Das polyzystische Ovarsyndrom (PCOS) mit einer Prävalenz von 5 % – 10 % ist eine der häufigsten Endokrinopathien bei Frauen vor der Menopause. Wie bisher vermutet, handelt es sich bei PCOS um ein sogenanntes multifaktorielles Krankheitsgeschehen. Einzelne Manifestationen des Metabolischen Syndroms (MetS), wie Hyperandrogenämie, Insulinresistenz (IR) und damit verbundene Hyperinsulinämie, Dyslipidämie und ein erhöhter CRP-Spiegel, werden bereits als Risikofaktoren für Typ 2 Diabetes mellitus (DM-II) und kardiovaskulären Krankheiten (KVK) bei den Patientinnen mit PCOS verwendet. Die Konzentrationen von Leptin und Adiponektin könnten nützliche und zuverlässige Marker für das Ausmaß der metabolischen Störung bei PCOS-Patientinnen sein. In zahlreichen Studien wurde davon berichtet, dass eine additive Gabe von Metformin die IR und andere Surrogat-Parameter des MetS in gleicher Weise bei adipösen und normalgewichtigen Probandinnen verbessert. In dieser Studie wurde der Insulin-Spiegel im Rahmen eines oralen Glukose-Toleranz-Test bei der Erstdiagnose und ca. ein bis eineinhalb Jahren nach der Metformintherapie bestimmt. Die Nüchtern-Insulinwerte der Vor-Therapie-Gruppe sind im Vergleich zur Nach-Therapie-Gruppe bei 75 % der Teilnehmerinnen signifikant aus dem hyperinsulinämischen Bereich in den normoinsulinämischen Bereich abgesunken (29.7 ± 6.7 µU/ml bzw. 13.7 ± 2.7 µU/ml, P = 0.045). Vergleichbar signifikant haben sich die Werte nach ein und zwei Stunden verbessert (154.5 ± 13.6 µU/ml vs. 96.2 ± 13.9 µU/ml, P = 0.0096 bzw. 128.0 ± 19.0 µU/ml vs. 59.2 ± 13.3 µU/ml, P = 0,0104). Konsistent damit senkte sich der HOMA-Index (5.9 ± 1.4 vs. 2.8 ± 1.6, P = 0,521). Die Leptin-Konzentration sank um 50 % (39.9 ± 9.7 vs. 20.3 ± 2.9 ng/ml, P = 0.0737 bzw. (mittlere Insulinspiegel nüchtern) 29.7 ± 6.7 µU/ml vs. 13.7 ± 2.7 µU/ml, P = 0,045), und die Adiponektin-Konzentration der Nach-Therapie-Gruppe im Vergleich zur Vor-Therapie-Gruppe stieg deutlich an (5.34 ± 0.6 vs. 6.35 ± 0.8 ug/ml, P = 0.4666, ns). Somit sind die Plasmaspiegel von Leptin und Adiponektin günstige Marker zur Risikoabschätzung und Diagnostik eines PCOS, zweitens eine metabolische Frühdiagnostik, und eine frühere Erwägung und Anwendung einer Strategie zur Senkung der Insulinresistenz sind aus präventiver Sicht ratsam.

Major depression is a highly prevalent mood disorder with chronic debilitating effects. Additional to a rising rate in incidence, depression is highly co–morbid with other psychiatric disorders, but also chronic cardiometabolic illnesses that present with an inflammatory component. The exact aetiology of depression is still unknown, being multifactorial in its possible aetiology. Various hypotheses have attempted to shed light on both endogenous and exogenous risk factors as well as the underlying pathology that may lead to the development of the disease. This has led to a wide range of mediators being implicated, including biogenic amines, the HPA–axis, neurotrophic factors, inflammatory agents, the cholinergic system and circadian rhythm, to name a few. The mechanisms of action of current treatment strategies, except for a few atypical and novel treatment approaches, are limited to interactions with monoamines and are at best only 65% effective. Many of these are also plagued by troubling side–effects, relapse and recurrence. It has therefore become imperative to explore novel targets for the treatment of depression that may produce more rapid, robust and lasting antidepressant effects with a less daunting side–effect profile. The strong co–morbidity between depression and various cardiometabolic disorders, including cardiovascular disease, atherosclerosis, type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) has led to the proposal that a metabolic disturbance may be a vital component that drives inflammatory and immunological dysfunction in depression. Supporting of this is evidence for a role of inflammatory cytokines and neurotrophic factors in the pathogenesis of depression. It has also been demonstrated that a link exists between insulin– and nitric oxide (NO)– mediated pathways in the brain, which further highlights the role of oxidative stress and cell damage. Furthermore, evidence supports a role for oxidative stress and NO in T2DM and/or insulin resistance. Insulin has also been implicated in various physiological processes in the central nervous system (CNS) and may also influence the release and reuptake of neurotransmitters. Preclinical and clinical evidence has provided support for the antidepressant–like effects of insulin–sensitizing peroxisome proliferator activated receptor (PPAR)– agonists, such as rosiglitazone and pioglitazone. In preclinical studies, however, these effects are limited to acute treatment with pioglitazone or sub–chronic (5 days) treatment with rosiglitazone. It is well–recognized that such findings need to be confirmed by chronic treatment paradigms. The aim of the current study was therefore to further investigate the proposed antidepressant–like effects of pioglitazone in a genetic animal model of depression, the Flinders sensitive line (FSL) rat, using a chronic treatment protocol. The FSL rat model was reaffirmed as presenting with inherent depressive–like behaviour compared to its more resilient counterpart, the Flinders resistant line (FRL) rat. Moreover, imipramine demonstrated a robust and reliable antidepressant–like effect in these animals using the forced swim test (FST), thus confirming the face and predictive validity of the FSL rat model for depression. In contrast to previous preclinical studies, acute dose–ranging studies with pioglitazone in Sprague Dawley rats delivered no significant anti–immobility effects in the FST, whereas results similar to that seen in the dose–ranging studies were observed following chronic treatment using FSL rats. Since altered pharmacokinetics could possibly influence the drug’s performance, another route of administration, viz. the subcutaneous route, was utilized as an additional measure to exclude this possibility. The results of the subcutaneous study, however, were congruent with that observed after oral treatment. In order to confirm an association between altered insulin sensitivity and antidepressant action and demonstration by recent studies that thiazolidinediones may augment the efficacy of existing antidepressants, we therefore investigated whether concomitant treatment with gliclazide (an insulin releaser and insulin desensitizer) or pioglitazone (an insulin sensitizer) may alter the antidepressant–like effects evoked by chronic treatment with imipramine. Pioglitazone did not positively or negatively affect the antidepressant effect of imipramine, although gliclazide tended to decrease the anti–immobility effects induced by this antidepressant. Taken together and considering the current available literature, this finding supports evidence linking the insulin–PPAR pathway to depression. However, further explorative studies are required to delineate the role of insulin sensitivity and glucose homeostasis in depression and antidepressant response. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2012.

Major depression is a highly prevalent mood disorder with chronic debilitating effects. Additional to a rising rate in incidence, depression is highly co–morbid with other psychiatric disorders, but also chronic cardiometabolic illnesses that present with an inflammatory component. The exact aetiology of depression is still unknown, being multifactorial in its possible aetiology. Various hypotheses have attempted to shed light on both endogenous and exogenous risk factors as well as the underlying pathology that may lead to the development of the disease. This has led to a wide range of mediators being implicated, including biogenic amines, the HPA–axis, neurotrophic factors, inflammatory agents, the cholinergic system and circadian rhythm, to name a few. The mechanisms of action of current treatment strategies, except for a few atypical and novel treatment approaches, are limited to interactions with monoamines and are at best only 65% effective. Many of these are also plagued by troubling side–effects, relapse and recurrence. It has therefore become imperative to explore novel targets for the treatment of depression that may produce more rapid, robust and lasting antidepressant effects with a less daunting side–effect profile. The strong co–morbidity between depression and various cardiometabolic disorders, including cardiovascular disease, atherosclerosis, type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) has led to the proposal that a metabolic disturbance may be a vital component that drives inflammatory and immunological dysfunction in depression. Supporting of this is evidence for a role of inflammatory cytokines and neurotrophic factors in the pathogenesis of depression. It has also been demonstrated that a link exists between insulin– and nitric oxide (NO)– mediated pathways in the brain, which further highlights the role of oxidative stress and cell damage. Furthermore, evidence supports a role for oxidative stress and NO in T2DM and/or insulin resistance. Insulin has also been implicated in various physiological processes in the central nervous system (CNS) and may also influence the release and reuptake of neurotransmitters. Preclinical and clinical evidence has provided support for the antidepressant–like effects of insulin–sensitizing peroxisome proliferator activated receptor (PPAR)– agonists, such as rosiglitazone and pioglitazone. In preclinical studies, however, these effects are limited to acute treatment with pioglitazone or sub–chronic (5 days) treatment with rosiglitazone. It is well–recognized that such findings need to be confirmed by chronic treatment paradigms. The aim of the current study was therefore to further investigate the proposed antidepressant–like effects of pioglitazone in a genetic animal model of depression, the Flinders sensitive line (FSL) rat, using a chronic treatment protocol. The FSL rat model was reaffirmed as presenting with inherent depressive–like behaviour compared to its more resilient counterpart, the Flinders resistant line (FRL) rat. Moreover, imipramine demonstrated a robust and reliable antidepressant–like effect in these animals using the forced swim test (FST), thus confirming the face and predictive validity of the FSL rat model for depression. In contrast to previous preclinical studies, acute dose–ranging studies with pioglitazone in Sprague Dawley rats delivered no significant anti–immobility effects in the FST, whereas results similar to that seen in the dose–ranging studies were observed following chronic treatment using FSL rats. Since altered pharmacokinetics could possibly influence the drug’s performance, another route of administration, viz. the subcutaneous route, was utilized as an additional measure to exclude this possibility. The results of the subcutaneous study, however, were congruent with that observed after oral treatment. In order to confirm an association between altered insulin sensitivity and antidepressant action and demonstration by recent studies that thiazolidinediones may augment the efficacy of existing antidepressants, we therefore investigated whether concomitant treatment with gliclazide (an insulin releaser and insulin desensitizer) or pioglitazone (an insulin sensitizer) may alter the antidepressant–like effects evoked by chronic treatment with imipramine. Pioglitazone did not positively or negatively affect the antidepressant effect of imipramine, although gliclazide tended to decrease the anti–immobility effects induced by this antidepressant. Taken together and considering the current available literature, this finding supports evidence linking the insulin–PPAR pathway to depression. However, further explorative studies are required to delineate the role of insulin sensitivity and glucose homeostasis in depression and antidepressant response. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2012.

No description available.

Das polyzystische Ovarsyndrom (PCOS) mit einer Prävalenz von 5 % – 10 % ist eine der häufigsten Endokrinopathien bei Frauen vor der Menopause. Wie bisher vermutet, handelt es sich bei PCOS um ein sogenanntes multifaktorielles Krankheitsgeschehen. Einzelne Manifestationen des Metabolischen Syndroms (MetS), wie Hyperandrogenämie, Insulinresistenz (IR) und damit verbundene Hyperinsulinämie, Dyslipidämie und ein erhöhter CRP-Spiegel, werden bereits als Risikofaktoren für Typ 2 Diabetes mellitus (DM-II) und kardiovaskulären Krankheiten (KVK) bei den Patientinnen mit PCOS verwendet. Die Konzentrationen von Leptin und Adiponektin könnten nützliche und zuverlässige Marker für das Ausmaß der metabolischen Störung bei PCOS-Patientinnen sein. In zahlreichen Studien wurde davon berichtet, dass eine additive Gabe von Metformin die IR und andere Surrogat-Parameter des MetS in gleicher Weise bei adipösen und normalgewichtigen Probandinnen verbessert. In dieser Studie wurde der Insulin-Spiegel im Rahmen eines oralen Glukose-Toleranz-Test bei der Erstdiagnose und ca. ein bis eineinhalb Jahren nach der Metformintherapie bestimmt. Die Nüchtern-Insulinwerte der Vor-Therapie-Gruppe sind im Vergleich zur Nach-Therapie-Gruppe bei 75 % der Teilnehmerinnen signifikant aus dem hyperinsulinämischen Bereich in den normoinsulinämischen Bereich abgesunken (29.7 ± 6.7 µU/ml bzw. 13.7 ± 2.7 µU/ml, P = 0.045). Vergleichbar signifikant haben sich die Werte nach ein und zwei Stunden verbessert (154.5 ± 13.6 µU/ml vs. 96.2 ± 13.9 µU/ml, P = 0.0096 bzw. 128.0 ± 19.0 µU/ml vs. 59.2 ± 13.3 µU/ml, P = 0,0104). Konsistent damit senkte sich der HOMA-Index (5.9 ± 1.4 vs. 2.8 ± 1.6, P = 0,521). Die Leptin-Konzentration sank um 50 % (39.9 ± 9.7 vs. 20.3 ± 2.9 ng/ml, P = 0.0737 bzw. (mittlere Insulinspiegel nüchtern) 29.7 ± 6.7 µU/ml vs. 13.7 ± 2.7 µU/ml, P = 0,045), und die Adiponektin-Konzentration der Nach-Therapie-Gruppe im Vergleich zur Vor-Therapie-Gruppe stieg deutlich an (5.34 ± 0.6 vs. 6.35 ± 0.8 ug/ml, P = 0.4666, ns). Somit sind die Plasmaspiegel von Leptin und Adiponektin günstige Marker zur Risikoabschätzung und Diagnostik eines PCOS, zweitens eine metabolische Frühdiagnostik, und eine frühere Erwägung und Anwendung einer Strategie zur Senkung der Insulinresistenz sind aus präventiver Sicht ratsam.

L’association de la bière avec les mets apparaît comme une nouvelle tendance en France. Il est donc nécessaire pour les promoteurs de bière et les professionnels de la gastronomie de fournir à leurs clients des conseils de qualité en terme d’accord bière et mets. Au vu de ce contexte, l’objectif de la thèse était d’identifier les principes d’association et de mieux comprendre les mécanismes perceptuels qui les sous-tendent. Les déterminants des accords mets et boissons ont, dans un premier temps, été identifiés à partir du discours d’experts. Les résultats ont montrés que les associations mets et boissons sont régies par des caractéristiques perceptuelles, conceptuelles et affectives, liées à des mécanismes physico-chimiques, perceptuels et cognitifs. Les experts ont souvent mentionné la «similarité aromatique» comme l'un des principaux principes d'association. Ce principe consiste à associer deux produits partageant des arômes similaires. Les mécanismes perceptuels sous-jacents à ce principe ont été investigués. Les résultats ont montrés qu’une similarité aromatique entre un mets et une boisson augmente le niveau d’harmonie et d’homogénéité de leur association et diminue sa complexité. Ces effets peuvent être renforcés en orientant l’attention du dégustateur sur l’arôme partagé. D’un point de vue théorique, cette thèse conclut que l’association bières et mets inclut des dimensions sensorielles avec une recherche d’harmonie, mais aussi des dimensions symboliques et contextuelles. D’un point de vue plus appliqué, cette thèse fournit aux professionnels de la gastronomie, de nouvelles informations concernant les mécanismes perceptifs sous-tendant les principes d’associations. / Pairing between beer and dishes emerges as a new trend in France. Beer promoters or gastronomy professionals need to offer high-quality advices in terms of beer and food pairing to their customers. Within this context, the objective of the research was to identify pairing principles and to better understand the underlying perceptual mechanisms. Determinants of food and beverage pairing were first analysed from experts’ discourses. Results showed that food and beverage pairings are governed by perceptual, conceptual and affective features, related to physio-chemical, perceptual and cognitive processes. Experts often mentioned “Aromatic Similarity” as one of the main pairing principles. This “Aromatic similarity” principle consists in matching two products sharing similar aromas. Underlying perceptual mechanisms were then investigated. Results showed that aromatic similarity in food and beverage generally increases harmony and homogeneity and decreases complexity of the match. These effects can be reinforced by orientating the attentional focus on the shared aroma. From a theoretical point of view, this work concludes that beer and food pairing includes sensory dimensions with the search for harmony, as well as symbolic and contextual dimensions. From an applied point of view, this work provides useful information to gastronomy professionals with recent knowledge on perceptual mechanisms underlying food and beverage pairing principles.

No description available.

No description available.

Metabolic syndrome (MetS), a global public health problem, is the primary cause of type 2 diabetes and cardiovascular disorders. Lifestyle modification interventions (dietary and physical activity modifications) are effective in preventing and ameliorating MetS and associated comorbidities. However, the impact of lifestyle changes on MetS among Mexican Americans has yet to be investigated, particularly due to high attrition rates in this population. The overall goal of the explanatory mixed-methods study presented in this dissertation was to identify efficacious lifestyle modification efforts directed towards Mexican Americans to promote their retention in lifestyle modification programs, ameliorate the severity of MetS, and understand underlying behavior modification process. In particular, we examined secondary data from an extensive study Beyond Sabor to 1) examine predictors of program completion, 2) compare variation in MetS severity scores (z-scores) between intervention (Beyond Sabor) and attention control (Healthy Living) groups, over time and, 3) investigate processual development of self-efficacy in a sample of 1153 disadvantaged Mexican Americans participants. Findings suggest that program completers were more likely to be older, had more years of education, lower fasting blood glucose levels, and participated in sites with high group cohesiveness. Results also revealed that when compared with the standard nutrition program, Healthy Living, the lifestyle modification intervention, Beyond Sabor, was more effective in ameliorating MetS severity, systolic blood pressure, triglyceride, and fasting plasma glucose levels among study participants. Qualitative results demonstrate the high acceptability of Beyond Sabor intervention. Four sub-themes emerged illustrating important underlying conditions contributing to participants’ improved self-efficacy: desire to gain knowledge about ways to improve health, development of social support, adoption of program teachings in family lifestyle, and improvement in health outcomes. Findings of the current study may allow researchers to identify Mexican Americans at risk of non-completion and to develop strategies to improve lifestyle modification program attendance, and thus health outcomes. Qualitative findings underscore the importance of sociocultural context on individuals’ attempts to make lifestyle changes to manage their chronic illnesses. Successful adaptation of lifestyle interventions such as Beyond Sabor for at-risk populations in community-based settings will be critical in stemming the tide of MetS.

THESIS SUBMITED IN FULFILMENT OF THE REQUIREMENT FOR THE AWARD OF THE DEGREE OF DOCTOR OF TECHNOLOGY OF BIOMEDICAL TECHNOLOGTY IN THE FACULTY OF HEALTH AND WELLNESS SCIENCES AT THE CAPE PENINSULA UNIVERSITY OF TECHNOLOGY SUPERVISORS: PROF T.E. MATSHA PROF R.T. ERASMUS DR A. ZEMLIN SUBMITED DECEMBER 2013 / Introduction: Cardiovascular diseases (CVD) have become the leading cause of morbidity and mortality amongst the global population. Originally thought to be a health burden of high income countries, the prevalence is rapidly increasing in developing countries. For example, in 2008, an estimated 17.3 million died from CVD, and 80% of these (13.8 mil) were from low to middle income countries. Epidemiological data on CVD in Africa is scanty and of poor quality and national vital registration is available in only 5% of Africa’s 53 countries. Furthermore, data on CVD risk amongst the South African population and specifically the mixed ancestry community is poorly described. The increasing global population of people with CVD has been largely attributed to increasing rates of determinants and risk factors which include obesity, metabolic syndrome (MetS), type 2 diabetes mellitus (DM) and chronic kidney diseases (CKD). The prevalence of DM in South Africa is known to be on the rise with more affected communities being South African Asians followed by coloureds. Aims and objectives: The aim of this study was to determine the CVD risk profile of the Bellville South community during a baseline and three year follow-up study, by assessment of known risk factors, MetS, type 2 DM, obesity and CKD. Methods: Participants for this study were drawn from an urban community of the Bellville South suburb of Cape Town. At baseline (January 2008 and March 2009) 946 individuals aged 16 to 95 participated. All participants received a standardized interview and physical examination during which anthropometric measurements were performed three times and their average used for analysis: weight (kg), height (cm), waist (cm) and hip (cm) circumferences. Body Mass Index (BMI) was calculated as weight per square metre (kg/m2). A blood sample was obtained from all participants after an overnight fast for the determination of biochemical profiles: glucose, glycated haemoglobin, creatinine, total cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides and low density lipoprotein cholesterol (LDL-C) which was calculated using Friedewald’s formula. Kidney function test was assessed through estimated glomerular filtration rate (eGFR) using the cockcroft-Gault and MDRD equations. Blood pressure was measured according to the World Health Organisation (WHO) guidelines. Participants with no history of doctor diagnosed DM underwent a 75 g oral glucose tolerance test as recommended by the WHO. Metabolic syndrome was determined using JIS, NCEP ATPIII and IDF criteria. The follow-up examination was conducted in 2011 (3 years from vii baseline) using similar procedures. A total of 198 participants formed the follow-up cohort whose measurements were compared to those of the baseline. Finally, the prediction and processes/progression of the risk factors were determined. Results: At both baseline and follow-up studies, females had a higher BMI compared to their male counterparts. The crude prevalence of type 2 DM, including the previously diagnosed type 2 DM was 28.59% (age-adjusted = 33.5%, 95%CI: 30.01 – 36.92), and that of undiagnosed type 2 DM was 17.8% (age-adjusted = 12.4%, 95%CI: 9.8 – 14.8). The overall prevalence of CKD was 28.7% (269) and was higher in females (31.4%) compared to 20.2% in males. MetS was present in 46.5% of the participants. Gender-specific prediction for CVD risk calculated using the 30-year CVD interactive risk calculator showed that high CVD risk was present in normoglycaemic and younger subjects (under 35 years). At follow-up, the cumulative incidence of progression in glucose tolerance status was: 16.2% (32 participants including 11 with new-onset diabetes), and increased in a stepwise fashion with the number of components of MetS. Between baseline and 3-year evaluation glomerular filtration rate (eGFR) increased by 8.7 ml/min (95% confidence interval: 6.9-10.7), reflecting variables trajectories across baseline strata of kidney functions. Conclusion: Given the findings of this study and the estimated increases in the determinants and risk factors of CVD in the mixed ancestry population of South Africa this trend may continue to worsen if current trajectories do not change.