A redução nos níveis de atividade física nos últimos tempos, devido ao aumento do uso de novas tecnologias e a vida sedentária, agregada ao consumo excessivo de alimentos, tem promovido uma epidemia de obesidade e doenças metabólicas. No contraponto deste caminho, está a realização de exercícios físicos. O exercício intervalado surge como uma boa opção para a obtenção de bons resultados físicos, principalmente, quando as pessoas possuem um tempo reduzido para a realização do seu treinamento. Muitos esportes como futebol, vôlei, tênis e atletismo, assim como o exercício intervalado, necessitam de indivíduos que possam competir, ou simplesmente praticar, várias vezes dentro de um intervalo de poucos dias. Atletas profissionais ou amadores treinam quase todos os dias e necessitam de uma intervenção dietética para manter o seu nível de energia estável para a realização de treinos e partidas, fazendo uso frequente de suplementos alimentares. Dentro desta gama de suplementos alimentares a Creatina é um dos mais utilizados coadjuvantes na melhoria do desempenho atlético, demonstrando potencial aumento de força, bem como aumento de massa magra, o que pode estar relacionado com o sistema do fator de Crescimento semelhante à insulina 1 (IGF-1) ou o seu receptor celular o IGF-1R. O objetivo deste trabalho foi analisar o impacto da suplementação de Creatina juntamente com o treinamento intervalado de alta intensidade na expressão proteica de IGF-1R no tecido muscular, além de analisar as concentrações sanguíneas de lactato e glicemia, avaliar o desempenho ou a performance, dos ratos antes e após o treinamento intervalado e verificar o ganho de peso dos animais nos diferentes grupos. Trinta e sete (37) ratos Wistar machos com 75 dias no começo do experimento foram randomizados e separados em três grupos: A (Treinado sem suplementação, 13 animais), B (Treinado suplementado com Creatina e Carboidrato, 12 animais) e C (Treinado suplementado com Creatina, 12 animais). O protocolo de treinamento consistiu em 1 minuto de exercício a 110% da velocidade de fadiga do teste máximo em esteira, seguidos por 30 segundos a 40% desta, totalizando 30 min, cinco vezes por semana durante trinta e dois dias corridos. A suplementação de Creatina ocorreu durante todo o período de treinamento, duas horas antes do exercício. A água foi utilizada como veículo de infusão nos grupos A e C e uma solução de glicose a 10% no grupo B. Como resultado foi verificada uma melhoria no desempenho físico dos ratos em todos os grupos. Bem como uma maior expressão proteica do IGF-1R nos grupos treinados suplementados (B e C) quando comparados ao grupo treinado sem suplementação (A). Já os dados de glicemia, lactato e ganho de massa não apresentaram diferença significativa entre os grupos. Conclui-se que o treinamento intervalado de alta intensidade se apresenta como uma boa opção para melhorias na performance física, e que a suplementação de Creatina está envolvida no aumento da expressão proteica do IGF-1R. Contudo o protocolo de treinamento e suplementação utilizados no estudo não se refletiram em diferenças nas análises glicemia, lactato e massa dos animais. / The reduction in levels of physical activity in recent times, due to the increased use of new technologies and sedentary life, added to the excessive consumption of food, has promoted an epidemic of obesity and metabolic diseases. In contrast this way, is physical exercises. The interval exercise appears as a good option for getting good physical results, mainly, when people don’t have enough time to do their training. Many sports such as football, volleyball, tennis and athletics, as well as the interval exercise, require athletes to compete, or simply practicing several times within a few days. These professional or amateur athletes train almost every day and need a dietary intervention to keep your energy level stable for training and matches appropriately, making use often, dietary supplements. Within this range of dietary supplements, Creatine is one of the most used resource for improving athletic performance, demonstrating increased strength and power, as well as increased lean mass, which may be related to the insulin-like growth factor 1 (IGF-1) system or its cellular receptor IGF-1R. The aim of this study was to analyze the impact of creatine supplementation along with high intensity interval training on protein expression of IGF-1R in muscle tissue, and analyzing blood concentrations of lactate and glucose, evaluate the performance of rats before and after interval training, examine the weight gain of the animals in different groups. Thirty-seven (37) male Wistar rats at 75 days at the beginning of the experiment were randomly divided into three groups: A (Trained without supplementation, 13 animals), B (Trained supplemented with creatine and Carbohydrate, 12 animals) and C (Trained supplemented with creatine, 12 animals). The training protocol consisted of a 1 minute to 110% of the test speed of fatigue, followed by 30 seconds at 40% of this, totaling 30 minutes, five times a week for consecutive thirty-two days. The creatine supplementation occurred throughout the training period, two hours before the exercise, with water as a vehicle for infusion in groups A and C, and 10% glucose solution in group B. As a result we had improvement in physical performance of rats in all groups. As well as increased protein expression of IGF-1R in groups trained supplemented (B and C) when compared to the trained group without supplementation (A). Meanwhile, data from the glucose, lactate and mass gain did not differ significantly between groups. It is concluded that high-intensity interval training is presented as a good option to improve physical performance, and that creatine supplementation is involved in the increased protein expression of IGF-1R. The training and supplementation protocol used in the study were not reflected in differences in the analysis of IGF-1R, glucose, lactate and gain mass in the animals.

Early Effects of Castration Therapy in Non-malignant and Malignant Prostate Tissue BACKGROUND. Androgen ablation, the standard treatment for advanced prostate cancer, results in increased apoptosis, decreased cell proliferation and subsequent involution of the prostate gland. The mechanisms behind these responses are largely unknown, but effects in the prostatic epithelium are believed to be mediated by primary changes in the stroma. The purpose of this thesis was to investigate short-term cellular effects of castration-induced prostate tissue involution in mice and humans. METHODS. Prostate tissue factors affected by castration were investigated using cDNA-arrays, micro-dissection, RT-PCR, immunohistochemistry and Western blot analysis. The effects of local insulin-like growth factor-1 (IGF-1) administration were investigated in intact and castrated mice. Non-malignant and malignant epithelial and stromal cells were micro-dissected from human prostate biopsies taken before and within two weeks after castration treatment from patients with advanced prostate cancer. These tissue compartments were analyzed by RT-PCR and/or immunohistochemistry for IGF-1, IGF-1 receptor, androgen receptor (AR) and prostate specific antigen (PSA) expression. Treatment-induced changes in these factors were related to apoptosis and proliferation as well as to clinical data and cancer specific survival. RESULTS. Similar to our observations in mouse ventral prostate (VP), non-malignant and malignant human prostate tissues responded with increased epithelial cell apoptosis and decreased proliferation after androgen withdrawal. Also, the PSA mRNA levels were reduced within the first days after therapy both in non-malignant and malignant human prostate epithelial cells. However, neither of these changes was related to subsequent nadir serum PSA or to survival. Locally injected IGF-1 increased epithelial cell proliferation and vascular volume in intact but not in castrated mice. IGF-1 was found to be mostly, but not exclusively, expressed in the stroma, and it decreased rapidly after castration in both humans and mice. This decrease was, however, largely absent in prostate tumor stroma, and tumor stroma cells showed lower pre-treatment levels of AR than stroma surrounding normal epithelial glands. Furthermore, decreased levels of IGF-1 mRNA in the non-malignant and tumor stroma cells, and in tumor epithelial cells in response to castration, were associated with high levels of apoptosis in epithelial cells after therapy. CONCLUSIONS. In the prostate, IGF-1 may be an important mediator of stroma-epithelial cell interaction that is involved in castration-induced epithelial and vascular involution. Moreover, reduced AR in the tumor stroma may play an important role in prostate cancer progression towards androgen-independency, resulting in inadequate IGF-1 reduction and apoptosis induction in response to castration. Most primary tumors initially respond to castration with markedly decreased PSA synthesis and cell proliferation, and moderately increased apoptosis. Death due to metastatic disease is, however, still common, despite primary tumor regression. This may suggest that tumor cells in metastases respond differently to treatment than primary tumor cells, probably influenced by a different and possibly androgen-independent stroma. Further studies should test the hypothesis that the effect of castration therapy can be enhanced by simultaneous blocking of IGF-1 signaling.

Alzheimer’s disease (AD) is a neurodegenerative disorder which is histopathologically characterised by amyloid plaques and neurofibrillary tangles. Amyloid plaques consist of the amyloid β-peptide (Aβ) that can form aggregates in the brain. Aβ is generated from the amyloid precursor protein (APP) through proteolytic cleavage. APP belongs to a conserved protein family that also includes the two paralogues, APP-like proteins 1 and 2 (APLP1 and APLP2). Despite the immense amount of research on APP, motivated by its implication in AD, the function of this protein family has not yet been determined. In this thesis, we have studied the expression and proteolytic processing of the APP protein family. Our results are consistent with previous findings that suggest a role for APP during neuronal development. Treatment of cells with retinoic acid (RA) resulted in increased synthesis. In addition, we observed that RA treatment shifted the processing of APP from the amyloidogenic to the non-amyloidogenic pathway. The proteins in the APP family have been hard to distinguish both with respect to function and proteolytic processing. However, for development of new drugs with APP processing enzymes as targets this is of great importance. Our studies suggest similarities, but also differences in the mechanism regulating the processing of the different paralogues. We found that brain-derived neurotrophic factor (BDNF) had different impact on the members of the APP family. Most interestingly, we also found that the mechanism behind the increased processing in response to IGF-1 was not identical between the homologous proteins. In summary, our results indicate that in terms of regulation APLP1 and APLP2 differ more from each other than from APP. Our studies open up the possibility of finding means to selectively block Aβ production without interfering with the processing and function of the paralogous proteins.

L'anguille a un cycle de vie complexe avec une reproduction océanique et une croissance dans les eaux continentales. La phase de croissance se termine par une "métamorphose secondaire " ou argenture, dernier stade accessible dans les conditions naturelles. La maturation sexuelle naturelle n'a encore jamais été observée et le développement des gonades reste bloqué du fait d'un déficit en hormones gonadotropes, LH et FSH. Comprendre les mécanismes de régulation de LH et FSH chez l'anguille présente un intérêt fondamental pour l'évolution du contrôle de la puberté et un enjeu appliqué pour la maîtrise de la reproduction chez cette espèce en danger. Après avoir développé les outils moléculaires pour l'étude de l'expression des sous-unités de LH et FSH, nous montrons qu'au cours de l'argenture seul l'axe gonadotrope est activé, avec une augmentation de l'expression de FSHβ puis de LHβ, sans activation des axes thyréotrope et somatotrope, ce qui apparente l'argenture à une puberté plutôt qu'à une métamorphose. Nous observons aussi une régulation différentielle de l'expression de LHβ et FSHβ au cours de la maturation sexuelle expérimentale avec une amplification sélective de l'expression de LHβ. Grâce à l'utilisation de culture primaire de cellules hypophysaires d'anguille, nous montrons que les stéroïdes sexuels (estradiol et androgènes), les peptides gonadiques (activine/follistatine) et les facteurs métaboliques (IGF-1, cortisol) exercent des effets directs sur l'expression de LHβ ou FSHβ et peuvent être impliqués dans leur régulation différentielle.

The complicated problem of efficient stimulation of elastic fiber production in already developed human tissues has not yet been solved. The present study introduces sodium ascorbate (SA) as a stimulator of elastogenesis in cultures of different cell types including fibroblasts isolated from patients with elastopathy genetic diseases. We then elucidated mechanisms of elastogenic action of SA. SA exercises its net elastogenic effect only after being actively transported into the cell interior through two separate mechanisms. These are the “fast effect,” which reflects the greater stability of intracellular tropoelastin, and the “late effect,” which reflects the true enhancement of the elastin gene expression occurring after SA-induced activation of c-src tyrosine kinase and the consecutive phosphorylation of IGF-1 receptor, which triggers the downstream signals leading to activation of the elastin gene expression. In conclusion, for the first time we have established that SA is a potent stimulator of elastic fiber production.

The complicated problem of efficient stimulation of elastic fiber production in already developed human tissues has not yet been solved. The present study introduces sodium ascorbate (SA) as a stimulator of elastogenesis in cultures of different cell types including fibroblasts isolated from patients with elastopathy genetic diseases. We then elucidated mechanisms of elastogenic action of SA. SA exercises its net elastogenic effect only after being actively transported into the cell interior through two separate mechanisms. These are the “fast effect,” which reflects the greater stability of intracellular tropoelastin, and the “late effect,” which reflects the true enhancement of the elastin gene expression occurring after SA-induced activation of c-src tyrosine kinase and the consecutive phosphorylation of IGF-1 receptor, which triggers the downstream signals leading to activation of the elastin gene expression. In conclusion, for the first time we have established that SA is a potent stimulator of elastic fiber production.

Die subklinische Klauenrehe ist eine weltweit vorkommende, multifaktorielle und bei Rindern vor allem nach der Abkalbung gehäuft auftretende Erkrankung. Als prädisponierender Faktor für weitere, z. T. sehr schmerzhafte Klauenerkrankungen wie Sohlengeschwüre oder White-Line-Disease besitzt sie nicht nur eine hohe tierschutzrelevante, sondern auch eine große wirtschaftliche Bedeutung. Die Ätiologie und Pathogenese der Klauenrehe sind bis heute nicht hinreichend geklärt. In neuerer Zeit konzentrieren sich die Forschungen auf den peripartalen Zeitraum und den damit verbundenen metabolischen und hormonellen Einflüssen auf das Klauengewebe. In dieser Arbeit wird der Frage nachgegangen, inwieweit eine erhöhte Fettmobilisation bei Kühen in der negativen Energiebilanz nach der Abkalbung sowie eine verstärkte Lipolyse bei antepartal verfetteten Kühen zur Entstehung der subklinischen Klauenrehe beitragen. Gleichzeitig soll die Frage beantwortet werden, welche Rolle die postpartale Insulinresistenz und die dadurch verminderte Glucoseaufnahme ins periphere Gewebe bei der Ausbildung der subklinischen Klauenrehe spielen. Außerdem soll untersucht werden, inwiefern sich systemische Einflüsse auf die verstärkte Ausbildung der Sohlenhämorrhagien nach der Abkalbung nachweisen lassen und ob diese anhand ausgewählter Blutparameter vorhersehbar sind. Für die Untersuchung wurden 30 primi- und 44 multipare Milchkühe aus drei Betrieben mit Laufstallhaltung ausgewählt. Die Sohlenflächen aller acht Hauptklauen eines Tieres wurden nach funktionellem Klauenschnitt 1 Woche und 8 Wochen p.p. fotografiert, in fünf Zonen eingeteilt und anhand Anzahl, Größe und Schweregrad der sichtbaren Läsionen beurteilt. Zur weiteren Differenzierung wurden verschiedene Klauenscores gebildet. 2 - 3 Wochen vor der Abkalbung sowie 1 Woche, 4 und 8 Wochen p.p. wurden Blutproben entnommen und die Konzentrationen der Freien Fettsäuren (FFS), ß-Hydroxy-Butyrat (BHB), Glucose, Insulin und Haptoglobin bestimmt. Die IGF-1-Konzentration wurde zur weiteren Einschätzung der Energiebilanz bzw. Energieaufnahme und der Körperkondition gemessen. Die Insulinresistenz wurde anhand basaler Insulin- und Glucose-Konzentrationen bestimmt. Des Weiteren wurde vor und nach der Abkalbungdie Rückenfettdicke sonographisch gemessen und die peripartale Fettmobilisierung über die Rückenfettdickenänderung errechnet. Nahezu alle untersuchten Tiere (96 %) zeigten für die subklinische Klauenrehe typische Veränderungen. Bei über der Hälfte der Kühe waren 8 Wochen p.p. an allen vier Gliedmaßen Sohlenhämorrhagien vorhanden. Es konnten signifikante Korrelationen der Klauenscoreparameter sowohl zwischen den einzelnen Zonen als auch zwischen den Hinter- und Vordergliedmaßen gefunden werden. 8 Wochen p.p. war eine signifikante Verschlechterung der Klauengesundheit im Gegensatz zur ersten Woche p.p. zu verzeichnen. Da diese Hämorrhagien erst nach zwei Monaten an der Fußungsfläche sichtbar werden, sind die ursächlichen Veränderungen in der Lederhaut zum Zeitpunkt der Abkalbung entstanden. Dabei waren die lateralen Klauen der Hintergliedmaße an der Rusterholzstelle am stärksten betroffen. Ein Einfluss auf die Klauengesundheit durch die Fütterung, die Bodenbeschaffenheit der Haltungssysteme, altersbedingt sowie durch peripartale Erkrankungen konnte nicht gefunden werden. Ungefähr zwei Drittel der untersuchten Kühe hatten nach der Abkalbung eine negative Energiebilanz. Sie zeigten signifikant weniger Läsionen an den Sohlenflächen als Kühe mit positiver Energiebilanz. Eine übermäßige Rückenfettmobilisierung führte in diesen Untersuchungen nicht zu einer Verschlechterung der Klauengesundheit. Antepartal unterkonditionierte Tiere mit wenig Fettmobilisierung waren sogar stärker von Klauenläsionen betroffen als normal- oder überkonditionierte Kühe. Bei Tieren mit einem peripartalen Abfall der IGF-1-Konzentration waren signifikant mehr Veränderungen an der Sohlenfläche nachzuweisen. Die IGF-1-Konzentration korrelierte dabei aber, im Gegensatz zu vielen Angaben in der Literatur, hochsignifikant negativ mit der Energiebilanz und zeigte keinen Bezug zur RFD, so dass fraglich ist, ob dieser Parameter alleine überhaupt geeignet wäre, eine Aussage über die Energiebilanz oder die Ausbildung einer subklinischen Klauenrehe zu treffen. Bei insulinresistenten Kühen waren eine signifikante Erhöhung der Klauenläsionen sowie ein signifikanter Abfall der IGF-1-Konzentration zu verzeichnen. Die Bestimmung der Insulinresistenz anhand basaler Blutglucose- und Insulin-Konzentrationen bei Kühen nach der Abkalbung erwies sich jedoch als äußerst fragwürdig. Signifikante Korrelationen zwischen den Konzentrationen der einzelnen Blutparameter und den Klauenscoreparametern bestanden, bis auf die FFSKonzentration 2 - 3 Wochen a.p., ausschließlich 1 Woche p.p.. Allerdings blieben die Korrelationen insgesamt relativ niedrig. Die IGF-1-Konzentration korrelierte am häufigsten sowie am engsten, Insulin und Haptoglobin korrelierten zu keinem Zeitpunkt mit den Klauenscoreparametern. Es kann davon ausgegangen werden, dass es sich bei den gefundenen Hämorrhagien an der Sohlenfläche um die Ausbildung einer subklinischen Klauenrehe aufgrund systemischer Einflüsse im peripartalen Zeitraum handelt. Eine negative Energiebilanz sowie die antepartale Verfettung der Milchkühe stellen nach den vorliegenden Untersuchungen keinen Risikofaktor dar. In dieser Arbeit konnte nicht bestätigt werden, dass Lipidmobilisation oder mangelnde Glucoseversorgung nach der Abkalbung eine Rolle bei der Entstehung der subklinischen Klauenrehe spielen.

Les patients atteints de dystrophies musculaires présentent de plus en plus fréquemment des complications cardiaques, qui sont majoritairement des cardiomyopathies dilatées (CMD), et qui déterminent leur pronostic vital. Dans ce contexte, les traitements de l'atteinte cardiaque sont ceux de l'insuffisance cardiaque, qui agissent sur l'environnement fonctionnel du cœur, mais pas directement sur l'atteinte myocardique.<br /> L'objectif de cette thèse a été d'évaluer les effets d'un traitement novateur de la CMD dans les dystrophies musculaires, en utilisant le hamster de la lignée CHF147. La démarche proposée est d'induire un phénomène compensateur de la dilatation cardiaque et ainsi d'améliorer le pronostic vital, en utilisant les propriétés de l'Insulin-like Growth Factor 1 (IGF-1).<br /> Des hamsters CHF147 jeunes ont été traités pendant un temps court, de façon systémique avec la protéine recombinante IGF-1 (rhIGF-1) à faible dose. Les effets macroscopiques, histologiques et fonctionnels du traitement ont été évalués 35 jours après le début de celui-ci et les voies de signalisation impliquées dans l'induction des effets observés ont été étudiées. Une étude de survie a été réalisée afin de mesurer les effets du traitement à long terme. L'évaluation des effets à court terme de l'administration de rhIGF-1 sur la CMD du hamster CHF147 indique un ralentissement de la dilatation des cavités cardiaques ainsi que de l'extension de la fibrose myocardique, et une préservation de multiples paramètres fonctionnels, tels que le débit cardiaque, le volume d'éjection, la pression de fin de diastole et, en particulier, la contractilité myocardique. Les effets observés sont dus en partie à des modifications au niveau des protéines impliquées dans le cycle du calcium. A long terme, la survie des hamsters CHF147 traités augmente significativement d'environ 20% et est associée à une préservation partielle de la fonction cardiaque.<br />Toutefois, une augmentation du niveau sérique d'IGF-1 pourrait augmenter le risque d'effets secondaires délétères. Afin de limiter les effets systémiques d'IGF-1 et de cibler son administration au cœur, nous avons injecté localement le plasmide pCMV-IGF1 codant pour l'IGF-1 dans le myocarde des hamsters CHF147. Les effets du traitement ont été évalués après 35 jours et montrent des résultats comparables à ceux obtenus avec la protéine rhIGF-1.<br />En conclusion, ce travail de thèse a montré qu'un traitement basé sur IGF-1 permet de ralentir l'évolution de la CMD des hamsters CHF147, en préservant la structure et la fonction cardiaques, et d'améliorer significativement leur survie. IGF-1 semble donc être un candidat prometteur pour la mise au point d'une approche par thérapie génique dans l'insuffisance cardiaque, due à une CMD, dans le contexte des dystrophies musculaires.

A redução nos níveis de atividade física nos últimos tempos, devido ao aumento do uso de novas tecnologias e a vida sedentária, agregada ao consumo excessivo de alimentos, tem promovido uma epidemia de obesidade e doenças metabólicas. No contraponto deste caminho, está a realização de exercícios físicos. O exercício intervalado surge como uma boa opção para a obtenção de bons resultados físicos, principalmente, quando as pessoas possuem um tempo reduzido para a realização do seu treinamento. Muitos esportes como futebol, vôlei, tênis e atletismo, assim como o exercício intervalado, necessitam de indivíduos que possam competir, ou simplesmente praticar, várias vezes dentro de um intervalo de poucos dias. Atletas profissionais ou amadores treinam quase todos os dias e necessitam de uma intervenção dietética para manter o seu nível de energia estável para a realização de treinos e partidas, fazendo uso frequente de suplementos alimentares. Dentro desta gama de suplementos alimentares a Creatina é um dos mais utilizados coadjuvantes na melhoria do desempenho atlético, demonstrando potencial aumento de força, bem como aumento de massa magra, o que pode estar relacionado com o sistema do fator de Crescimento semelhante à insulina 1 (IGF-1) ou o seu receptor celular o IGF-1R. O objetivo deste trabalho foi analisar o impacto da suplementação de Creatina juntamente com o treinamento intervalado de alta intensidade na expressão proteica de IGF-1R no tecido muscular, além de analisar as concentrações sanguíneas de lactato e glicemia, avaliar o desempenho ou a performance, dos ratos antes e após o treinamento intervalado e verificar o ganho de peso dos animais nos diferentes grupos. Trinta e sete (37) ratos Wistar machos com 75 dias no começo do experimento foram randomizados e separados em três grupos: A (Treinado sem suplementação, 13 animais), B (Treinado suplementado com Creatina e Carboidrato, 12 animais) e C (Treinado suplementado com Creatina, 12 animais). O protocolo de treinamento consistiu em 1 minuto de exercício a 110% da velocidade de fadiga do teste máximo em esteira, seguidos por 30 segundos a 40% desta, totalizando 30 min, cinco vezes por semana durante trinta e dois dias corridos. A suplementação de Creatina ocorreu durante todo o período de treinamento, duas horas antes do exercício. A água foi utilizada como veículo de infusão nos grupos A e C e uma solução de glicose a 10% no grupo B. Como resultado foi verificada uma melhoria no desempenho físico dos ratos em todos os grupos. Bem como uma maior expressão proteica do IGF-1R nos grupos treinados suplementados (B e C) quando comparados ao grupo treinado sem suplementação (A). Já os dados de glicemia, lactato e ganho de massa não apresentaram diferença significativa entre os grupos. Conclui-se que o treinamento intervalado de alta intensidade se apresenta como uma boa opção para melhorias na performance física, e que a suplementação de Creatina está envolvida no aumento da expressão proteica do IGF-1R. Contudo o protocolo de treinamento e suplementação utilizados no estudo não se refletiram em diferenças nas análises glicemia, lactato e massa dos animais. / The reduction in levels of physical activity in recent times, due to the increased use of new technologies and sedentary life, added to the excessive consumption of food, has promoted an epidemic of obesity and metabolic diseases. In contrast this way, is physical exercises. The interval exercise appears as a good option for getting good physical results, mainly, when people don’t have enough time to do their training. Many sports such as football, volleyball, tennis and athletics, as well as the interval exercise, require athletes to compete, or simply practicing several times within a few days. These professional or amateur athletes train almost every day and need a dietary intervention to keep your energy level stable for training and matches appropriately, making use often, dietary supplements. Within this range of dietary supplements, Creatine is one of the most used resource for improving athletic performance, demonstrating increased strength and power, as well as increased lean mass, which may be related to the insulin-like growth factor 1 (IGF-1) system or its cellular receptor IGF-1R. The aim of this study was to analyze the impact of creatine supplementation along with high intensity interval training on protein expression of IGF-1R in muscle tissue, and analyzing blood concentrations of lactate and glucose, evaluate the performance of rats before and after interval training, examine the weight gain of the animals in different groups. Thirty-seven (37) male Wistar rats at 75 days at the beginning of the experiment were randomly divided into three groups: A (Trained without supplementation, 13 animals), B (Trained supplemented with creatine and Carbohydrate, 12 animals) and C (Trained supplemented with creatine, 12 animals). The training protocol consisted of a 1 minute to 110% of the test speed of fatigue, followed by 30 seconds at 40% of this, totaling 30 minutes, five times a week for consecutive thirty-two days. The creatine supplementation occurred throughout the training period, two hours before the exercise, with water as a vehicle for infusion in groups A and C, and 10% glucose solution in group B. As a result we had improvement in physical performance of rats in all groups. As well as increased protein expression of IGF-1R in groups trained supplemented (B and C) when compared to the trained group without supplementation (A). Meanwhile, data from the glucose, lactate and mass gain did not differ significantly between groups. It is concluded that high-intensity interval training is presented as a good option to improve physical performance, and that creatine supplementation is involved in the increased protein expression of IGF-1R. The training and supplementation protocol used in the study were not reflected in differences in the analysis of IGF-1R, glucose, lactate and gain mass in the animals.

After the findings were reported for the Women’s Health Initiative (WHI) study in the past decade, there has been a significant decline in the overall use of hormone replacement therapy (HRT) among women. However, there are still millions of middle-aged, menopausal women in the U.S. who are currently undergoing hormone therapy. Their reasons for continuing treatment include relief of severe menopausal symptoms, aid in the management of osteoporosis and reduction in the risk of colon cancer (Ness et al., 2005). The purpose of the following investigation was to evaluate the impact of HRT on the central and peripheral auditory systems both during and after treatment. Over the course of the study, hormone treatments were administered to female aging CBA/CaJ mice to observe what effects estrogen (E) and progestin (P) have on the peripheral and central auditory systems. Female CBA/CaJ middle age mice were ovariectomized and placed into 4 HRT groups (E, P, E+P and Placebo [Pb]). Hormone treatment lasted 6 months followed by a recovery/washout period of 1 month. During this time, electrophysiology tests such as auditory brainstem responses (ABR) and ABR gap in noise (GIN) were used to measure neural activity for the auditory nerve and brainstem. Distortion product otoacoustic emission (DPOAE) testing was also implemented to assess the functional status of the outer hair cells (OHC) and their ability to amplify sound in the cochlea. After 6 months of treatment, animals treated with E exhibited the least amount of changes in ABR thresholds and ABR GIN amplitudes than any other subject groups. Interestingly, P animals exhibited an abrupt increase in ABR thresholds only 3 months after treatment; however, for ABR GIN amplitude levels a progressive reduction observed throughout the study. E+P and Pb animals showed signs of accelerated age-related hearing loss (ARHL) with significantly elevated ABR thresholds and dwindling ABR GIN amplitude levels. No significant signs of recovery were observed for any of the hormone groups. Therefore, in the present murine investigation, the effects of HRT were long lasting. To further expand on the results obtained for the electrophysiology tests, molecular biology experiments were performed to evaluate the expression of IGF-1R and FoxO3 in the cochlea during hormone therapy, from both in vitro and in vivo perspectives. Both genes play significant roles in the PI3K/AKT pathway and were specifically chosen because of their role in anti-apoptotic responses and cell survival. It was hypothesized that E attenuates the effects of ARHL via the PI3K/AKT pathway by up-regulating IGF-1R and FoxO3 to counteract the effects of oxidative stress in the aging mammalian cochlea. qPCR experiments were performed with stria vascularis (SV) lateral wall cells extracted from the cochlea of each animal in the hormone groups post-treatment (in vivo) and in SVK-1 cells treated with HRT over various lengths of time (in vitro) to evaluate the expression levels of IGF-1R and FoxO3. In-vivo experiments showed that the E-treated animals had significantly higher IG-1R levels compared to the other subject groups after treatment was discontinued. Similarly, IGF-1R levels steadily increased for E-treated SVK-1 cells over the course of hormone therapy, compared to P and E+P cells. FoxO3 expression, on the other hand, declined for all of the hormone-treated cells groups, relative to control SVK-1 cells (in vitro), and no statistical differences were detected for FoxO3 levels among the post-treatment animals (in vivo). These findings indicate that there is cross talk between E and IGF-1R involving the PI3K/AKT pathway, which contributes to the delayed onset of ARHL observed during HRT with E. Meanwhile, FoxO3 may not play a role in neuro-protective properties in the cochlea during HRT, as initially hypothesized.