Metabolically healthy obese individuals present similar chronic inflammation level but less insulin-resistance than obese individuals with metabolic syndrome.

The Metabolic Syndrome (MetS) is a cluster of cardiometabolic risk factors, usually accompanied by the presence of insulin resistance (IR) and a systemic subclinical inflammation state. Metabolically healthy obese (MHO) individuals seem to be protected against cardiometabolic complications. The aim of this work was to characterize phenotypically the low-grade inflammation and the IR in MHO individuals in comparison to obese individuals with MetS and control non obese. We studied two different populations: 940 individuals from the general population of Buenos Aires and 518 individuals from the general population of Venado Tuerto; grouped in three groups: metabolically healthy non-obese individuals (MHNO), MHO and obese individuals with MetS (MSO). Inflammation was measured by the levels of hs-CRP (high-sensitivity C reactive protein), and we found that MHO presented an increase in inflammation when compared with MHNO (Buenos Aires: p<0.001; Venado Tuerto: p<0.001), but they did not differ from MSO. To evaluate IR we analyzed the HOMA (Homoeostatic Model Assessment) values, and we found differences between MHO and MSO (Buenos Aires: p<0.001; Venado Tuerto: p<0.001), but not between MHNO and MHO. In conclusion, MHO group would be defined as a subgroup of obese individuals with an intermediate phenotype between MHNO and MSO individuals considering HOMA, hs-CRP and central obesity.

Metabolically healthy obese women have longer telomere length than obese women with metabolic syndrome.

INTRODUCTION: Obesity is the principal component in the Metabolic Syndrome (MetS) that determines the progression of metabolic complications. Metabolically healthy obese (MHO) individuals seem to be protected against those complications. Telomere length (TL) as a novel marker of cellular aging had a complex relationship to the MetS. The principal aim of this study was to investigate the TL in MHO, and to study the association between TL and the worsening of the metabolic condition. MATERIAL AND METHODS: We have determined the absolute TL (aTL) in 400 women (mean age of 46.76 ± 15.47 years; range: 18-86 years), grouped according to the metabolic condition in three groups: metabolically healthy non-obese women (MHNO), MHO and obese women with MetS (MSO); and grouped according to the number of components of MetS. RESULTS: We found that MHO displays significantly higher aTL than MSO (p = 0.033; r = -4.63; 95% CI r = -8.89 / -0.37), but did not differ from MHNO. A decrease in aTL with the progressive increase in the number of MetS components was also observed (p < 0.001; r = -2.06; 95% CI r = -3.13 / -0.99). In this way, our results indicate that aTL is influenced by the presence of MetS, but it is not affected by the presence of obesity. DISCUSSION: We found that shorter aTL is not associated with MHO, but is related to MetS and with the increased number of metabolic abnormalities.

Análisis de la longitud de los telómeros en obesos metabólicamente sanos / Analysis of telomere length in the metabolically healthy obese

La obesidad es el principal componente del síndrome metabólico (SM) y determina la progresión de la enfermedad a las complicaciones metabólicas. Los individuos obesos metabólicamente sanos (OMS) parecen estar protegidos contra esas complicaciones. La longitud de los telómeros (LT) es un nuevo marcador del envejecimiento celular, que tiene una relación compleja con el SM. El objetivo principal de este estudio fue investigar por primera vez la LT en OMS y estudiar la asociación entre LT y el número de componentes del SM. Se estudió a 398 mujeres con una edad media de 46,76 ± 15,47 años (rango: 18-86 años), que se agruparon en: individuos con normopeso sin ningún componente del SM (NP0), obesos sin SM (OMS) y de acuerdo con el número de componentes de SM en los grupos sin ningún componentes de SM (0), con uno o 2 componentes (1 + 2) y con SM por la presencia de 3 o más componentes (SM). La LT de los OMS no se diferenció de la de los NP0, pero fue significativamente mayor que la de los individuos con SM (p = 0,032). Se observó una disminución de la LT con el aumento progresivo del número de componentes del SM (p = 0,004), en donde el grupo 0 presentó una LT significativamente mayor que los grupos 1 + 2 (p = 0,027) y SM (p = 0,003). Demostramos por primera vez que las mujeres OMS presentan una LT similar a las mujeres NP0 y más larga que aquellas mujeres con SM. Además, confirmamos que la LT se acorta con el aumento en el número de alteraciones del SM.

Obesity is the principal component in Metabolic Syndrome (MetS) and determines the progression of metabolic complications. Metabolically healthy obese individuals (MHO) seem to be protected against those complications. Telomere length (TL), as a novel marker of cellular aging, has a complex relationship with MetS. The principal aim of this study was to investigate TL in MHO, and to study the association between TL and the number of MetS components. A study was conducted on 398 women (mean age: 46.76 ± 15.47 years; range: 18 - 86 years), grouped according to the number of MetS components (0, 1 + 2, MetS), a group of normal-weight individuals with 0 MetS components (NW0), and a group of obese without MetS (MHO). No differences were found in the TL of the MHO group compared to the NW0, but it was significantly higher than that of individuals with MetS (P = .032). A decrease in TL was observed with a progressive increase in the number of MetS components (P = .004), whereas the group of individuals without MetS components had significantly longer TL than the groups with 1 and 2 components (P = .027), and MetS (P = .003). Shorter TL is not associated with MHO, but is related to MetS and with an increased number of metabolic abnormalities.

Functional characterization of TLR4 +3725 G/C polymorphism and association with protection against overweight.

Subclinical low-grade systemic inflammation has been associated with obesity, insulin resistance and metabolic syndrome (MS). Recent studies have highlighted the role of gut microbiota in these disorders. The toll-like receptor 4 (TLR4) plays a key role in the innate immune response activation. We studied two polymorphisms (+3725G/C and 11350G/C) in the 3' untranslated region (3'UTR) of the TLR4 gene that may alter its expression and their association with metabolic disorders related to systemic inflammation. We cloned the 3'UTR into a luciferase reporter system and compared wild-type 3'UTR (WT) and +3725C variant (MUT) constructs luciferase activities. MUT construct reduced the reporter gene activity by 30% compared to WT (P = 0.0001). To evaluate the association between these polymorphisms with biochemical and clinical overweight related variables, we conducted a population cross-sectional study in 966 men of Argentine general population. Considering smoking as a confounding variable that causes systemic inflammation, we studied these possible effects in both, smokers and nonsmokers. The 11350G/C polymorphism was not detected in our sample whereas the CC genotype of +3725 polymorphism was associated with lean subjects (p = 0.011) and higher Adiponectin levels (p = 0.021). Subjects without any NCEP/ATP III MS component were associated with this genotype as well (p = 0.001). These results were strengthened in nonsmokers, in which CC genotype was associated with lean subjects (p = 0.003) and compared with G carriers showed significantly lower BMI (25.53 vs. 28.60 kg/m2; p = 0.023) and waist circumference (89.27 vs. 97.51 cm; p = 0.025). None of these associations were found in smokers. These results showed that +3725C variant has a functional effect down-regulating gene expression and it could be considered as a predictive factor against overweight, particularly in nonsmokers. Considering the role of TLR4 in inflammation, these findings would suggest that the presence of +3725C variant could predict a lower prevalence of chronic metabolic disorders.

Endothelial dysfunction in normal and abnormal glucose metabolism.

The endothelium is the common target of all cardiovascular risk factors, and functional impairment of the vascular endothelium in response to injury occurs long before the development of visible atherosclerosis. The endothelial cell behaves as a receptor-effector structure which senses different physical or chemical stimuli that occur inside the vessel and, therefore, modifies the vessel shape or releases the necessary products to counteract the effect of the stimulus and maintain homeostasis. The endothelium is capable of producing a large variety of different molecules which act as agonists and antagonists, therefore balancing their effects in opposite directions. When endothelial cells lose their ability to maintain this delicate balance, the conditions are given for the endothelium to be invaded by lipids and leukocytes (monocytes and T lymphocytes). The inflammatory response is incited and fatty streaks appear, the first step in the formation of the atheromatous plaque. If the situation persists, fatty streaks progress and the resultant plaques are exposed to rupture and set the conditions for thrombogenesis and vascular occlusion. Oxidant products are produced as a consequence of normal aerobic metabolism. These molecules are highly reactive with other biological molecules and are referred as reactive oxygen species (ROS). Under normal physiological conditions, ROS production is balanced by an efficient system of antioxidants, molecules that are capable of neutralizing them and thereby preventing oxidant damage. In pathological states, ROS may be present in relative excess. This shift of balance in favor of oxidation, termed 'oxidative stress', may have detrimental effects on cellular and tissue function, and cardiovascular risk factors generate oxidative stress. Both type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients have mostly been described under enhanced oxidative stress, and both conditions are known to be powerful and independent risk factors for coronary heart disease, stroke, and peripheral arterial disease. Hyperglycemia causes glycosylation of proteins and phospholipids, thus increasing intracellular oxidative stress. Nonenzymatic reactive products, glucose-derived Schiff base, and Amadori products form chemically reversible early glycosylation products which subsequently rearrange to form more stable products, some of them long-lived proteins (collagen) which continue undergoing complex series of chemical rearrangements to form advanced glycosylation end products (AGEs). Once formed, AGEs are stable and virtually irreversible. AGEs generate ROS with consequent increased vessel oxidative damage and atherogenesis. The impressive correlation between coronary artery disease and alterations in glucose metabolism has raised the hypothesis that atherosclerosis and diabetes may share common antecedents. Large-vessel atherosclerosis can precede the development of diabetes, suggesting that rather than atherosclerosis being a complication of diabetes, both conditions may share genetic and environmental antecedents, a 'common soil'.

Endothelial dysfunction: a comprehensive appraisal.

The endothelium is a thin monocellular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the vasodilatation produced by drugs that are NO donors, such as nitroglycerine, called "endothelium independent". The vasodilatation is quantified by measuring the arterial diameter with high resolution ultrasonography. Laser-Doppler techniques are now starting to be used that also consider tissue perfusion. There is so much proof about endothelial dysfunction that it is reasonable to believe that there is diagnostic and prognostic value in its evaluation for the late outcome. There is no doubt that endothelial dysfunction contributes to the initiation and progression of atherosclerotic disease and could be considered an independent vascular risk factor. Although prolonged randomized clinical trials are needed for unequivocal evidence, the data already obtained allows the methods of evaluation of endothelial dysfunction to be considered useful in clinical practice and have overcome the experimental step, being non-invasive increases its value making it use full for follow-up of the progression of the disease and the effects of different treatments.

Evaluación de la función endotelial por eco-Doppler. Influencia de la edad, sexo y factores de riesgo / Endothelial function assessment by ultrasonography. Effect of age, sex and cardiovascular risk factors

La vasodilatación y el aumento de flujo posisquemia de la arteria humeral, evaluados por eco-Doppler, son provocados por la liberación de sustancias vasodilatadoras del endotelio arterial, principalmente óxido nítrico, y expresan su estado funcional. La arteria humeral es considerada "subrogante" de las arterias coronarias y su respuesta es similar a la del resto de la circulación, permitiendo conocer el estado funcional del endotelio de la circulación coronaria y general. En el presente estudio se observó una marcada disminución de la vasodilatación posisquémica en sujetos asintomáticos, sin evidencia clínica de enfermedad cardiovascular y portadores de factores de riesgo, especialmente en los fumadores, hipercolesterolémicos e hipertensos. Por otra parte, se comprobó un deterioro de la función endotelial inversamente proporcional a la edad de los sujetos, independiente del sexo o los factores de riesgo. La prueba de vasodilatación posisquémica es incruenta, reproducible, al alcance de cualquier centro médico, y permite estratificar riesgos y evaluar terapéuticas en todas las edades

Estudo epidemiológico da contracepçäo em Santa Maria / Epidemiologic study of contraception in Santa Maria

Este estudo teve como objetivo avaliar o conhecimento e o uso de métodos contraceptivos pelas mulheres, entre 15 e 44 anos, da zona urbana de Santa Maria, RS. Estudo transversal e analítico da prevalência da contracepçäo em uma amostra de 355 mulheres, com amostragem de 22 setores censitários da cidade. A média de idade foi de 28,7 anos (dp 8,7). Das mulheres entreveistadas, 47 por cento (n=168) tinham um companheiro sexual definido e destas, 88,6 por cento usavem algum método contraceptivo. Entre as mulheres que näo tinham um companheiro sexual definido (n=187), 48,6 por cento usavam algum método contraceptivo. Afirmaram ir regularmente ao ginecologista, 72,2 por cento e usavam algum método, 68 por cento. Os mais usados foram: pílula 60 por cento, laqueadura 21,7 por cento, camisinha 7,9 por cento DIU 5,4 por cento e tabelinha 2,9 por cento. Das mulheres que engravidaram (n=213), 33 por cento referiram estar usando algum método contraceptivo. Com relaçäo à pílula e fatores de risco a seu uso, observou-se que 25 por cento de usuárias eram fumantes, 10,4 por cento eram hipertensas e 21,5 por cento tinham problemas circulatórios. Observa-se, pelos resultados, que cinco métodos säo conhecidos por 3/4 das mulheres de Santa Maria. Contraceptivo oral e laqueadura tubária säo os métodos mais usados. Mulheres com companheiro sexual definido utilizam 1,6 vezes mais métodos ...

Perfil da automedicaçäo em município do Sul do Brasil / Self-medication profile in a city in South Brazil

Caracteriza o usuário de medicamentos, especialmente aquele que se automedica. Foram entrevistadas 413 pessoas do Município de Santa Maria, Estado do Rio Grande do Sul, Brasil, sobre o consumo de medicamentos no último mês. Dos entrevistados, 69,9 por cento utilizaram medicamentos e destes 76,1 por cento o fizeram através de automedicaçäo. Cefaléia (28,8 por cento) foi a principal queixa motivadora de automedicaçäo. O ácido acetilsalicílico foi a droga mais utilizada (25,4 por cento). Dos fármacos utilizados na automedicaçäo, 51,2 por cento foram indicados por terceiros e 51,7 por cento dessas indicaçöes eram prescriçöes médicas emitidas em consultas anteriores. Idade, grau de escolaridade e acompanhamento médico periódico correlacionaram-se significativamente com automedicaçäo

Miocardio atontado, hibernado, viabilidad miocárdica y reserva contráctil: su significado para el clínico / Stunned myocardium, hibernating, myocardial viability and reserve contractile. Its significance for clinical

En la cardiopatía isquémica la valoración de la función ventricular de reposo es un índice de alto valor predictivo. Numerosos estudios demostraron el rol de la cirugía de by pass coronario en pacientes con fracción de eyección <0.35. Tambien es sabido que estos pacientes con mal ventrículo tienen mayor mortalidad quirúrgica. Se han desarrollado métodos sensitivos para valorar la "viabilidad miocárdica" y poder seleccionar cuáles individuos tendrán mejor sobrevida al ser sometidos a técnicas de revascularización. Para esto se describe un algoritmo diagnóstico y terapéutico. Sin embargo, es preciso profundizar acerca de la biologia del miocardio atontado (M.A) y del miocardio hibernado (M.H), para obtener una buena relación costo-beneficio en la utilización de dichos procedimientos.