Pax3 protein is initially expressed in the dermomyotome of embryonic somites, which gives rise to skeletal muscle. Following myogenesis, Pax3 expression is mostly down-regulated and becomes restricted to a few satellite cells (SCs) of select mature muscles. SCs are activated to form new myonuclei during muscle hypertrophy, regeneration and repair. Intrafusal fibers of muscle spindles are thought to persist in a comparatively immature state as, unlike extrafusal fibers, they maintain small diameters, developmental myosins, Myf5 expression and high SC concentrations. This thesis tests the hypotheses that Pax3 expression is preferentially maintained in SCs of adult skeletal muscle spindles and can be augmented under conditions of SC activation. To study Pax3 through development, immunohistochemical techniques were used to identify SCs by their Pax7 expression, and analyze the proportion of SCs and myonuclei (MN) expressing Pax3 in chicken anterior latissimus dorsi (ALD) muscle excised at 9, 30, 62, and 145 days post-hatch. To induce SC activation, tenotomy was performed on the right ALD muscle of 138-day post-hatch chicks to induce compensatory hypertrophy of the ipsilateral synergistic posterior latissimus dorsi (PLD) muscle. The PLD was analyzed seven days after ALD tenotomy using similar immunohistochemical techniques. This is the first study to show Pax3 expressing SCs within intrafusal fibers of muscle spindles. This thesis demonstrates that throughout development there is a higher percentage of Pax3 expressing SCs within intrafusal fibers of muscle spindles than the surrounding extrafusal fibers that compose the bulk of the muscle. It is also revealed that the proportion of the SC population expressing Pax3 declines with age in both intrafusal and extrafusal fibers. Compensatory hypertrophy of the PLD resulted in a greater percentage of Pax3 expressing SCs in intrafusal and extrafusal fibers than under control conditions. The percentage of SCs expressing Pax3 after PLD overload was similar to that seen in young control muscle. The percentage of Pax3 expressing MN also increased after muscle overload to levels seen in young muscle. A disproportionate decrease in the proportion of SCs expressing Pax3 during development, and a disproportionate increase in the percentage of Pax3 positive SCs as a result of experimentally induced muscle hypertrophy, suggests that Pax3 expression in maturing muscle may be more than just a developmental vestige. Pax3 may be a factor in the activation and differentiation of SCs in maturing muscle.

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Subject of the study. Aerobic capacity and cardiac structure and function of healthy young males. Background. Data regarding the relationship between the parameters of aerobic capacity (such as maximal oxygen uptake or anaerobic threshold) and cardiac structure as well as function remain sparse and controversial. Aim. To determine how the parameters of aerobic capacity are correlated with those of cardiac structure and function. Objectives: 1. To determine the correlation between anaerobic thresholds and myocardial structure. 2. To determine how strongly the maximal oxygen uptake and cardiac structure are correlated. 3. To determine the correlation of indices of aerobic capacity to the parameters of myocardial function at rest. Hypothesis. Cardiac structure and function of healthy young men is directly linked not only to maximal oxygen uptake but anaerobic thresholds as well. Conclusions. The direct correlation of the parameters of concentric cardiac hypertrophy with aerobic capacity (anaerobic thresholds as well as maximal oxygen uptake) indices was detected. However, we failed to detect a significant correlation between indices of eccentric cardiac hypertrophy or myocardial function and aerobic capacity.

Key-words: echocardiography, cardiac hypertrophy, aerobic capacity. Subject of the study. Endurance athletes' left ventricular morphofunction. Background. Whether left ventricular structure and function depend on the mode of the regularly performed endurance exercise is not conclusive. If it depended indeed, specialists in sports medicine, exercise physiologist, as well as athletic coaches would have a great possibility to design the architecture and predict the function of athletes' and possibly certain type of patients myocardium in response to aerobic exercise of different kind. Aim. To determine the peculiarities of the left ventricular structure and function between athletes of different endurance sports. Objectives: 1. To compare endurance athletes' left ventricular structure and function with that of healthy sedentaries. 2. To compare left ventricular structure between athletes of different endurance sports. 3. To compare left ventricular function between athletes of different endurance sports. Hypothesis. Distance-running- and swimming-induced haemodynamic overload triggers more substantial eccentric left ventricular remodelling when compared with canoe-kayak- and road-cycling-training. Regular paddling induces concentric left ventricular hypertrophic adaptation to similar extent as road cyclists' performed loads. Either mode of endurance exercise training has negative effect upon myocardial function. Conclusions. Myocardial mass is significantly greater in endurance... [to full text]

Reguliarios aerobinės treniruotės sąlygoja saikingą ištvermę lavinančių sportininkų kairiojo širdies skilvelio hipertrofiją. Vyrauja nuomonė, kad sportuojančių moterų struktūrinė – miokardo adaptacija yra mažesnė nei vyrų. Nėra tiksliai žinoma, ar ištvermę lavinančiųjų sportininkių miokardo hipertrofija yra kitokia nei sportuojančiųjų vyrų. Mūsų tyrimo tikslas buvo nustatyti ilgųjų nuotolių bėgikų ir bėgikių bei trumpųjų nuotolių bėgikių širdies struktūros ir funkcijos ypatumus. Tyrimo metodai: echokardiografija; anketavimas; antropometrija; matematinė statistika. Tyrimo kontingentą sudarė 10 sprinterių ir 10 ilgųjų nuotolių bėgikės, kurios pagal amžių (amžiaus vidurkis – apie 25 metus), treniravimo stažą ir meistriškumo lygį nesiskyrė, buvo pasiekusios šalies arba tarptautinį pripažinimą. Ilgųjų nuotolių bėgikės (n = 10) specializavosi bėgimuose nuo 3000 m iki maratono; sprinterių grupę sudarė trumpųjų nuotolių (nuo 100 m iki 400 m, n = 8) ir barjerinio bėgimo (100 m b/b, n = 2) bėgikės. Jos mažiausiai penkerius metus reguliariai startavo savo rungtyse, intensyviai treniravosi keturis – septynis kartus per savaitę. Tyrimo kontrolinę grupę sudarė sveikos tokio pat amžiaus nesportuojančios moterys, kurios sportavo ne ilgiau kaip 1 valandą per savaitę. Tyrime taip pat dalyvavo 67 ilgųjų nuotolių bėgikai, kurių amžiaus vidurkis buvo 24,0 ± 6,7 metai. Rezultatai. Reikšmingi echokardiografiniai rodiklių skirtumai tarp sprinterių ir nesportuojančių moterų nenustatėme (p>0,05)... [toliau žr. visą tekstą] / Regular participation in certain competitive endurance sports such as cycling, rowing, paddling, and running causes moderate left ventricular (LV) hypertrophy in males. Female athletes, however, are considered to possess less pronounced structural cardiac adaptation, and the type of cardiac hypertrophy in female (endurance) athletes remains vaguely understood. The aim of this study was to shed more light on the topic of gender influence on the extent and type of cardiac hypertrophic response to two different types athletic conditioning.   Raktiniai žodžiai   Methods. Standard transthoracic two-dimensional M-mode and Doppler echocardiography was performed at rest in Caucasian female sprinters (n = 10) and long?distance runners (n = 10) of similar age (average 25 years, range 16 to 34 years), training experience (5 to 18 years), and competitive level, as well as in age-matched healthy female sedentary controls (n = 10), and also compared with Caucasian male endurance runners (n = 67) of similar age, training experience, and competitive level. Runners were considered endurance athletes if their favorite event was 3000 m or longer, and sprinters, if they preferred to compete in distances of 400 m or shorter (two of our sprinters were 100 m hurdlers). Results. No significant echocardiographic differences between female sprinters and sedentary controls were detected (p>0,05). Interventricular septum and LV wall (p<0,05) were thicker, and LV mass was greater (p<0,01) in female... [to full text]

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Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

In setting the AMDR for protein at 10-35% of daily energy, the Institute of Medicine acknowledged a lack of data regarding the safety of long-term intakes. The current study assessed the impact of chronic (17 months) protein consumption at the upper end of the AMDR on renal function, histology, and inflammation. Using plant and animal whole protein sources, female Sprague-Dawley rats (70 days old; n=8-11 at 4, 8, 12, or 17 mo.) were randomized to either a normal (NP; 15% of energy) or high protein (HP; 35% of energy) diet. Egg albumen and skim milk replaced carbohydrates in the HP diet. Diets were balanced for energy, fat, vitamins and minerals, and offered ad libitum. Renal function was analyzed by creatinine clearance and urinary protein levels. Glomerular hypertrophy, glomerulosclerosis and tubulointerstitial fibrosis were assessed on kidney sections. Kidney disease progression was determined by the measurement of transforming growth factor beta-1 (TGF-β1) and renal inflammation by the measurement of chemokines monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation normal T-cell expressed and secreted (RANTES). Rats consuming the HP compared to NP diet had ~17% higher kidney weights (P<0.0001) and ~4.8 times higher proteinuria (P<0.0001). There was a trend towards higher creatinine clearance with HP (P=0.055). Consistent with this, HP compared to NP rats had ~22% larger glomeruli (P<0.0001) and ~33% more glomerulosclerosis (P=0.0003). The HP diet had no significant effect on tubulointerstitial fibrosis and renal TGF-β1 levels and did not result in higher renal levels of MCP-1 and RANTES. In fact, per mg renal protein, HP rats had ~16% lower MCP-1 (P<0.0001) and ~34% lower levels of RANTES (P<0.0001) than NP. The absence of an increase in cytokine levels may be a reflection of the moderate changes in renal pathology observed in rats offered HP diets. These data in normal female rats suggest that protein intakes at the upper end of the AMDR are detrimental to kidney health in the long-term. While modest, this may have implications for individuals whose kidney function is compromised, especially given the prevalence of those unaware of their kidney disease within North America.

In the heart, the primary role of the L-type calcium channel (LTCC) CaV1.2 is to conduct calcium into cardiomyocytes and initiate contraction. However, part of the CaV1.2 channel itself, the cleaved carboxyl-terminus (CCt) can also localize to the nucleus and regulate gene transcription. Therefore, the goal of this dissertation project was to determine the role and regulation of CCt in the embryonic and adult heart. The global hypothesis of my dissertation project is that CCt localizes to the nucleus in embryonic and adult cardiomyocytes via a calcium-mediated mechanism and regulates transcription. A model of pharmacological LTCC block-induced perturbation of murine embryonic heart development was first utilized to study the role of CCt. Pharmacological block at embryonic day 10 perturbed cardiogenesis and increased CaV1.2 expression. This result was not mimicked by removal of extracellular calcium or inhibition of calcium release from the sarcoplasmic reticulum. Co-currently, pharmacological block decreased CCt nuclear localization in embryonic cardiomyocytes. At the transcriptional level, CCt suppressed the CaV1.2 promoter. This indicated that the observed upregulation of CaV1.2 induced by pharmacological block may be caused by nuclear localization of the transcriptional repressor, CCt. Therefore, the conclusion was made that pharmacological LTCC block perturbed embryonic cardiogenesis by decreasing nuclear localization of the transcription factor CCt; implying a role for CCt in embryonic heart development. Next, CCt regulation was studied in the adult heart. Similar to the embryonic heart, pharmacological LTCC block decreased nuclear localization of CCt. Inhibition of the calcium activated phosphatase calcineurin also decreased CCt nuclear localization. To determine a role for CCt in the adult heart, CCt nuclear localization was measured in response to hypertrophic stimuli. Serum-induced cardiomyocyte hypertrophy significantly increased nuclear localization of CCt. In conclusion, this dissertation supports the hypothesis that CCt localizes to the nucleus in embryonic and adult cardiomyocytes, and that this regulation is mediated by calcium entry into the cardiomyocyte. Furthermore, data from this dissertation suggests that CCt nuclear localization may play an important role in embryonic heart development and adult cardiac hypertrophy.

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