The purpose of this project was to develop an educational program to assist educators in keeping school children healthy. This program is designed to support professionals who are working to reduce the problem of oobesity in children and adolescents in elementary and middle school setting.

Background Osteoarthritis (OA) of the hip is a common disease among elderly adults and its prevalence increases with age. Hip OA is presumed to be a group of diseases resulting in the same pathological pathway, but its etiology is not completely understood. The major symptoms are joint pain, joint stiffness, impaired range of motion, and muscle weakness resulting in increased levels of physical disability (PD) and reduced quality of life. Besides the impairments of the individual subject a heavy economic burden goes along with the disease and is expected to increase due to aging societies in western countries throughout the upcoming years. Exercise therapy (ET), including elements to strengthen the hip muscles, is a common treatment in hip OA and considered to reduce pain and PD. Currently, there is only silver-level scientific evidence regarding the effectiveness of ET in hip OA due to a limited number of high quality studies. Furthermore, the optimal content and dosage, as well as the mode of delivery of ET need to be evaluated. This doctoral thesis deals with three specific aspects of hip muscle strength (HMS) in patients with hip OA: the precision of measuring HMS, training HMS, and the relevance of HMS to physical disability (PD). Three studies and one study protocol provide the scientific program of this thesis, referring to these aspects of HMS. Methods The first study (S1) investigated the reproducibility of isokinetic and isometric HMS measures in patients with hip OA. 16 subjects with unilateral or bilateral hip OA and 13 healthy subjects were tested twice, 7 days apart. A subpopulation of 11 hip OA patients was tested a third time to evaluate familiarization to these measurements. The standard error of measurement (SEM) served as the reproducibility outcome parameter. The second study (S2) investigated the feasibility of strengthening exercises and their effect on HMS in hip patients. 36 participants from an institutional training group for hip patients were allocated randomly to an intervention or control group. While the intervention group completed an eight-week progressive home-based strengthening exercise program (PHSEP) in addition to the weekly institutional supervised group-based exercise therapy (ISET), the control group continued weekly ISET, only. Exercise logs were used to monitor adherence, pain, and the applied exercise intensity of the PHSEP. Before and after the intervention period, HMS was determined using isokinetic concentric and isometric HMS measurements. Additionally, health-related quality of life was assessed by the SF36 questionnaire. These two studies served as a basis for developing strength-specific aspects of a study design for a randomized controlled trial (RCT), which was in progress at the writing of this thesis. This RCT addresses the above-mentioned lack of scientific evidence about the effectiveness of ET in hip OA. A study protocol (P1) describes this RCT, which evaluates the effectiveness of ET on pain and PD in patients with hip OA. 217 patients with hip OA were recruited from the community and allocated to one of the four groups: (1) exercise group, n = 70 (2) non-intervention group, n = 70, (3) “Sham” ultrasound group, n = 70, and (4) ultrasound group, n = 7. The main outcome measure is the change in the subscale bodily pain of the SF36. Secondary outcomes are PD assessed by the SF36 and the WOMAC questionnaire, isometric HMS, several gait variables and postural control. Finally, the relationship of HMS and PD in hip OA was investigated in a third (cross-sectional) study (S3). A stepwise regression model was applied with data from 149 subjects suffering from hip OA. The outcome variable was the self-reported physical disability, assessed with the physical function subscale of the WOMAC questionnaire. Age, gender, body mass index BMI , HMS, pain, stiffness, and range of motion were included in the statistical model as associated factors of PD. Results The results of S1 showed high variability in HMS measurements between days. The highest SEM values, indicating poorest reproducibility, were obtained for hip extension, followed by hip adduction and hip flexion measures, while the smallest values were found for hip abduction measures. Lower reproducibility occurred in patients with hip OA in comparison to healthy controls during the isometric measures of hip abduction, adduction, and flexion. Reproducibility of 11 hip OA patients was lower for the second test sequence (test-day 2 and 3) than for the first test sequence (test-day 1 and 2). The findings of S2 indicated high exercise adherence (99%) of the intervention group to the applied PHSEP. Furthermore, exercise logs reported that pain resulting from the PHSEP was low. HMS improved about 7-11% in comparison to the control group. The SF36 variables did not change throughout the exercise period. In S3, the statistical model revealed stiffness, pain, and HMS to be significant factors of self-reported physical disability in hip OA. Conclusion In conclusion, the precision of several HMS measures may be affected by hip OA and clinicians should be aware of a higher measurement error in patients with hip OA under isometric test conditions than for healthy subjects. A familiarization measurement may be an approach to diminish the measurement error. The applied PHSEP amended to an ISET is feasible for hip patients to carry out and can be applied to improve HMS. Furthermore, a significant cross-sectional relationship between HMS and PD has been evaluated, indicating that HMS may be an important factor to stimulate during exercise therapy in hip OA. The upcoming results of the RCT (P1) described in the study protocol will help to reduce the shortcomings in scientific evidence regarding the effectiveness of strengthening exercise regimes to reduce pain and PD in patients with hip OA.:List of content 1 List of figures 3 List of tables 4 List of abbreviations 5 Abstract 8 Zusammenfassung 11 Structure of the thesis 15 1 Background 16 1.1 Osteoarthritis of the hip joint 16 1.1.1 Prevalence and incidence 16 1.1.2 Etiology 17 1.1.3 Clinical symptoms and diagnosis 18 1.1.4 Socioeconomic burden 20 1.2 Hip muscle strength in osteoarthritis of the hip 23 1.2.1 Anatomical and functional aspects of the hip and its muscles 23 1.2.2 General aspects of muscle strength 25 1.2.3 Hip muscle weakness and muscle imbalances 28 1.2.4 Assessment of hip muscle strength 29 1.3 Physical disability in hip OA 35 1.3.1 General aspects of physical disability in hip OA 35 1.3.2 Assessment of physical disability in hip OA 36 1.4 Exercise therapy in hip OA 38 1.4.1 Efficacy of exercise therapy 38 1.4.2 Strengthening exercises in hip OA 39 1.5 Context of the thesis 43 1.5.1 OsteoArthritisGroup (OAG) 43 2 Scientific program - research papers 47 2.1 Research paper 1: Reproducibility of hip muscle strength measurements in hip OA 48 2.2 Research paper 2: Feasibility and efficacy of an 8-week progressive home-based strengthening exercise 58 2.3 Research paper 3: Evaluation of the therapeutic exercise regimen “Hip School": A protocol for a randomized, controlled trial 68 2.4 Research paper 4: Factors of physical disability in patients with hip osteoarthritis 81 3 Comprehensive and supplementary discussion 103 3.1 Strength measurements at the hip 103 3.1.1 Body position and fixation 103 3.1.2 Torque overshoots 104 3.1.3 Objectivity of hip muscle strength measures in osteoarthritis of the hip 104 3.1.4 Reproducibility of hip muscle strength measures in osteoarthritis of the hip 104 3.1.5 Validity of hip muscle strength measures in osteoarthritis of the hip 105 3.1.6 Isometric versus isokinetic hip muscle strength measures 106 3.2 Strengthening exercises in patients with hip OA 106 3.2.1 Feasibility and adherence to the progressive home-based strengthening exercise program 106 3.2.2 Adverse events due to the exercise intervention 107 3.2.3 Strength gains 108 3.2.4 Adaptations of the PHSEP for the RCT 109 3.3 Hip muscle strength and its relation to physical disability in patients with hip OA 110 4 Limitations 112 5 Conclusion and future perspectives 114 6 Reference list 116 7 Appendix 126 8 Affidavit 131 9 Curriculum vitae 132 / Hintergrund Coxarthrose ist eine weit verbreitete Krankheit in der älteren Bevölkerung westlicher Industrienationen. Die Bedeutung und Zahl der Neuerkrankungen nehmen mit steigendem Lebensalter zu. Schmerz, Steifheit, Bewegungseinschränkungen und Muskelschwäche zählen zu den Leitsymptomen dieser Krankheit, die sich in einer zunehmenden körperlichen Funktionseinschränkung und eingeschränkten Lebensqualität der Patienten äußern. Neben der Bedeutung für die betroffenen Patienten selbst wachsen in westlichen Industrienationen aufgrund der demographischen Entwicklung hin zu einer alternden Gesellschaft der Druck und die finanzielle Belastung auf die Renten- und Gesundheitssysteme. Die Sporttherapie wird häufig in frühen Stadien der Krankheit eingesetzt und zählt zu den konservativen Therapieverfahren. Nach aktuellem Stand der Wissenschaft scheinen sporttherapeutische Interventionen mit Trainingselementen zur Kräftigung der hüftumgebenden Muskulatur sinnvoll. Dennoch wurde die Wirksamkeit von Sporttherapie bei Coxarthrose bisher nur in einzelnen Studien nachgewiesen (Silver-level Evidence). Es fehlen qualitativ hochwertige randomisierte Kontrollgruppenstudien (RCTs). Zudem ist bislang ungeklärt, wie ein optimales Trainingsprogramm bei Coxarthrose hinsichtlich der Inhalte, Dosierung und Durchführungsmodalität zu gestalten ist, um Schmerz und körperliche Funktionseinschränkungen bestmöglich zu therapieren. Vor diesem Hintergrund beschäftigt sich die vorliegende Dissertation mit drei Aspekten der Hüftmuskelkraft bei Patienten mit Coxarthrose. Drei entsprechende Studien, die in vier wissenschaftlichen Artikeln aufgearbeitet wurden, bilden den wissenschaftlichen Schwerpunkt der Arbeit. Methode Die erste Studie (S1) befasst sich mit der Messgenauigkeit von Hüftkraftmessungen bei Coxarthrosepatienten. Unter diesem Aspekt wurden isometrische und isokinetische Kraftmessgrößen an der Hüfte bei 16 Coxarthrosepatienten und 13 gesunden Personen zwei Mal im Abstand von sieben Tagen erhoben. Bei einer Teilstichprobe von 11 Coxarthrosepatienten wurden die Messungen ein drittes Mal durchgeführt, um mögliche Gewöhnungseffekte zu evaluieren. Der Standard Error of Measurement (SEM) wurde verwendet, um den Messfehler zu quantifizieren. Die zweite Studie (S2) greift einen weiteren Aspekt auf, der sich auf das Training der Hüftmuskelkraft bei Hüftpatienten bezieht. Hier wurde die Machbarkeit eines ergänzenden Heimtrainingsprogramms zur Kräftigung der hüftumgebenden Muskulatur evaluiert sowie mögliche Auswirkungen auf die Hüftmuskelkraft untersucht. 36 Teilnehmer einer Hüftsportgruppe mit Coxarthrose und/oder einer Total-Endoprothese (TEP) wurden randomisiert in zwei Untersuchungsgruppen aufgeteilt. Während die Patienten der Kontrollgruppe im Untersuchungszeitraum weiterhin wöchentliche institutionelle sporttherapeutische Trainingseinheiten wahrnahmen, führten die Patienten der Interventionsgruppe zusätzlich Heimtrainingseinheiten zur Kräftigung der Hüftmuskeln durch. Vor und nach der Intervention wurden isometrische und isokinetische Maximalkraftmessungen durchgeführt. Die Patienten der Trainingsgruppe haben ein Trainingstagebuch geführt, um die Teilnahme am Heimtrainingsprogramm und mögliche Schwierigkeiten damit zu dokumentieren. Der SF36 Fragebogen wurde eingesetzt, um die gesundheitsbezogene Lebensqualität im Verlauf zu kontrollieren. Die Erkenntnisse der beiden beschriebenen Studien wurden verwendet, um kraftspezifische Aspekte eines Studiendesigns zu entwickeln. Dieses Studiendesign entspricht einem RCT und soll die Effektivität eines sporttherapeutischen Trainingskonzepts hinsichtlich Schmerzreduktion und Verbesserung der körperlichen Funktionsfähigkeit überprüfen. 217 Hüftarthrosepatienten werden rekrutiert und randomisiert auf eine der folgenden Untersuchungsgruppen aufgeteilt: (1) Trainingsgruppe, n = 70 (2) Kontrollgruppe ohne Intervention, n = 70, (3) “Schein” Ultraschallgruppe, n = 70, und (4) Ultraschallgruppe, n = 7. Die primäre Zielgröße ist Veränderung in der Subskala „Körperliche Schmerzen“ des SF36-Fragebogens. Sekundäre Zielgrößen sind Schmerz und Körperliche Funktionsfähigkeit aus dem WOMAC-Fragebogen, weiteren Subskalen des SF36-Fragebogens, isometrische Hüftmuskelkraft, verschiedene Variablen des Gangs und posturale Kontrolle. Die Bedeutung der Hüftmuskelkraft auf die alltagsrelevante körperliche Funktionsfähigkeit stellt den dritten Aspekt dieser Dissertation dar und wurde in Studie 3 (S3), einer Querschnittsuntersuchung an 149 Coxarthrosepatienten behandelt. Ziel der Studie war die Untersuchung des Zusammenhangs verschiedener Variablen und der alltagsbezogenen körperlichen Funktionsfähigkeit. In einem statistisches Modell wurde die Beziehung zwischen den Variablen: Hüftmuskelkraft, Body Mass Index (BMI), Alter, Geschlecht, Schmerz, Steifheit und Beweglichkeit der Hüfte und der Subskala „Körperliche Funktionsfähigkeit“ des WOMAC-Fragebogens als Maß für die alltagsbezogene körperlichen Funktionsfähigkeit berechnet. Ergebnisse In der ersten Studie (S1) wurden die größten Messfehler in den Messgrößen Hüftextension ermittelt. Danach folgten die Messgrößen Hüftadduktion und -flexion. Der geringste Messfehler wurde für Hüftabduktion ermittelt. Unter isometrischen Bedingungen wurden in den Kraftmessgrößen Hüftabduktion, -adduktion und -flexion bei Coxarthrosepatienten größere Messfehler quantifiziert als bei gesunden Personen. Zudem war die Reproduzierbarkeit in der ersten Test-Sequenz (Messtag 1 und 2) im Vergleich zur zweiten Test-Sequenz reduziert (Messtag 2 und 3). In der zweiten Studie (S2) konnte gezeigt werden, dass das verwendete Heimtrainingsprogramm sicher und selbstständig von den Hüftpatienten durchgeführt werden konnte. Die Trainingstagebücher ließen auf eine nahezu hundertprozentige Teilnahme am ergänzenden Heimtrainingsprogramm schließen und zeigten außerdem, dass das Heimtrainingsprogramm keine schmerzverursachende Wirkung hatte. Nach der Intervention war die Kraft der hüftumgebenden Muskulatur im Vergleich zur Kontrollgruppe um 7-9% gesteigert. Befunde hinsichtlich einer veränderten Lebensqualität konnten nicht registriert werden. Das statistische Modell, das in der dritten Studie (S3) eingesetzt wurde, erkannte Schmerz, Steifheit und Hüftmuskelkraft als die drei bedeutsamsten Faktoren für die alltagsbezogene körperliche Funktionsfähigkeit bei Patienten mit Coxarthrose. Schlussfolgerungen Kraftmessungen an der Hüfte scheinen erheblichen Tagesschwankungen ausgesetzt zu sein. Bei Coxarthrosepatienten und gesunden Personen scheint sich die Wiederholbarkeit von isokinetischen Kraftmessungen zu ähneln. Unter isometrischen Testbedingungen muss mit höheren Messfehlern bei Coxarthrosepatienten gerechnet und entsprechend bei der Interpretation von Ergebnissen berücksichtigt werden. Eine Gewöhnungsmessung kann den Messfehler reduzieren, birgt allerdings einen erheblich höheren finanziellen und personellen Aufwand. Das ergänzende Heimtrainingsprogramm wurde von den Patienten gut angenommen, so dass lediglich kleinere Modifikationen vorgenommen werden mussten, um es in dem geplanten RCT zu evaluieren. Zudem konnte gezeigt werden, dass die Hüftmuskelkraft zu den drei bedeutsamsten Faktoren zählt, die Einfluss auf die alltagsbezogene körperliche Funktionsfähigkeit bei Patienten mit Coxarthrose haben können. Ob diese Beziehung tatsächlich kausaler Natur ist, werden zukünftige Verlaufsstudien aufzeigen, in denen gezielt solche Faktoren der alltagsrelevanten körperliche Funktionsfähigkeit durch sporttherapeutische Maßnahmen modifiziert werden. Die ausstehenden Ergebnisse des RCT sollen die noch unzureichende wissenschaftliche Beweislage bezüglich der Wirksamkeit sporttherapeutischer Interventionen bei Coxarthrose verbessern. Dabei soll gezeigt werden, ob und in welchem Maß eine Schmerzreduktion und Verringerung der körperlichen Funktionseinschränkung erzielt werden kann.:List of content 1 List of figures 3 List of tables 4 List of abbreviations 5 Abstract 8 Zusammenfassung 11 Structure of the thesis 15 1 Background 16 1.1 Osteoarthritis of the hip joint 16 1.1.1 Prevalence and incidence 16 1.1.2 Etiology 17 1.1.3 Clinical symptoms and diagnosis 18 1.1.4 Socioeconomic burden 20 1.2 Hip muscle strength in osteoarthritis of the hip 23 1.2.1 Anatomical and functional aspects of the hip and its muscles 23 1.2.2 General aspects of muscle strength 25 1.2.3 Hip muscle weakness and muscle imbalances 28 1.2.4 Assessment of hip muscle strength 29 1.3 Physical disability in hip OA 35 1.3.1 General aspects of physical disability in hip OA 35 1.3.2 Assessment of physical disability in hip OA 36 1.4 Exercise therapy in hip OA 38 1.4.1 Efficacy of exercise therapy 38 1.4.2 Strengthening exercises in hip OA 39 1.5 Context of the thesis 43 1.5.1 OsteoArthritisGroup (OAG) 43 2 Scientific program - research papers 47 2.1 Research paper 1: Reproducibility of hip muscle strength measurements in hip OA 48 2.2 Research paper 2: Feasibility and efficacy of an 8-week progressive home-based strengthening exercise 58 2.3 Research paper 3: Evaluation of the therapeutic exercise regimen “Hip School": A protocol for a randomized, controlled trial 68 2.4 Research paper 4: Factors of physical disability in patients with hip osteoarthritis 81 3 Comprehensive and supplementary discussion 103 3.1 Strength measurements at the hip 103 3.1.1 Body position and fixation 103 3.1.2 Torque overshoots 104 3.1.3 Objectivity of hip muscle strength measures in osteoarthritis of the hip 104 3.1.4 Reproducibility of hip muscle strength measures in osteoarthritis of the hip 104 3.1.5 Validity of hip muscle strength measures in osteoarthritis of the hip 105 3.1.6 Isometric versus isokinetic hip muscle strength measures 106 3.2 Strengthening exercises in patients with hip OA 106 3.2.1 Feasibility and adherence to the progressive home-based strengthening exercise program 106 3.2.2 Adverse events due to the exercise intervention 107 3.2.3 Strength gains 108 3.2.4 Adaptations of the PHSEP for the RCT 109 3.3 Hip muscle strength and its relation to physical disability in patients with hip OA 110 4 Limitations 112 5 Conclusion and future perspectives 114 6 Reference list 116 7 Appendix 126 8 Affidavit 131 9 Curriculum vitae 132

No description available.

End-stage conditions such as chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) have shown some of the most dramatic increases in mortality in the developed world over the past 40 years. Both are therefore leading causes of morbidity and mortality worldwide and should be considered as a major economic and social burden that is both substantial and increasing. In these conditions, exercise therapy should play an integral part in maintaining the patient’s maximal level of independence and functioning, as well as slowing or possibly even stopping the progression of the condition. In this context the main objectives of these doctoral theses are: a. Proving the safety of different exercise modalities. b. Identifying the most effective exercise interventions in regards to clinical parameters. c. Proving the feasibility of outpatient rehabilitation programmes for these high risk populations. This work, therefore, combines three studies looking into the effects of non-pharmaceutical interventions – predominantly different exercise regimes in the two major conditions in the mortality statistics of CHF and COPD - both with a very poor prognosis. In conclusion it can be said that the results and experience of all three studies demonstrate the safe feasibility of different outpatient exercise interventions and suggest specific positive adaptations in patients with heart failure and COPD which also led to a lower hospitalisation rate. There are clear hints that the therapy spectrum could be supplemented significantly by specific training interventions. The financial implications for any health care system are also highly relevant.

Indiana University-Purdue University Indianapolis (IUPUI) / Given the numerous benefits of a healthy diet and exercise for cancer survivors, there has been an increase in the number of lifestyle intervention trials for this population in recent years. However, the extent to which adherence to a diet and exercise intervention predicts health-related outcomes among cancer survivors is currently unknown. To address this question, data from the Reach out to ENhancE Wellness in Older Cancer Survivors (RENEW) diet and exercise intervention trial were analyzed. RENEW was a yearlong telephone and mailed print intervention for 641 older (>65 years of age), overweight (body mass index: 25.0-39.9), long-term (>5 years post-diagnosis) survivors of colorectal, breast, and prostate cancer. Participants were randomized to the diet and exercise intervention or a delayed-intervention control condition. The RENEW telephone counseling sessions were based on determinants of behavior derived from Social Cognitive Theory (SCT) (e.g., building social support, enhancing self-efficacy). These factors have been hypothesized to improve health behaviors, which in turn should improve health outcomes. Thus, drawing on SCT and prior diet and exercise research with cancer survivors, I hypothesized that telephone counseling session attendance would be indirectly related to health-related outcomes (i.e., physical function, basic and advanced lower extremity function, mental health, and body mass index) through intervention-period strength and endurance exercise and dietary behavior (i.e., fruit and vegetable intake, saturated fat intake). The proposed model showed good fit to the data; however, not all of the hypothesized relationships were supported. Specifically, increased telephone counseling session attendance was related to engagement in all of the health behaviors over the intervention period. In turn, (a) increased endurance exercise was related to improvement in all of the health-related outcomes with the exception of mental health; (b) increased strength exercise was solely related to improved mental health; (c) increased fruit and vegetable intake was only related to improved basic lower extremity function; and (d) saturated fat intake was not related to any of the health-related outcomes. Taken together, these findings suggest that SCT determinants of behavior and the importance of session attendance should continue to be emphasized in diet and exercise interventions. Continued exploration of the relationship between adherence to a diet and exercise intervention and health-related outcomes will inform the development of more cost-effective and efficacious interventions for cancer and other medical populations.

INTRODUÇÃO: Capítulo 1. A Insuficiência Cardíaca (IC) é acompanhada de uma hiperativação simpática e do sistema renina-angiotensina (SRA). As ações deletérias do SRA são atribuídas à Angiotensina II (AngII), mas a Angiotensina-(1- 7) (Ang-(1-7)), um metabólito da AngII, demonstra efeitos cardiovasculares benéficos, contrários aos da AngII. O conceito tradicional é de que as concentrações sistêmicas mediam as respostas do SRA, mas evidências emergem acerca da importância funcional do SRA local. Nesse estudo, estudou-se o SRA circulante e muscular esquelético na IC, testando-se a hipótese de que as alterações seriam diferentes nesses dois territórios, e que o treinamento físico corrigiria essas alterações. Capítulo 2. A IC é uma síndrome sistêmica, onde fatores neuroendócrinos, como a AngII, podem levar a alterações periféricas. Na musculatura esquelética, a hiperatividade do sistema ubiquitina-proteassoma (SUP) é um dos elementos que compõem um quadro de miopatia, aumentando o catabolismo muscular em direção à atrofia, e contribuindo com o agravamento da síndrome. O treinamento físico normaliza o SUP e reduz as concentrações plasmáticas de AngII na IC. Dessa forma, testamos a hipótese de que a redução do SUP mediada pelo treinamento físico na IC depende da queda das concentrações plasmáticas de AngII. MÉTODOS: Capítulo 1. Ratos Wistar, machos, foram induzidos à IC por ligadura da artéria coronária descendente anterior, ou cirurgia fictícia (Sham, SH). Os animais foram divididos em grupos mantidos sedentários, SD (SHSD, n=10 e ICSD, n=12) ou submetidos ao treinamento físico, TR (SHTR, n=10, ICTR, n=12). O treinamento físico foi realizado em esteira, a 60% do consumo máximo de oxigênio, 5 dias por semana durante 8 semanas, quando foram sacrificados para coleta de sangue e músculos (sóleo e plantar). As angiotensinas circulantes e musculares foram dosadas por HPLC. A atividade sérica e muscular da ECA e da ECA2 por fluorimetria. Os receptores AT1 e AT2 foram analisados por expressão gênica (RT-PCR) e proteica (Western Blot), e o receptor Mas por expressão gênica. Capítulo 2. Ratos Wistar, machos, foram induzidos à IC por ligadura da artéria coronária descendente anterior, ou cirurgia fictícia (Sham). Após 4 semanas, os animais Sham (n=10) constituíram um grupo sedentário saudável (SHSD) e os animais com IC (n=30) foram igualmente alocados em 3 grupos: um mantido sedentário (ICSD), um treinado (ICTR) e um treinado com as concentrações plasmáticas de AngII nos mesmos níveis dos animais do grupo ICSD (ICTRAII), mantidas através de minipump osmótica. O treinamento físico foi realizado em esteira, a 60% do consumo máximo de oxigênio, 5 dias por semana durante 8 semanas, quando foram sacrificados para coleta de sangue e músculos (sóleo e plantar). As angiotensinas circulantes e musculares foram dosadas por HPLC. A expressão gênica das enzimas ligases E3?, MuRF e Atrogin foi realizada por RT-PCR. O receptor AT1, as proteínas ubiquitinadas e as proteínas carboniladas (Oxyblot) foram quantificadas por Western Blot. A atividade da porção 26S do proteassoma foi determinada por fluorimetria. RESULTADOS: Capítulo 1. Na circulação, a atividade da ECA2 estava reduzida na IC, e o treinamento físico reduziu a atividade da ECA e restaurou a atividade da ECA2 esses animais. A concentração de AngII reduziu nos grupos treinados, e a razão Ang-(1-7)/AngII aumentou no grupo ICTR. Nos músculos, não houve alteração em relação à atividade ou expressão proteica da ECA ou da ECA2, mas a concentração de AngII estava aumentada com a IC, e normalizou com o treinamento físico. A concentração de Ang-(1-7) aumentou no músculo plantar do grupo ICTR, e a razão Ang-(1-7)/AngII apresentou forte tendência de aumento no músculo sóleo dos animais treinados. No músculo sóleo, o AT1 estava aumentado nos animais com IC, e o treinamento físico normalizou a expressão gênica e proteica desse receptor, e também aumentou a expressão gênica do receptor Mas nos grupos treinados. No músculo plantar, normalizou a expressão gênica do receptor Mas, sem alterar o AT1. Não foram encontradas diferenças significativas na expressão do receptor AT2 nos músculos estudados. Capítulo 2. O treinamento físico promoveu uma melhora da capacidade de exercício em ambos os grupos treinados. A AngII aumentou nos músculos dos animais com IC, e o treinamento físico normalizou esses valores. Na circulação, como se esperava, a AngII diminuiu apenas no grupo ICTR. A expressão do receptor AT1 aumentou no músculo sóleo com a IC e normalizou com o treinamento físico, sem diferenças entre grupos no músculo plantar. Em relação à expressão gênica das E3 ligases e na quantidade de proteínas ubiquitinadas e carboniladas, não houve diferenças entre os grupos no músculo sóleo. Já no músculo plantar, a expressão do atrogin estava aumentada nos animais com IC, e o treinamento físico reduziu a expressão tanto da atrogin quanto da E3? e da MuRF. Essa melhora foi prejudicada com a infusão de AngII. Refletindo esse cenário, a quantidade de proteínas ubiquitinadas e carboniladas estavam aumentadas na IC e reduziram com o treinamento físico, e a infusão de AngII atenuou a redução das proteínas ubiquitinadas e aboliu a diminuição das oxidadas. A atividade do proteassoma aumentou em ambos os músculos de animais com IC, e o treinamento físico reduziu a atividade nos animais treinados, sendo significativamente menor no grupo ICTRAII. CONCLUSÕES: Capítulo 1. Em modelo de IC crônica, os níveis de AngII estão aumentados na musculatura esquelética, mas não na circulação. O treinamento físico reduz os níveis plasmáticos de AngII na circulação e normaliza nos músculos. Essa redução é acompanhada de um aumento dos níveis de Ang-(1-7) ou da melhora na razão Ang-(1-7)/AngII em ambos os territórios, indicando uma atenuação da hiperativação do SRA na IC com o treinamento físico. Capítulo 2. Em modelo isquêmico de IC crônica em ratos, há uma diferença no perfil do SUP no músculo sóleo e no músculo plantar. O treinamento físico reduz a atividade do SUP e, ao menos no músculo plantar, essa melhora parece ser dependente da redução dos níveis de AngII / INTRODUCTION: Chapter 1. Heart Failure (IC) is a syndrome accompanied by a sympathetic and renin-angiotensin system (RAS) hyperactivity. The deleterious actions of RAS are attributed to Angiotensin II (AngII), but Angiotensin-(1-7) (Ang-(1- 7)), a metabolite of AngII, shows benefic cardiovascular effects opposing to AngII. The traditional concept states that the systemic concentrations are responsible for RAS actions, although increasingly evidence emerge about the functional role of local RAS. The working hypothesis was that the RAS alterations, if any, would be different on this two territories of heart failure rats, and the exercise training should correct this alterations. Chapter 2. Heart failure is a systemic syndrome in which neuroendocrine factors, such as angiotensin II (AngII), can lead to peripheral damage. In skeletal muscle, the hyperactivity of ubiquitin-proteasome system (SUP) is one of the elements composing the myopathy framework, elevating the catabolism toward atrophy, and contributing to the worsening of the syndrome. Exercise training normalizes SUP and reduces plasmatic concentrations of AngII. On this way, we tested the hypothesis that exercise training-mediated SUP deactivation is dependent on plasma falls of AngII. METHODS: Chapter 1. Male Wistar rats underwent left coronary artery ligation or Sham (SH) operation. They were allocated in sedentary, SD (SHSD, n=10 and ICSD, n=12) or trained, TR (SHTR, n=10 and ICTR, n=12) groups. The exercise training consisted in treadmill running, at 60% of maximal oxygen uptake, 5 days per week, during 8 weeks, when they were killed for blood and skeletal muscle (soleus and plantaris) collection. Angiotensin\'s concentrations were determined by HPLC. ACE and ACE2 activity were accessed in serum and muscles by fluorimetry, and by protein expression (Western Blot) in the muscles. AT1 and AT2 receptors were quantified by protein and gene (RT-PCR) expression, and Mas receptor by gene expression. Chapter 2. Male Wistar rats underwent left coronary artery ligation or Sham operation. After 4 weeks, Sham operated rats (n=10) constituted a healthy, sedentary control group (SHSD), and the heart failure rats (n=30) were equally allocated into 3 groups: sedentary (ICSD), trained (ICTR) and trained with plasma AngII at the same level of sedentary, heart failure rats (ICTRAII), kept by an osmotic minipump. The exercise training consisted in treadmill running, at 55% of maximal oxygen uptake, 5 days per week, during 8 weeks, when they were killed for blood and skeletal muscle (soleus and plantaris) collection. AngII concentrations were determined by HPLC. Gene expression of E3?, MuRF e Atrogin were performed by PR-PCR. AT1 receptor, ubiquitinated and carbonylated (oxyblot) proteins were quantified by Western Blot. Proteasomal 26S activity were determined by fluorimetry. RESULTS: Chapter 1. Heart failure reduced circulating ACE2 activity, and exercise training reduced ACE and normalized ACE2 activity in this rats. AngII concentration reduced in both trained groups, increasing Ang-(1-7)/AngII ratio on ICTR group. The studied skeletal muscles did not change activity or protein expression of ACE and ACE2, although the AngII, which was increased with heart failure, has normalized with exercise training. Absolute Ang-(1-7) concentration increased in plantaris muscle, and a strong tendency of significant increase was shown in soleus muscle of trained rats. Also in the soleus, AT1 receptor raised with heart failure, and the exercise training normalized the gene as well as protein expression of this receptor, also increasing gene expression of Mas receptor of trained groups. In plantaris muscle, exercise normalized Mas receptor in ICTR, without influencing AT1 receptor. No significant changes among groups were found in relation to AT2 receptor of the studied muscles. Chapter 2. Exercise training promoted an improvement of exercise capacity in trained groups. AngII raised in skeletal muscle of rats with heart failure, and exercise training normalized this. Circulating AngII, as expected, reduced only in ICTR group. AT1 receptor expression increased in soleus muscle of heart failure, and normalized after exercise in trained rats, without any difference among groups in plantaris muscle. Regarding E3 ligases gene expression and quantity of ubiquitinated and carbonylated proteins, there were no differences among groups in soleus muscle. Nevertheless, in plantaris muscle, atrogin expression was increased in heart failure rats, and exercise training reduced atrogin, as well as E3alpha and MuRF expression. These improvements were impaired by AngII infusion. Mirroring this scenario, the amount of ubiquitinated and carbonylated proteins increased with heart failure and reduced with exercise training, but AngII infusion lessen the reduction of ubiquitinated proteins and completely blunted the effects of exercise on carbonylated proteins. Proteasome 26S activity was increased in both muscles of heart failure rats, and exercise avoided this increase in trained rats, being significantly reduced in ICTRAII. CONCLUSIONS: Chapter 1. In a model of chronic heart failure rats, AngII levels are increased in skeletal muscle, but not in the circulation. The exercise training reduces plasma and normalizes skeletal muscle concentration of AngII. This reduction is accompanied by an increase Ang-(1-7) levels, or improvements of Ang-(1-7)/AngII ratio in both systemic and local territories, indicating an attenuation of RAS hyperactivity with exercise training in heart failure rats. Chapter 2. In a model of chronic heart failure rats, there is a difference on SUP activation profile in soleus and plantaris muscle. Exercise training reduces SUP activity and, in plantaris muscle, this amelioration seems to be, at least in part, dependent of a reduction in AngII levels

Este estudo mostra como o rolamento do pé de pacientes com polineuropatia diabética pode ser melhorado com exercícios para pés e tornozelos, visando a recuperação muscular e articular comprometidos pela doença. Um ensaio clínico randomizado, paralelo, com um braço de crossover, e avaliador cego, foi conduzido. Cinquenta e cinco pacientes com polineuropatia diabética foram randomizados e alocados para o grupo controle (n=29) e grupo intervenção (n=26). A intervenção foi aplicada por 12 semanas, 2 vezes por semana, por 40 a 60 minutos cada sessão. As variáveis primárias foram definidas como as que descrevem o rolamento do pé: pressão plantar em seis regiões plantares de interesse. As variáveis secundárias foram a cinética e cinemática de tornozelo no plano sagital, e as medidas clínicas da função de pés e tornozelo (teste de função muscular manual, testes funcionais), de sinais e sintomas da polineuropatia diabética, exame físico dos pés e teste de confiança e equilíbrio em atividades da marcha. Os efeitos de tempo (baseline e 12 semanas), de grupo (controle e intervenção) e de interação foram calculados por meio de ANOVAs casewise 2 fatores, e para as comparações intragrupo do grupo intervenção (baseline, 12 semanas e 24 semanas) foram usadas ANOVAs para medidas repetidas. As variáveis não paramétricas foram comparadas entre grupos por meio de testes de Mann-Whitney e entre os tempos de intervenção por meio do teste de Wilcoxon. Adotou-se um ? de 5% para diferenças estatísticas e o coeficiente d de Cohen para descrição do tamanho do efeito da intervenção. Após 12 semanas de exercícios, observou-se mudanças positivas no rolamento do pé. Houve uma suavização do contato do calcanhar no apoio inicial, refletido pelo aumento do tempo do pico de pressão e da integral do pico de pressão. O médio-pé aumentou sua participação no rolamento observado pela diminuição da velocidade média do deslocamento do centro de pressão e aumento da integral do pico de pressão. O antepé lateral passou a realizar o apoio no solo antecipadamente em relação ao antepé medial, que previamente à intervenção aconteciam concomitantemente, e esse resultado foi evidenciado pela antecipação do tempo do pico de pressão em antepé lateral após a intervenção. A ação de hálux e dedos também aumentou (aumento de integral do pico de pressão e picos de pressão), em uma patologia marcada pela diminuição do contato do hálux e desenvolvimento de dedos em garra, que diminui o contato dos dedos com o solo. O grupo controle apresentou algumas pioras com relação à função muscular e parâmetros cinéticos e cinemáticos de tornozelo, enquanto que o grupo intervenção mostrou melhora na função de muitos grupos musculares, em testes funcionais e no pico de momento extensor na fase de aplainamento do pé. Apesar do protocolo de intervenção ter sido construído de modo a permitir que o paciente incorpore os exercícios na sua rotina diária, a aderência a este tipo de intervenção deve ser estudada, já que grande parte das variáveis retornaram ao baseline após o período de follow up. Ações preventivas são fundamentais para diminuir as complicações devastadoras da neuropatia diabética / This study shows how the foot rollover process during gait of patients with diabetic polyneuropathy can be improved with exercises for foot and ankle, aiming at the recovery of the muscles and joints affected by the disease. A clinical trial randomized, parallel, one arm of crossover, with blind assessment was conducted. Fifty-five patients with diabetic polineuropathy were randomly allocated to the control group (n = 29) and intervention group (n = 26). The intervention was applied for 12 weeks, twice a week, for 40 to 60 minutes per session. The primary variables were defined as those that describe the foot rollover: plantar pressure in 6 plantar areas of interest. The secondary variables were kinetic and kinematics of the ankle in the sagittal plane were calculated, and the clinical measures of foot and ankle function (manual muscle function testing, functional testing), signs and symptoms of diabetic polyneuropathy, physical examination of the feet and balance and confidence test in gait activities. The time effects (baseline and 12 weeks), group effects (control and intervention groups) and interaction effects were calculated using casewise two factos ANOVAs, and for intragroup comparisons of intervention group (baseline, 12 weeks and 24 weeks) it was used ANOVAs for repeated measures. The nonparametric variables were compared between groups using Mann-Whitney tests and between periods of assessment using Wilcoxon test. We adopted an ? of 5% for statistical differences and the Cohen\'s d coefficient for description of the effect size. After 12 weeks ofexercises, there were positive changes in the foot rollover process. There was a softening of heel contact in initial contact, reflected by the increase in time to peak pressure and the pressure time integral. The midfoot increased its participation observed by the decrease in speed of displacement of the center of pressure and increased pressure time integral. The lateral forefoot contact was earlier relative to the medial forefoot, that occurred at the same time before intervention, observed by the early time to peak pressure of lateral forefoot after the intervention. The participation of the hallux and toes also increased (increase of pressure time integral and peak pressure), in a pathology that is marked by decreased contact of the hallux and development of claw toes, which reduces contact of the toes with the ground. CG showed some worsening in relation to muscle function and kinematic and kinetic parameters of the ankle, while the IG showed improvement in the function of many muscles groups, functional tests and peak extensor moment during the forefoot contact. The intervention protocol was constructed to allow the patient to incorporate exercise into their daily routine, but adherence to treatment should be studied and motivational strategies need to be applied, since most of the variables returned to baseline after the follow up period (12 weeks after the intervention). Preventive actions are critical to reducing the devastating complications of diabetic neuropathy

Submitted in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, Durban University of Technology, 2014. / Background: Myofascial Pain and Dysfunction (MPD) is a diagnosis commonly encountered by practitioners, hence, there are several treatment approaches employed by various practicing physicians. Practitioners are required to perform evidence-based protocols on patients; however, such intervention becomes increasingly difficult with the increasing volume of evidence available with regards to treatment of MPD. A systematic review provides a well-structured, critical analysis of the available protocols, and as such, provides practitioners with an evidence-based summary of the available modalities and the effectiveness of these modalities. Thus, the aim of the study was to systematically review and evaluate the literature to determine the effects of various non-invasive modalities on MPD. Objectives: Studies investigating various non-invasive modalities were identified, evaluated against the inclusion criteria and then reviewed against PEDro criteria to present current available evidence regarding their effectiveness as a source of treatment for MPD. Methods: A literature search was conducted, based on key terms including: active and latent myofascial trigger points, manual therapy, manipulation, acupressure, massage, muscle stretching, ultrasound, transcutaneous electric nerve stimulation, electric stimulation therapy, magnetic field therapy, and exercise therapy. Databases searched were: PubMed, EBSCOhost, Medline, CINAL, Proquest, Health Source, Sport Discus, Science Direct, Springer Link, Google Scholar and Summons. The articles were screened according to inclusion and exclusion criteria, after which a secondary hand and reference searches were performed. Thereafter, the articles were reviewed by four independent reviewers and the researcher. The PEDro Scale was used to determine methodological rigor of the included studies. The results were then analysed and ranked. Results: Following the screening process during data collection for this study, a total of 25 studies were identified and included. The review and ranking of these studies revealed a moderate level of evidence present for the effectiveness of Topical Agents. A limited level of evidence was noted for TENS, Ischemic Compression, Ultrasound, Laser and Other Modalities. Approximately 25% of the reviewed studies involved combination therapies; hence their outcomes cannot be applied to the effectiveness of individual modalities. Conclusion: Upon comparison of the quality of evidence available for the various types of modalities present for the treatment of MPD, it was noted that Topical Agents were supported by a stronger level of evidence than TENS, Ischeamic Compression, Ultrasound, Laser and Other Modalities. However, due to a lack of strong overall evidence for any of these modalities it has been concluded that more research is required to establish which modality is in fact the most effective.

INTRODUÇÃO: Capítulo 1. A Insuficiência Cardíaca (IC) é acompanhada de uma hiperativação simpática e do sistema renina-angiotensina (SRA). As ações deletérias do SRA são atribuídas à Angiotensina II (AngII), mas a Angiotensina-(1- 7) (Ang-(1-7)), um metabólito da AngII, demonstra efeitos cardiovasculares benéficos, contrários aos da AngII. O conceito tradicional é de que as concentrações sistêmicas mediam as respostas do SRA, mas evidências emergem acerca da importância funcional do SRA local. Nesse estudo, estudou-se o SRA circulante e muscular esquelético na IC, testando-se a hipótese de que as alterações seriam diferentes nesses dois territórios, e que o treinamento físico corrigiria essas alterações. Capítulo 2. A IC é uma síndrome sistêmica, onde fatores neuroendócrinos, como a AngII, podem levar a alterações periféricas. Na musculatura esquelética, a hiperatividade do sistema ubiquitina-proteassoma (SUP) é um dos elementos que compõem um quadro de miopatia, aumentando o catabolismo muscular em direção à atrofia, e contribuindo com o agravamento da síndrome. O treinamento físico normaliza o SUP e reduz as concentrações plasmáticas de AngII na IC. Dessa forma, testamos a hipótese de que a redução do SUP mediada pelo treinamento físico na IC depende da queda das concentrações plasmáticas de AngII. MÉTODOS: Capítulo 1. Ratos Wistar, machos, foram induzidos à IC por ligadura da artéria coronária descendente anterior, ou cirurgia fictícia (Sham, SH). Os animais foram divididos em grupos mantidos sedentários, SD (SHSD, n=10 e ICSD, n=12) ou submetidos ao treinamento físico, TR (SHTR, n=10, ICTR, n=12). O treinamento físico foi realizado em esteira, a 60% do consumo máximo de oxigênio, 5 dias por semana durante 8 semanas, quando foram sacrificados para coleta de sangue e músculos (sóleo e plantar). As angiotensinas circulantes e musculares foram dosadas por HPLC. A atividade sérica e muscular da ECA e da ECA2 por fluorimetria. Os receptores AT1 e AT2 foram analisados por expressão gênica (RT-PCR) e proteica (Western Blot), e o receptor Mas por expressão gênica. Capítulo 2. Ratos Wistar, machos, foram induzidos à IC por ligadura da artéria coronária descendente anterior, ou cirurgia fictícia (Sham). Após 4 semanas, os animais Sham (n=10) constituíram um grupo sedentário saudável (SHSD) e os animais com IC (n=30) foram igualmente alocados em 3 grupos: um mantido sedentário (ICSD), um treinado (ICTR) e um treinado com as concentrações plasmáticas de AngII nos mesmos níveis dos animais do grupo ICSD (ICTRAII), mantidas através de minipump osmótica. O treinamento físico foi realizado em esteira, a 60% do consumo máximo de oxigênio, 5 dias por semana durante 8 semanas, quando foram sacrificados para coleta de sangue e músculos (sóleo e plantar). As angiotensinas circulantes e musculares foram dosadas por HPLC. A expressão gênica das enzimas ligases E3?, MuRF e Atrogin foi realizada por RT-PCR. O receptor AT1, as proteínas ubiquitinadas e as proteínas carboniladas (Oxyblot) foram quantificadas por Western Blot. A atividade da porção 26S do proteassoma foi determinada por fluorimetria. RESULTADOS: Capítulo 1. Na circulação, a atividade da ECA2 estava reduzida na IC, e o treinamento físico reduziu a atividade da ECA e restaurou a atividade da ECA2 esses animais. A concentração de AngII reduziu nos grupos treinados, e a razão Ang-(1-7)/AngII aumentou no grupo ICTR. Nos músculos, não houve alteração em relação à atividade ou expressão proteica da ECA ou da ECA2, mas a concentração de AngII estava aumentada com a IC, e normalizou com o treinamento físico. A concentração de Ang-(1-7) aumentou no músculo plantar do grupo ICTR, e a razão Ang-(1-7)/AngII apresentou forte tendência de aumento no músculo sóleo dos animais treinados. No músculo sóleo, o AT1 estava aumentado nos animais com IC, e o treinamento físico normalizou a expressão gênica e proteica desse receptor, e também aumentou a expressão gênica do receptor Mas nos grupos treinados. No músculo plantar, normalizou a expressão gênica do receptor Mas, sem alterar o AT1. Não foram encontradas diferenças significativas na expressão do receptor AT2 nos músculos estudados. Capítulo 2. O treinamento físico promoveu uma melhora da capacidade de exercício em ambos os grupos treinados. A AngII aumentou nos músculos dos animais com IC, e o treinamento físico normalizou esses valores. Na circulação, como se esperava, a AngII diminuiu apenas no grupo ICTR. A expressão do receptor AT1 aumentou no músculo sóleo com a IC e normalizou com o treinamento físico, sem diferenças entre grupos no músculo plantar. Em relação à expressão gênica das E3 ligases e na quantidade de proteínas ubiquitinadas e carboniladas, não houve diferenças entre os grupos no músculo sóleo. Já no músculo plantar, a expressão do atrogin estava aumentada nos animais com IC, e o treinamento físico reduziu a expressão tanto da atrogin quanto da E3? e da MuRF. Essa melhora foi prejudicada com a infusão de AngII. Refletindo esse cenário, a quantidade de proteínas ubiquitinadas e carboniladas estavam aumentadas na IC e reduziram com o treinamento físico, e a infusão de AngII atenuou a redução das proteínas ubiquitinadas e aboliu a diminuição das oxidadas. A atividade do proteassoma aumentou em ambos os músculos de animais com IC, e o treinamento físico reduziu a atividade nos animais treinados, sendo significativamente menor no grupo ICTRAII. CONCLUSÕES: Capítulo 1. Em modelo de IC crônica, os níveis de AngII estão aumentados na musculatura esquelética, mas não na circulação. O treinamento físico reduz os níveis plasmáticos de AngII na circulação e normaliza nos músculos. Essa redução é acompanhada de um aumento dos níveis de Ang-(1-7) ou da melhora na razão Ang-(1-7)/AngII em ambos os territórios, indicando uma atenuação da hiperativação do SRA na IC com o treinamento físico. Capítulo 2. Em modelo isquêmico de IC crônica em ratos, há uma diferença no perfil do SUP no músculo sóleo e no músculo plantar. O treinamento físico reduz a atividade do SUP e, ao menos no músculo plantar, essa melhora parece ser dependente da redução dos níveis de AngII / INTRODUCTION: Chapter 1. Heart Failure (IC) is a syndrome accompanied by a sympathetic and renin-angiotensin system (RAS) hyperactivity. The deleterious actions of RAS are attributed to Angiotensin II (AngII), but Angiotensin-(1-7) (Ang-(1- 7)), a metabolite of AngII, shows benefic cardiovascular effects opposing to AngII. The traditional concept states that the systemic concentrations are responsible for RAS actions, although increasingly evidence emerge about the functional role of local RAS. The working hypothesis was that the RAS alterations, if any, would be different on this two territories of heart failure rats, and the exercise training should correct this alterations. Chapter 2. Heart failure is a systemic syndrome in which neuroendocrine factors, such as angiotensin II (AngII), can lead to peripheral damage. In skeletal muscle, the hyperactivity of ubiquitin-proteasome system (SUP) is one of the elements composing the myopathy framework, elevating the catabolism toward atrophy, and contributing to the worsening of the syndrome. Exercise training normalizes SUP and reduces plasmatic concentrations of AngII. On this way, we tested the hypothesis that exercise training-mediated SUP deactivation is dependent on plasma falls of AngII. METHODS: Chapter 1. Male Wistar rats underwent left coronary artery ligation or Sham (SH) operation. They were allocated in sedentary, SD (SHSD, n=10 and ICSD, n=12) or trained, TR (SHTR, n=10 and ICTR, n=12) groups. The exercise training consisted in treadmill running, at 60% of maximal oxygen uptake, 5 days per week, during 8 weeks, when they were killed for blood and skeletal muscle (soleus and plantaris) collection. Angiotensin\'s concentrations were determined by HPLC. ACE and ACE2 activity were accessed in serum and muscles by fluorimetry, and by protein expression (Western Blot) in the muscles. AT1 and AT2 receptors were quantified by protein and gene (RT-PCR) expression, and Mas receptor by gene expression. Chapter 2. Male Wistar rats underwent left coronary artery ligation or Sham operation. After 4 weeks, Sham operated rats (n=10) constituted a healthy, sedentary control group (SHSD), and the heart failure rats (n=30) were equally allocated into 3 groups: sedentary (ICSD), trained (ICTR) and trained with plasma AngII at the same level of sedentary, heart failure rats (ICTRAII), kept by an osmotic minipump. The exercise training consisted in treadmill running, at 55% of maximal oxygen uptake, 5 days per week, during 8 weeks, when they were killed for blood and skeletal muscle (soleus and plantaris) collection. AngII concentrations were determined by HPLC. Gene expression of E3?, MuRF e Atrogin were performed by PR-PCR. AT1 receptor, ubiquitinated and carbonylated (oxyblot) proteins were quantified by Western Blot. Proteasomal 26S activity were determined by fluorimetry. RESULTS: Chapter 1. Heart failure reduced circulating ACE2 activity, and exercise training reduced ACE and normalized ACE2 activity in this rats. AngII concentration reduced in both trained groups, increasing Ang-(1-7)/AngII ratio on ICTR group. The studied skeletal muscles did not change activity or protein expression of ACE and ACE2, although the AngII, which was increased with heart failure, has normalized with exercise training. Absolute Ang-(1-7) concentration increased in plantaris muscle, and a strong tendency of significant increase was shown in soleus muscle of trained rats. Also in the soleus, AT1 receptor raised with heart failure, and the exercise training normalized the gene as well as protein expression of this receptor, also increasing gene expression of Mas receptor of trained groups. In plantaris muscle, exercise normalized Mas receptor in ICTR, without influencing AT1 receptor. No significant changes among groups were found in relation to AT2 receptor of the studied muscles. Chapter 2. Exercise training promoted an improvement of exercise capacity in trained groups. AngII raised in skeletal muscle of rats with heart failure, and exercise training normalized this. Circulating AngII, as expected, reduced only in ICTR group. AT1 receptor expression increased in soleus muscle of heart failure, and normalized after exercise in trained rats, without any difference among groups in plantaris muscle. Regarding E3 ligases gene expression and quantity of ubiquitinated and carbonylated proteins, there were no differences among groups in soleus muscle. Nevertheless, in plantaris muscle, atrogin expression was increased in heart failure rats, and exercise training reduced atrogin, as well as E3alpha and MuRF expression. These improvements were impaired by AngII infusion. Mirroring this scenario, the amount of ubiquitinated and carbonylated proteins increased with heart failure and reduced with exercise training, but AngII infusion lessen the reduction of ubiquitinated proteins and completely blunted the effects of exercise on carbonylated proteins. Proteasome 26S activity was increased in both muscles of heart failure rats, and exercise avoided this increase in trained rats, being significantly reduced in ICTRAII. CONCLUSIONS: Chapter 1. In a model of chronic heart failure rats, AngII levels are increased in skeletal muscle, but not in the circulation. The exercise training reduces plasma and normalizes skeletal muscle concentration of AngII. This reduction is accompanied by an increase Ang-(1-7) levels, or improvements of Ang-(1-7)/AngII ratio in both systemic and local territories, indicating an attenuation of RAS hyperactivity with exercise training in heart failure rats. Chapter 2. In a model of chronic heart failure rats, there is a difference on SUP activation profile in soleus and plantaris muscle. Exercise training reduces SUP activity and, in plantaris muscle, this amelioration seems to be, at least in part, dependent of a reduction in AngII levels

Este estudo mostra como o rolamento do pé de pacientes com polineuropatia diabética pode ser melhorado com exercícios para pés e tornozelos, visando a recuperação muscular e articular comprometidos pela doença. Um ensaio clínico randomizado, paralelo, com um braço de crossover, e avaliador cego, foi conduzido. Cinquenta e cinco pacientes com polineuropatia diabética foram randomizados e alocados para o grupo controle (n=29) e grupo intervenção (n=26). A intervenção foi aplicada por 12 semanas, 2 vezes por semana, por 40 a 60 minutos cada sessão. As variáveis primárias foram definidas como as que descrevem o rolamento do pé: pressão plantar em seis regiões plantares de interesse. As variáveis secundárias foram a cinética e cinemática de tornozelo no plano sagital, e as medidas clínicas da função de pés e tornozelo (teste de função muscular manual, testes funcionais), de sinais e sintomas da polineuropatia diabética, exame físico dos pés e teste de confiança e equilíbrio em atividades da marcha. Os efeitos de tempo (baseline e 12 semanas), de grupo (controle e intervenção) e de interação foram calculados por meio de ANOVAs casewise 2 fatores, e para as comparações intragrupo do grupo intervenção (baseline, 12 semanas e 24 semanas) foram usadas ANOVAs para medidas repetidas. As variáveis não paramétricas foram comparadas entre grupos por meio de testes de Mann-Whitney e entre os tempos de intervenção por meio do teste de Wilcoxon. Adotou-se um ? de 5% para diferenças estatísticas e o coeficiente d de Cohen para descrição do tamanho do efeito da intervenção. Após 12 semanas de exercícios, observou-se mudanças positivas no rolamento do pé. Houve uma suavização do contato do calcanhar no apoio inicial, refletido pelo aumento do tempo do pico de pressão e da integral do pico de pressão. O médio-pé aumentou sua participação no rolamento observado pela diminuição da velocidade média do deslocamento do centro de pressão e aumento da integral do pico de pressão. O antepé lateral passou a realizar o apoio no solo antecipadamente em relação ao antepé medial, que previamente à intervenção aconteciam concomitantemente, e esse resultado foi evidenciado pela antecipação do tempo do pico de pressão em antepé lateral após a intervenção. A ação de hálux e dedos também aumentou (aumento de integral do pico de pressão e picos de pressão), em uma patologia marcada pela diminuição do contato do hálux e desenvolvimento de dedos em garra, que diminui o contato dos dedos com o solo. O grupo controle apresentou algumas pioras com relação à função muscular e parâmetros cinéticos e cinemáticos de tornozelo, enquanto que o grupo intervenção mostrou melhora na função de muitos grupos musculares, em testes funcionais e no pico de momento extensor na fase de aplainamento do pé. Apesar do protocolo de intervenção ter sido construído de modo a permitir que o paciente incorpore os exercícios na sua rotina diária, a aderência a este tipo de intervenção deve ser estudada, já que grande parte das variáveis retornaram ao baseline após o período de follow up. Ações preventivas são fundamentais para diminuir as complicações devastadoras da neuropatia diabética / This study shows how the foot rollover process during gait of patients with diabetic polyneuropathy can be improved with exercises for foot and ankle, aiming at the recovery of the muscles and joints affected by the disease. A clinical trial randomized, parallel, one arm of crossover, with blind assessment was conducted. Fifty-five patients with diabetic polineuropathy were randomly allocated to the control group (n = 29) and intervention group (n = 26). The intervention was applied for 12 weeks, twice a week, for 40 to 60 minutes per session. The primary variables were defined as those that describe the foot rollover: plantar pressure in 6 plantar areas of interest. The secondary variables were kinetic and kinematics of the ankle in the sagittal plane were calculated, and the clinical measures of foot and ankle function (manual muscle function testing, functional testing), signs and symptoms of diabetic polyneuropathy, physical examination of the feet and balance and confidence test in gait activities. The time effects (baseline and 12 weeks), group effects (control and intervention groups) and interaction effects were calculated using casewise two factos ANOVAs, and for intragroup comparisons of intervention group (baseline, 12 weeks and 24 weeks) it was used ANOVAs for repeated measures. The nonparametric variables were compared between groups using Mann-Whitney tests and between periods of assessment using Wilcoxon test. We adopted an ? of 5% for statistical differences and the Cohen\'s d coefficient for description of the effect size. After 12 weeks ofexercises, there were positive changes in the foot rollover process. There was a softening of heel contact in initial contact, reflected by the increase in time to peak pressure and the pressure time integral. The midfoot increased its participation observed by the decrease in speed of displacement of the center of pressure and increased pressure time integral. The lateral forefoot contact was earlier relative to the medial forefoot, that occurred at the same time before intervention, observed by the early time to peak pressure of lateral forefoot after the intervention. The participation of the hallux and toes also increased (increase of pressure time integral and peak pressure), in a pathology that is marked by decreased contact of the hallux and development of claw toes, which reduces contact of the toes with the ground. CG showed some worsening in relation to muscle function and kinematic and kinetic parameters of the ankle, while the IG showed improvement in the function of many muscles groups, functional tests and peak extensor moment during the forefoot contact. The intervention protocol was constructed to allow the patient to incorporate exercise into their daily routine, but adherence to treatment should be studied and motivational strategies need to be applied, since most of the variables returned to baseline after the follow up period (12 weeks after the intervention). Preventive actions are critical to reducing the devastating complications of diabetic neuropathy