disease that affects millions of people around the world. Only in Brazil some 10 million people suffer from osteoporosis. The hormone estrogen deficiency induced by ovariectomy (OVX) rats, demonstrably stimulates increased bone resorption, especially in long bones and spine, mimicking what happens in postmenopausal osteoporosis. In this work we used OVX rats to investigate the interaction of alendronate (a drug widely used to treat osteoporosis) and vitamin K (VK) (recent investigations have pointed anabolic bone tissue of osteoporotic patients) in the metabolism osteomineral. This study revealed that administration of alendronate (ALE) and VK with ALE (ALE+VK) produced significant recovery in bone mineral density (BMD) in OVX rats. However, the use of VK alone did not appear to make any significant effect on BMD in OVX rats. We observed an increased excretion of urinary deoxypyridinoline (DPD), a marker of bone resorption, in OVX group, and statistically significant reduction of DPD when the animals were treated with VK, ALE, or both. There was no statistically significant difference in bone mineral content and body surface area. Was verified statistically significant difference in the thickness of compact bone in the different study groups. There was also a statistically significant reduction in wet weight and endometrium of OVX rats, demonstrating the effectiveness of ovariectomy. Therefore, the animal model used in this study efficiently mimicked estrogen deficiency induced by ovariectomy, resulting in increased bone resorption; treatment with ALE and VK+ALE increases BMD in OVX rats, while the VK alone does not produce this effect; treatment with ALE and VK reduces bone resorption in OVX rats, verified by the reduction in the excretion of DPD / O osso é uma forma especializada de tecido conjuntivo que fornece suporte biomecânico e metabólico para todo o corpo. Para tanto, o tecido ósseo é muito dinâmico, apresentando-se em constante renovação. Sua integridade depende, portanto, do equilíbrio entre os processos de formação e reabsorção óssea. Ademais, desequilíbrios no processo de remodelamento ósseo podem resultar no desenvolvimento de doenças esqueléticas sistêmicas, como a osteoporose. A osteoporose é uma doença crônica e progressiva que afeta milhões de pessoas em todo o mundo. Somente no Brasil cerca de 10 milhões de pessoas sofrem de osteoporose. A deficiência hormonal estrogênica, induzida pela ovariectomia (OVX) em ratos, comprovadamente estimula o aumento da reabsorção óssea, principalmente em ossos longos e coluna vertebral, mimetizando o que acontece na osteoporose pós-menopausa. No presente trabalho foram utilizadas ratas OVX para se investigar a interação do alendronato (fármaco extensamente utilizado no tratamento da osteoporose) e da vitamina K (VK) (recentes investigações apontam possuir ação anabólica do tecido ósseo de pacientes osteoporóticas) no metabolismo osteomineral. Este estudo revelou que a administração de alendronato (ALE) e de VK juntamente com ALE (VK+ALE) produziu significante recuperação na densidade mineral óssea (DMO) de ratas OVX. No entanto, a utilização da VK isoladamente não pareceu exercer nenhum efeito significante na DMO de ratas OVX. Observou-se uma maior excreção de deoxipiridinolinas urinárias (DPD), marcador de reabsorção óssea no grupo OVX, e redução estatisticamente significante da DPD quando os animais foram tratados com VK, ALE ou ambas. Não houve diferença estatisticamente significante do conteúdo mineral ósseo e da área corporal. Também não foi verificada diferença estatisticamente significante na espessura do osso compacto nos diferentes grupos de estudo. Verificou-se ainda redução estatisticamente significante do peso úmido e do endométrio de ratas OVX, comprovando a eficiência da ovariectomia. Portanto, o modelo animal utilizado neste estudo mimetizou eficientemente a deficiência estrogênica induzida pela ovariectomia, resultando em aumento da reabsorção óssea; o tratamento com ALE e VK+ALE aumenta a DMO de ratas OVX, embora a VK isoladamente não apresente esse efeito; o tratamento com ALE e VK reduz a reabsorção óssea de ratas OVX, verificada pela redução na excreção de DPD

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The modification of sedentary patterns added to sedentarism are strictly related to the increase in obesity and the onset of metabolic syndrome (MS). Obesity sets a causal relation with many diseases, including insulin resistance, cardiovascular disease, type II diabetes and a systemic inflammatory state common to such diseases. MS is closely associated with chronic low-grade inflammation and oxidative stress. The index of women in post menopause with MS is growing, according to studies, since they are susceptible to oxidative stress frame. Although the regular practice of regular physical exercise is indicated as one of the best non-pharmacological interventions for the prevention and treatment of MS, few studies have examined the effects of high-intensity interval training HIIT - isolated on oxidative, inflammatory, and anthropometric parameters for functional postmenopausal in women with MS, not concurrently it is not found in literature a period of detraining in the same population. The intervention consisted of three weekly sessions of HIIT protocol on treadmills, and the prescribed training intensity was individualized and controlled by heart monitors. The training consisted of 12 weeks and two weeks of detraining, with an effective increased estimating the maximum oxygen consumption after training, but after two weeks of detraining, it was observed a significant reduction. The following training protocol levels of nitrite and nitrate (NOx) increased and remained in the detraining period, as well as advanced products of protein oxidation (advanced oxidation protein products - AOPP). After twelve weeks of HIIT, it was not observed weight loss. Although we found significant improvement in the inflammatory profile, interleukin-1 beta levels (IL-1β), interleukin- 6 (IL-6), tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) showed significant reduction after this period and returned to significant levels after the two weeks of detraining. HIIT also proved to be effective in increasing the levels of interleukin-10 (IL-10) and subsequently to two weeks of detraining partially reversed this benefit. Thus, it is concluded that this HIIT protocol was not sufficient to reduce oxidative stress, although the benefits of the inflammatory profile of this population given by the regular practice of high-intensity aerobic exercise are independent of weight loss. / As modificações nos padrões nutricionais somados ao sedentarismo estão relacionados com o aumento da obesidade e o surgimento da síndrome metabólica (SM). A obesidade estabelece relação de causa com diversas doenças, incluindo resistência insulínica, doenças cardiovasculares, diabetes tipo II e um estado inflamatório sistêmico comum a estas doenças. A SM está intimamente associada a inflamação crônica de baixo grau e ao estresse oxidativo. Mulheres na pós menopausa estão mais susceptíveis ao quadro de estresse oxidativo. A maior prevalência de SM é entre mulheres e o risco da SM aumenta em 60% na pós menopausa. Apesar da prática regular de exercícios físicos ser indicada como uma das melhores intervenções não farmacológicas para a prevenção e o tratamento da SM, poucos estudos analisaram os efeitos do treinamento aeróbio intervalado de alta intensidade (HIIT- high intesity interval training) isolado sobre parâmetros oxidativos, inflamatórios, antropométricos, funcionais de mulheres na pós menopausa com SM. Concomitantemente não encontra-se na literatura efeitos de um período de destreino nesta mesma população. A intervenção foi composta por três sessões semanais de um protocolo de HIIT em esteiras, sendo que a intensidade prescrita do treinamento foi individualizada e controlada através de monitores cardíacos. O treinamento foi composto de doze semanas e duas semanas de destreino e se mostrou efetivo na estimativa do consumo máximo de oxigênio após o treinamento, porém após as duas semanas de destreino observou-se uma redução significativa. O após o protocolo de treinamento os níveis de nitritos e nitratos (NOx) aumentaram e se mantiveram no período de destreino, assim como os produtos avançados de oxidação de proteínas (AOPP - advanced oxidation protein products). Após as doze semanas de HIIT não foi constatada redução ponderal, apesar de encontrarmos melhoras significativas no perfil inflamatório. Os níveis de interleucina-1 beta (IL-1β), interleucina-6 (IL-6), fator de necrose tumoral alfa (TNF-α), interferon-gama (INF-γ), apresentaram significativa redução após esse período, bem como retornaram a níveis significativos depois de duas semanas de destreino. O HIIT também se mostrou efetivo no aumento dos níveis da interleucina-10 (IL-10), e posterior a estas duas semanas reverteram parcialmente esse benefício. Assim, conclui-se que este protocolo HIIT não foi suficiente para reduzir o estresse oxidativo, porém os benefícios sobre o perfil inflamatório dessa população oportunizados pela prática regular de exercícios aeróbios de alta intensidade são independentes da perda ponderal.

This dissertation is focused on the problematic period in postmenopausal women. The women in age from 45 to 60 are in our current society under many pressures which can have a negative influence on their quality of living. The goal of this dissertation is to define these specific factors into biological, psychological and social factors and also to analyse their possible negative consequences and suggest the ways of prevention. The climacterium, partnership relations, divorces, children´s walk-out from home, the part of grandparents or also the old parent-care belong among these factors. These could be marked as a difficult living situations which could cause stress, coflicts or frustration. If this stage stays uncontrolled, many psychological troubles could start leading up to many kinds of addictions or self-destructions. That is why is the last chapter focused on the possibilities of prevention, both from the women point of view and from the society.

Introdução: O tratamento hormonal para amenizar sintomas do climatério é bem conhecido, mas nem sempre pode ser indicado para grande parte das mulheres. Por estes motivos, tem-se testado várias opções de tratamento não hormonal, cujos resultados nem sempre são satisfatórios e conclusivos. Objetivo: Avaliar a eficácia da cinarizina no tratamento dos sintomas climatéricos. Casuística e método: Foram estudadas prospectivamente 62 mulheres climatéricas sintomáticas com predomínio de ondas de calor que preencheram os critérios de inclusão e exclusão com idade variando de 45 a 60 anos, as quais foram avaliadas pelo Índice Menopausal de Kupperman (IMK), e atendidas no Setor de Ginecologia Endócrina e Climatério do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Foram divididas aleatoriamente em dois grupos: S com 27 pacientes (25 mg de Cinarizina a cada 12 hs, v.o., por 6 meses) e M com 35 pacientes (1 comprimido de placebo a cada 12hs, v.o., por 6 meses). Resultados: No grupo S a média etária foi 53,9 anos; 51,9% brancas e 48,1% negras; e no grupo M a média etária foi de 54,7 anos; 51,4% brancas e 48,6% negras. Os níveis pressóricos e o índice de massa corpórea foram semelhantes, entre os grupos. A análise do IMK e suas variantes comparativamente nos grupos S e M nos tempos 0 e 1 foi p=0,235 e p=0,406, respectivamente. Conclusões: A cinarizina foi semelhante ao placebo no alívio dos sintomas do climatério avaliados pelo IMK. Houve melhora significante do sintoma vertigem nas pacientes que receberam cinarizina. / Introduction: The hormonal treatment for relief of climateric symptoms is well-known but most women can not be treated with homones. For this reason several treatments without hormones has been evaluated with no conclusive results yet. Objective: Evaluate the efficacy of cinnarizine in the treatment of climacteric symptoms. Casuistry and Method: Were prospectively studied 62 symptomatic climacteric women with prevalence of hot flashes who met the inclusion and exclusion criteria aged from 45 to 60 years, evaluated by Kupperman\'s Menopause Index (KMI) attended at the Sector of Endocrinology Gynecology and Climacteric from the Medical School of the Hospital das Clinicas of the University of São Paulo. The subjects were divided alleatory in two: 27 patients Group S (Cinnarizine 25mg every 12h) and Group M with 35 (1 Placebo each 12h). Results: In group S the mean age was 53.9 years; 51.9% white and 48.1% black; and in group M the mean age was 54.7 years; 51.4% white and 48.6% black. Blood pressure levels and body mass index were similar in both groups. The analysis of the KMI and their variables comparision betwen groups (S and M) at time 0 and 1 was p=0.235 and p=0.406 respectively. Conclusions: Cinnarizine was similar to placebo for recipe of climacteric symptoms evaluated by KMI. There was significant improvement of symptom vertigo in patients treated with cinnarizine.

Submitted by Rosangela Silva (rosangela.silva3@unioeste.br) on 2018-05-23T13:56:08Z No. of bitstreams: 2 Camila Mayumi Martin Kakihata.pdf: 1187703 bytes, checksum: 1254b570ed82583edc71e880d005902b (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-05-23T13:56:08Z (GMT). No. of bitstreams: 2 Camila Mayumi Martin Kakihata.pdf: 1187703 bytes, checksum: 1254b570ed82583edc71e880d005902b (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-02-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Vibratory platform vibration therapy used in the treatment of postmenopausal osteoporosis because it can promote anabolic effects on bone tissue, but the parameters of use, especially the time of application, are not established. In addition, despite the beneficial effects of vibration, it is known that it can cause peripheral nerve damage. However although mentioned, there is no scientific evidence documenting the effects of this stimulus on the peripheral nerve in parameters used in therapies. Thus, is relevant the study of the mechanical vibration during different periods on the bone tissue, besides analyzing the effects on the nervous tissue. The aim of this study was to analyze and compare the effects of mechanical vibration applied over four and eight weeks on the femur and sciatic nerve of oophorectomized Wistar rats. Sixty-six randomized rats were used in the oophorectomy (GO) and sham-oophorectomy (GP) groups (n = 32 / group). Subsequently, each group was subdivided into 4, euthanized groups in the 12th week of experiment (GP4, GO4, GPV4 and GOV4), and GPV4 and GOV4 were submitted to vibration for 4 weeks; (GP8, GO8, GPV8 and GOV8), and GPV8 and GOV8 groups were submitted to vibration for 8 weeks. The vibration was performed with frequency of 60Hz, for 10 minutes, three days a week. Nociception of the right hind paw was evaluated before the surgical procedure, at the beginning of the treatment and at the end of the treatment with vibration. After the experimental period, the animals were euthanized, and the right sciatic nerve and femur were dissected for histomorphometric analysis. Were measured in 100 fibers nerve the diameter of the fiber, axon, myelin sheath, and quotient g, also were realized the counts of smaller fibers and larger than four micrometers and of the Schwann cell nuclei, as well as the percentage of connective tissue. The femur was analyzed for femoral neck diameter, mean area of cortical bone, percentage of spongy bone, thickness measurement and percentage of cortical bone, as well as osteocyte count. From the analyzes it was observed that the nociception and morphometry of the sciatic nerve morphometry did not have a statistically significant difference; in addition, in the morphological analysis of the sciatic nerve, the groups presented similar characteristics among themselves, without altering the typical morphology. While in the femur, the vibration in the oophorectomized groups led to the increase of the bone mass, being observed the increase of the percentage of the spongy tissue, which was also evidenced in the cortical tissue, with increase of the thickness and the percentage of bone tissue, being the was able to reverse these changes. However, the variables of the mean area of the cortical bone, number of osteocytes and the diameter of the femoral neck were not altered by vibration. With this, it was concluded that the vibration during four and eight weeks promoted increase of the bone mass, whereas it did not have effects on the sciatic nerve of oophorectomized Wistar. / A terapia de vibração com plataforma vibratória é utilizada no tratamento de osteoporose pós-menopausa, pois pode promover efeitos anabólicos sobre o tecido ósseo; porém, os parâmetros de utilização, principalmente o tempo de aplicação, não estão bem estabelecidos. Além disso, apesar dos efeitos benéficos da vibração, esse estímulo pode causar lesão nervosa periférica e seus efeitos sobre o nervo periférico são ainda pouco explorado em parâmetros utilizados em terapias. Diante desses fatores, torna-se relevante o estudo da vibração mecânica durante diferentes períodos sobre o tecido ósseo, além de analisar os efeitos sobre o tecido nervoso. Sendo assim, o objetivo deste estudo foi analisar e comparar os efeitos da vibração mecânica aplicada durante quatro e oito semanas, sobre o fêmur e nervo isquiático de ratas Wistar ooforectomizadas. Foram utilizadas 64 ratas randomizadas nos grupos ooforectomia (GO) e pseudoooforectomia (GP) (n=32/grupo). Posteriormente, cada grupo foi subdividido em 4, grupos eutanasiados na 12ª semana de experimento (GP4, GO4, GPV4 e GOV4), sendo que GPV4 e GOV4 foram submetidos à vibração por 4 semanas; e os grupos eutanasiados na 16ª semana de experimento (GP8, GO8, GPV8 e GOV8), sendo que GPV8 e GOV8 foram submetidos à vibração por 8 semanas. A vibração foi realizada com frequência de 60Hz, por 10 minutos, três vezes por semana. Foi avaliada a nocicepção da pata posterior direita antes do procedimento cirúrgico, prévio e ao final do tratamento com vibração. Após o período experimental, os animais foram devidamente eutanasiados, e o nervo isquiático e o fêmur direitos foram dissecados para análise histomorfométrica. Foi mensurado em 100 fibras nervosas o diâmetro da fibra, axônio, bainha de mielina e quociente g; realizou-se a contagem de fibras menores e maiores que quatro micrometros, e dos núcleos de células de Schwann, além da porcentagem do tecido conjuntivo. O fêmur foi analisado quanto ao diâmetro do colo do fêmur, à porcentagem do osso esponjoso, à mensuração da espessura, à porcentagem e área média do osso cortical, além da contagem do número de osteócitos. A partir das análises, observou-se que a variável da nocicepção e da morfometria do nervo isquiático não houve diferença estatística significativa, além disso, na análise morfológica do nervo isquiático, os grupos apresentaram características semelhantes entre si, sem alteração da morfologia típica. Enquanto que no fêmur, a vibração nos grupos ooforectomizados levou ao aumento da massa óssea, sendo observado o aumento da porcentagem do tecido esponjoso, o que também foi evidenciado no tecido cortical, com aumento da espessura e da porcentagem de tecido ósseo. Porém, as variáveis da área média do osso cortical, o número de osteócitos e o diâmetro do colo do fêmur não foram alterados pela vibração. Com isso, conclui-se que a vibração durante quatro e oito semanas promoveu aumento da massa óssea e não apresentou efeitos sobre o nervo isquiático de ratas Wistar ooforectomizadas.