Dissertations / Theses on the topic 'Grave insult'

Orientador: Sarah Monte Alegre<br>Dissertação (mestrado) - Universidade Estadual de Campinas. Faculdade de Ciencias Medicas<br>Made available in DSpace on 2018-08-11T07:51:04Z (GMT). No. of bitstreams: 1 Ortiz_JosianeNovetiMorais_M.pdf: 1470071 bytes, checksum: 08c02e85220eefda78e3311ccc0a0153 (MD5) Previous issue date: 2007<br>Resumo: A obesidade é uma doença cuja prevalência vem aumentando de forma global em todas as faixas etárias, raças e em ambos os sexos, e está associada a altas taxas de morbidade e mortalidade. Obesos desenvolvem também hiperinsulinemia e resistência à insulina, o que pode levar ao aparecimento de diabetes tipo 2 (DM). Recentemente foi demonstrado que o tecido adiposo, mais que um local de acúmulo de reservas energéticas, desempenha papel de um verdadeiro órgão secretor de moléculas sinalizadoras (adipocinas) que atuam em diversos locais do organismo. O acúmulo de tecido adiposo causado pela obesidade acarreta um aumento da produção de adipocinas, como o Fator de Necrose Tumoral Alfa (TNF-a) e a Interleucina-6 (IL-6), que ao estimular a produção de proteínas de fase aguda pelo fígado, conduzem a um estado inflamatório subclínico, associado ao surgimento das comorbidades presentes na obesidade. A adiponectina, produzida pelo tecido adiposo, ao contrário, exerce um papel protetor, diminuindo a resistência à insulina, porém encontra-se paradoxalmente diminuída em obesos. Ajudar a entender as interações existentes entre obesidade, adipocinas e resistência à insulina, avaliando concentrações séricas de adiponectina, TNF-a, IL-6, Proteína C-reativa (CRP) em pacientes obesos graves com (IT) ou sem (NT) intolerância à glicose, bem como em controles, antes e após infusão de insulina, é o objetivo deste trabalho. Para tanto, 32 indivíduos obesos (15 NT, 11 IT e 6 DM; IMC=50,2±2,2; 48,3±2,2 e 51,0±3,0Kg/m2) e 9 indivíduos eutróficos (CT=22,3±0,6Kg/m2) classificados a partir de teste oral de tolerância à glicose, pareados por idade e sexo, realizaram clamp euglicêmico hiperinsulinêmico (180 min; infusão de insulina - 40µU/min·m2). Adiponectina, TNF-a, IL-6, e CRP foram dosados em jejum e aos 180 minutos do clamp. Antes do início do estudo foi realizada bioimpedância elétrica (BIA) para determinação da composição corporal. Os pacientes obesos eram resistentes à insulina (sensibilidade à insulina ou ¿M¿: NT=28,5±3,4 IT=23,3±1,6 e DM=16,8±3,4; todos p<0,001 vs. CT=52,5±2,7 µmol/min/KgMM). As concentrações basais de TNF-a, IL-6 e CRP eram similares entre os subgrupos de obesos, maiores que nos controles (todos p<0.01) e relacionadas independentemente ao IMC e/ou à % gordura corporal. As concentrações basais de adiponectina eram menores nos obesos (NT=7,5±1,4; IT=5,6±0,9; DM=3,3±0,7 vs. CT=11,6±1,4 µg/ml) e direta e independentemente relacionadas à sensibilidade à insulina e inversamente com as medidas de adiposidade, glicemia e insulinemia. A infusão de insulina diminuiu a adiponectinemia nos obesos independentemente do grau de tolerância à glicose (p =0,009) e exerceu pouco efeito sobre as demais citocinas. Portanto, as concentrações circulantes elevadas de TNF-a, IL-6 e CRP em pacientes com obesidade grau III não dependem do grau de tolerância à glicose e não se modificam sob infusão aguda de insulina. As concentrações circulantes de adiponectina encontram-se diminuídas, variando de acordo com o grau de tolerância à glicose, e sofrem ação inibitória da insulina. A hiperinsulinemia presente nos pacientes obesos pode contribuir para diminuir a adiponectinemia acarretando um aumento ainda maior da resistência à insulina e da conseqüente hiperinsulinemia<br>Abstract: Obesity is associated with a cluster of metabolic alterations such as insulin resistance, hypertension, and dyslipidemia and with a low-grade systemic inflammation, which is presumed to play a role in the development of insulin resistance, cardiovascular disease (CVD) and type 2 diabetes mellitus (DM). Adipocytokines or adipokines are synthesized by adipose tissue, released into the circulation and may act as signaling molecules. High circulating levels of Tumor Necrosis Factor-Alpha (TNF-a) and Interleukin-6 (IL-6) in adipose tissue have been demonstrated in obesity. Adiponectin, abundantly expressed in white adipose tissue, seems to play a protective role against atherosclerosis and insulin resistance but is decreased in obesity. The role of insulin sensitivity and insulin levels on the modulation of adiponectin concentrations in humans remains unclear. Aim: to evaluate the acute insulin effect on circulating adiponectin, TNF-a, IL-6 and C-reactive protein (CRP) and their relationship with insulin resistance in normal subjects and in class III obese subjects with normal (NGT) or impaired glucose tolerance (IGT). Methods: 32 obese, 15 NGT, 11 IGT and 6 DM subjects (BMI=50.2±2.2; 48.3±2.2 and 51.0±3.0Kg/m2) and 9 lean subjects (CT 22.3±0.6Kg/m2) received an OGTT and a 3h-euglycemic clamp (insulin infusion - 40µU/min·m2). Adiponectin, TNF-a, IL-6 and CRP were assayed at fasting and at 180min of insulin infusion. BIA was performed before the study to assess body composition. Results: Obese patients were insulin resistant (M:NGT=28.5±3.4; IGT=23.3±1.6 and DM=16.8±3.4; all p<0.001 vs. CT=52.5±2.7 µmol/KgFFM·min). Fasting TNF-a IL-6 and CRP were similar among obese subgroups, higher than CT (p<0.01) and related to BMI and/or fat mass. Adiponectin was lower in obese (NGT=7.55±1.26; IGT=5.55±0.95; DM=3.31±0.75 vs. CT=11.56±1.37 µg/ml) and directly and independently related to M after adjustment for waist, fat mass and BMI (p<0.001). Insulin infusion lowered adiponectin only in obese subjects and little affected the other cytokines. Discussion: In severely obese subjects, TNF-a, IL-6 and CRP are increased independently of glucose tolerance status, and are not affected in the short-term by insulin. Adiponectin levels are decreased in these subjects, according to the glucose tolerance degree, and are downregulated by insulin infusion. More importantly, the persistent hyperinsulinemia can contribute to reduce the adiponectin expression, contributing to further insulin resistance and hyperinsulinemia<br>Mestrado<br>Ciencias Basicas<br>Mestre em Clinica Medica

O objetivo do presente estudo foi verificar o grau de resistência insulínica (RI) em pacientes infectados com o vírus da hepatite C (VHC) genótipo 1 versus genótipo 3. Foi incluído um total de 44 pacientes com hepatite crônica C, sendo 23 pacientes infectados com genótipo 1 e 21 pacientes infectados com genótipo 3. Nenhum paciente incluído tinha fatores de risco para Síndrome Metabólica e não foram submetidos a tratamento antiviral prévio. Trinta pacientes eram homens (68%). A média de idade em anos na amostra global foi de 47,5±9,1. Quanto ao genótipo do VCH, 23 pacientes (52%) tinham genótipo 1 e 21 (48%) genótipo 3. O grau de esteatose hepática (EH) entre 5% e 66% foi encontrado em 35 dos 44 pacientes. Não houve diferença significativa entre os genótipos 1 e 3 do VHC. Quanto aos níveis de colesterol total, colesterol HDL, colesterol LDL e as transaminases, não houve diferenças significativas entres os genótipos em estudo. A média do Índice de Massa Corporal (IMC) na amostra global foi de 25±1,8. A prevalência de resistência insulínica, medida pelo teste de HOMA (Modelo de avaliação de homeostase), foi verificada em 27 pacientes (61%). A média do HOMA entre os genótipos não atingiu diferença significativa. Fibrose moderada e severa foi encontrada em 14 (38%) dos 37 pacientes com esteatose hepática e em apenas 2 (27%) dos 7 sem esteatose hepática. A correlação entre resistência insulínica e fibrose hepática na população estudada foi estatisticamente significativa (P<0,001). Na análise de nossos dados, portanto, encontramos Resistência Insulínica em 61% dos 44 pacientes com hepatite crônica C sem fatores de risco para Doença Hepática Gordurosa Não Alcoólica (DHGNA). O grau de RI em pacientes, infectados com genótipo 1 versus genótipo 3 do VHC não foi estatisticamente diferente, tanto no que diz respeito à prevalência (65% versus 57%, respectivamente) quanto à magnitude (2,6 verus 2,8, respectivamente). Quanto à relação entre RI e EH nesses pacientes, verificou-se correlação positiva, havendo RI em 68% dos pacientes com EH versus 29% dos sem EH, sem atingir, no entanto, diferença estatisticamente significativa. Ao analisar a relação entre RI e fibrose hepática, houve diferença estatisticamente significativa em nossa casuística, sendo encontrada maior prevalência de fibrose intensa (F2 e F3 na classificação Metavir) nos 27 pacientes com RI em comparação com os 17 pacientes sem RI (56% versus 6%, respectivamente; P<0,01).<br>The main goal of this research was to verify the insulin resistance (IR) in patients infected with HCV genotype 1 versus genotype 3. A total of 44 patients with chronic hepatitis C were included in the study, 23 patients infected with genotype 1 and 21 patients infected with genotype 3. None of the patients had any risk for the Metabolic Syndrome and had not been submitted to any antiviral therapy before. 30 patients were males (68%). The age average was 47, 5 ± 9,1. About the VHC genotype, 23 (52%) had the genotype 1 and 21 (48%) had genotype 3. Liver steatosis grade (LS) was found in the range of 5% and 66% in 35 patients. There was no significant difference between the genotypes. About the total cholesterol levels, HDL-C and LDL-C, as well as the serum transaminases, there was no significant difference between the genotypes. The average of the body mass was 25 ± 1,8. The prevalence of insulin resistance (IR), measured by HOMA-IR test was verified in 27 patients (61%). The average of the HOMA-IR test between the genotypes was not statistically significant. Moderate and severe liver fibrosis was found in 14 patients (38%) out of the 37 patients with liver steatosis and only in 2 patients (29%) out of the 7 patients without steatosis. The relationship between insulin resistance and liver fibrosis in our sample was statistically significant (p<0,001). Analyzing our data, we found insulin resistance in 61% out of 44 patients with chronic hepatitis C without risks factors for non-alcoholic fatty liver disease (NAFLD). The amount of the insulin resistance between patients infected with genotype 1 versus genotype 3 of HCV was not statistically different both in the prevalence (65% versus 57% respectively) and in the magnitude (2,6 versus 2,8, respectively). About the relationship between IR and LS in our patients, there was a positive relationship, with IR in 68% of the patients with LS versus 29% of the patients without LS, but without a statistically significant difference. However, the relationship between IR and hepatic fibrosis showed a statistically significant difference, with a greater prevalence of intense fibrosis (F2 and F3 in METAVIR classification) in the 27 patients with IR compared to the 17 patients without IR (56% versus 6%, respectively - p< 0,01).

La malignité des astrocytomes est établie sur base de critères morphologiques définis au sein de la classification de l’Organisation Mondiale de la Santé (OMS). Ce système de gradation, qui s’échelonne de I à IV, constitue actuellement l’outil pronostique le plus fiable. Par facilité, les cliniciens regroupent les astrocytomes de grade I (astrocytomes pilocytiques) et les astrocytomes diffus de grade II sous le terme d’« Astrocytomes de bas-grade » par opposition aux astrocytomes de haut-grade, constitués des astrocytomes anaplasiques (grade III) et des glioblastomes (GBM ;grade IV). Cette terminologie conduit à des prises en charge cliniques inadéquates car elle englobe des tumeurs très différentes en terme d’agressivité :les astrocytomes de grade I, majoritairement non infiltrants, non évolutifs et indolents et les astrocytomes diffus de grade II, toujours infiltrants et évolutifs, progressant systématiquement en astrocytomes de haut-grade et entraînant le plus souvent le décès prématuré du patient. Bien que ces tumeurs soient définies par la classification de l’OMS comme des entités clinicopathologiques distinctes, peu de données sont disponibles dans la littérature pour expliquer leurs particularités biologiques et la pratique quotidienne montre que les différencier peut être difficile. <p><p>Le but des études entreprises au cours de ce travail de thèse est d’apporter une contribution à la compréhension des mécanismes de tumorigenèse qui différencient l’astrocytome de grade I des astrocytomes diffus (grade II-IV), de manière à identifier des voies biologiques qui permettraient, au moins en partie, d’expliquer ces différences de comportement. <p><p>Au cours de la première partie de ce travail, nous avons caractérisé les profils d’expression génomique des astrocytomes de grade I et de grade II, en comparant les données d’expression de gènes (évaluées par des technologies de micropuces d’ADN) de travaux publiés entre 2000 et 2005. L’expression des gènes identifiés a été validée par des analyses de RT-PCR quantitative sur une série indépendante d’astrocytomes de grade I, II et IV. Les fonctions biologiques des protéines codées par chacun de ces gènes ont fait l’objet de recherches bibliographiques détaillées afin de proposer un modèle permettant d’approcher les différences de comportement de ces tumeurs. Cette analyse nous a permis d’identifier TIMP4 (tissue inhibitor of metalloproteinases 4) et IGFBP2 (insulin-like growth factor binding protein 2) comme gènes candidats pour améliorer la caractérisation biologique et clinique des astrocytomes de grade I par rapport aux astrocytomes diffus. TIMP4 et IGFBP2 codent respectivement pour un inhibiteur endogène des métalloprotéinases matricielles (MMPs) et une protéine de liaison capable d’inhiber l’action des « insulin-like growth factors » (IGFs, dont IGFI et IGFII), des facteurs impliqués dans la croissance et la migration des astrocytes normaux et tumoraux. <p><p>Sur base de la surexpression de TIMP4 et d’IGFBP2 dans les astrocytomes de grade I, en comparaison aux astrocytomes diffus de grade II, nous avons posé l’hypothèse suivante :« L’absence d’agressivité des astrocytomes de grade I, en comparaison aux astrocytomes diffus (grade II-IV) pourrait en partie être liée à l’inhibition par TIMP-4 de la protéolyse des complexes IGFBP2-IGFII au sein de ces tumeurs ». Cette protéolyse, qui diminue l’affinité d’IGFBP2 pour IGFII, pourrait contribuer à libérer IGFII dans la matrice extracellulaire (MEC), favoriser la liaison d’IGFII à son récepteur IGF-IR et stimuler la croissance et la migration des cellules astrocytaires tumorales. Pour tester cette hypothèse, nous avons réalisé différentes analyses biochimiques afin i) de caractériser les actions protéolytiques de MMP-2, MMP-9 et MT1-MMP sur le complexe IGFBP2-IGFII, ii) d’identifier la libération d’IGFII lors du clivage de ce complexe, et iii) d’étudier l’action inhibitrice de TIMP-4. A l’aide d’un modèle cellulaire in vitro (lignée astrocytaire tumorale LN229), nous avons ensuite observé l’influence de la protéolyse du complexe IGFBP2-IGFII sur la croissance et la motilité cellulaire. Cette étude a montré :(1) la protéolyse du complexe IGFBP2-IGFII par MMP-9, (2) l’inhibition partielle de cette protéolyse par TIMP-4, (3) la libération d’IGFII résultant de cette protéolyse et (4) les effets stimulants de la libération d’IGFII sur la croissance et la motilité des cellules LN229. Cette étude souligne le rôle important de la protéolyse des complexes IGFBP2-IGFII dans l’agressivité des astrocytomes diffus. Elle confirme les effets stimulants propres d’IGFII, d’IGFBP2 et de MMP-9 sur la motilité et/ou la croissance des cellules astrocytaires tumorales. Enfin, elle identifie un rôle inhibiteur potentiel de TIMP-4 sur la protéolyse du complexe IGFBP2-IGFII, qui pourrait contribuer à expliquer le caractère plus indolent des astrocytomes de grade I en comparaison aux astrocytomes diffus.<p><p>\<br>Doctorat en Sciences médicales<br>info:eu-repo/semantics/nonPublished

Abstract Alopecia has been suggested to be associated with coronary artery diseases (CAD). However, the mechanism underlying this association has remained unclear. The purpose of the present study was to examine the relationships between metabolic syndrome-related risk factors, cardiovascular diseases (CVD) and alopecia among Finnish population. In addition, health-related quality of life (HRQOL) was studied in respect of alopecia among both genders. The data come from the national Finrisk survey alopecia sub-study (4 066 men aged 25–74 years old) and two community samples of men and women (aged 55 and 63 years) living in the city of Oulu in 2001 and 1998, respectively. The degree of alopecia was assessed using the Norwood-Hamilton classification scale for men and the Ludwig scale for women. This study showed a high prevalence of alopecia in the general male Finnish population varying from 17% to 73% among men aged 25–74 years, and its association with CVD particularly in age-groups older than 55 years. In addition, insulin resistance, as a metabolic syndrome-related risk factor, was associated with alopecia in middle-aged men. Among men younger than 35 years, low-grade inflammation was associated with alopecia, especially combined with central obesity. Further, in middle-aged general Finnish population, obesity associated most closely with low-grade inflammation, which is in line with the findings among young men with alopecia. Compared to subjects with no alopecia, HRQOL dimension scores (RAND-36) were significantly lower in physical functioning, role limitations due to physical health and general health among women with alopecia, and in physical functioning and social functioning among men with alopecia. Regression analyses of HRQOL-related factors revealed that alopecia was associated with role limitations due to physical health in women but not in men. An association between alopecia and CVD was strengthened in this study. In addition, low-grade inflammation and insulin resistance were associated with alopecia, especially with early onset alopecia. In elderly women, alopecia seemed to be associated with morbidity in vascular diseases. In the future, recognition of the risk factors for cardiovascular disease among subjects with alopecia is a challenge for primary health care that may prevent the development of arterial diseases<br>Tiivistelmä Hiustenlähdön yhteys sydän- ja verisuonisairauksiin on ollut tiedossa jo pitkään, mutta yhteyden taustalla olevat patofysiologiset mekanismit ovat edelleenkin epäselviä. Tässä väitöskirjatyössä tutkittiin hiustenlähdön yhteyksiä metaboliseen oireyhtymään ja siihen liittyviin riskitekijöihin suomalaisessa väestössä yleisesti. Lisäksi tutkittiin elämänlaadun yhteyttä hiustenlähtöön 63-vuotiailla miehillä ja naisilla. Tutkimukseen käytettiin kolmea aineistoa; kansallisen Finrisk 2002 tutkimuksen alopecia (hiustenlähtö) alaotos (4066 iältään 25–74-vuotiasta miestä) ja kaksi aineistoa Oulun kaupungista (Oulussa asuneet 55- ja 63-vuotiaat miehet ja naiset vuonna 2001 ja 1998). Hiustenlähdön laajuus määriteltiin miehillä Norwood-Hamiltonin ja naisilla Ludwigin luokitteluasteikon mukaan. Hiustenlähdön esiintyvyys suomalaisessa miesväestössä vaihteli 17 %:sta (25–34-vuotiaat) 73 %:iin (65–74-vuotiaat) ja se näytti liittyvän sydän- ja verisuonisairauksiin 55-vuotiailla ja sitä vanhemmilla miehillä. Lisäksi alentunut insuliiniherkkyys metabolisen oireyhtymän merkkinä oli yhteydessä hiustenlähtöön keski-ikäisillä miehillä. Varhain alkanut hiustenlähtö (alle 35-vuotiaat) liittyi matala-asteiseen tulehdukseen erityisesti keskivartalolihavilla kaljuuntuvilla nuorilla miehillä. Samansuuntainen tulos tuli esille myös väestötutkimuksessa 55-vuotiailla oululaisilla miehillä ja naisilla, jonka mukaan matala-asteinen tulehdus oli yhteydessä erityisesti yleiseen lihavuuteen eikä pelkästään vyötärölihavuuteen. Terveyteen liittyvän elämänlaadun osa-alueiden pisteet (RAND-36) 63-vuotialla hiustenlähdöstä kärsivillä naisilla olivat merkittävästi matalampia kolmella osa-alueella; fyysiset toiminnot, fyysisen terveydentilan aiheuttamat muutokset roolitoiminnoissa ja yleinen terveys. Samanikäisillä kaljuuntuvilla miehillä merkittävästi matalammat terveyteen liittyvät elämänlaadun osakomponentit olivat fyysisten ja sosiaalisten toimintojen alueella. Tilastollisessa regressioanalyysissä ilmeni, että hiustenlähtö selitti fyysisen terveydentilan aiheuttamia rajoituksia roolitoimintoihin erityisesti kaljuuntuvilla naisilla, mutta ei miehillä. Hiustenlähdön yhteys eri sydän- ja verisuonisairauksiin vahvistui tässä tutkimuksessa. Varhainen hiustenlähtö on ilmeisesti merkki sekä matala-asteisesta tulehduksesta että alentuneesta insuliiniherkkyydestä. Myös naisilla hiustenlähtö näyttäisi liittyvän suurempaan sairastavuuteen. Terveydenhuollon tulisi jatkossa tarkemmin paneutua sydän- ja verisuonisairauksien riskin kartoittamiseen hiustenlähdöstä kärsivien potilaiden kohdalla

Estudos epidemiológicos e experimentais têm sugerido que fatores de risco cardiovasculares podem ser parcialmente atribuídos às influências do ambiente em que vive o indivíduo, e que a nutrição materna influencia na programação de alterações metabólicas e cardiovasculares no indivíduo adulto e que caracterizam a síndrome metabólica (SM). Em contrapartida, estudos prévios de nosso laboratório demonstram que o extrato da casca de uva Vitis labrusca (GSE) possui efeito vasodilatador, antihipertensivo e antioxidante. Desta forma, o objetivo deste estudo foi avaliar o efeito do tratamento oral com GSE (200mg/kg/dia), sobre as alterações cardiovasculares e metabólicas e estresse oxidativo observados na prole adulta (fêmea e machos) com 3 e 6 meses, cujas mães foram submetidas a uma dieta rica em gordura (hiperlipídica) durante a lactação. Quatro grupos de ratas foram alimentados com dietas experimentais: controle (7% de gordura); controle + GSE (7% de gordura + GSE), hiperlipídica (24% de gordura); hiperlipídica + GSE (24% de gordura + GSE) durante a lactação. Após o desmame, todos os filhotes passaram a ser alimentados com uma dieta controle e foram sacrificados aos 3 ou 6 meses de idade. A pressão arterial sistólica (PAS) foi medida por pletismografia de cauda e o efeito vasodilatador da acetilcolina (ACh) foi avaliado em leito arterial mesentérico (LAM) perfundido. Foram avaliados o peso corporal, adiposidade (intra-abdominal e gonadal), níveis plasmáticos de colesterol total, triglicerídeos, glicose e insulina, e a resistência à insulina (RI) foi calculada pelo índice de HOMA IR. As expressões do IRS-1, Akt e GLUT-4 foram determinadas em músculo soleus. O dano oxidativo, níveis de nitritos e a atividade das enzimas antioxidantes: superóxido dismutase, catalase e glutationa peroxidase foram dosados no plasma e homogenato de LAM. A PAS e tecido adiposo foram aumentados nas proles adultas de ambos os sexos e idades do grupo hiperlipídico e revertidos pelo tratamento com o GSE. A resposta vasodilatadora à ACh em LAM não foi diferente entre os grupos de ambos os sexos, mas foram reduzidas com o envelhecimento. Nas proles fêmeas e machos do grupo hiperlipídico também foram observados o aumento dos níveis de triglicerídeos, de glicose e RI em ambas as idades e foram reduzidos pelo GSE. No grupo hiperlipídico houve redução nas expressões de IRS-1, Akt e GLUT-4 e o GSE reverteu estas expressões. Os níveis plasmáticos de malondialdeído estavam aumentados e os níveis de nitrito diminuídos no grupo hiperlipídico, de ambos os sexos e idades e foram revertidos pelo GSE. As atividades das enzimas antioxidantes no plasma e no mesentério foram reduzidas no grupo hiperlipídico e restauradas pelo GSE. Em conclusão, O GSE parece proteger as proles fêmeas e machos, cujas mães foram expostas a uma dieta hiperlipídica durante a lactação, dos fatores de riscos cardiovasculares, proporcionando uma fonte alternativa nutricional para a prevenção da SM.<br>Epidemiological and experimental studies have suggested that cardiovascular risk factors can be partly attributed to the influences of the environment in which the individual lives, and that maternal nutrition influences the programming of metabolic and cardiovascular diseases in adults characterizing the metabolic syndrome. On the other hand, previous studies from our laboratory show that the skin extract of grape Vitis labrusca (GSE) has antihypertensive, antioxidant and vasodilator effects. Thus, the aim of this study was to evaluate the effect of oral treatment with GSE (200mg/kg/day) on the cardiovascular and metabolic disorders and oxidative stress observed in adult offspring (female and male) at 3 or 6 months whose mothers were fed a high fat diet (HF) during lactation. Four groups of rats were fed experimental diets: control (7% fat), control + GSE (7% fat + GSE), diet (24% fat), HF + GSE (24% fat + GSE) during lactation. After weaning, all pups have become fed a control diet and were sacrificed at 3 or 6 months of age. Systolic blood pressure (SBP) was measured by plethysmography and the vasodilator effect of acetylcholine (ACh) was studied in perfused mesenteric arterial bed (MAB). We determined the body weight, adiposity, plasma total cholesterol, triglycerides, glucose, insulin, and insulin resistance was calculated by HOMA IR. The expression of IRS-1, Akt and GLUT-4 were determined in soleus muscle. Oxidative damage, nitrite levels and antioxidant enzyme activity: superoxide dismutase, catalase and glutathione peroxidase were measured in plasma and homogenate of mesentery bed. The SBP and adipose tissue were increased in adult offspring of both sex and ages of the HF group and reversed by treatment with GSE. The vasodilator response to ACh was not different between groups of both sex, but was reduced by aging. In offspring females and males of the HF group were also observed increased levels of triglycerides, glucose and insulin resistance in both ages and those changes were reduced by GSE. HF group showed a reduction in expression of IRS-1, Akt and GLUT-4 which was reversed by GSE. The malondialdehyde levels were increased and nitrite levels were decreased in the HF group of both sex and ages and those changes were reversed by GSE. The activities of antioxidant enzymes in plasma and mesentery were lower in HF group and restored by the GSE. In conclusion, GSE appears to protect the female and male offspring whose mothers were exposed to a high fat diet during lactation, against the cardiovascular risk factors, providing an alternative source of food for the prevention of metabolic syndrome.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2018-10-30T15:35:07Z No. of bitstreams: 2 Dissertação - Camila Grasiele Araújo de Oliveira - 2018.pdf: 1192973 bytes, checksum: 9cc6424879f7e347e318480fe993f8b3 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)<br>Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-10-31T10:17:45Z (GMT) No. of bitstreams: 2 Dissertação - Camila Grasiele Araújo de Oliveira - 2018.pdf: 1192973 bytes, checksum: 9cc6424879f7e347e318480fe993f8b3 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)<br>Made available in DSpace on 2018-10-31T10:17:45Z (GMT). No. of bitstreams: 2 Dissertação - Camila Grasiele Araújo de Oliveira - 2018.pdf: 1192973 bytes, checksum: 9cc6424879f7e347e318480fe993f8b3 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-09-27<br>Introduction: There is strong evidence that obesity leads to an imbalance of the Autonomic Nervous System (ANS), especially in the increase of sympathetic modulation and a decrease in vagal tone, and that associated cardiovascular risk factors may increase the risk of developing cardiovascular diseases. Objective: To analyze the association between cardiovascular autonomic modulation and clinical variables, food consumption and level of physical activity in obese patients. Methodology: A cross-sectional study with 64 volunteers submitted to biochemical tests, accelerometry, 24-hour recall (R24H), and evaluation of cardiac autonomic modulation. For the analysis of heart rate variability (HRV), the R-R (iRR) intervals were captured in the sitting position for 10 minutes. Statistical analysis: Kolmogorov-Smirnov test; linear regression to identify the association between HRV data and BMI, CC, HOMA-IR, insulin, glycemia, MVPAS, TS, VET, macronutrient, SBP and PAD. The multiple linear regression between the indexes of the frequency domain and the adjusted variables CC, HOMA-IR, insulin, glycemia, MVPA, TS, VET, carbohydrate and lipids (p <0.05). Results: Of the 64 severe obese patients analyzed in the present study, 9 were male (14.06%) and 55 female (85.93%), with a mean age of 39.10 ± 7.74 years ( 27 to 58 years). For the anthropometric data evaluated, the mean BMI was 46.61 ± 6.86 kg / m2, with a more frequent degree of morbid obesity (60.93%). The mean WC was 118.83 ± 10.66 cm for men and women, with a higher risk for all males and 84.37% for females. Patients were insulinresistant (HOMA-IR 6.03 ± 4.10 mg / dl). In the MVPA analysis it was verified that the obese patients had a mean of 98.92 ± 41.00 min / week. In the frequency domain, the severely obese had a sympathetic predominance (LF 56.44 ± 20.31 un) and low parasympathetic modulation (HF 42.52 ± 19.18 un). From the Simple Linear Regression analysis, it was observed that the BMI, CC, VET, carbohydrate, lipid, protein, SBP and DBP were not associated with cardiovascular autonomic modulation (p> 0.05). However, a negative association between HOMA-IR and HF (p = 0.049), HOMA-IR and LF / HF variables was observed (p = 0.001). For insulin and glycemia, there was a negative association with the sympatho-vagal balance (p = 0.002 and p = 0.021, respectively). In the AF analysis, there was a negative association between MVPA and the sympathetic component (p = 0.042), and for TS there was a negative association with HF (p = 0.049) and LF / HF (p = 0.036) and LF p = 0.014). For multiple linear regression, CC and HOMAIR values were negatively and significantly associated with HF (p = 0.010). HOMA-IR and lipid values were negatively associated with LF / HF (p = 0.003 and p = 0.043, respectively). There were no associations between insulin, glycemia, MVPA, TS, VET and carbohydrate and cardiac autonomic modulation. Conclusion: The study reveals that, among cardiovascular risk factors, insulin resistance, glycemia, and sedentary time influence the cardiac autonomic modulation of the severely obese, increasing the risk for the occurrence of cardiovascular diseases<br>Introdução: Existem fortes evidências que a obesidade leva a um desequilíbrio do Sistema Nervoso Autônomo (SNA), sobretudo no aumento da modulação simpática e uma diminuição do tônus vagal e que os fatores de risco cardiovasculares associados podem aumentar o risco de desenvolvimento de doenças cardiovasculares. Objetivo:Analisar a associação entre a modulação autonômica cardiovascular e as variáveis clínicas, consumo alimentar e nível de atividade física em obesos graves.Metodologia: Estudo transversal realizado com 64 voluntários submetidos a exames bioquímicos, acelerometria, recordatório 24 horas (R24H) e avaliação da modulação autonômica cardíaca. Para a análise da variabilidade da frequência cardíaca (VFC), os intervalos R-R (iRR) foram captados na posição sentada durante 10 minutos. Análise estatística: Teste KolmogorovSmirnov; regressão linear simples para identificar a associação entre os dados de VFC e IMC, CC, HOMA-IR, insulina, glicemia, MVPAS, TS, VET, macronutriente, PAS e PAD. A regressão linear múltipla entre os índices do domínio da frequência e as variáveis ajustadas CC, HOMA-IR, insulina, glicemia, MVPA, TS, VET, carboidrato e lipídeos (p<0,05). Resultados: Dentre os 64 pacientes obesos graves analisados no presente estudo, 9 eram do sexo masculino (14,06%) e 55 do sexo feminino (85,93%), com média de idade de 39,10± 7,74 anos (27 a 58 anos). Para os dados antropométricos avaliados, o IMC médio de 46,61 ± 6,86 kg/m2 , com grau de obesidade mórbida mais frequente (60,93%). A CC média de 118,83 ± 10,66 cm para homens e mulheres, com maior risco para todos os homens e para 84,37% das mulheres. Os pacientes demonstraram ser insulinoresistentes (HOMA-IR 6,03 ± 4,10 mg/dl). Na análise do MVPA verificou-se que os obesos graves realizaram uma média de 98,92 ± 41,00min/semana. No domínio da frequência, os obesos graves apresentaram predomínio simpático (LF 56,44 ± 20,31 un) e baixa modulação parassimpática (HF 42,52 ± 19,18 un). A partir da análise de Regressão Linear Simples, foi observado que o IMC, CC, VET, carboidrato, lipídeo, proteína, PAS e PAD não foram associados à modulação autonômica cardiovascular (p>0,05). Porém, foi observado associação negativa entre as variáveis HOMA-IR e HF (p=0,049), HOMA-IR e LF/HF (p=<0,001). Para a insulina e glicemia houve associação negativa com o balanço simpato-vagal (p=0,002 e p=0,021, respectivamente). Na análise da AF, houve associação negativa entre MVPA e o componente simpático (p=0,042), e para o TS verificou-se associação negativa com HF (p=0,049) e LF/HF (p=0,036) e positiva com LF (p=0,014). Para a regressão linear múltipla, os valores de CC e HOMA-IR foram associados negativa e significativamente com HF (p=0,010). Os valores de HOMA-IR e lipídeos em porcentagem foram associados negativamente com a LF/HF (p=0,003 e p=0,043, respectivamente). Não foram observadas associações entre insulina, glicemia, MVPA, TS, VET e carboidrato e modulação autonômica cardíaca. Conclusão: O estudo revela que, dentre os fatores de risco cardiovasculares, a resistência à insulina, glicemia, e o tempo sedentário influenciam na modulação autonômica cardíaca dos obesos graves, aumentando o risco para a ocorrência de doenças cardiovasculares.

Los pacientes con Diabetes tipo 1 (DM1) e hipoglucemias graves de repetición presentan de manera generalizada una alteración en la percepción y la respuesta sintomática ante las mismas. La utilización de sistemas de infusión subcutánea contínua de insulina mejora ambas alteraciones y estas mejoras se producen sin objetivarse un deterioro en el control glucémico evaluado por hemoglobina glucosilada (HbA1c) junto con una mejoría en los parámetros de variabilidad glucémica. Asimismo, su uso se asocia a una mejoría en la calidad de vida de estos pacientes. Inclusive en un grupo de pacientes jóvenes con DM1, la presencia de un mayor grado de aterosclerosis preclínica se asocia fundamentalmente a la edad y a la duración de la enfermedad. Las alteraciones pueden observarse en diferentes territorios vasculares y se asocian a defectos en la función endotelial. Aquellos pacientes con un mayor grado de aterosclerosis preclínica tienden a presentar peores perfiles de control metabólico y de parámetros de inflamación crónica. Los episodios repetidos de hipoglucemia confieren además de lo ya mencionado, un peor pronóstico cardiovascular a estos pacientes.<br>Title: “Continuous subcutaneous insulin infusion and continuous glucose monitoring systems in Type 1 Diabetes. Cardiovascular risk profile in patients with labile glycemic control due to repeated severe hypoglycemia” Short running title: “Hypoglycemia and atherosclerosis in Type 1 Diabetes” Abstract: Type 1 diabetic (T1D) patients with repeated severe hypoglycemic episodes usually show a reduced ability to recognize hypoglycemic signs and symptoms. The use of continuous subcutaneous insulin infusion not only improves both alterations but also is associated with a non deletereous effect in metabolic control evaluated in terms of glycated hemoglobin (HbA1c) and with an improvement in glycemic variability. Moreover, the use of these systems is associated with an improvement in self-reported quality-of-life. Even in a group of young adult patients with T1D, the presence of atherosclerosis is mostly related to age and disease duration. Both endothelial dysfunction and structural damage in different territories might be present in these subjects. Patients with higher degrees of atherosclerosis present worse glycemic control and alterations in different inflammation parameters. Repeated episodes of hypoglycemia are also associated with a worse cardiovascular prognosis in these subjects.

Background Obesity, in particular abdominal adiposity, is associated with elevated fatty acids and pro-inflammatory adipokines, which are linked to ectopic fat storage and insulin resistance. During menopause, there is a redistribution of fat from the peripheral to abdominal depots. This transition is associated with an increased risk of type 2 diabetes and cardiovascular diseases. We hypothesized that a Paleolithic diet, with high proportions of lean meat, fish, vegetables, fruits, and oils, but devoid of dairy products and cereals, might have long-term beneficial effects on inflammation, fat metabolism, and circulating fatty acids. These effects might potentially reduce the risk of metabolic complications in postmenopausal women that are obese.  Methods Postmenopausal women with obesity were studied before, after six months, and after 24 months of one of two specified ad libitum diets. One diet was a Paleolithic diet, in which approximately 30% of the total energy (E%) was protein, 30 E% was fat, and 40 E% was carbohydrate. The other diet was a prudent control diet, consistent with Nordic Nutrition recommendations of 15 E% protein, 25 E% fat, and 55 E% carbohydrate. Dietary intakes of polyunsaturated fatty acids and protein were validated objectively by measuring circulating and urinary biomarkers. Anthropometrics and diet reports were analyzed, and abdominal subcutaneous fat samples were evaluated for the expression of proteins key in inflammation and fat metabolism and for lipoprotein lipase mass and activity. In addition, blood samples were analyzed to determine concentrations of specific serum proteins, serum lipids, and the fatty acids carried in cholesterol esters. Results The Paleolithic diet group reported reduced intakes of saturated fatty acids and carbohydrates and elevated intakes of protein and unsaturated fatty acids, compared to baseline. The elevated intakes of polyunsaturated fatty acids and protein were objectively verified for this group. After 24 months, both diets were found to have beneficial effects on the expression of inflammation-related genes in adipose tissue and pro-inflammatory factors in the circulation. Compared to the control group, the Paleolithic diet group exhibited more pronounced reductions of circulating cardiometabolic risk factors, including the ratio of triglycerides to high density lipoprotein, lipogenic index, specific fatty acids, and indices of desaturase activities. After six months, the Paleolithic group also exhibited more pronounced reductions in lipogenesis-promoting factors, including the expression of key proteins in fat synthesis, the activity of lipoprotein lipase, and the activity of stearoyl-CoA desaturase 1, compared to the control group. Conclusion Long-term weight loss in postmenopausal obese women was accompanied by reductions in low-grade inflammation in adipose tissue and in the circulation. In addition, a Paleolithic diet, with a high content of unsaturated fatty acids and a low content of refined carbohydrates, appeared to provide greater reductions in cardiometabolic risk factors associated with insulin resistance and lipogenesis, compared to a prudent control diet.<br>Bakgrund De senaste decennierna har förekomsten av övervikt och fetma ökat kraftigt i stora delar av världen. Detta beror på en kombination av olika faktorer såsom specifika gener vilka främjar fettinlagring, men kanske främst ett överintag av energirik mat i kombination med minskad fysisk aktivitet. Fetma och specifikt bukfetma, vilket tilltar hos kvinnor efter klimakteriet (postmenopausala), ökar risken för höjda blodfettsnivåer och låggradig inflammation, vilket kan leda till utveckling av typ 2-diabetes samt hjärt- och kärlsjukdomar. Kost och viktnedgång är avgörande för bibehållen hälsa och av stort intresse är att urbefolkningar runt om i världen har låg förekomst av fetma, diabetes, hjärt- och kärlsjukdom, troligtvis kopplat till olika livsstilsfaktorer som högre fysisk aktivitet samt kostfaktorer.  Syfte Vårt syfte var att undersöka metabola förändringar i fettväv och cirkulation hos postmenopausala kvinnor med fetma kopplat till en 24 månaders paleolitisk kostintervention. Den paleolitiska kosten, som ingick i studien består av en hög andel magert kött, fisk, grönsaker, frukt, nötter, oliv- och rapsolja och där mjölkprodukter och spannmål är uteslutna. Vår hypotes var att en paleolitisk kost med hög andel protein och omättade fettsyror har fördelaktiga långtidseffekter på inflammation, fettmetabolism och cirkulerande fettsyror jämfört med en kost baserad på Nordiska näringsrekommendationer med ett högt intag av kolhydrater. Metoder Postmenopausala kvinnor med fetma studerades före, vid sex månader och efter 24 månaders intag, utan energirestriktioner, av antingen en paleolitisk kost eller en kost enligt Nordiska näringsrekommendationer. Kroppsmätningar, kostregistreringar, genuttryck av nyckelproteiner i inflammation och fettmetabolism i fettväv samt koncentrationer av blodfetter, specifika proteiner och fettsyror bestämdes i plasma. Resultat I linje med rekommendationerna så rapporterade gruppen som åt den paleolitiska kosten ett minskat intag av mättat fett och kolhydrater samt ett ökat intag av protein och omättat fett jämfört med baslinjenivåerna. Det ökade intaget av fleromättade fettsyror och protein bekräftades med objektiva mätmetoder. Efter 24 månaders intervention uppvisade båda grupperna en jämförbar viktnedgång och en minskning av flertalet proinflammatoriska faktorer i såväl fettväv som i cirkulation. Den grupp som åt paleolitisk kost uppvisade en kraftigare reduktion av cirkulerande kardiometabola riskfaktorer som index för fettsyntes och desaturaser, specifika fettsyror samt kvoten triglycerider till HDL (high density lipoprotein). Efter sex månader bidrog den paleolitiska kosten också till en mer påtaglig minskning av faktorer involverade i fettinlagring, som uttryck av specifika nyckelproteiner i fettsyntes, aktivitet för lipoprotein lipas och stearoyl-CoA desaturase 1 index jämfört med kontrollkosten. Slutsatser En långvarig viktminskning hos postmenopausala kvinnor med fetma åtföljs av en minskad låggradig inflammation i fettväv och i cirkulation. En paleolitisk kost med hög andel omättade fettsyror och låga halt kolhydrater är kopplat till en kraftigare minskning av riskparametrar för insulinresistens och nyckelfaktorer för fettinlagring jämfört med en kontrollkost enligt Nordiska näringsrekommendationer.

Lors des interactions tri-trophiques impliquant une plante hôte, ses insectes phytophages et leurs ennemis naturels (parasitoïdes, prédateurs...), chaque niveau trophique est fortement dépendant des autres. La plante hôte peut influencer directement les traits d’histoire de vie des insectes phytophages et indirectement les ennemis naturels se développant aux dépens de ces insectes phytophages. Lorsque qu’un ennemi naturel comme un parasitoïde attaque l’insecte phytophage, son système immunitaire constitue sa dernière chance de survie. Une grande variation dans l’immunité des insectes est généralement observée dans les populations naturelles, suggérant que différentes pressions de sélection peuvent moduler et conduire à une adaptation des paramètres immunitaires. Ma thèse vise à déterminer les influences conjointes de la plante hôte et des parasitoïdes, sur les paramètres immunitaires des chenilles de deux ravageurs de la vigne, Cochylis (Eupoecilia ambiguella) et Eudémis (Lobesia botrana).Durant ces 3 années, nous avons mis en évidence une forte influence du cépage de vigne sur les effecteurs immunitaires des chenilles de vers de la grappe. De plus, le cépage de vigne semble être à l'origine d'un compromis entre les voies immunitaires constitutives et induites. La présence variable de bactéries à la surface des baies ne semble pas être à l'origine de ce compromis. Outre le cépage de vigne, nous avons démontré une forte action des parasitoïdes sur l'immunité des vers de la grappe. A l'échelle nationale, les populations d’Eudémis les plus immunocompétentes sont également les populations les plus parasitées. Cette corrélation positive entre le succès de parasitisme et les paramètres immunitaires des chenilles ne semble pas expliquée par une réponse plastique du système immunitaire des chenilles à la présence des parasitoïdes, mais plutôt par une sélection locale du système immunitaire, en réponse à la pression de parasitisme subie par ces chenilles sur plusieurs années. Les différentes études réalisées dans le cadre de ma thèse confirment la complexité des relations tri-trophiques entre la plante hôte, l’insecte phytophage et ses ennemis naturels. L’intégration du système immunitaire de l’insecte phytophage semble primordiale dans la compréhension des interactions unissant ces trois protagonistes<br>In tritrophic interactions involving phytophagous insects, host plants and natural enemies, trophic levels are highly dependent on each other. Host plant may strongly affect directly phytophagous insect and indirectly natural enemies growing on these phytophagous insects. When a natural enemy attacks a phytophagous insect, the host immune system constitutes the last chance for the host to survive to an infection. A great variation of insect immune system is generally found in populations for susceptibility to pathogens, suggesting that variable selection pressures may have shaped and driven adaptation of immune traits. This project aims to determine the influence of both host plant and natural enemies on the larval immune system of grapevine moth pests, Lobesia botrana and Eupoecilia ambiguella.During these three years, we have demonstrated a strong influence of grape variety on immune effectors of grapevine moth larvae. In addition, the grape variety modulates a trade-off between the constitutive and induced immune pathways. The variable presence of microbes on the surface of grape berries does not explain the trade-off in immune function. Beyond the grape variety effect, we also demonstrated a strong influence of parasitoids on the immune parameters of the grapevine moth larvae. In France, the most immunocompetent populations of grapevine moth are also the most parasitized. This positive correlation between successful parasitism and larval immune parameters seems not explained by a plastic response of the larval immune system to parasitoids presence, but rather by a local selection of larval immune system in response to parasitism pressure suffered by larvae for several years.The different experiments realized in my thesis confirm the complexity of the tri-trophic interactions between host plant, phytophagous insects and natural enemies. The integration of phytophagous insect immune system seems essential in understanding the interactions linking these three protagonists

Austenitic stainless steel is one of the most important engineering materials with wide variety of applications. Superior resistance to corrosion and compatibility in high temperature and high vacuum have particularly made it an attractive choice. However, the machinability of austenitic stainless steel is not very promising owing to lower thermal conductivity, higher degree of ductility and work hardenability Grade 316 is the standard molybdenum-bearing grade. Molybdenum gives 316 better corrosion resistance properties than crevice corrosion in chloride environment. It has excellent forming and welding characteristics. Over the years, cemented carbide (WC-Co) has overcome many drawbacks of high speed steel (HSS) as cutting tool materials and become one of the most versatile cutting tool materials during machining both ferrous and non ferrous alloys. There are mainly three grades of cemented carbide cutting tools i.e. K, P and M grades. Steel being very ductile in nature produces long, continuous chips during machining. Moreover, iron in steel has greater affinity towards carbon of WC of the tool. P grade, is more diffusion resistant grade due to presence of more stable carbides like TiC, TaC and NbC. Therefore, P grade is also known as mixed carbide grade and more suitable for machining steel. Since P 30 grade of cemented carbide would provide excellent balance of hardness, wear resistance and toughness, the same grade has been chosen for machining of stainless steel. In the first phase of work, tool life test would be carried out using three different cutting velocities i.e. 100, 150 and 200 m/min with constant feed of 0.2 mm/rev and constant depth of cut of 1 mm for different duration of machining. Tool life study would be based on average flank wear, VB= 0.3 mm criterion. Flank wear would be measured using a stereo zoom optical microscope. Therefore, effect of cutting speed on tool life of uncoated P30 grade carbide insert would be studied during dry machining of 316 grade of austenitic stainless steel. Also effect of cutting speed on various chip characteristics during machining of austenitic stainless steel was studied. The different chip characteristic include types of chips, colour of chips, micro and macro morphology of chips, chip thickness and chip reduction coefficient.

RESUMO CONTEXTUALIZAÇÃO: A tiroidite de Hashimoto (TH) pode associar-se a diferentes níveis de disfunção tiroideia. Ainda não está esclarecido de que forma a disfunção tiroideia ligeira, a autoimunidade e a inflamação crónica contribuem para um risco cardiovascular aumentado nos doentes com TH. Desta forma, este estudo pretende avaliar o grau de insulinorresistência, o perfil lipídico e a inflamação de baixo grau nos doentes com TH. MÉTODOS: Este estudo inclui um total de 228 indivíduos com tiroidite de Hashimoto, que foram divididos em três grupos de acordo com os níveis de TSH - TSH 0.35-2.49 μUI/ml, TSH 2.50-4.94 μUI/ml e TSH>4.94 μUI/ml. Foram determinados os testes de função tiroideia, anticorpos anti-tiroideus, perfil lipídico, índices de insulinorresistência, proteína C reativa de alta sensibilidade, vitamina B12, ácido fólico e homocisteína. A análise estatística foi realizada com ANOVA, t-test de Student, correlações de Pearson e regressão linear múltipla. RESULTADOS: 93.9% da nossa população é do sexo feminino e a média das idades é 47.1±15.4 anos. Não foram encontradas diferenças estatisticamente significativas entre os grupos, relativamente à idade, sexo e índice de massa corporal (IMC). Os valores de Modelo de Avaliação da Homeostasia da Insulinorresistência (HOMA-IR) foram estatisticamente diferentes entre os três grupos (p<0.001). No grupo total, níveis aumentados de TSH foram associados a valores superiores de triglicerídeos (r=0.206, p=0.002) e de HOMA-IR (r=0.209, p=0.002). Ambas as correlações se mantiveram significativas após ajustamento da idade, sexo e IMC. Foram encontradas correlações positivas entre os títulos de anticorpos anti-peroxidase tiroideia e colesterol total (r=0.166, p=0.013), colesterol LDL (r=0.173, p=0.01), Apolipoproteína B (r=0.190, p=0.006) e HOMA-IR (r=0.141, p=0.033). Os títulos de anticorpos anti-tiroglobulina correlacionaram-se positivamente com triglicerídeos (r=0.140, p=0.036). CONCLUSÕES: Os pacientes com TH e disfunção tiroideia ligeira apresentam um perfil lipídico mais aterogénico, bem como maior resistência à ação da insulina. Desta forma, o rastreio de comorbilidades cardiovasculares nestes doentes é essencial, de forma a fornecer um diagnóstico precoce e melhores decisões terapêuticas.<br>BACKGROUNDː Hashimoto thyroiditis (HT) may present different levels of thyroid function impairment. It remains unclear how mild thyroid dysfunction, autoimmunity and chronic inflammation contribute to an increased cardiovascular risk in HT. Therefore, this study aims to assess insulin resistance, lipid panel and low-grade inflammation in HT patients. METHODSː A total of 228 patients with HT were enrolled and divided into 3 groups, accordingly to TSH levels - TSH 0.35-2.49 μUI/ml, TSH 2.50-4.94 μUI/ml and TSH>4.94 μUI/ml. We assessed thyroid function tests and antibodies, lipid profile, insulin resistance indexes, high-sensitivity C-reactive protein, vitamin B12, folic acid and homocysteine. Statistical analysis was made using ANOVA, Student's t-test, Pearson's correlations and multiple linear regression. RESULTSː 93.9% of our population were women and mean age was 47.1±15.4 years. No significant differences were found between groups, regarding age, sex and body mass index (BMI). Homeostasis model assessment-insulin resistance (HOMA-IR) levels were significantly different in the three groups (p<0.001). In the total group, higher TSH values were associated to higher levels of triglycerides (r=0.206, p=0.002) and HOMA-IR (r=0.209, p=0.002), even after adjustment for age, sex and BMI. Thyroid peroxidase antibodies titers correlated positively with total cholesterol (r=0.166, p=0.013), LDL-cholesterol (r=0.173, p=0.010), ApoB (r=0.190, p=0.006) and HOMA-IR (r=0.141, p=0.033). Thyroglobulin antibodies correlated positively with triglycerides (r=0.140, p=0.036). CONCLUSIONSː HT patients with mild thyroid dysfunction present a more atherogenic lipid profile and higher resistance to insulin action. Therefore, screening for cardiovascular comorbidities in these patients is essential to provide an early diagnosis and better treatment decisions.

RESUMO CONTEXTUALIZAÇÃO: A tiroidite de Hashimoto (TH) pode associar-se a diferentes níveis de disfunção tiroideia. Ainda não está esclarecido de que forma a disfunção tiroideia ligeira, a autoimunidade e a inflamação crónica contribuem para um risco cardiovascular aumentado nos doentes com TH. Desta forma, este estudo pretende avaliar o grau de insulinorresistência, o perfil lipídico e a inflamação de baixo grau nos doentes com TH. MÉTODOS: Este estudo inclui um total de 228 indivíduos com tiroidite de Hashimoto, que foram divididos em três grupos de acordo com os níveis de TSH - TSH 0.35-2.49 μUI/ml, TSH 2.50-4.94 μUI/ml e TSH>4.94 μUI/ml. Foram determinados os testes de função tiroideia, anticorpos anti-tiroideus, perfil lipídico, índices de insulinorresistência, proteína C reativa de alta sensibilidade, vitamina B12, ácido fólico e homocisteína. A análise estatística foi realizada com ANOVA, t-test de Student, correlações de Pearson e regressão linear múltipla. RESULTADOS: 93.9% da nossa população é do sexo feminino e a média das idades é 47.1±15.4 anos. Não foram encontradas diferenças estatisticamente significativas entre os grupos, relativamente à idade, sexo e índice de massa corporal (IMC). Os valores de Modelo de Avaliação da Homeostasia da Insulinorresistência (HOMA-IR) foram estatisticamente diferentes entre os três grupos (p<0.001). No grupo total, níveis aumentados de TSH foram associados a valores superiores de triglicerídeos (r=0.206, p=0.002) e de HOMA-IR (r=0.209, p=0.002). Ambas as correlações se mantiveram significativas após ajustamento da idade, sexo e IMC. Foram encontradas correlações positivas entre os títulos de anticorpos anti-peroxidase tiroideia e colesterol total (r=0.166, p=0.013), colesterol LDL (r=0.173, p=0.01), Apolipoproteína B (r=0.190, p=0.006) e HOMA-IR (r=0.141, p=0.033). Os títulos de anticorpos anti-tiroglobulina correlacionaram-se positivamente com triglicerídeos (r=0.140, p=0.036). CONCLUSÕES: Os pacientes com TH e disfunção tiroideia ligeira apresentam um perfil lipídico mais aterogénico, bem como maior resistência à ação da insulina. Desta forma, o rastreio de comorbilidades cardiovasculares nestes doentes é essencial, de forma a fornecer um diagnóstico precoce e melhores decisões terapêuticas.<br>BACKGROUNDː Hashimoto thyroiditis (HT) may present different levels of thyroid function impairment. It remains unclear how mild thyroid dysfunction, autoimmunity and chronic inflammation contribute to an increased cardiovascular risk in HT. Therefore, this study aims to assess insulin resistance, lipid panel and low-grade inflammation in HT patients. METHODSː A total of 228 patients with HT were enrolled and divided into 3 groups, accordingly to TSH levels - TSH 0.35-2.49 μUI/ml, TSH 2.50-4.94 μUI/ml and TSH>4.94 μUI/ml. We assessed thyroid function tests and antibodies, lipid profile, insulin resistance indexes, high-sensitivity C-reactive protein, vitamin B12, folic acid and homocysteine. Statistical analysis was made using ANOVA, Student's t-test, Pearson's correlations and multiple linear regression. RESULTSː 93.9% of our population were women and mean age was 47.1±15.4 years. No significant differences were found between groups, regarding age, sex and body mass index (BMI). Homeostasis model assessment-insulin resistance (HOMA-IR) levels were significantly different in the three groups (p<0.001). In the total group, higher TSH values were associated to higher levels of triglycerides (r=0.206, p=0.002) and HOMA-IR (r=0.209, p=0.002), even after adjustment for age, sex and BMI. Thyroid peroxidase antibodies titers correlated positively with total cholesterol (r=0.166, p=0.013), LDL-cholesterol (r=0.173, p=0.010), ApoB (r=0.190, p=0.006) and HOMA-IR (r=0.141, p=0.033). Thyroglobulin antibodies correlated positively with triglycerides (r=0.140, p=0.036). CONCLUSIONSː HT patients with mild thyroid dysfunction present a more atherogenic lipid profile and higher resistance to insulin action. Therefore, screening for cardiovascular comorbidities in these patients is essential to provide an early diagnosis and better treatment decisions.

碩士<br>國防醫學院<br>生理學研究所<br>93<br>Background: A strong correlation between Type 2 diabetes mellitus and hepatic inflammation, in particular non-alcoholic steatohepatitis (NASH) has been dermonstrated in clinical investigations. However, it is unclear whether chronic low-grade hepatic inflammation could affect insulin secretory function in the presence of normal and fatty liver condition. Purpose: The aim of this study was to investigate the effect of chronic hepatic inflammation induced by intraportal low dose LPS infusion on insulin secretory function in normal and fructose-induced fatty liver rats. Materials and methods: Sprague-Dawley rats fed with 60% fructose-enriched or regular diets for 4 weeks and then combined with LPS (0.417 ng/kg/min) or vehicle infusion (Alzet Osmotic minipump) intraportally for another 4 weeks. At the end of study, hyperglycemic clamp study was performed to assess glucose-stimulated insulin secretion. Results: During hyperglycemic clamp period, the glucose-stimulated increase in insulin levels were significantly reduced in fructose-fed rats compared to rats with regular diet throughout the study. Chronic intraportal LPS infusion further attenuated the augmentation of glucose-stimulate insulin secretion in fructose-fed rats. Histological data showed that signs of hepatic and pancreas inflammation were exhibited only in normal and fructose-fed rats with chronic intraportal LPS infusion. The numbers of circulating white blood cells were increased in both normal and fructose –fed rats with intraportal LPS infusion. Conclusion: Our results suggest that inflammatory factors released by chronic hepatic inflammation deteriolate β-cell dysfunction in normal and fructose-induced insulin resistant rats.

碩士<br>中原大學<br>教育研究所<br>100<br>Abstract This research aims at exploring an integrated study of scientific toys instruction on the concept a learning impacts in insects unit for fourth-graders students and their "attitudes toward science". This research uses a quasi-experimental approach ranging group with pretests &; posttest design. We took samples from two classes of the fourth graders at Taoyuan County Elementary School. The experimental group adopted science toys as teaching tools; the control group adopts "Teachers' Guide Teaching". The duration of the teaching activities of this study was approximately five weeks, a total of fifteen lessons. The research tools include: "Two-stage questionnaires for the insects concept of elementary school children" and "Science Attitude Scale". The information obtained was collected and analyzed by descriptive statistics and single factor variable. The findings are shown as follows: 1. Students receiving an integrated study of scientific toys on instruction in the experimental group on the performance of the "Two-stage questionnaires for the insect concept of elementary school children"; the ANCOVA analysis results are significantly better than students in the control group. Therefore, The implementation of scientific toys combined into teaching can effectively enhance the learning outcomes about insect concept for the fourth graders. 2. Students receiving an integrated study of scientific toys on instruction in the experimental group have alternative conceptions for the concept of insect. 3. After scientific toys combined into the teaching curriculum and teaching, the experimental group students are significantly better than students in the control group on Total Scale of "Science Attitude Scale " and the four subscales i.e. "Attitude toward Science Curriculum", "Science Learning Motivation ", "Science Learning Strategy", and "Attitude toward science teachers". Therefore, Implementation of scientific toys on instruction can effectively enhance the fourth grader’s "attitudes toward science".

碩士<br>國立臺北教育大學<br>自然科學教育學系碩士班<br>101<br>The purpose of the study is to investigate the effects of the elementary student teaching program about insects’ habitat-making. Comparing the differences between the pre-program and the post-program, the study is to explore the concept levels and the subject feelings of the students. The subjects are 26 first or second graders of the New Taipei City elementary school. The one-year program is edited by the researcher and includes three parts, respectively the characteristics and ecology of insects, the habitat-making of insects, and the ecology of insects and the school campus. The data are collected mainly by interviewing these students, the researcher’s observation records, and the scales made by the researcher. Major findings are as following: 1. The program could help the students build the correct concept about insects and the right attitude of environment. The elementary students could take advantage of the "six-foot" trait to identify the insects. 2. From May to September, the reproduction rate of insects is much higher than other seasons because of stable temperature. Therefore, it is better time for the program. 3. By participating the program, the scores of pre-post program are significantly different(t=0, p<0) and the concept of insects is also improved. 4. Based on the observation records, the students are more easily to touch the insects and their observations are composed of more details than ever. Based on the abovementioned results, the conclusion are drawn and the recommendations of future studies and applications are proposed.

碩士<br>國立臺中教育大學<br>科學應用與推廣學系環境教育及管理碩士班<br>101<br>Insects are the largest group in the nature in terms of species and quantity, making them perfect materials of teaching. However, in the official curricula of elementary school, lessons related to insects seem to account for a relatively low percentage. Concerning the curricula plan and teaching design, they do not show much understanding of insects, either. Besides, school teachers tend to teach their students in a traditional manner. In this case, school children do not have deep impression and may have misunderstanding of insects, affecting their attitude and behavior towards insects. This study aim to achieve the following five objectives. Firstly, it adopts flow learning and action research to develop teaching activities and teaching aids about insects. Secondly, this study intends to disuss whether the students with various background variables may have different in terms of their insect knowledge, attitude, and behavior. Thirdly, this study will discuss whether students show any difference in the aspects of insect knowledge, attitude, and behavior. Fourthly, it tries to disuss the correlation among insect knowledge, attitude, and behavior. Fifthly, it tries to disuss whether students to promote the knowledge, attitudes, and behavior about insects from the qualitative data, This study is designed mainly on the basis of questionnaire survey, complemented by teachers’ journals, worksheet, and interviews. It chooses two out of ten elementary schools sponsored by MOXA Foundation, selecting 100 middle graders as the study subject in the manner of purposive sampling. Moreover, it conducts the teaching activities on Nov. 13th and 14th, 2012, issuing questionnaires before and after the class. The collected valid questionnaires are 100 copies. Based on the analysis of questionnaire survey, the study concludes its study result as follows: I. The teaching activities are divided into “the lecture of fundamental insect knowledge” and the insect education activities designed on the basis of flow learning. II. There are significant difference in terms of the participants’ response in seeing insects and their attitude towards insects if they had insects prior to the teaching. After the teaching, participants of various grades show significant difference in terms of insect knowledge. III. The teaching activities of insect education improve student’s knowledge of insects significantly. IV. Insect knowledge is positively related to student’s attitude and behavior significantly. Likewise, their attitude towards insects is positively related to their behavior significantly. V. From qualitative data, the teaching activities of insect education improve student’s knowledge, attitudes, and behaviors about insects. Based on the study results, this study suggests that (i) the teaching activities may integrate the knowledge into outdoor education curriculum so that student may learn more and better; (ii) teachers might make more use of the school ecological garden to design more activities of insects and extend the time of teaching activity moderately; (iii) schools should promote curricula related to environment education; (iv) before designing teaching activities, it is necessary to comprehend the prior knowledge of third and fourth grader concerning Grade 1-9 Curriculum.

碩士<br>國立臺北教育大學<br>自然科學教育學系碩士班<br>100<br>The main way of learning science and technology was based on exploring as well as on practical work in elementary schools. But there were still some difficulties in teaching and learning. This study was designed with the aid of integrating digital archives into instruction, the problems of learning insect unit could be hopefully solved. The purposes of this study were to design and construct an instructional module of integrating digital archives about insect unit and to explore the effects of students’ learning. Quasi-experimental research was designed as the research method in the study. The subjects are four classes of the fourth grade students in the same elementary school in New Taipei City, Taiwan. Two of the classes were set to be the experimental group accepting the instructional module of integrating digital archives and other two classes were set to be the control group receiving the general instructional module. During science teaching, students were received Insect Learning Performance Test which contained observation, comparison and classification, organization and connection, and communication of science process skills. And the end of the teaching, students were taken an Insect Concept Learning Achievement Test. One-way analysis of covariance (ANCOVA) and independent sample t test were used to analyze the data from these two groups. The results indicated that the two groups had no significant difference in the Insect Concept Learning Achievement. But, there was significant difference in Insect Learning Performance Test. That is, integrating digital archives in insect unit had improved the students to have the abilities in insect learning performance. Therefore, the study suggests that teachers should select the resources of digital archives according to teaching objectives and the limitation of teaching time in the teaching process to improve students’ practical abilities.

碩士<br>嘉南藥理科技大學<br>生物科技系暨研究所<br>95<br>Polycystic ovary syndrome (PCOS) is a common endocrinologic disease in women. It will increase the risks of cardiovascular disease, insulin resistance and diabetes. The symptoms are including hyperinsulinemia, ovulatory dysfunction, hyperandrogenism, infertility and abortion. At present, the first line treatment for PCOS is the use of insulin sensitizer or combined with clomiphene. The studies about the use of metformin in PCOS are well-documented, recently. In addition, metformin will improve the severity of metabolic syndrome and decrease the complication. In genetic study, there are gene polymorphism in insulin receptor that will result in the occurrence of this disease, especially in the change of insulin receptor substrate-1 (IRS-1). The polymorphism in IRS-1 (Gly972Arg) will lead to the occurrence of insulin resistance, and type II diabetes and reflect low-grade chronic inflammation. The laboratory data in women with PCOS demonstrated several significant changes: (1)(Gly/Arg) group of Body weight : pre-tx 63.70 ± 14.00 kg, post-tx 62.12 ± 13.76 kg; (2)(Gly/Arg) group of the HOMA-IR: pre-tx 10.21±10.72,post-tx 4.44±2.86，(3)(Gly/Gly) group of the soluble vascular adhesion molecule-1 (sVCAM-1), the marker of low-grade chromic inflammation, decreased significantly from pre-tx421.81±133.68 decrease to post-tx 331.32±118.31(ng/ml). Elevated serum levels of sVCAM-1 has been associated with the severity of insulin-resistant states, and the higher level of sVCAM-1 might increase the risk of diabetes and potentially changes those may lead to cardiovascular disease. Herein, in this study we have distinguished these different phenotypes on the basis of their endocrine and metabolic features and their circulating markers of CV risk, and correlate to IRS-1 polymorphism. The results showed the benefits of using metformin to PCOS patients. It still needs more cases to clarify the relationship between IRS gene polymorphism after metformin use in PCO women.

碩士<br>國立新竹教育大學<br>數理研究所(自然組)<br>101<br>This study aims to explore the effects of digital storybooks on fourth grade students’ conceptual understanding and attitudes toward science class. The study also explored the pupils’ own feelings about the digital storybooks. Quasi-experimental design was applied in this study. The participants were from two classes of fourth graders in a public elementary school in Miaoli county. The digital storybooks were integrated in the experimental group, whereas the traditional instruction was used in the control group. Data were collected from three data sources: (a) Insect-Related Achievement Test, (b) The Attitudes toward Science Class Survey, and (c) The Views toward Science Teaching Questionnaire. The research findings showed: 1. The students in the experimental group with the use of digital storybooks were significantly better than the students in the control group with the use of traditional instruction in the conceptual understanding. 2. The students in the experimental group with the use of digital storybooks exhibited more positive attitudes toward science class compared to the students in the control group with the use of traditional instruction. 3. Nearly 94% of the school children enjoyed and were interested in the digital storybooks. They believed that the digital storybooks helped them to learn.

碩士<br>國立臺北教育大學<br>自然科學教育學系碩士班<br>100<br>As the information technology is booming, computer network has changed the learning mode of human, and digital learning has become a new trend. The digital archive resources developed by National Science Council encourage teachers to integrate them into teaching. Therefore, this study aimed at discussing the effectiveness of integrating digital archives into insect teaching in grade fourth. It was hoped that through integrating digital archive resources into pedagogy, the teacher’s teaching process could be improved, and the science cognition and science attitudes of students can also be fostered. The research adapted the quasi-experimental research, and the participants were six classes of students from grade 4 in an elementary school of Xin-Yi District, Taipei. Three classes designed as experimental group are implemented by insect digital archive resources integrating into insect teaching, and another three classes are comparative groups implemented by ordinary teaching . Both of the groups are completed 18 classes of teaching activities. The research tools included Insect Cognition Test and Insect Science Attitudes Test”. The results were analyzed through Analysis of Covariance (ANCOVA) , to understand the influence of students’ cognition and science attitudes through the insect digital archive resources integrating into insect teaching. There is a significant difference in the Insect Cognition Test , and three items which are observing animals, characterizing insect body, and eating habits of insect in the Test constitute the significance. But there is no significant difference in the Insect Science Attitudes Test. Therefore, digital archive resources are suitable to be integrated into insect teaching and to promote students science cognition in their science learning.

碩士<br>開南大學<br>觀光運輸學院碩士在職專班<br>102<br>The purpose of this study was to investigate the interpretation effectiveness of the insect ecology interpretation at middle- and high-grade elementary students who visited Ta-Hwa High School after interpretation activities. A survey was conducted to evaluate four dimensions including: feeling from interpretation, knowledge gained, recreational experiences and behavior intention. Accordingly, a questionnaire was later constructed and 239 questionnaires were distributed before and after interpretation at the elementary students. The research showed that students tended a high satisfaction about “feeling from interpretation”, “recreational experiences” and “behavior intention”. And the students’ knowledge was significantly different before and after interpretation. However, there were no differences in the “feeling from interpretation” dimension, there were significant differences between different genders in the “knowledge gained” Students also showed significant differences in the “recreational experience” dimension in terms of performing in science, reading books on the natural environment, and whether or not they enjoyed reading insect books. The study found that the “feeling from interpretation” about the interpretation activities of insect ecology showed significantly positive correlation with “knowledge gained”, “recreational experiences”, and “behavior intention” by Pearson’s correlation analysis. Based on the findings of this study, not only some suggestions for Ta-Hwa High School were proposed to improve and modify the quality of interpretation, but also make specific recommendations for following studies. Keywords：Interpretation、Interpretative effects、 Insect ecology