Submitted by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-21T19:24:15Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Renata_Zanella.pdf: 575197 bytes, checksum: 59c20b438c7e122081f43156f1b94bf3 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-21T20:15:45Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Renata_Zanella.pdf: 575197 bytes, checksum: 59c20b438c7e122081f43156f1b94bf3 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-21T20:15:53Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Renata_Zanella.pdf: 575197 bytes, checksum: 59c20b438c7e122081f43156f1b94bf3 (MD5) / Made available in DSpace on 2018-05-21T20:15:53Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Renata_Zanella.pdf: 575197 bytes, checksum: 59c20b438c7e122081f43156f1b94bf3 (MD5) Previous issue date: 2016-08-26 / Sem bolsa / O sistema calicreínas-cininas (SCC) está envolvido em diversos processos biológicos como modulação de dor, vasodilatação, permeabilidade vascular, edema e inflamação, tendo seus efeitos mediados por dois receptores específicos acoplados a proteína G, o receptor B1 e B2 de cininas. O SCC tem sido recentemente relacionado com a homeostase da glicose e resistência à insulina. O objetivo do presente estudo foi investigar a participação do receptor B1 (B1R) de cininas nos processos metabólicos relacionados à obesidade e ao diabetes mellitus tipo 2 em camundongos obesos. Para isso foram utilizados camundongos deficientes para a leptina e nocautes para o B1R de cininas (obB1). Quando comparados, os animais obB1 mostraram uma redução na ingestão alimentar em todo período avaliado (4° a 26° semana de vida); menor ganho de peso, tanto aos 3 meses (obWT, 63,79 ± 1,59; obB1, 51,22 ± 1,09 g, p < 0,001) quanto aos 6 meses de idade (obWT, 74,61 ± 1,04; obB1, 57,98 ± 1,58 g, p < 0,001); e menor depósito de gordura. No teste de tolerância a glicose, animais obB1 apresentaram maior captação de glicose do que seus controles quando jovens (obWT, 46045 ± 3492; obB1, 30875 ± 2311 (mg/dL).min, p< 0,01). Adicionalmente, foi observado aumento do peso do fígado nestes animais, quando mais velhos (obWT, 3,29 ± 0,24; obB1 4,09 ± 0,06 g, p<0,001). Em conclusão, o silenciamento do gene do B1R oferece uma proteção contra a obesidade com um significativo impacto na homeostase da glicose. Estes resultados sugerem que o SCC pode ser um novo alvo para desenvolvimento de novas estratégias farmacológicas para o tratamento de doenças metabólicas como obesidade e diabetes mellitus tipo 2. / The kallikrein-kinin system (KKS) is involved in many biological processes such as modulating pain, vasodilation, vascular permeability, edema and inflammation, with effects mediated by two specific receptors coupled to G protein, B1 and B2 kinin receptor. The KKS has recently been associated with glucose homeostasis and insulin resistance. The aim of this study was to investigate the participation of B1 receptor (B1R) of kinins in the metabolic processes related to obesity and type 2 diabetes in obese mice. For this we used mice deficient for leptin and knockouts for B1R kinin (obB1). When compared, the animals obB1 showed a reduction in food intake in the whole study period (4 to 26 ° week of life); less weight gain, both at 3 months (obWT, 63.79 ± 1.59; obB1, 51.22 ± 1.09 g, p <0.001) and at 6 months of age (obWT, 74.61 ± 1, 04; obB1, 57.98 ± 1.58 g, p <0.001); and less fat deposit. In the glucose tolerance test, obB1 animals had higher glucose uptake than their controls when young (obWT, 46045 ± 3492; obB1, 30875 ± 2311 (mg / dL) .min, p <0.01). Additionally, there was an increase in liver weight in these animals, while older (obWT, 3.29 ± 0.24, 4.09 ± 0.06 g obB1, p <0.001). In conclusion, the B1R gene silencing offers a protection against obesity have a significant impact on the glucose homeostasis. These results suggest that the KKS may be a new target for the development of new pharmacologic strategies for treating metabolic diseases such as obesity and type 2 diabetes mellitus.

Bakgrund: Patienter med psykossjukdom lider ofta av somatisk ohälsa som uttrycker sig i metabolt syndrom. Dåliga levnadsvanor som till exempel dålig kosthållning, inaktivitet, droger etcetera, samt den nödvändiga läkemedelsbehandling är faktorer som bidrar till utvecklandet av metabolt syndrom. Dessa faktorer leder till att denna patientgrupp riskerar att dö upp till 25 år tidigare än den övriga populationen. Syfte: Syftet med studien var att belysa preventiva och lindrande omvårdnadsinterventioner mot metabolt syndrom hos personer som behandlas för psykossjukdomar. Metod: Studien är utformad och genomförd som en allmän litteraturstudie med systematisk ansats. Databassökningen utfördes i Cinahl, Pubmed, Scopus, Psycinfo och Psycarticle. Artiklarna kvalitetsgranskades utifrån Linköpings universitets granskningsmallar och kvalitetsbedömdes utifrån författarnas kvalitetskrav. Resultat: Resultatet bildade tre kategorier; Levnadsvanor, Socialt stöd och Prevention, vilka står i beroende till varandra. Patienternas levnadsvanor är det huvudsakliga fyndet för att lindra och förhindra metabolt syndrom, men för att kunna genomföra livsstilsinterventioner hos patienter med psykos behövs socialt stöd och information. Dessa faktorer utgör även grunden för det preventiva arbetet för att förhindra metabolt syndrom innan det utvecklats. Konklusion: Sammanfattningsvis kan sägas att de preventiva och lindrande åtgärderna mot metabolt syndrom för personer som behandlas för psykossjukdom är att stödja och uppmuntra patienten till en hälsosammare livsstil, innefattande ökad fysisk aktivitet och förbättrad kosthållning. Det åligger även sjuksköterskans arbetsuppgift att individanpassa vården och skapa en personcentrerad vård, skräddarsydd för den enskilde patientens förmågor och behov. Nyckelord: Psykossjukdom, Metabolt syndrom, Omvårdnad, Sjuksköterska. / Background: Patient with psychosis often suffer from somatic illness that is expressed as metabolic syndrome. Bad living habits such as bad diet, inactivity, drugs etcetera is factors that contribute to the development of metabolic syndrome. Also, the necessary drug treatment is important for the development of metabolic syndrome. These factors sets the patient group in a risk to die up to 25 years earlier than the average population. Aim: The purpose of the study was to highlight preventive and mitigating nursing interventions against metabolic syndrome in people treated for psychiatric diseases. Method: This study was designed and implemented as a general literature study with a systematic approach. The database research was performed in Cinahl, Pubmed, Scopus, Psycinfo and Psycarticle. The articles was quality-reviewed by Linköpings University’s review-templates and was quality assessed by the authors quality requirement. Result: The result formed three categories; Lifestyles, Social support and Prevention, which depend on each other. Patients' living habits are the main finding for relieving and preventing metabolic syndrome, but in order to be able to implement lifestyle interventions in patients with psychosis, social support and information are needed. These factors also form the basis for preventive work to prevent metabolic syndrome before it develops. Conclusion: In summary, it can be said that the preventative and alleviate measures against metabolic syndrome for people treated for psychiatric disease are to support and encourage the patient to a healthier lifestyle, including increased physical activity and improved diet. It is also the duty of the nurse to personalize care and create a person-centered care tailored to the individual's abilities and needs. Keywords: Psychotic Disease, Metabolic Syndrome, Nursing, Nurse.

The overall aim of this master thesis was to get an overview on how milk and dairy consumption affect development of the metabolic syndrome, and from this review to formulate a milk product with potentially beneficial effects. A cluster of metabolic abnormalities such as insulin resistance and type 2 diabetes, hypertension, obesity and dyslipidaemia are known as the metabolic syndrome. Epidemiological studies performed to investigate the relation between milk and dairy intake and the metabolic syndrome, suggests that low-fat milk and dairy intake have a positive effect in the prevention of the disease. Many dairy components might contribute to this effect. There are promising effects seen by whey amino acids on the glucose and insulin control, but the long-term effects are warranted. Low-fat milk and dairy as part of a diet rich in fruits and vegetables have the most blood pressure reducing effect. This beneficial effect is in part believed to be due to the calcium content of milk and dairy products. In addition, it is also hypothesised that calcium plays an important roll in weight management. However, the evidence up to date is contradictorily. Weight control, on the other hand, can be improved by affecting satiety. Acute intervention studies show that whey, in particular, alfa-lactalbumin, is more satiating than other proteins, resulting in a lower energy intake in a subsequent meal. It is of interest to the dairy industry to provide milk and dairy consumers with milk products that have beneficial effects on wellness and health. Therefore, based on the literatured reviewed on milk and dairy intake and the metabolic syndrome, a milk product with beneficial effects on weight was formulated and developed.

The metabolic syndrome is a cluster of metabolic risk factors such as diabetes type II, dyslipidemia, hypertension, obesity, microalbuminurea and insulin resistance, which in the recent years has increased greatly in many parts of the world. In this thesis decision trees were applied to the BioExpress database, including both clinical data about donors and gene expression data, to investigate nuclear receptors ability to serve as markers for the metabolic syndrome. Decision trees were created and the classification performance for each individual risk factor were then analysed. The rules generated from the risk factor trees were compared in order to search for similarities and dissimilarities. The comparisons of rules were performed in pairs of risk factors, in groups of three and on all risk factors and they resulted in the discovery of a set of genes where the most interesting were the Peroxisome Proliferator Activated Receptor - Alpha, the Peroxisome Proliferator Activated Receptor - Gamma and the Glucocorticoid Receptor. These genes existed in pathways associated with the metabolic syndrome and in the recent scientific literature.

No description available.

Abstract Schizophrenia is associated with a shortened life expectancy and increased somatic comorbidity with e.g. cardiovascular disorders. The purpose of this study was to evaluate hyperlipidemia and metabolic syndrome in schizophrenia and thus find specific risk factors for excess mortality and morbidity. The study population was a subsample of the Northern Finland 1966 Birth Cohort, a general population-based birth cohort. In 1997, 8,463 members of the cohort were invited to a clinical examination, where e.g. blood samples were taken after an overnight fast. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides (TG) were determined. The following psychiatric diagnostic categories were used: 1) DSM-III-R schizophrenia (n = 31), 2) other psychoses (n = 21), 3) non-psychotic disorders (n = 104), 4) comparison group (n = 5,498), having no psychiatric hospital treatment. Mean TC (5.5 mmol/l) and TG (1.5 mmol/l) were significantly higher in the schizophrenia group than in the comparison group (5.1 mmol/l and 1.2 mmol/l, respectively). To evaluate serum lipid levels in subjects with and without antipsychotic medication the sample was analyzed according to used medication. The prevalence of hypercholesterolemia, high LDL cholesterol and hypertriglyceridemia was high in persons using antipsychotic medication (31%, 20% and 22%, respectively) compared to persons without such medication (12%, 10% and 7%, respectively). We found higher triglyceride levels in patients who were ≤ 20 years old at the onset of schizophrenia (mean 1.7 mmol/l; N = 17) as compared with patients with later onset (mean 1.4 mmol/l; N = 14) or non-hospitalized controls (mean 1.2 mmol/l; N = 5,453). The difference between the first and third group was significant (p &lt; 0.01), and there was a negative correlation between the age at onset and the level of serum triglycerides (r = -0.35, p = 0.05). To evaluate the prevalence of metabolic syndrome, the subjects were assessed for the presence of metabolic syndrome according to the criteria of the National Cholesterol Education Program. The prevalence of metabolic syndrome was high in subjects with schizophrenia compared with the comparison group (19% vs. 6%, p = 0.010). The results indicate an elevated risk for hyperlipidemia and metabolic syndrome in persons with schizophrenia or on antipsychotic medication. Regular monitoring of weight, serum lipid and glucose levels and blood pressure is important. Comprehensive efforts directed at controlling weight and improving physical activity are needed.

Philosophiae Doctor - PhD / The metabolic syndrome (MetS) is a collection of various metabolic, hormonal and immunological risk factors that cluster together, closely related to poorly understood phenomena such a hyperinsulinaemia (insulin resistance), hyperleptinaemia (leptin resistance), a low grade, systemic and chronic inflammation and, in males, hypogonadism. Infertility is increasing globally, and male factor infertility accounts for a large percentage of couples who are not able to conceive. The relationship between components of MetS and male reproductive health is not clear, and requires further investigation, as does the impact of MetS on male reproductive health in a case controlled study. The impact of hyperinsulinaemia, hyperleptinaemia and inflammatory cytokines on the male reproductive tract also requires investigation. Furthermore, it is hypothesised that these phenomena negatively impact steroidogenesis cascades. In order to investigate this, a case controlled study and TM3 Leydig cell culture experiments were designed.Participants were recruited from public advertisements, and screened for strict exclusion criteria, including acute or chronic inflammation, hormonal treatments, vasectomy and leukocytospermia (> 106/ml). Following clinical diagnostics, 78 males were either placed into a control group (CG) or the MetS group, with numerous parameters compared between them. Serum was assayed for routine risk markers including HDL cholesterol, triglycerides, glucose and C-reactive protein (CRP). Saliva was assayed for free testosterone and progesterone. Semen samples underwent semen analysis for ejaculation volume, sperm concentration and motility, vitality, morphology and leukocyte concentration, in addition to mitochondrial membrane potential (MMP) and DNA fragmentation (DF). Both serum and seminal fluid were further assayed for insulin, leptin, tumour necrosis factor-alpha (TNF ) and interleukins 1-beta (IL1 ), 6 (IL6) and 8 (IL8). Glucose was also assayed in seminal fluid. Separately, hCG stimulated TM3 Leydig cells were exposed to varying concentrations of insulin (0.01, 0.1, 1 & 10 pg/ml), TNF , IL1 , IL6 and IL8 (0.1, 1, 10 & 100 pg/ml) for 48 hours at optimal cell culture conditions. TM3 cell viability, protein concentration and testosterone and progesterone concentrations were assessed.XXII Results indicated that males in the MetS group (n=34) had significantly increased body mass index, waist circumference, blood pressure, triglycerides, glucose, and Creactive protein (CRP) with decreased HDL cholesterol, as compared to the CG. Furthermore, ejaculation volume, sperm concentration, total sperm count, progressive and total motility were significantly decreased in the MetS group, and sperm with abnormal MMP and DF were increased in this group. No difference was found for morphology. Serum and seminal insulin, leptin, TNF , IL1 , IL6 and IL8 were all significantly increased in the MetS group. Both testosterone and progesterone were also significantly decreased in the MetS group. Insulin increased testosterone and decreased progesterone in the TM3 cells. TNF , IL1 and IL6 all decreased testosterone and progesterone concentrations and TM3 cell viability. IL8 increased TM3 cell viability and decreased progesterone, will no effect on testosterone. These results suggest MetS is associated with decreased fertility potential in males. Furthermore, a significant increase in seminal insulin, leptin, TNF , IL1 , IL6 and IL8 suggests local reproductive tract inflammation in the absence of leukocytospermia. Strong correlations between serum and seminal insulin, leptin, TNF , IL1 , IL6 and IL8, as well as serum CRP, imply that these systemic phenomenons are related to the reproductive tract changes observed. Therefore, the underlying pathophysiology of MetS negatively affects male reproduction, in addition to general health and wellbeing. A decrease in progesterone and testosterone suggests a collapse in steroidogenesis cascades. Additionally, inflammation, increased leptin and insulin resistance likely contribute to this collapse in steroidogenesis based on TM3 cell culture experiments. These results provide novel avenues for further investigations.

Introducción: Pocos son los estudios que analizan la relación entre el síndrome metabólico y la enfermedad nodular tiroidea, tema en el que existe un vacío de conocimiento. El objetivo de este estudio es determinar la asociación entre síndrome metabólico y enfermedad nodular tiroidea en un hospital de Lima, Perú. Materiales y métodos: Estudio longitudinal, prospectivo, analítico, observacional de casos y controles, realizado en el Hospital Nacional Edgardo Rebagliati Martins en Lima - Perú. Un total de 182 pacientes se separaron como casos a los pacientes en los que se encontrara por lo menos un nódulo tiroideo detectado por ultrasonografía mayor a 3 mm (n=91) y como controles a los pacientes en los cuales se excluyera la presencia del nódulo de las características descritas por la misma técnica diagnostica (n=91). Se evaluaron el nivel y la fuerza de asociación entre la presencia de síndrome metabólico y cada uno de sus componentes por separado con la presencia de enfermedad nodular tiroidea. Resultados: El análisis bivariado muestra asociación significativa entre la presencia de nódulo tiroideo y síndrome metabólico con un OR de 2.56 (IC: 95% 1.41 a 4.66, p < 0.05). Se evidenció que los niveles de HDL bajo y la glicemia basal alterada se encuentran asociadas significativamente con la presencia de nódulo tiroideo, independientemente de la presencia de síndrome metabólico con OR de 2.81 ( IC: 95% 1.54 a 5.12, p<0.05) y 2.05 (IC:95% 1.10 a 3.78, p<0.05) respectivamente. El análisis multivariado mantuvo la asociación entre nódulo tiroideo y el síndrome metabólico con un OR de 2.96 (IC: 95% 1,47 a 5,95 , p<0.05), así mismo con niveles de HDL bajo con un OR de 2.77 (IC:95 % 1,44 a 5,3, p<0.05) y con la glicemia basal alterada con un OR de 2,23 (IC:95% 1,14 a 4,34, p<0,05). Conclusiones: El Síndrome metabólico incrementa el riesgo de padecer enfermedad nodular tiroidea, específicamente la disminución de valores de HDL y la glicemia basal alterada fueron los factores en los que halló mayor asociación. / Introduction: Few studies analyses the relation between metabolic syndrome and thyroid nodular disease, subject in which there is a knowledge gap. The object of this study is to determinate the association between metabolic syndrome and thyroid nodular disease in a hospital in Lima, Peru. Materials and methods: A longitudinal, prospective, analytic, observational, case - control study, was performed “Hospital Nacional Edgardo Rebagliati Martins” in Lima- Peru. A total of 182 patients were separated as cases in which at least find a thyroid nodule detected by ultrasonography greater than 3 mm ( n = 91) and controls as patients in whom the presence of the node with the characteristics described was excluded by the same technique (n=91). The level and strength of association was evaluated between the presence of metabolic syndrome and each of its components by itself with the presence of thyroid nodular was evaluated. Results: Bivariate analysis shows significant association between the presence of thyroid nodule and metabolic syndrome with an OR of 2.56 (IC:95% 1.41 to 4.66, p < 0.05). Low levels of HDL and impaired fasting glucose are significant associated with the presence of thyroid nodule, independent of the presence of metabolic syndrome, with an OR of 2.81 (IC:95% 1.54 to 5.12, p<0.05) and 2.05 (IC: 95% 1.10 to 3.78, p<0.05) respectively. The multivariate analysis maintained the association between thyroid nodule and metabolic syndrome with an OR of 2.96 (IC: 95% 1,47 to 5,95 , p<0.05); like was the low levels of HDL with an OR of 2.77 ( IC: 95% 1,44 to 5,3, p<0.05) and with impaired fasting glucose with an OR of 2,23 ( IC 95% 1,14 to 4,34, p<0,05).Conclusions: Metabolic syndrome increases de risk of having thyroid nodule disease. Low HDL levels and impaired fasting glucose were the factors with more association.

Activation of inducible nitric oxide synthase (iNOS) and oxidative stress have been shown to be associated with compromised cardiovascular function in streptozotocin (STZ)-induced type 1 diabetes. The aim of the project is to investigate cardiovascular abnormalities in a rat model of type 2 diabetes (Zucker diabetes fatty or ZDF rats) and two models of metabolic syndrome (fructose-fed rats and Zucker obese rats), and to provide direct evidence linking iNOS and oxidative stress to abnormal cardiovascular function in these disorders. Blood pressure, cardiac contractility, cardiac index, regional flow, vascular resistance and venous tone were measured in diseased as well as normal rats. Biochemical analyses such as activities of iNOS, immunostaining of iNOS and western-blot analysis of iNOS in the heart tissue were carried out. The results showed that cardiac contractile response to dobutamine was compromised in the ZDF rats, and this was associated with increased myocardial protein expression as well as activity of iNOS. The formation of peroxynitrite was increased in the heart tissue of the ZDF rats. Selective inhibition of iNOS by 1400W (N-3-aminomethyl-benzyl-acetamidine) did not alter responses to dobutamine in the control rats, but augmented the contractile effects of dobutamine in the diabetic rats. The regional blood flow was altered in the ZDF rats, and iNOS played a negligible role in regulating regional flow in the ZDF rats. Although venous response to noradrenaline was also altered in the Zucker obese rats, NOS may not be involved in venous tone regulation. Anti-oxidative treatment with N-acetylcysteine inhibited the development of insulin resistance, blood pressure elevation and the increase of 8-isoprostane formation in the fructose-fed rats. We conclude that heart function is compromised and regional blood flow is altered in the ZDF rats. Activation of iNOS plays an important role in suppressing heart dysfunction but does not affect regional blood flow. In Zucker obese rats with metabolic syndrome, iNOS may not be involved in changes of venous function. Oxidative stress is associated with both abnormality of heart dysfunction in type 2 diabetes (by formation of peroxynitrite due to iNOS activation) and development of hypertension and insulin resistance in metabolic syndrome. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

Introduction: Metabolic syndrome (MetS) is a risk condition describing a clustering of traditional cardiovascular risk factors. A number of risk and protective factors have been associated with MetS, and individuals with MetS are at a higher risk for developing chronic diseases such as diabetes, cancer, and cardiovascular disease. Objective: To contribute to the understanding of MetS in Canada, and to describe how it is a risk state through which material, psychosocial, and behavioural factors associate with chronic diseases. This was examined through three objectives: (i) to describe the prevalence and distribution of MetS; (ii) to examine potential pathways linking income and education with MetS; and (iii) to examine the interplay between non-movement behaviours (NMBs, namely sleep, screen time, and sedentary behaviour) and MetS. Methods: The Canadian Health Measures Survey (2007-2009, 2009-2011, ages 18 and older) was used for all analyses, which include logistic regression, multinomial regression, and calculation of standardized logit coefficients. Results: MetS was prevalent among approximately 20% of Canadian adults. It was significantly associated with chronic diseases, such as diabetes (11.2% vs. 3.4% among those with MetS vs. the general population). A social gradient in MetS was identified, and the behavioural risk factors of alcohol use, smoking, physical inactivity, and screen time were suggested to be partial mediators of this pathway. Findings demonstrated that not adhering to physical activity guidelines (150 minutes or more of moderate-to-vigorous physical activity per week) was associated with increased odds of MetS. A stepwise moderating effect of guideline adherence on screen time and sleep behaviours was demonstrated. Conclusion: MetS is prevalent in Canadian adults, and a high proportion of individuals with MetS have chronic conditions. Addressing the modifiable determinants of physical inactivity, excess screen time, alcohol consumption, and smoking may reduce the social gradient in MetS. Furthermore, adhering to physical activity guidelines may mitigate the associations of NMBs with MetS. The current thesis suggests that healthy behaviours are associated with lower risk for MetS, and therefore, possibly for future chronic disease.