Objetivo: O objetivo desse estudo foi avaliar a expressão gênica e a determinação proteica de receptores de LDL (LDL-R e LRP-1) na lesão de endometriose profunda e comparar com o endométrio de mulheres com e sem endometriose, assim como determinar o perfil lipídico de pacientes com e sem endometriose profunda. Pacientes e métodos: Realizamos estudo transversal, caso-controle, exploratório com 39 pacientes, sendo 20 pacientes com diagnóstico histológico de endometriose profunda com comprometimento intestinal e 19 pacientes sem endometriose submetidas à laqueadura tubária laparoscópica. Foram coletadas amostras de sangue periférico no dia do procedimento cirúrgico para análise do perfil lipídico por meio da determinação de Colesterol total, HDL, LDL, VLDL, Triglicérides, APO A I e APO B 100. Foram também coletadas amostras de tecido endometrial com cureta de Pipelle e lesão de endometriose como parte do tratamento cirúrgico laparoscópico. Todas as amostras foram enviadas para análise histológica e submetidas à pesquisa de expressão gênica por PCR Real Time e à determinação proteica por imunoistoquímica dos receptores de LDL (LDL-R e LRP-1). A fase do ciclo menstrual foi determinada no momento do procedimento cirúrgico. Resultados: As pacientes com endometriose profunda apresentaram níveis séricos de LDL-c significativamente inferiores às pacientes sem a doença (119 ± 23 vs 156 ± 35; p=0,001). O mesmo não foi observado com o colesterol total (187 ± 27 vs 194 ± 37; p=0,562), HDL-c (42 ± 9 vs 43 ± 14; p=0,792), Triglicérides (130 ± 40 vs 119 ± 55; p=0,486), APO A I (128,1 ± 33,3 vs 136,5 ± 19,9; p=0,373) e APO B 100 (76 ± 20,9 vs 91,7 ± 30,8; p=0,085). A análise de expressão gênica por PCR Real Time dos receptores de LDL revelou que o LDL-R foi significativamente mais expresso na lesão de endometriose comparado ao endométrio da mesma paciente, mas não ao endométrio de mulheres sem endometriose (0,012 ± 0,009 vs 0,019 ± 0,01 vs 0,027 ± 0,022; p < 0,001) e o LRP-1 foi significativamente mais expresso na lesão de endometriose tanto quando comparado ao endométrio da mesma paciente, quanto quando comparado ao endométrio das pacientes sem a doença (0,089 ± 0,076 vs 0,126 ± 0,072 vs 0,307 ± 0,207; p < 0,001). A análise de determinação proteica por imunoistoquímica dos mesmos receptores revelou que o endométrio de mulheres sem a doença apresentou score de intensidade de marcação de LDL-R significativamente maior que o endométrio e a lesão de mulheres com endometriose (15 ± 78,9 vs 9 ± 45 vs 2 ± 10; p=0,026), porém a marcação para o receptor LRP-1 não apresentou diferença estatisticamente significativa (9 ± 47,4 vs 6 ± 30 vs 0 ± 0; p=0,073). O estudo também demonstrou que houve expressão significativamente maior de RNAm do receptor LDL-R (p=0,001) na fase secretora do ciclo menstrual e o mesmo pode ser observado com relação à expressão de RNAm do receptor LRP-1, que foi superexpresso (p=0,008) no endométrio de mulheres sem a doença. Conclusões: De acordo com os resultados de nossa pesquisa, concluímos que há redução dos níveis séricos de LDL em pacientes com endometriose profunda. Além disso, observamos maior expressão gênica de receptores de LDL em membrana celular de focos de endometriose profunda, comparado ao endométrio, tanto de mulheres sem endometriose quanto de mulheres com endometriose, achado não similar ao observado com a determinação proteica. Houve maior expressão de receptores de LDL em endométrio na fase secretora do ciclo. Este estudo abre oportunidade para viabilização de nanoemulsões lipídicas para acoplamento e direcionamento de drogas antiproliferativas no tratamento da endometriose profunda / Objective: The objective of this study was to evaluate the gene expression and protein determination of LDL receptor (LDL-R and LRP-1) in deep endometriosis lesions and compare with the endometrium of women with and without endometriosis, as well as to profile lipid patients with and without deep endometriosis. Methods: We conducted an transversal, exploratory, case-control study with 39 patients: 20 patients with a histological diagnosis of deep endometriosis with intestinal involvement and 19 women without endometriosis who underwent laparoscopic tubal ligation. Peripheral blood samples were collected on the day of surgery for analysis of lipid profile by determining total cholesterol, HDL, LDL, VLDL, triglycerides, APO AI and APO B 100. Specimens of endometrial tissue were collected using a Pipelle curette and endometriosis lesion specimens were obtains during therapeutic laparoscopic surgery. All samples were sent for histological evaluation and gene expression analysis by Real Time PCR and protein determination by immunohistochemistry of the LDL receptor (LDL-R and LRP-1). The phase of the menstrual cycle was determined at the time of surgery. Results: Patients with severe endometriosis had serum LDL-C levels significantly lower than the patients without the disease (119 ± 23 vs 156 ± 35; p = 0.001). The same was not observed with total cholesterol (187 ± 27 vs 194 ± 37, p = 0.562), HDL-C (42 ± 9 vs 43 ± 14, p = 0.792), triglycerides (130 ± 40 vs 119 ± 55; p = 0.486), APO AI (128.1 ± 33.3 vs 136.5 ± 19.9; p = 0.373) and APO B 100 (76 ± 20.9 vs 91.7 ± 30.8, p = 0.085). The analysis of gene expression by Real Time PCR of LDL receptors revealed that there was significantly greater expression of LDL-R in endometriosis lesions as compared to the endometrium of the same patient, but not when compared to the endometrium of women without endometriosis (0.012 ± 0.009 vs 0.019 ± 0, 01 vs 0.027 ± 0.022, p &lt;0.001). LRP-1 was significantly expressed in endometriotic lesions both when compared to the endometrium of the same patient as compared to the endometrium of patients without the disease (0.089 ± 0.076 vs 0.126 ± 0.072 vs 0.307 ± 0.207, p &lt;0.001). Protein determination by immunohistochemistry of the same receptors revealed that the endometrium of women without endometriosis had a significantly higher staining intensity score than the endometrium and the lesions of women with endometriosis (15 ± 78.9 vs 9 ± 2 vs 45 ± 10, p = 0.026) but the measurement for the LRP-1 receptor showed no statistically significant difference (9 ± 47.4 vs 6 ± 30 vs 0 ± 0; p = 0.073). The study also demonstrated that there was significantly higher mRNA expression of the LDL-R receptor (p = 0.001) in the secretory phase of the menstrual cycle, and the same can be observed with respect to the mRNA expression of LRP-1 receptor, which was overexpressed (p = 0.008) in the endometrium of women without the disease. Conclusion: Based on the findings of our research, we concluded that there is a reduction of serum LDL levels in patients with deep endometriosis. Moreover, we observed higher gene expression of LDL receptors on the cell membrane of foci of deep endometriosis, compared to the endometrium, both in women without endometriosis and women with endometriosis, a finding unlike that observed with the protein determination. There was greater expression of LDL receptors in the endometrium during the secretory phase of the cycle. These findings suggest the feasibility of using lipid nanoemulsions for coupling and targeted delivery of antiproliferative drugs in the treatment of deep endometriosis

As extrassístoles são achados frequentes em pacientes ambulatoriais, o que suscita o interesse em avaliar o seu significado clínico e fatores associados. O objetivo do estudo foi investigar as variáveis relacionadas com a presença de extrassístoles identificadas em pacientes ambulatoriais selecionados ao terem recebido a indicação de eletrocardiograma de rotina na rede básica de saúde. Foi realizado estudo transversal com 407 pacientes (idade média 55,8 anos ± 12 anos, 56% mulheres) encaminhados de Unidades Básicas de Saúde para o Hospital Municipal Doutor Fernando Mauro Pires da Rocha para realização de eletrocardiograma de repouso. Os participantes foram submetidos a questionário, exame físico, exames laboratoriais, ecocardiograma e monitorização eletrocardiográfica ambulatorial de 24 horas, a qual foi empregada para categorizar a frequência de extrassístoles. Depois de análise descritiva e exploratória, a regressão logística foi utilizada para avaliar as associações entre as variáveis. Extrassístoles supraventriculares ( >= 4/hora) se relacionaram com a idade (razão de chances 1,030; intervalo de confiança 95% 1,002 - 1,059; p=0,029), níveis de peptídeos natriuréticos > 20mg/dL (razão de chances 4,489; intervalo de confiança 95% 1,918 - 10,507; p=0.0005), bloqueios intraventriculares (razão de chances 4,184; intervalo de confiança 95% 1,861 - 9,406; p=0,0005) e diâmetro de átrio esquerdo (razão de chances 1,065; intervalo de confiança 95% 1,001 - 1,134; p=0,046). Extrassístoles ventriculares ( >= 5/hora) se associaram com a idade (razão de chances 1,032; intervalo de confiança 95% 1,010 - 1,054; p=0,004), uso de bloqueadores de canais de cálcio (razão de chances 2,248; intervalo de confiança 95% 1,019 - 4,954; p=0,045), níveis de peptídeos natriuréticos > 20mg/dL (razão de chances 2,079; intervalo de confiança 95% 1,062 - 4,068; p=0,033), taxas de HDL-colesterol (razão de chances 0,971; intervalo de confiança 95% 0,951 - 0,992; p=0,007), frequência cardíaca no eletrocardiograma (razão de chances 1,019; intervalo de confiança 95% 1,001 - 1,038; p=0,041), hipertrofia ventricular esquerda (razão de chances 2,292; intervalo de confiança 95% 1,402 - 3,746; p=0,001) e fração de ejeção ventricular esquerda (razão de chances 0,938; intervalo de confiança 95% 0,900 - 0,978; p=0,002). Na população estudada, os batimentos prematuros foram achados recorrentes e de baixa densidade na eletrocardiografia dinâmica de 24 horas. Extrassístoles mais frequentes se associaram a níveis de peptídeos natriuréticos > 20mg/dL e taxas mais baixas de HDL-colesterol; além disso, foi identificada maior dilatação atrial e hipertrofia ventricular no ecocardiograma dos pacientes com esse achado, sugerindo acometimento de órgão alvo decorrente de hipertensão arterial não controlada. Portanto, a detecção de extrassístoles frequentes na monitorização eletrocardiográfica de 24 horas, em pacientes acompanhados no nível de atenção primária, reitera as recomendações dirigidas principalmente para os cuidados com os fatores de risco associados com a sua presença / Premature complexes are common findings in outpatients; thus, it is important to evaluate their clinical significance and related factors. The aim of our study was to examine the variables associated with premature beats identified in outpatients who were followed by general practitioners in a primary public healthcare setting. We performed a cross-sectional study of 407 outpatients (mean age: 55.8±12 years; 56% women) who were referred from Basic Health Units to Doctor Fernando Mauro Pires da Rocha Municipal Hospital to perform a resting 12-lead electrocardiogram for clinical follow-up. They answered a questionnaire and submitted the physical examination, fasting laboratory testing, transthoracic echocardiogram and 24-hour Holter monitoring, which were used to categorize the frequency of premature complexes. After the univariate analysis, logistic regression analyses were performed to evaluate the independent association among the variables. Premature atrial complexes ( >= 4/hour) were associated with age (odds ratio 1.030; confidence interval 95% 1.002 - 1.059; p=0.029), peptide natriuretic levels > 20mg/dL (odds ratio 4.489; confidence interval 95% 1.918 - 10.507; p=0.0005), intraventricular blocks (odds ratio 4.184; confidence interval 95% 1.861 - 9.406; p=0.0005) and left atrium diameter (odds ratio 1.065; confidence interval 95% 1.001 - 1.134; p=0.046). Premature ventricular complexes ( >= 5/hour) were associated with age (odds ratio 1.032; confidence interval 95% 1.010 - 1.054; p=0.004), the use of calcium channels blockers (odds ratio 2.248; confidence interval 95% 1.019 - 4.954; p=0.045), peptide natriuretic levels > 20mg/dL (odds ratio 2.079; confidence interval 95% 1.062 - 4.068; p=0.033), HDL-cholesterol levels (odds ratio 0.971; confidence interval 95% 0.951 - 0.992; p=0.007), heart rate (odds ratio 1.019; confidence interval 95% 1.001 - 1.038; p=0.041), left ventricle hypertrophy (odds ratio 2.292; confidence interval 95% 1.402 - 3.746; p=0.001) and left ventricle ejection fraction (odds ratio 0.938; confidence interval 95% 0.900 - 0.978; p=0.002). In our population, premature complexes were common findings on 24-hour Holter monitoring, but of low density. Frequent ectopic beats were associated with peptide natriuretic levels > 20mg/dL and lower levels of HDL-cholesterol; left atrial enlargement and ventricular hypertrophy were also identified on the echocardiograms of these patients, suggesting that target organ damage was due to uncontrolled arterial hypertension. Therefore, the identification of frequent premature complexes on 24-hour Holter monitor recording of outpatients in a primary public healthcare setting reaffirms the need for monitoring for the risk factors associated with this finding

Although the clinical efficacy of statins has been well established, there is a wide inter-individual variation in the lipid responses to statins. Pharmacogenetic studies have identified some genetic differences that contribute to the variation, but overall the results have been disappointing. The studies described in this thesis were performed to examine whether certain genetic variants predicted the lipid responses to rosuvastatin in Chinese patients. Over 400 Chinese patients with increased risk of cardiovascular disease (CVD) who were treated with rosuvastatin 10 mg daily for at least 4 weeks (more than 97% of patients had at least 6 weeks treatment) were studied, including 166 having familial hypercholesterolaemia (FH) and 36 having rheumatoid arthritis (RA). They were genotyped for 135 polymorphisms in 62 candidate genes/loci potentially related to pharmacokinetics or pharmacodynamics of statins and lipid metabolism. Associations between genetic polymorphisms and the lipid responses to rosuvastatin were analyzed in 386 patients with good compliance. The associations between genetic polymorphisms and some risk factors for CVD including baseline lipid levels, high-sensitivity C-reactive protein (hsCRP), uric acid and bilirubin levels were also analyzed. / Some novel genetic determinants of the LDL-C response to rosuvastatin treatment have been identified in this study. The responses in HDL-C and triglycerides were related more closely to the baseline levels of these lipids than to any of the polymorphisms examined. Genetic associations with baseline lipid parameters, hsCRP, uric acid and bilirubin were identified and generally correspond with some of the previous reports of studies in Chinese and other ethnic groups. / The key findings of the study are as follows: 1. The polymorphisms most highly associated with the low-density lipoprotein cholesterol (LDL-C) response were 421C>A in the ATP-binding cassette G2 (ABCG2) gene (P=9.2x10 -7), followed by 18281G>A (V257M) in the flavin-containing monooxygenase 3 (FMO3) gene (P=0.0002), 1421C>G in the lipoprotein lipase (LPL) gene (P=0.002), and rs4420638 in the apolipoprotein E/C-I/C-IV/C-II (APOE/C1/C4/C2) gene cluster (P=0.004). These genetic polymorphisms and having FH totally explained 13.6% of the variance in percentage change in LDL-C in response to rosuvastatin. The greater percentage reduction in LDL-C in patients with the ABCG2 421AA genotype compared to those with the ABCG2 421CC genotype was equivalent to at least doubling the dose of rosuvastatin. 2. Three SNPs (glucokinase regulator [ GCKR] rs1260326, apolipoprotein AS [APOA5] -1131T>C and the solute carrier organic anion transporter 1B1 [SLCO1B1] 521T>C) tended to be associated with percentage changes in high-density lipoprotein cholesterol (HDL-C) (P&lt;0.05), but none of these reached the overall significance level. In multivariate stepwise regression analysis, baseline HDL-C (P=1.6x10 -6), having diabetes (P=0.0004) or RA (P=0.002) and the SLCO1B1 521T>C polymorphism (P=0.03) were determinants of HDL-C responses, contributing 9.9% of the variance in percentage change in HDL-C, but the genetic factors only contributed to 0.8% of the variance. 3. The triglyceride response to rosuvastatin was highly variable and was strongly related to baseline levels. The diacylglycerol acyltransferase-2 (DGAT2) rs10899113 C>T polymorphism tended to be associated with reduced triglyceride response in a gene-dose dependent manner. However, in multivariate stepwise regression analysis, baseline triglyceride level was the only factor that strongly related to the triglyceride response, explaining 14.4% of the variance. 4. This study has also analyzed relationships between on-treatment plasma hsCRP concentrations and cardiovascular risk factors and 14 single nucleotide polymorphisms in CRP and other candidate genes, which showed that central obesity, low HDL-C and CRP polymorphisms are major determinants of higher hsCRP levels in Chinese patients on treatment with rosuvastatin. 5. The association between genetic polymorphisms and lipid traits were analyzed in FH and non-FH patients separately due to their different lipid profiles. The analysis has shown that there were different genetic predictors of lipid levels in patients with and without FH and that more genetic factors appeared to affect the baseline lipid levels in patients with FH compared to non-FH patients, suggesting complex interactions between genetic and environmental factors and plasma cholesterol levels in patients with and without FH. 6. The SLC2A9 (solute carrier family 2, member 9) rs1014290 T>C was significantly associated with plasma uric acid levels in a gene-dose dependent manner (P=1.0x10-5) and the relationship was more pronounced in women or in patients without hypertension than in men or patients with hypertension. The ABCG2 421 C>A did not show a significant effect on uric acid levels. 7. The UGT1A1 (uridine diphosphate glucuronosyltransferases family, polypeptide A1) variants *28 (P=1.5x10 -9) and *6 (P=2.2x10-7) were independently associated with increased baseline bilirubin levels. Polymorphisms in SLCO1B1 did not appear to affect bilirubin levels in this study. / Hu, Miao. / Adviser: Brian Tomlinson. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 230-264). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Abstract Increased plasma cholesterol is a well-known risk factor for cardiovascular diseases in middle and early old age. At older ages, this association seems to disappear. Very few studies have assessed the impact of the lifelong cholesterol burden on old age, the purpose of this thesis. Study populations consisted of 1) old persons with familial hypercholesterolemia (FH), a genetic disorder associated with an increased risk of coronary heart disease (CHD) if untreated, and 2) initially healthy men (The Helsinki Businessmen Study, HBS) followed-up from midlife to old age. A population-based FH cohort, aged&#160;&#8805;&#160;65 years (n=37, aged 65 to 84 years) agreed to participate in this study. All but one of them had been using statin therapy for approx. 15 years. Variables studied were: health-related quality of life (HRQoL) with questionnaires (RAND-36, 15D), a brain magnetic resonance imaging (MRI) scan and cognitive tests (CERAD). These older FH patients enjoyed a similar HRQoL as controls in the general population. Only two (6%) of the older FH patients had clinically silent brain infarcts detected by MRI and those aged 65 to 74 years did not have more white matter hyperintensities (WMHIs) when compared to middle-aged controls. In the cognitive assessments, FH patients, especially those with duration of statin therapy longer than median, even expressed better episodic memory than population controls. HBS consists of a cohort of men (3277 men) who at baseline (1964–1973) were healthy and in their 40s. They were subdivided into seven groups according to baseline total cholesterol value at 1 mmol/L intervals starting from &#8804; &#160;4 mmol/L. In 2000, at a mean age of 73 years, they filled a postal questionnaire including RAND-36. Cumulative mortality data were collected up to January 2010. A strong and graded relation was found between the cholesterol level and total mortality, those men with a cholesterol level &#8804; &#160;4 mmol/L exhibiting the lowest mortality. A low cholesterol value at midlife also predicted a better score in the Physical functioning scale of RAND-36 in old age. In conclusion, in initially healthy men, a low cholesterol value at midlife was associated with better survival and better physical function in old age. Despite their genetic risk, FH patients on long-term statin medication seemed to enjoy a health and cognitive status similar to the general population. / Tiivistelmä Suurentunut plasman kolesterolipitoisuus on tunnettu valtimotautien riskitekijä keski-iässä, mutta vanhuusiässä kolesterolin merkitys näyttää vähentyvän. Hyvin harvassa tutkimuksessa on tutkittu elämänaikaisen kolesterolitason vaikutuksia vanhuusiän terveydentilaan, kuten tässä väitöskirjatyössä. Tutkimuskohteina olivat 1) iäkkäät, joilla on familiaalinen hyperkolesterolemia (FH) eli perinnöllinen sairaus, johon hoitamattomana liittyy lisääntynyt sepelvaltimotaudin riski, sekä 2) alun perin terveet miehet (Helsingin Johtajatutkimus), joita seurattiin keski-iästä vanhuuteen. Väestöpohjainen, 65 vuotta täyttänyt (65–84 vuotta, 37 henkilöä) FH-potilaiden ryhmä oli yhtä lukuun ottamatta käyttänyt keskimäärin 15 vuoden ajan statiinilääkitystä. Heille tehtiin seuraavat tutkimukset: terveyteen liittyvän elämänlaadun kyselyt (RAND-36- ja15D-mittarit), aivojen magneettitutkimus (MRI) ja kognitiota tutkivat testit (CERAD). FH-potilaiden elämänlaatu ei eronnut väestöverrokeista. Aivojen MRI tutkimuksessa vain kahdella (6&#160;%) FH-potilaalla oli todettavissa kliinisesti hiljainen aivoinfarkti ja 65–74-vuotiailla FH-potilailla ei ollut enempää valkean aineen muutoksia kuin keski-ikäisillä verrokeilla. Kognitiotutkimuksissa FH-potilailla oli parempi episodinen muisti kuin väestöverrokeilla, etenkin niillä FH-potilailla, joiden statiinihoidon kesto oli mediaania pidempi. Helsingin Johtajatutkimukseen kuului alun perin 3 277 lähtötilanteessa (1964–1973) tervettä keski-ikäistä miestä. Heidät jaettiin lähtövaiheen kolesterolitason perusteella seitsemään ryhmään yhden millimoolin välein siten, että alin ryhmä oli alle 4 mmol/l. Vuonna 2000 (keski-ikä 73 vuotta) lähetettiin postikysely, johon kuului myös RAND-36. Kokonaiskuolleisuutta seurattiin tammikuuhun 2010 asti. Kokonaiskuolleisuuden ja keski-iän kokonaiskolesterolin välillä oli vahva ja asteittainen suhde siten, että niillä miehillä oli pienin kuolleisuus, joilla oli alin kolesteroli (alle 4 mmol/l). Pienin kolesterolipitoisuus keski-iässä oli myös yhteydessä RAND-36-mittarin Fyysinen toimintakyky -osion parempaan pistemäärään. Yhteenveto: Alun perin terveillä miehillä pieni kolesterolipitoisuus keski-iässä ennusti pitempää elämää ja myös parempaa fyysisistä toimintakykyä vanhalla iällä. Huolimatta perinnöllisestä riskistä oli pitkäaikaista statiinilääkitystä käyttäneiden FH-potilaiden terveydentila muuta väestöä vastaava.

Treinamento físico é considerado um dos principais instrumentos para promover um estilo de vida saudável. No entanto, os efeitos do treinamento resistido sobre as vias metabólicas, especialmente o metabolismo lipídico intravascular é em grande parte inexplorada e merece uma investigação mais aprofundada. No presente estudo nós avaliamos os efeitos do treinamento resistido sobre o metabolismo de uma nanoemulsão artificial lipídica e na transferência de lípides para HDL, uma importante etapa do metabolismo da HDL. A cinética plasmática da nanoemulsão artificial lipídica foi estudada em 15 homens saudáveis com treinamento resistido regular de 1-4 anos (idade = 25 ± 5 anos, VO2máx = 50 ± 6 mL/kg/min) e em 15 homens saudáveis sedentários (28 ± 7 anos, VO2máx = 35 ± 9 mL/kg/min). A nanoemulsão artificial lipídica marcada com éster de colesterol-14C e colesterol livre-3H foi injetada por via intravenosa, as amostras de plasma foram coletadas por 24 h para determinar curvas de cinéticas e a taxa fracional de remoção (TFR). Transferência de lípides para HDL foi determinada in vitro pela incubação de amostras de plasma com nanoemulsões (doadores de lípides) marcada com o isótopo radioativo colesterol livre, éster de colesterol, triglicérides e fosfolípides. Tamanho da HDL, atividade da paraoxonase 1 e os níveis de LDL oxidada também foram determinadas. Os dois grupos apresentaram LDL-colesterol, HDL-colesterol e triglicérides semelhantes, mas a LDL oxidada foi menor no grupo treinamento resistido (30 ± 9 vs 61 ± 19 U/L, p = 0,0005). No treinamento resistido, a nanoemulsão éster de colesterol-14C foi removida duas vezes mais rápido do que em indivíduos sedentários (TFR: 0,068 ± 0,023 vs 0,037 ± 0,028, p = 0,002), bem como o colesterol livre-3H (0,041 ± 0,025 vs 0,022 ± 0,023, p = 0,04). Embora ambos os componentes da nanoemulsão tenham sido removidos na mesma proporção em indivíduos sedentários, no grupo treinamento resistido o colesterol livre-3H foi removido mais lento do que o éster de colesterol-14C (p = 0,005). Tamanho da HDL, paraoxonase 1 e as taxas de transferência de HDL dos quatro lipídios foram as mesmas em ambos os grupos. Portanto, concluímos que o treinamento resistido acelera a remoção da nanoemulsão artificial lipídica, o que provavelmente explica a redução dos níveis de LDL oxidada no grupo treinamento resistido. O treinamento resistido também alterou o equilíbrio da TFR do colesterol livre e esterificado. No entanto, o treinamento resistido não teve efeito nos parâmetros relacionados ao metabolismo da HDL / Exercise training is considered one of the main instruments to promote a healthy lifestyle. However, effects resistance training on the metabolic pathways, specially the intravascular lipid metabolism is largely unexplored and deserves further investigation. In this study we evaluated the effects of resistance training on the metabolism of an LDL-like nanoemulsion and on lipid transfer to HDL, an important step of HDL metabolism. LDL-like nanoemulsion plasma kinetics was studied in 15 healthy men under regular resistance training for 1-4 years (age = 25 ± 5 years, VO2peak = 50 ± 6 mL/kg/min) and in 15 healthy sedentary men (28 ± 7 years, VO2peak = 35 ± 9 mL/kg/min). LDL-like nanoemulsion labeled with 14C-cholesteryl ester and 3H-free cholesterol was injected intravenously, plasma samples were collected over 24 h to determine kinetics curves and fractional clearance rates (FCR). Lipid transfer to HDL was determined in vitro by incubating of plasma samples with nanoemulsions (lipid donors) labeled with radioactive free cholesterol, cholesteryl ester, triglycerides and phospholipids. HDL size, paraoxonase 1 activity and oxidized LDL levels were also determined. The two groups showed similar LDL and HDL-cholesterol and triglycerides, but oxidized LDL was lower in resistance training group (30 ± 9 vs 61 ± 19 U/L, p = 0.0005). In resistance training, the nanoemulsion 14Ccholesteryl ester was removed twice as fast than in sedentary individuals (FCR: 0.068 ± 0.023 vs 0.037 ± 0.028, p = 0.002), as well as 3H-free cholesterol (0.041 ± 0.025 vs 0.022 ± 0.023, p = 0.04). While both nanoemulsion labels were removed at the same rate in sedentary individuals, in resistance training group 3H-free cholesterol was removed slower than 14C-cholesteryl ester (p = 0.005). HDL size, paraoxonase 1 and the transfer rates to HDL of the four lipids were the same in both groups. Therefore, we conclude that the resistance training accelerated the clearance of LDL-like nanoemulsion, which probably accounts for the oxidized LDL levels reduction in resistance training group. Resistance training also changed the balance of free and esterified cholesterol FCRs. However, RT had no effect on HDL metabolism related parameters

A dieta Mediterrânea (DM) tem sido amplamente estudada do ponto de vista epidemiológico porém, o efeito pleno específico da DM, bem como os mecanismos pelos quais esse padrão dietético contribui para redução do risco cardiovascular em prevenção secundária, são desconhecidos. Isso ocorre, em parte, devido à dificuldade de aderência observada em ensaios clínicos de intervenção dietética, especialmente estudos comparativos com dietas hipolipemiantes, por exemplo, a dieta TLC, Therapeutic Lifestyle Changes Diet (TLCD) do National Cholesterol Education Program-ATPIII. Assim, realizamos um estudo clínico, controlado, não randomizado, comparando o perfil de risco cardiovascular de dieta Mediterrânea (DM) versus dieta TLC (DTLC) em 40 pacientes com doença arterial coronariana, homogeneamente selecionados (45-65 anos de idade, homens, que tiveram ao menos um evento coronariano nos 2 últimos anos) e intensamente medicados. Uma questão paralela foi entender os efeitos de ambas as dietas nos processos de inflamação, disfunção endotelial e do estresse oxidativo, fatores-chave na aterogênese e particularmente importantes na prevenção secundária. Os hábitos culturais e dietéticos foram relevantes para alocação dos pacientes nos grupos de dieta Mediterrânea (n = 21; dieta rica em grãos integrais, vegetais, frutas, oleaginosas 10 g/dia, azeite de oliva extra-virgem 30 g/dia e vinho tinto 250 ml/dia) ou dieta TLC (n = 19; suplementada com fitosteróis 2g/dia através de creme vegetal 20 g/dia). Escores de aderência validados na literatura e específicos às dietas mostraram resultado > 90% no índice de aderência aos dois padrões dietéticos. Alguns efeitos foram comuns à dieta Mediterrânea e à dieta TLC. Com ambas, houve redução significativa de peso, índice de massa corporal (kg/m²), variáveis de composição corporal e pressão arterial. Além disso, ambas as dietas promoveram redução dos níveis plasmáticos de ADMA e da relação L-arginina/ADMA. A reatividade da artéria braquial dependente do endotélio permaneceu inalterada em ambos os grupos; no entanto, pacientes sob DM e sob DTLC melhoraram a velocidade de fluxo no momento basal (pré-hiperemia vascular). Outros efeitos foram específicos a cada padrão dietético. Com a DM, foram observados diminuição na contagem total de leucócitos versus DTLC (p =0.025) e aumento nos níveis de HDL-colesterol em 3 mg/dL (p = 0.053) versus DTLC, que mantiveram níveis de HDL-C inalterados. O diâmetro basal da artéria braquial aumentou com a DM, mas não com a DTLC. Com a DTLC, houve redução estatisticamente significante versus DM nas variáveis lipídicas colesterol total, LDL-colesterol (p < 0.05) e LDL oxidada (p = 0.009), embora a razão LDL oxidada/LDL total não tenha se alterado. Níveis séricos/plasmáticos de apolipoproteína A-1, lipoproteína(a), glicose, mieloperoxidase, sICAM, sVCAM, e as razões glutationa reduzida/oxidada em plasma e eritrócitos não se alteraram em ambos os grupos. Em conjunto, estes dados indicam um perfil de efeitos da DM e DTLC compatíveis com redução do risco cardiovascular, mesmo em pacientes intensamente medicados, em prevenção secundária. Embora estes efeitos tenham sido equivalentes entre DM e DTLC, eles parecem ser mediados tanto por alguns mecanismos comuns, como alguns mecanismos específicos de cada dieta / The Mediterranean Diet (MD) has been widely studied with respect to epidemiology, but mechanisms whereby the Mediterranean Diet (MD) is cardioprotective are unclear. This is partly because of the difficulties of adherence in clinical trials of dietary intervention, particularly trials comparing it to traditional lipid-restraining diets, e.g., Therapeutic Lifestyle Changes Diet (TLCD) from National Cholesterol Education Program ATPIII. We performed a controlled, non-randomized clinical trial comparing the cardiovascular risk profile of the Mediterranean Diet (MD) versus the TLC Diet (TLCD) in 40 selected, highly-homogeneous, and intensively medicated patients with coronary heart disease (45-65 years, males, at least one coronary event over prior 2 years). In addition, we sought to investigate both diets effects on inflammation, endothelial dysfunction and oxidative stress, all key factors in atherogenesis and particularly important in secondary prevention. Dietary/cultural habits were the basis to allocate patients for 3 months to either MD (n = 21; rich in whole grains, vegetables, fruits, nuts 10g/day, extra-virgin olive oil 30g/day, red wine 250ml/day) or TLCD (n = 19; plus phytosterols 2g/day). Specific scores showed that both diets had >90% adherence. Some effects were common to both diets. Patients in both groups showed a significant reduction in weight, body mass index, body composition and blood pressure. Also, both groups presented a reduction in plasma levels of ADMA and L-arginine/ADMA ratio. Endothelial-dependent brachial artery reactivity remained unaltered in both groups. However, patients under MD and TLCD improved flow velocity at baseline (prior to hyperemia). Nevertheless, other effects were specific to each diet. With MD, there was significant decrease in leukocyte count vs. TLCD (p = 0.03) and average increase in HDL-cholesterol by 3 mg/dL (p = 0.053) versus TLCD. The brachial arterials basal diameter increased with MD but not with TLCD. However, with TLCD there was a statistically significant reduction of lipid variables: total cholesterol, LDL-cholesterol (p < 0.05) and oxidized LDL (p = 0.009) vs. MD even though the ratio of oxidized / total LDL remained unaltered. Plasma and serum levels of apolipoprotein A-1, lipoprotein(a), glucose, myeloperoxidase, sICAM, sVCAM, and glutathione reduced/oxidized ratio in plasma and erithrocytes also remained unaltered in both groups. Together, these results demonstrate a pattern of effects of MD and TLCD compatible with cardiovascular risk reduction, in secondary prevention, even in intensely medicated patients. Although these effects were equivalent between MD and TLCD, they seem to be mediated by some common mechanisms, as well as by each diets specific mechanisms

Objetivo: comparar o perfil lipídico de em crianças e adolescentes, com e sem inflamação, atendidas num pronto atendimento geral de pediatria de um hospital universitário de nível de atendimento secundário, segundo estado nutricional, sexo e idade. Métodos: Estudo transversal, realizado entre outubro de 2012 e agosto de 2013, avaliou 124 crianças e adolescentes (3 meses a 14 anos de idade) em atendimento na unidade de emergência do Hospital Universitário da Universidade de São Paulo, com queixa relacionada a processo inflamatório/infeccioso. Os pacientes foram separados em dois grupos de acordo com os níveis de proteína C reativa (PCR): grupo I se maior ou igual a 5 mg/L, e grupo II se menor que 5mg/L. Dosagens de colesterol total, lipoproteína de alta densidade (HDL) e baixa densidade (LDL), triglicerídeos e albumina foram comparadas entre os dois grupos, levando em conta o estado nutricional (avaliado através de medidas antropométricas), gênero e idade. Resultado: A mediana de idade foi de 51 meses, com maioria dos pacientes classificados como eutróficos (76,5%). Do total da amostra, 34,7% dos pacientes apresentaram colesterol total e/ou triglicerídeos alterados e 67% apresentaram baixos níveis de HDL. Não houve diferença significativa do perfil lipídico entre os dois grupos de pacientes separados de acordo com PCR. Dentre os pacientes com PCR >= 5mg/L, a PCR apresentou correlação inversa com HDL [r= (-)0,363 e p=0,001], com LDL [r= (-) 0,235 e p=0,034], com albumina [r= (-) 0,308 e p=0,005] e correlação direta com TG (r=0,426 e p > 0,001). Na analise de regressão linear, se evidenciou que para cada aumento de 1mg/L nos valores da PCR espera-se uma redução média de 0,072 mg/dL da HDL, de 0,083 mg/dL da LDL, de 0,002g/dL de albumina, e um aumento médio de 0,564 mg/dL do triglicerídeo. Conclusão: Pacientes com processo inflamatório apresentam alterações nos níveis séricos do HDL, LDL e triglicerídeos que se relacionam com o grau de inflamação, de forma independente do estado nutricional / Aim: To compare the lipid profile in children and adolescents with and without inflammation, met a ready general pediatric service of a university hospital secondary care level, according to nutritional status, gender and age. Methods: Cross-sectional study conducted between October 2012 and August 2013, assessed 124 children and adolescents (3 months to 14 years old) in the emergency department of the University Hospital of the University of São Paulo, with reports of inflammatory/ infectious process. The patients were divided into two groups according to the C reactive protein (CRP) levels: group I is higher than or equal to 5 mg/L, and Group II was lower than 5 mg/L. Total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL), triglycerides and albumin were compared between the two groups, taking into account the nutritional status (assessed by anthropometric measurements), gender and age. Results: The median age was 51 months, with patients mostly classified as well-nourished (76.5%). Of the overall sample, 34.7% of patients had total cholesterol and/or triglycerides altered and 67% had low levels of HDL. There was no significant difference in lipid profile between the two groups of PCR. For the patients with CPR > 5mg/L, CPR presented an inverse correlation with HDL [r = (-) 0.363 and p = 0.001], with LDL [r = (-) 0.235 and p = 0.034], with [r = albumin (-) 0.308 and p = 0.005] and direct correlation with TG (r = 0.426 and p < 0.001). Linear regression analysis it became clear that for each increase of 1 mg/L in the values of CRP expected an average reduction of 0,072 mg/dL of HDL, the 0,083 mg/dL of LDL, the 0,002 g /dL albumin, and an average increase of 0,564 mg/dL of triglycerides. Conclusion: Patients with an inflammatory process exhibit changes in the serum levels of the lipids HDL, LDL and TG that are related to the degree of inflammation. These changes occurred regardless of nutritional status

Objetivo: comparar o perfil lipídico de em crianças e adolescentes, com e sem inflamação, atendidas num pronto atendimento geral de pediatria de um hospital universitário de nível de atendimento secundário, segundo estado nutricional, sexo e idade. Métodos: Estudo transversal, realizado entre outubro de 2012 e agosto de 2013, avaliou 124 crianças e adolescentes (3 meses a 14 anos de idade) em atendimento na unidade de emergência do Hospital Universitário da Universidade de São Paulo, com queixa relacionada a processo inflamatório/infeccioso. Os pacientes foram separados em dois grupos de acordo com os níveis de proteína C reativa (PCR): grupo I se maior ou igual a 5 mg/L, e grupo II se menor que 5mg/L. Dosagens de colesterol total, lipoproteína de alta densidade (HDL) e baixa densidade (LDL), triglicerídeos e albumina foram comparadas entre os dois grupos, levando em conta o estado nutricional (avaliado através de medidas antropométricas), gênero e idade. Resultado: A mediana de idade foi de 51 meses, com maioria dos pacientes classificados como eutróficos (76,5%). Do total da amostra, 34,7% dos pacientes apresentaram colesterol total e/ou triglicerídeos alterados e 67% apresentaram baixos níveis de HDL. Não houve diferença significativa do perfil lipídico entre os dois grupos de pacientes separados de acordo com PCR. Dentre os pacientes com PCR >= 5mg/L, a PCR apresentou correlação inversa com HDL [r= (-)0,363 e p=0,001], com LDL [r= (-) 0,235 e p=0,034], com albumina [r= (-) 0,308 e p=0,005] e correlação direta com TG (r=0,426 e p > 0,001). Na analise de regressão linear, se evidenciou que para cada aumento de 1mg/L nos valores da PCR espera-se uma redução média de 0,072 mg/dL da HDL, de 0,083 mg/dL da LDL, de 0,002g/dL de albumina, e um aumento médio de 0,564 mg/dL do triglicerídeo. Conclusão: Pacientes com processo inflamatório apresentam alterações nos níveis séricos do HDL, LDL e triglicerídeos que se relacionam com o grau de inflamação, de forma independente do estado nutricional / Aim: To compare the lipid profile in children and adolescents with and without inflammation, met a ready general pediatric service of a university hospital secondary care level, according to nutritional status, gender and age. Methods: Cross-sectional study conducted between October 2012 and August 2013, assessed 124 children and adolescents (3 months to 14 years old) in the emergency department of the University Hospital of the University of São Paulo, with reports of inflammatory/ infectious process. The patients were divided into two groups according to the C reactive protein (CRP) levels: group I is higher than or equal to 5 mg/L, and Group II was lower than 5 mg/L. Total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL), triglycerides and albumin were compared between the two groups, taking into account the nutritional status (assessed by anthropometric measurements), gender and age. Results: The median age was 51 months, with patients mostly classified as well-nourished (76.5%). Of the overall sample, 34.7% of patients had total cholesterol and/or triglycerides altered and 67% had low levels of HDL. There was no significant difference in lipid profile between the two groups of PCR. For the patients with CPR > 5mg/L, CPR presented an inverse correlation with HDL [r = (-) 0.363 and p = 0.001], with LDL [r = (-) 0.235 and p = 0.034], with [r = albumin (-) 0.308 and p = 0.005] and direct correlation with TG (r = 0.426 and p < 0.001). Linear regression analysis it became clear that for each increase of 1 mg/L in the values of CRP expected an average reduction of 0,072 mg/dL of HDL, the 0,083 mg/dL of LDL, the 0,002 g /dL albumin, and an average increase of 0,564 mg/dL of triglycerides. Conclusion: Patients with an inflammatory process exhibit changes in the serum levels of the lipids HDL, LDL and TG that are related to the degree of inflammation. These changes occurred regardless of nutritional status