Οι ομάδες των ορμονών που επηρεάζουν σημαντικά την αύξηση και την ανάπτυξη των παιδιών και των εφήβων, ανήκουν κυρίως στον άξονα της αύξησης και της αναπαραγωγής, στο σύστημα του stress και στο ανοσολογικό σύστημα. Η κορτιλόλη, η λεπτίνη και η IL-6 αποτελούν στρεσογόνους παράγοντες οι οποίοι συνδέονται με τη δυναμική της ανάπτυξης και ενηβωσης του ανθρώπινου οργανισμού. Εκτός από την επίδραση τον ορμονών, η ενήβωση και η αναπαραγωγή του φύλου μπορεί να επηρεαστεί από φαρμακολογικούς παράγοντες, όπως είναι η υδροκορτιζόνη, τα αναβολικά στεροειδή και τα οιστρογόνα. Η φυσική άσκηση είναι ένας τύπος φυσικού stress που προκαλεί πλήθος ορμονικών, μεταβολικών και ανοσολογικών αλλαγών ενώ οι αθλητές και οι αθλήτριες ρυθμικής και ενόργανης γυμναστικής εκτίθονται σε έντονους φυσικούς και ψυχολογικούς στρεσογόνους παράγοντες. Τα τελευταία χρόνια οι προσδιορισμοί στο σίελο προσελκύουν τεράστιο ενδιαφέρον (λόγω του ανώδυνου τρόπου συλλογής του σιέλου) και κυρίως χρησιμοποιούνται στην Ενδοκρινολογία για την παρακολούθηση των επιπέδων των στεροειδών ορμονών. Υλικά και Μέθοδοι: Μελετήθηκαν 142 αθλήτριες και 97 αθηλτές της ενόργανης γυμναστικής υψηλού αγωνιστικού επιπέδου καθώς και 107 αθλήτριες της ρυθμικής γυμναστικής. Ως ομάδα ελέγχου μελετήθηκαν 73 κορίτσια και 68 αγόρια, τα οποία δεν αθλούνταν. Η συλλογή των δειγμάτων έγινε χρησιμοποιώντας μια ειδικά σχεδιασμένη συσκευή συλλογής σιέλου (Salivette). Για τον προσδιορισμό της λεπτίνης στο σίελο χρησιμοποιήθηκε ραδιοανοσολογική μέθοδος ενώ για τον προσδιορισμό της κορτιζόλης η μέθοδος ηλεκτροχημειοφωταύγειας. Για την μέτρηση της IL-6 στο σίελο αναπτύχθηκε και επικυρώθηκε μέθοδος Elisa υψηλής ευαισθησίας. Αποτελέσματα: Οι αθήτριες της ρυθμικής και της ενόργανης γυμναστικής χαρακτηρίζονται από υψηλότερα επίπεδα κορτιζόλης στο σίελο (p<0,01) συγκριτικά με τους μάρτυρες και τους αθλητές της ενόργανης. Τόσο στους αθλητές όσο και στις αθλήτριες της ενόργανης γυμναστικής, οι απογευματινές τιμές κορτιζόλης (μετά από άσκηση) παραμένουν στα ίδια επίπεδα με τις πρωινές τιμές. Στις αθλήτριες της ενόργανης τα επίπεδα της IL-6 παρουσιάζουν τάση αύξησης και της λεπτίνης τάση μείωσης μετά από άσκηση, αν και οι μεταβολές αυτές δεν είναι στατιστικά σημαντικές. Η συλλογή του σιέλου είναι μια μη επεμβατική, ανώδυνη τεχνική που επιτρέπει την επαναλαμβανόμενη δειγματοληψία. Η ραδιοανοσολογικής μέθοδος είναι απλή και εύκολη για τον προσδιορισμό της λεπτίνης στο σίελο, ενώ η μέθοδος της ηλεκτροχημειοφωταύγειας αποτελεί αξιόπιστη επιλογή για τη μέτρηση της κορτιζόλης στο σίελο. Για τον προσδιορισμό της IL-6 στο σίελο απαιτείται η ανάπτυξη και η επικύρωση μεθόδου Elisa, λόγω του ότι ο σίελος επηρεάζει τη μέτρηση της συγκεκριμένης κυτοκίνης. Τόσο στις αθλήτριες όσο και στους αθλητές της ενόργανης γυμναστικής υψηλού αγωνιστικού επιπέδου, ο νυχθημερήσιος ρυθμός έκκρισης της κορτιζόλης καταργείται. Επίσης οι αθλήτριες της ενόργανης γυμναστικής χαρακτηρίζονται από υψηλότερες τιμές δεικτών stress συγκριτικά με τους αθλητές. / The aim of this study was to evaluate the effects of intensive physical exercise and acute psychological stress during high level athletic competition as reflected on the levels of salivary cortisol, leptin and IL-6 in elite artistic and rytmic gymnasts. Design: The study included two hundred and forty-nine (249) Caucasian athletes (elite Gymnasts) -142 girls(aged 16.0 ± 1.6 years) and 97 boys (aged 16.8 ± 1.1 years) from 44 European countries, during theEuropean Championship of Gymnastics held in Volos-Greece on April 2006. One hundred and forty-one pubertal adolescents, who were recruited from public schools in Greece, not engaged in strenuous sports activities were used as controls (73 girls aged 16.0 ± 1.4 years and 68 boys aged 15.3 ±2.0 years). Methods: Saliva samples were collected, the morning before training and in the afternoon shortly after the competition. Cortisol concentrations were measured using a chemmiluminesce method. Leptin and IL-6 concentrations were measured using RIA and ELISA methods. Acute stress was assessed using a questionnaire designed for the study. Results: No difference was found between morning and afternoon salivary cortisol levels in both male and female AG. Female AG presented higher levels of morning salivary cortisol than female controls (p<0.05). Both male and female AG had higher degree of psychological stress in comparison with controls . Female AG had higher morning and afternoon salivary cortisol levels and higher degree of stress than males. Conclusions: In elite AG the diurnal rhythm of salivary cortisol has been abolished, probably due to the strenuous training and competition conditions. Female AG presented higher levels of morning salivary cortisol and psychological stress compared to both male AG and female controls. The long term consequences of these modifications of the HPA axis remain to be elucidated.

Recent studies support the association between metabolic syndrome (MetS), a cluster of cardiovascular risk factors, and diastolic dysfunction. Disproportionate collagen accumulation, particularly cross-linking of collagen, plays a key role in translating interstitial fibrosis into mechanical chamber stiffness and diastolic dysfunction. Characteristic changes in the expression and activity of myocardial lysyl oxidase (LOX), a matrix modifying enzyme that catalyzes cross-linked collagen, are unclear in MetS. We established a diet-induced MetS model to study diastolic dysfunction by treating male C57BL/6 mice a high-fat high-simple carbohydrate (HFHSC) diet for 6 months. Despite blunted gene expression of LOX isoforms, MetS mice demonstrated significant increase in the ratio of protein expression of mature to proenzyme LOX, enhanced LOX activity, and increased cardiac cross-linked collagen compared with controls. This fibrotic response coincided with marked increase in left ventricular end-diastolic pressure and stiffness and impaired diastolic filling pattern. Our data demonstrate that diet-induced MetS alters the remodeling enzyme LOX, thereby increasing the amount of crosslinking and inducing diastolic dysfunction.Furthermore we examined the role of T-lymphocytes in myocardial LOX regulation in diet-induced fibrotic hearts. Female SCID mice which are devoid of functional T-lymphocytes and C57BL/6 mice were treated with HFHSC diet for 12 months. Similar to male C67BL/6, female HFHSC-fed C57BL/6 mice demonstrated significant increase in maturation and catalytic activity of myocardial LOX, cross-linking, ventricular stiffness and diastolic dysfunction. Whereas induction of LOX protein was minimal in SCID mice compared with wild-type counterparts. Correspondingly fibrillar cross-linked collagen formation and diastolic dysfunction were less prominent in SCID mice. Our results suggest a potential role of T-lymphocytes in induction of myocardial stiffness and diastolic dysfunction through modulation of LOX-dependent collagen maturation.Moreover we studied the role of leptin, an adipokine over-produced in MetS with fibrotic effects in non-cardiac tissues, as a key mediator of profibrogenic responses in the heart by administrating leptin to C57BL/6 and leptin-deficient ob/ob mice. With exogenous leptin administration ob/ob mice displayed passive diastolic filling dysfunction that coincided with increase in myocardial collagen compared with ob/ob controls. Our findings suggest profibrotic effects of leptin in the heart, primarily through predominance of collagen synthesis over degradation.

Motivation: The prevalence of obesity is the highest among African women in South Africa. Since obesity is a major cardiovascular risk factor, African women in South Africa could be regarded as a high risk group. However, investigations on obesity-related hypertension are limited in this population group. The associations of body fat distribution and hormones such as leptin and endothelin-1 with cardiovascular function have not yet been determined in these women. It has been determined that endothelin-1 is a role player in the development and/or maintenance of hypertension in various population groups, especially African Americans. Endothelin-1 has also been found to be involved in obesity-related hypertension in non-African population groups. It has been indicated that the obesity-related hormone, leptin, also plays a role in obesity-related hypertension, especially in African Americans. Leptin levels have been found to be higher in obese hypertensive African American women compared to an obese normotensive control group. Since the above-mentioned two hormones playa prominent role in obesity and hypertension in African American and non-African population groups, the lack of data on African women in South Africa serves as motivation to conduct this investigation. Aim: To investigate obesity-related hypertension in African women through the determination of associations between various anthropometric and endocrinological variables with cardiovascular, especially vascular function. Methodology: Manuscripts presented in Chapters 2, 3 and 4 made use of data from the POWIRS (Profiles of Obese Women suffering from the Insulin Resistance Syndrome) I project where African women were selected from a government institution in the North West Province. A group of 98 women were divided into lean normotensive, overweight/obese normotensive and overweight/obese hypertensive groups. Anthropometric and cardiovascular measurements were taken and the lipid profile, leptin and endothelin-1 levels determined. The analysis of covariance (ANCOVA) was used to show significant differences between groups while adjusting for age. Partial correlation coefficients were used to show associations between various variables while adjusting for age. Stepwise linear regression analysis was also used to show associations between variables. The study presented in Chapter 5 made use of both POWIRS I and II, which are studies including Africans and Caucasians, respectively. The methodology of the two studies was the same. All subjects gave informed consent in writing and the Ethics Committee of the North-West University approved the study. The reader is referred to the "Materials and Methods" section of Chapters 2-5 for a more elaborate description of the subjects, study design and analytical methods used in each article. vii Results and conclusions of the individual manuscripts > Results from Chapter 2 showed that the volume loading effect associated with obesity was present in both overweight/obese normotensive and overweight/obese hypertensive groups, however, the accommodating effect observed in the overweight/obese normotensive group was absent in the overweight/obese hypertensive group due to decreased vascular function. This was confirmed by a high pulse pressure. Decreased vascular functioning was associated with the abdominal skin fold. This suggests that abdominal subcutaneous fat may either be a marker of visceral fat, or may in itself contribute to increased cardiovascular risk in Africans. > Results from Chapter 3 showed a negative result. Plasma endothelin-1 levels were similar for the lean normotensive, overweight/obese normotensive and overweight/obese hypertensive groups. After re-dividing the groups into normotensive and hypertensive, and then into lean and overweight/obese, still no differences could be obtained. Additionally, no correlations could be obtained between endothelin-1 and cardiovascular function in any of the groups. These findings suggest that endothelin-1 is not implicated in obesity-related hypertension in African women. > In Chapter 4, leptin levels were elevated in both overweight/obese normotensive and hypertensive groups compared to the lean normotensive group. However, leptin levels did not differ between the two overweight/obese groups. Even though leptin levels were the same, leptin was directly and positively associated with systolic blood pressure and pulse pressure and negatively with arterial compliance only in the overweight/obese hypertensive group, independent of obesity, insulin resistance, hyperinsulinemia and age. > In Chapter 5 the volume loading, as well as the accommodating effect, that is, decreased total peripheral resistance and increased arterial compliance, was present in both African and Caucasian obese groups compared to their lean controls. Even though leptin levels, body mass index and age were similar for both African and Caucasian obese groups, the accommodating effect seemed to be more prominent in the obese Caucasian group, explaining a lower diastolic blood pressure compared to the obese African group. Leptin showed a favourable negative association with diastolic blood pressure and total peripheral resistance in the obese Caucasian group, but not in the obese African group. This may indicate that leptin predominantly exerts pathological influences on obese African women, as determined previously in Chapter 4. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2005.

Background.  Sepsis is a syndrome associated with high mortality rates, substantial morbidity and high costs of care. The incidents of sepsis is reported to be high and controversy exists whether gender affect severity or outcome. Little is known about factors determining suscepti­bility for developing the syndrome and severity of the syndrome once developed. Early detection and adequate antibiotic administration are the mainstay of treatment and means to identify patients with particular high risk of adverse outcome are desirable. There are data to suggest that the course of sepsis and outcome from the syndrome may be influenced by inherited differences in the immunological response among humans Aims: Paper I: Assess incidence and outcome for ICU-treated sepsis patients in this region; Paper II: Assess if there are gender differences related to characteristics, aspects of treatment or out­come in sepsis in this region. Paper III: Assess the association of baseline levels of leptin and adiponectin and future sepsis event, and association of these adipokines in the cute phase and sepsis severity and outcome. Paper IV: Assess association of baseline levels of mannose-binding lectin (MBL) and future sepsis event, and MBL levels in the acute phase in relation to sepsis severity and outcome. Results. Paper I:  Overall ICU mortality rate was 25%, while the ICU mortality for patients with septic shock was 58% in this retrospective single university hospital cohort analysis. Cardio­vascular disease and diabetes were the most prevalent comorbidities among patients who died during hospital stay.  Paper II:  No gender-related differences in mortality or length of stay was found in this prospective single center observational study. Differences in aspects of treatment were related to differences in site of infection. Men had more often infections in skin and skin-structures, whereas women more often had abdominal infections. Early organ dysfunction asses­sed as SOFA score at admission was a stronger predictor for hospital mortality for women than for men. The discrepancy was related to the SOFA coagulation-sub score.  Paper III: In this nes­ted case-referent study hyperleptinemia at baseline predicted a first-ever sepsis event, even after adjustment for BMI and other cardiovascular risk factors. Hyperleptinemia in the acute sepsis phase was associated with reduced risk of in-hospital death in men, but associated with increased risk of in-hospital   death in women.  Paper IV: In the same matched cohort as in Paper III high baseline levels of MBL predicted a first ever sepsis event. High MBL levels in the acute phase or an increase from baseline to the acute phase associate with increased in-hospital death in women but not in men. Low MBL levels was not identified as a risk for acute sepsis or in-hospital death. Conclusions. Mortality from severe sepsis is high, equally affecting men and women. There are differences in patient characteristics and inflammatory markers, which associate with in-hospital mortality differentially in men and women. Aspects of gender should be mandatory, and genetic analysis are desired in future sepsis research.

No description available.

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Motivation: The prevalence of obesity is the highest among African women in South Africa. Since obesity is a major cardiovascular risk factor, African women in South Africa could be regarded as a high risk group. However, investigations on obesity-related hypertension are limited in this population group. The associations of body fat distribution and hormones such as leptin and endothelin-1 with cardiovascular function have not yet been determined in these women. It has been determined that endothelin-1 is a role player in the development and/or maintenance of hypertension in various population groups, especially African Americans. Endothelin-1 has also been found to be involved in obesity-related hypertension in non-African population groups. It has been indicated that the obesity-related hormone, leptin, also plays a role in obesity-related hypertension, especially in African Americans. Leptin levels have been found to be higher in obese hypertensive African American women compared to an obese normotensive control group. Since the above-mentioned two hormones playa prominent role in obesity and hypertension in African American and non-African population groups, the lack of data on African women in South Africa serves as motivation to conduct this investigation. Aim: To investigate obesity-related hypertension in African women through the determination of associations between various anthropometric and endocrinological variables with cardiovascular, especially vascular function. Methodology: Manuscripts presented in Chapters 2, 3 and 4 made use of data from the POWIRS (Profiles of Obese Women suffering from the Insulin Resistance Syndrome) I project where African women were selected from a government institution in the North West Province. A group of 98 women were divided into lean normotensive, overweight/obese normotensive and overweight/obese hypertensive groups. Anthropometric and cardiovascular measurements were taken and the lipid profile, leptin and endothelin-1 levels determined. The analysis of covariance (ANCOVA) was used to show significant differences between groups while adjusting for age. Partial correlation coefficients were used to show associations between various variables while adjusting for age. Stepwise linear regression analysis was also used to show associations between variables. The study presented in Chapter 5 made use of both POWIRS I and II, which are studies including Africans and Caucasians, respectively. The methodology of the two studies was the same. All subjects gave informed consent in writing and the Ethics Committee of the North-West University approved the study. The reader is referred to the "Materials and Methods" section of Chapters 2-5 for a more elaborate description of the subjects, study design and analytical methods used in each article. vii Results and conclusions of the individual manuscripts > Results from Chapter 2 showed that the volume loading effect associated with obesity was present in both overweight/obese normotensive and overweight/obese hypertensive groups, however, the accommodating effect observed in the overweight/obese normotensive group was absent in the overweight/obese hypertensive group due to decreased vascular function. This was confirmed by a high pulse pressure. Decreased vascular functioning was associated with the abdominal skin fold. This suggests that abdominal subcutaneous fat may either be a marker of visceral fat, or may in itself contribute to increased cardiovascular risk in Africans. > Results from Chapter 3 showed a negative result. Plasma endothelin-1 levels were similar for the lean normotensive, overweight/obese normotensive and overweight/obese hypertensive groups. After re-dividing the groups into normotensive and hypertensive, and then into lean and overweight/obese, still no differences could be obtained. Additionally, no correlations could be obtained between endothelin-1 and cardiovascular function in any of the groups. These findings suggest that endothelin-1 is not implicated in obesity-related hypertension in African women. > In Chapter 4, leptin levels were elevated in both overweight/obese normotensive and hypertensive groups compared to the lean normotensive group. However, leptin levels did not differ between the two overweight/obese groups. Even though leptin levels were the same, leptin was directly and positively associated with systolic blood pressure and pulse pressure and negatively with arterial compliance only in the overweight/obese hypertensive group, independent of obesity, insulin resistance, hyperinsulinemia and age. > In Chapter 5 the volume loading, as well as the accommodating effect, that is, decreased total peripheral resistance and increased arterial compliance, was present in both African and Caucasian obese groups compared to their lean controls. Even though leptin levels, body mass index and age were similar for both African and Caucasian obese groups, the accommodating effect seemed to be more prominent in the obese Caucasian group, explaining a lower diastolic blood pressure compared to the obese African group. Leptin showed a favourable negative association with diastolic blood pressure and total peripheral resistance in the obese Caucasian group, but not in the obese African group. This may indicate that leptin predominantly exerts pathological influences on obese African women, as determined previously in Chapter 4. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2005.

Thesis (M.Sc.)--York University, 2006. Graduate Programme in Biology. / Typescript. Includes bibliographical references. Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR19720

Thesis (M.S.)--University of Nevada, Reno, 2006. / "December 2006." Includes bibliographical references (leaves 77-87). Online version available on the World Wide Web.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available in print.