Adiposity indices in the prediction of insulin resistance in prepubertal Colombian children

248-255OBJECTIVE: To compare BMI with abdominal skinfold thickness (ASF), waist circumference and waist-to-height ratio in the prediction of insulin resistance (IR) in prepubertal Colombian children. DESIGN: We calculated age- and sex-specific Z-scores for BMI, ASF, waist circumference, waist-to-height ratio and three other skinfold-thickness sites. Logistic regression with stepwise selection (P = 0·80 for entry and P = 0·05 for retention) was performed to identify predictors of IR and extreme IR, which were determined by age- and sex-specific Z-scores to identify the ≥ 90th and ≥ 95th percentile of homeostasis model assessment (HOMAIR), respectively. We used receiver operating characteristic curves to compare the area under the curve between models. SETTING: Bucaramanga, Colombia. SUBJECTS: Children (n 1261) aged 6-10 years in Tanner stage 1 from a population-based study. RESULTS: A total of 127 children (seventy girls and fifty-seven boys) were classified with IR, including sixty-three children (thirty-three girls and thirty boys) classified with extreme IR. Only ASF and BMI Z-scores were retained as predictors of IR by stepwise selection. Adding ASF Z-score to BMI Z-score improved the area under the curve from 0·794 (95 % CI 0·752, 0·837) to 0·811 (95 % CI 0·770, 0·851; P for contrast = 0·01). In predicting extreme IR, the addition of ASF Z-score to BMI Z-score improved the area under the curve from 0·837 (95 % CI 0·790, 0·884) to 0·864 (95 % CI 0·823, 0·905; P for contrast = 0·01). CONCLUSIONS: ASF Z-score predicted IR independent of BMI Z-score in our population of prepubertal children. ASF and BMI Z-scores together improved IR risk stratification compared with BMI Z-score alone, opening new perspectives in the prediction of cardiometabolic risk in prepubertal children

Double blind, randomized controlled trial, to evaluate the effectiveness of a controlled nitric oxide releasing patch versus meglumine antimoniate in the treatment of cutaneous leishmaniasis [NCT00317629]

BACKGROUND: Cutaneous Leishmaniasis is a worldwide disease, endemic in 88 countries, that has shown an increasing incidence over the last two decades. So far, pentavalent antimony compounds have been considered the treatment of choice, with a percentage of cure of about 85%. However, the high efficacy of these drugs is counteracted by their many disadvantages and adverse events. Previous studies have shown nitric oxide to be a potential alternative treatment when administered topically with no serious adverse events. However, due to the unstable nitric oxide release, the topical donors needed to be applied frequently, making the adherence to the treatment difficult. The electrospinning technique has allowed the production of a multilayer transdermal patch that produces a continuous and stable nitric oxide release. The main objective of this study is to evaluate this novel nitric oxide topical donor for the treatment of cutaneous leishmaniasis. METHODS AND DESIGN: A double-blind, randomized, double-masked, placebo-controlled clinical trial, including 620 patients from endemic areas for Leishmaniasis in Colombia was designed to investigate whether this patch is as effective as meglumine antimoniate for the treatment of cutaneous leishmaniasis but with less adverse events. Subjects with ulcers characteristic of cutaneous leishmaniasis will be medically evaluated and laboratory tests and parasitological confirmation performed. After checking the inclusion/exclusion criteria, the patients will be randomly assigned to one of two groups. During 20 days Group 1 will receive simultaneously meglumine antimoniate and placebo of nitric oxide patches while Group 2 will receive placebo of meglumine antimoniate and active nitric oxide patches. During the treatment visits, the medications will be daily administered and the presence of adverse events assessed. During the follow-up, the research group will visit the patients at days 21, 45, 90 and 180. The healing process of the ulcer, the health of the participants, recidivisms and/or reinfection will also be assessed. The evolution of the ulcers will be photographically registered. In case that the effectiveness of the patches is demonstrated, a novel and safe therapeutic alternative for one of the most important public health problems in many countries will be available to patients

Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice

The impact of the neonatal environment on the development of adult cardiovascular disease is poorly understood. Systemic maternal inflammation is linked to growth retardation, preterm birth, and maturation deficits in the developing fetus. Often preterm or small-for-gestational age infants require medical interventions such as oxygen therapy. The long-term pathological consequences of medical interventions on an immature physiology remain unknown. In the present study, we hypothesized that systemic maternal inflammation and neonatal hyperoxia exposure compromise cardiac structure, resulting in LV dysfunction during adulthood.Pregnant C3H/HeN mice were injected on embryonic day 16 (E16) with LPS (80 µg/kg; i.p.) or saline. Offspring were placed in room air (RA) or 85% O(2) for 14 days and subsequently maintained in RA. Cardiac echocardiography, cardiomyocyte contractility, and molecular analyses were performed. Echocardiography revealed persistent lower left ventricular fractional shortening with greater left ventricular end systolic diameter at 8 weeks in LPS/O(2) than in saline/RA mice. Isolated cardiomyocytes from LPS/O(2) mice had slower rates of contraction and relaxation, and a slower return to baseline length than cardiomyocytes isolated from saline/RA controls. α-/β-MHC ratio was increased and Connexin-43 levels decreased in LPS/O(2) mice at 8 weeks. Nox4 was reduced between day 3 and 14 and capillary density was lower at 8 weeks of life in LPS/O(2) mice.These results demonstrate that systemic maternal inflammation combined with neonatal hyperoxia exposure induces alterations in cardiac structure and function leading to cardiac failure in adulthood and supports the importance of the intrauterine and neonatal milieu on adult health

Double blind, randomized, placebo controlled clinical trial for the treatment of diabetic foot ulcers, using a nitric oxide releasing patch: PATHON

<p>Abstract</p> <p>Background</p> <p>Diabetes Mellitus constitutes one of the most important public health problems due to its high prevalence and enormous social and economic consequences. Diabetic foot ulcers are one of the chronic complications of diabetes mellitus and constitute the most important cause of non-traumatic amputation of inferior limbs. It is estimated that 15% of the diabetic population will develop an ulcer sometime in their lives. Although novel therapies have been proposed, there is no effective treatment for this pathology. Naturally produced nitric oxide participates in the wound healing process by stimulating the synthesis of collagen, triggering the release of chemotactic cytokines, increasing blood vessels permeability, promoting angiogenic activity, stimulating the release of epidermical growth factors, and by interfering with the bacterial mitochondrial respiratory chain. Topically administered nitric oxide has demonstrated to be effective and safe for the treatment of chronic ulcers secondary to cutaneous leishmaniasis. However, due to their unstable nitric oxide release, the topical donors needed to be applied frequently, diminishing the adherence to the treatment. This difficulty has led to the development of a multilayer polymeric transdermal patch produced by electrospinning technique that guarantees a constant nitric oxide release. The main objective of this study is to evaluate the effectiveness and safety of this novel nitric oxide releasing wound dressing for the treatment of diabetic foot ulcers.</p> <p>Methods and design</p> <p>A double-blind, placebo-controlled clinical trial, including 100 diabetic patients was designed. At the time of enrollment, a complete medical evaluation and laboratory tests will be performed, and those patients who meet the inclusion criteria randomly assigned to one of two groups. Over the course of 90 days group 1 will receive active patches and group 2 placebo patches. The patients will be seen by the research group at least every two weeks until the healing of the ulcer or the end of the treatment. During each visit the healing process of the ulcer, the patient's health status and the presence of adverse events will be assessed. Should the effectiveness of the patches be demonstrated an alternative treatment would then be available to patients.</p> <p>Trial registration</p> <p>NCT00428727.</p

Papel del tejido perivascular en la regulación del tono vascular: repercusión en el uso de puentes aorto-coronarios para revascularización miocárdica Role of perivascular tissue in vascular tone regulation: repercussion in the use of aortocoronary bypass for myocardial revascularization

Desde hace más de treinta años, la inserción quirúrgica de puentes aorto-coronarios autólogos de vena safena y de arteria mamaria, constituye el tratamiento de elección para pacientes con enfermedad coronaria severa. La vida útil de estos injertos ha demostrado ser mayor en los colgajos de tipo arterial, aunque su uso está limitado por la restringida disponibilidad de los mismos. Por esta razón, y a pesar de que tienen mayor riesgo de presentar oclusión, los injertos de vena safena son los que más se usan en estos procedimientos de reperfusión miocárdica. Aún no se han esclarecido del todo las razones por las cuales los injertos venosos se ocluyen luego de su inserción en los lechos arteriales; no obstante, se ha propuesto que podría deberse a diferentes factores como: trauma mecánico quirúrgico, aumento de la presión arterial y disminuido estrés de fricción. En 1996 se describió la técnica "no-touch" de preparación de los injertos venosos, en la cual se implantaron los puentes venosos en los lechos coronarios junto con el tejido peri-vascular que los circunda, y demostró mejorar la vida útil de este tipo de injertos. Recientemente se ha propuesto que el tejido adiposo peri-vascular podría desempeñar un papel en la regulación del tono vascular, e incluso se ha descrito la existencia de un factor relajante derivado del adipocito (ADRF), cuya naturaleza no se ha esclarecido completamente. El objetivo de este articulo es revisar los diferentes factores vinculados con la oclusión de los injertos aorto-coronarios, las posibles vías fisiopatológicas que configuran este fenómeno, las nuevas alternativas quirúrgicas utilizadas para la preparación de los injertos venosos y los avances en la descripción del ADRF y su papel en la regulación del tono vascular.Since more than thirty years, surgical insertion of autologous aortocoronary bypasses from saphenous vein and mammary artery constitute the election treatment for patients with severe coronary disease. The lifespan of these grafts has shown to be longer with arterial tissue even though its use is limited by its restricted availability. This is why the saphenous vein bypasses, although having a greater risk of presenting occlusion, are the most used in these procedures of myocardial reperfusion. The reasons by which the venous grafts are occluded after its insertion in the arterial site are still not clear; nevertheless, it has been proposed that it could be due to different factors such as: surgical mechanical trauma, increment of arterial pressure and diminished friction stress. In 1996 the &laquo;no-touch&raquo; preparation technique of venous grafts was described, in which the venous bypasses were implanted in the coronary site along with the surrounding perivascular tissue and demonstrated to improve the lifespan of this type of grafts. Recently it has been proposed that the perivascular fat tissue could play a role in the vascular tone regulation and it has been even described the existence of an adipose cell derived relaxing factor (ADRF), whose nature has not been completely cleared yet. The objective of this article is to review the different factors related to the aortocoronary grafts’ occlusion, the possible physiopathologic channels that form this phenomenon, the new surgical alternatives used for vein grafts preparation and the advances in the description of ADRF and its role in vascular tone regulation