Dyslipidemia is Associated with Unfit and Overweight-Obese Children and Adolescents

Abstract Background: Both poor aerobic fitness and obesity, separately, are associated with abnormal lipid profiles. Objective: To identify possible relationships of dyslipidemia with cardiorespiratory fitness and obesity, evaluated together, in children and adolescents. Methods: This cross-sectional study included 1,243 children and adolescents (563 males and 680 females) between 7 and 17 years of age from 19 schools. Obesity was assessed using body mass index (BMI) measurements, and cardiorespiratory fitness was determined via a 9-minute run/walk test. To analyze the lipid profile of each subject, the following markers were used: total cholesterol, cholesterol fractions (high-density lipoprotein and low-density lipoprotein) and triglycerides. Data were analyzed using SPSS v. 20.0, via prevalence ratio (PR), using the Poisson regression. Results: Dyslipidemia is more prevalent among unfit/overweight-obese children and adolescents compared with fit/underweight-normal weight boys (PR: 1.25; p = 0.007) and girls (PR: 1.30, p = 0.001). Conclusions: The prevalence of dyslipidemia is directly related to both obesity and lower levels of cardiorespiratory fitness.

Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe

Abstract Background: The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective: To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods: Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results: The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion: The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms.

Early Markers of Atherosclerotic Disease in Individuals with Excess Weight and Dyslipidemia

Abstract Background: Excessive weight is a cardiovascular risk factor since it generates a chronic inflammatory process that aggravates the endothelial function. Objective: To evaluate the endothelial function in individuals with excess weight and mild dyslipidemia using brachial artery flow-mediated dilation (BAFMD), and the association of endothelial function with anthropometric and biochemical variables. Methods: Cross-sectional study that included 74 individuals and evaluated anthropometric variables (body mass index [BMI], waist-hip ratio [WHR], waist circumference [AC], and percentage of body fat [PBF]), biochemical (blood glucose, insulinemia, ultrasensitive C-reactive protein, fibrinogen, total cholesterol, HDL-cholesterol, triglycerides, and LDL-cholesterol) and endothelial function (BAFMD, evaluated by ultrasound). The statistical analysis was performed with SPSS, version 16.0. To study the association between the variables, we used chi-square, Student's t and Mann-Whitney tests, and Pearson's correlation. Logistic regression analyzed the independent influence of the factors. Values of p < 0.05 were considered significant. Results: The participants had a mean age of 50.8 years, and 57% were female. BMI, WC, WHR, and PBF showed no significant association with BAFMD. The male gender (p = 0.02) and higher serum levels of fibrinogen (p = 0.02) were significantly and independently associated with a BAFMD below 8%. Conclusions: In individuals with excess weight and mild untreated dyslipidemia, male gender and higher levels of fibrinogen were independently associated with worse BAFMD.

Caracterização preliminar de Amaranthus hybridus L. e Amaranthus viridis L. através de isoenzimas

Através da técnica de eletroforese de gel de amido com migração horizontal, pode-se observar que para esterase, apenas o Amaranthus hybridus tipo verde apresentou variação, na forma de presença ou ausência da banda na posição 0.7. Por outro lado, para peroxidase, para todas as espécies e biótipos (A.viridis e A.hybridus tipo verde e tipo roxo) houve variação no padrão de bandas. Através da existência de bandas comuns às duas espécies, pode-se detectar evidências de hibridação e introgressãc entre elas.

Lipoides do plasma normal

1. In a series of 21 normal cases we found for fatty acids per 100 cc. of plasma an average of 332 mgm., being 314 mgm. for the male sex and 350 mgm. for the female sex. 2.- For lecithin, in four normal cases we found per 100 cc. of plasma 182 mgm. estimated by the contents is phosphorus which ranged from 6.12 to 9.0 mgrs. 3.- Cholesterol in 20 normal cases showed 172 mgm. per 100 cc. of plasma. The averages were 151 mgm. for men and 194 mgm. for women. 4.- The readings of the fractions were 2.01 for the ratio fatty acids divided by lecithins 0.90 for lecithin divided by cholesterol and 1.93 for fatty acids divided by cholesterol. 5.- On comparing the results obtained by us with those reported in foreign literature an absolute conformity is noted chiefly with the values supplied by Bloor and Horiuchi for the ratios among the various lipoid fractions. The average for Cholesterol is comparable with that obtained by Myers but is slightly under that of Bloor's. The lecithin contents found by us did not reach such high values as those supplied by foreign authors.

Estudos sobre o xanthoma: biochimica e pathogenia

1. No presente trabalho são descriptos dois casos de xanthelasmatose (xanthoma) com perturbações accentuadas do metabolismo dos lipides e esteroes. 2. Um dos casos apresentou notavel cholesteroluria não mostrando o doente lesões renaes, ao passo que o outro caso sendo portador de pyelonephrite não eliminava cholesterol. 3. Foram feitas dosagens de cholesterol, acidos graxos totaes e lecithina, no sangue, urina e tumores, obtendo-se valores muito elevados. As demais provas (histo-chimicas, polarização microscopica) confirmaram a presença de abundante infiltração de lipides e cholesterol nos tecidos. 4. A prova de carga de Bürger feita no caso I demonstrou diminuição da tolerancia para o cholesterol. 5. A therapeutica insulinica fez baixar o cholesterol e a glycose do sangue sem, comtudo, offerecer melhora clinica do paciente. No caso II houve baixa da cholesterolemia e da glycemia com desapparecimento dos tumores, evidenciando a diversidade das formas clinicas destes casos. 6. A intradermo-reacção feita com o cholesterol no caso I produziu reacção positiva, suggerindo um estado de hypensensibilidade para as substancias de infiltração no xanthelasma (xanthoma). 7. Os aspectos clinico-morphologicos dos casos estudados indicam tambem a ocorrencia de processos de sensibilisação cutanea. 8. As lipidoses são encaradas neste trabalho como toxicodermias hematogenicas, sendo proposto para seu estudo os mesmos methodos de exploração cutanea.

Intoxicação por veneno de cobra: necrose symetrica da cortex renal: uremia

Em um caso fatal de ophidismo, em individuo de 15 annos de edade, picado por uma cobra jararaca (Bothrops jararaca) na face externa da perna direita e que veio a fallecer 26 dias apoz o accidente, os A.A, descrevem as lesões anatomo-pathologicas encontradas e as modificações do metabolismo, evidenciadas pelos exames chimicos do sangue. As principaes alterações existentes, acham-se localisadas nos rins os quaes apresentam lesões de glomerulonephrite diffusa e o aspecto typico da necrose cortical symmetrica. Como alterações de maior significação observam-se ainda lesões vasculares de grande intensidade e constituidas essencialmente por processo de endoarterite productiva. A necrose symmetrica da cortex renal, a vista das intensas alterações vasculares (endoarterite productiva) que acarretaram a obliteração das arterías, é considerada como a consequencia immediata de taes lesões vasculares. Os vasos renaes, séde do processo inflammatorio, são as arterias interlobar, arciforme e interlobular, mas principalmente as arteriolares da camada cortical. O processo de endoarterite assume sempre o carater progressivo, de modo que a luz vascular vae sendo aos poucos, totalmente obstruida. Ao contrario do que se tem observado nos casos de necrose cortical symmetrica, citados na literatura, em que as alterações parenchymatosas são consequentes a thrombose dos vasos reanes, no caso presente esse aspecto não foi verificado mas tão sómente a existencia da endoarterite productiva obliterante. Consideram os A.A. as lesões renaes no caso que estudaram, como a resultante da actuação lenta e prolongada do veneno de cobra sobre as estructuras renaes, baseados nos seguintes factos já conhecidos e admittidos: eliminação do veneno de cobra pelos rins; capacidade do mesmo veneno, determinar a glomerulo-nephrite diffusa e acção do veneno de cobra sobre o endothelio vascular, facilitada essencialmente pela funcção especifica do orgão. As modificações do metabolismo se traduziram por alterações urinarias e sanguineas. As urinas foram emitidas em muito pequena quantidade (50 cc. em 24 horas) não havendo comtudo, anuria absoluta. Cylindros hyalinos e granulosos, bem como leucocytos e cellulas renaes, associadas á albuminoria, era presentes. Os exames chimicos do sangue, revelaram: Proteinas totaes 7,61 grs. em 1000 cc.; Albumina 2,39 grs em 1000 cc.; Globulina 5,22 grs. em 1000 cc.; Uréa 6,42 grs. em 1000 cc.; Fibrinogeneo 0,324 grs. em 1000 cc.; Indican +++; Cl. plasmatico 339 mgrs. em 100 cc.; Cl. globular 170 mgrs. em 100 cc.; Cholesterol 163 mgrs. em 100 cc.; Creatinia 260 mgrs. em 100 cc.; Ph. inorganico 13,4 mgrs. em 100 cc.; Calcio 10,3 mgrs em 100 cc.; Potassio 28 mgrs. em 100 cc.; Sodio 328 mgrs. em 100 cc.. O exame hematologico revelou 11% de hemoglobina; 960.000 hematias por mm.³; e 5.200 leucocytos por mm.³. A formula leucocytaria revelou augmento dos neutrophilos, com 74% dos segmentados. A proporção entre sôro o coagulo foi 9 x 3 cc. A reacção de Wassermann no sôro sanguineo foi negativa. A insufficiencia renal se traduziu no caso em estudo, por modificações humoraes, particularmente pela azotemia elevada, pelo augmento da creatinina, do phosphoro inorganico e do indican. Em contraste com a existencia de taes modificações, o doente não apresentou os signaes clinicos observados nos casos emque a azotemia se mantem elevada, reproduzindo tal facto, o quadro clinico descripto para a necrose symmetrica da cortex renal.

Aliesterase no sôro de alguns animais de laboratório

A esterase, aliesterase, foi determinada no sôro de 38 ratos de ambos os sexos, 6 hamsters, 34 cobaias e S coelhos, pela técnica de Huggins e Lapides. Os resultados obtidos para os machos e fêmeas foram tabelados em separado. As fêmeas apresentaram uma esterasemia maior que os machos, com uma média global de 11.6 U/ml ± 4.01 e um erro padrão de 0.83 enquanto que para os machos a média foi de 6.9 U ml ± 0.99 com um erro padrão de 0.26. A significância calculada pclo t foi de 4.4 Isto demonstra a interferência da aliesterase na produção ou no metabolismo dos estrogênios. Os valores médios encontrados para as cobaias foram 4.50 U/ ml ± 0.15, com um êrro padrão de 0.036 para as fêmeas e 4.28 U / ml ± 0.30 com um êrro padrão de 0.073 para os machos, sendo a significância (t) de 2.6. Para os coelhos (machos) a média foi de 4.41 U / ml ± 0.16, com um erro padrão de 0.058 enquanto para os hamsters os valores foram de 4.01 U/l ± 0.085, êrro padrão de 0.049 para os machos e 3.81 U/ml ± 0.227, êrro padrão de 0.133 para as fêmeas. Os animais castrados mostram uma diminuição progressiva da esterase no sôro, enquanto que nos castrados e tratados com estrogênios, êstes valores atingem o teôr normal. Os resultados obtidos nestes casos serão objeto de publicação ulterior.

Métodos histoquímicos para a identificação de leucócitos e macrófagos

Os autores descrevem a padronização de técnicas histoquímicas, fosfatase ácida, alfa-naftil-acetato esterase e peroxidase para identificação de linfócitos e macrófagos em tecido. Recomenda-se a fixação em formol sacarose tamponado e inclusão em goma de Holt como a mais eficaz ja que não só conserva a atividade enzimática, como também e de realização acessivel.

Caracterização morfológica e funcional de células aderentes de baço de camundongo

A separação, caracterização e ensaio funcional das células inflamatórias presentes no local de lesão têm se tornado imperiosos no estudo de diversas doenças. Através da utilização de métodos histoquímicos para esterase e fosfatase ácida, bem como do Teste de Fagocitose e da coloração pelo Giemsa, realizados nas células esplénicas de dez camundongos, foi possível se caracterizar bem os componentes do Sistema Fagocítico Mononuclear e distinguir os outros tipos de células presentes, além de permitir a quantificação diferencial das mesmas.

Risk prediction of prevalent diabetes in a Swiss population using a weighted genetic score--the CoLaus Study.

AIMS/HYPOTHESIS: Several susceptibility genes for type 2 diabetes have been discovered recently. Individually, these genes increase the disease risk only minimally. The goals of the present study were to determine, at the population level, the risk of diabetes in individuals who carry risk alleles within several susceptibility genes for the disease and the added value of this genetic information over the clinical predictors. METHODS: We constructed an additive genetic score using the most replicated single-nucleotide polymorphisms (SNPs) within 15 type 2 diabetes-susceptibility genes, weighting each SNP with its reported effect. We tested this score in the extensively phenotyped population-based cross-sectional CoLaus Study in Lausanne, Switzerland (n = 5,360), involving 356 diabetic individuals. RESULTS: The clinical predictors of prevalent diabetes were age, BMI, family history of diabetes, WHR, and triacylglycerol/HDL-cholesterol ratio. After adjustment for these variables, the risk of diabetes was 2.7 (95% CI 1.8-4.0, p = 0.000006) for individuals with a genetic score within the top quintile, compared with the bottom quintile. Adding the genetic score to the clinical covariates improved the area under the receiver operating characteristic curve slightly (from 0.86 to 0.87), yet significantly (p = 0.002). BMI was similar in these two extreme quintiles. CONCLUSIONS/INTERPRETATION: In this population, a simple weighted 15 SNP-based genetic score provides additional information over clinical predictors of prevalent diabetes. At this stage, however, the clinical benefit of this genetic information is limited.

Comparing impact and cost-effectiveness of primary prevention strategies for lipid-lowering.

BACKGROUND: Lipid-lowering therapy is costly but effective at reducing coronary heart disease (CHD) risk. OBJECTIVE: To assess the cost-effectiveness and public health impact of Adult Treatment Panel III (ATP III) guidelines and compare with a range of risk- and age-based alternative strategies. DESIGN: The CHD Policy Model, a Markov-type cost-effectiveness model. DATA SOURCES: National surveys (1999 to 2004), vital statistics (2000), the Framingham Heart Study (1948 to 2000), other published data, and a direct survey of statin costs (2008). TARGET POPULATION: U.S. population age 35 to 85 years. Time Horizon: 2010 to 2040. PERSPECTIVE: Health care system. INTERVENTION: Lowering of low-density lipoprotein cholesterol with HMG-CoA reductase inhibitors (statins). OUTCOME MEASURE: Incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: Full adherence to ATP III primary prevention guidelines would require starting (9.7 million) or intensifying (1.4 million) statin therapy for 11.1 million adults and would prevent 20,000 myocardial infarctions and 10,000 CHD deaths per year at an annual net cost of $3.6 billion ($42,000/QALY) if low-intensity statins cost $2.11 per pill. The ATP III guidelines would be preferred over alternative strategies if society is willing to pay $50,000/QALY and statins cost $1.54 to $2.21 per pill. At higher statin costs, ATP III is not cost-effective; at lower costs, more liberal statin-prescribing strategies would be preferred; and at costs less than $0.10 per pill, treating all persons with low-density lipoprotein cholesterol levels greater than 3.4 mmol/L (>130 mg/dL) would yield net cost savings. RESULTS OF SENSITIVITY ANALYSIS: Results are sensitive to the assumptions that LDL cholesterol becomes less important as a risk factor with increasing age and that little disutility results from taking a pill every day. LIMITATION: Randomized trial evidence for statin effectiveness is not available for all subgroups. CONCLUSION: The ATP III guidelines are relatively cost-effective and would have a large public health impact if implemented fully in the United States. Alternate strategies may be preferred, however, depending on the cost of statins and how much society is willing to pay for better health outcomes. FUNDING: Flight Attendants' Medical Research Institute and the Swanson Family Fund. The Framingham Heart Study and Framingham Offspring Study are conducted and supported by the National Heart, Lung, and Blood Institute.

Role of intracellular signaling pathways activated in fibroblasts in response to lipoproteins

Summary The best described physiological function of low-density lipoproteins (LDL) is to transport cholesterol to target tissues. LDL deliver their cholesterol cargo to cells following their interaction with the LDL receptor. LDL, when their vascular concentrations increase, have also been implicated in pathologies such as atherosclerosis. Among the cell types that are found in blood vessels, endothelial and smooth muscle cells have dominated cellular research on atherosclerotic mechanisms and LDL activation of signaling pathways, while very little is known about adventitial fibroblast activation caused by elevated lipoprotein levels. Since fibroblasts participate in wound repair and since it has recently been recognized that fibroblasts may play pivotal roles in vascular remodeling and repair of injury, we assessed whether lipoproteins affect fibroblast function. We have found that LDL specifically mediate the activation of a class of mitogen-activated protein kinases (MAPKs): the p38 MAPKs. The activation of this pathway in turn modulates cell shape by promoting lamellipodia formation and extensive cell spreading. This is of particular interest because it provides a mechanism by which LDL can promote wound healing or vessel wall remodeling as observed during the development of atherosclerosis. In order to understand the molecular mechanisms by which LDL induce p38 activation we searched for the component in the LDL particle responsible for the induction of this pathway. We found that cholesterol is the major component of lipoprotein particles that mediates their ability to stimulate the p38 MAPK pathway. Furthermore, we investigated the cellular mechanisms underlying the ability of LDL to induce cell shape changes and whether this could participate in wound repair. Our recent data demonstrates that the capacity of LDL to induce fibroblast spreading relies on their ability to stimulate IL-8 secretion, which in turn leads to accelerated wound healing. LDL-induced IL-8 production and subsequent wound closure are impaired upon inhibition of the p38 MAPK pathway indicating that the LDL-induced spreading and accelerated wound sealing rely on the ability of LDL to stimulate IL-8 secretion in a p38 MAPK-dependent manner. Therefore, regulation of fibroblast shape and migration by lipoproteins may be relevant to atherosclerosis that is characterized by increased LDL-cholesterol levels, IL-8 production and extensive remodeling of the vessel wall. Résumé: La fonction physiologique des lipoprotéines à faible densité (LDL) la mieux décrite est celle du transport du cholestérol aux tissus cibles. Les LDL livrent leur cargaison de cholestérol aux cellules après leur interaction avec le récepteur au LDL. Une concentration vasculaire des LDL augmenté est également impliquée dans le développement de l'athérosclérose. Parmi les types de cellule présents dans les vaisseaux sanguins, les cellules endothéliales et les cellules du muscle lisse ont dominé la recherche cellulaire sur les mécanismes athérosclérotiques et sur l'activation par les LDL des voies de signalisation intracellulaire. A l'inverse peu de choses sont connues sur l'activation des fibroblastes de l'adventice par les lipoprotéines. Puisqu'il a été récemment reconnu que les fibroblastes peuvent jouer un rôle central dans la remodélisation vasculaire et la réparation tissulaire, nous avons étudié si les lipoprotéines affectent la fonction des fibroblastes. Nous avons constaté que les LDL activent spécifiquement une classe de protéines kinases: les p38 MAPK (mitogen-activated protein kinases). L'activation de cette voie module à son tour la forme de la cellule en favorisant la formation de lamellipodes et l'agrandissement des cellules. Cela a un intérêt particulier car il fournit un mécanisme par lequel les LDL peuvent promouvoir la cicatrisation ou la remodélisation des parois vasculaires comme observés lors du développement de l'athérosclérose. Pour comprendre les mécanismes moléculaires par lesquels les LDL provoquent l'activation des p38 MAPK, nous avons cherché à identifier les composants dans la particule de LDL responsables de l'induction de cette voie. Nous avons constaté que le cholestérol est l'élément principal des particules de lipoprotéine qui contrôle leur capacité à stimuler la voie des p38 MAPK. En outre, nous avons examiné les mécanismes cellulaires responsables de la capacité des LDL à induire des changements dans la forme des cellules. Nos données récentes démontrent que la capacité des LDL à induire l'agrandissement des cellules, ainsi que leur aptitude à favoriser la cicatrisation, reposant sur leur capacité à stimuler la sécrétiond'IL-8. La production d'IL-8 induite par les LDL est bloquée par l'inhibition de la voie p38 MAPK, ce qui indique que l'étalement des cellules induit par les LDL ainsi que l'accélération de la cicatrisation sont liés à la capacité des LDL à stimuler la sécrétion d'IL8 via l'activation des p38 MAPK. La régulation de la forme et de la migration des fibroblastes par les lipoprotéines peuvent donc participer au développement de l'athérosclérose qui est caractérisée par l'augmentation des niveaux de production de LDL-cholestérol et d'IL-8 ainsi que par une remodélisation augmentée de la paroi du vaisseau.