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BACKGROUND: The functionality of high-density lipoproteins (HDL) is a better cardiovascular risk predictor than HDL concentrations. One of the key elements of HDL functionality is its apolipoprotein composition. Lecithin-cholesterol acyl transferase (LCAT) and cholesterol-ester transfer protein (CETP) are enzymes involved in HDL-mediated reverse cholesterol transport. This study assessed the concentration and activity of LCAT and CETP in HDL subspecies defined by their content of apolipoproteins E (apoE) and C-III (apoC-III) in humans. METHODS: Eighteen adults (ten women and eight men, mean age 55.6, BMI 26.9 Kg/m2, HbA1c 5.4%) were studied. HDL from each participant were isolated and divided into four subspecies containing respectively: No apoE and no apoC-III (E-C-), apoE but not apoC-III (E + C-), apoC-III but no apoE (E-C+) and both apoE and apoC-III (E + C+). The concentration and enzymatic activity of LCAT and CETP were measured within each HDL subspecies using immunoenzymatic and fluorometric methods. Additionally, the size distribution of HDL in each apolipoprotein-defined fraction was determined using non-denaturing electrophoresis and anti-apoA-I western blotting. RESULTS: HDL without apoE or apoC-III was the predominant HDL subtype. The size distribution of HDL was very similar in all the four apolipoprotein-defined subtypes. LCAT was most abundant in E-C- HDL (3.58 mg/mL, 59.6% of plasma LCAT mass), while HDL with apoE or apoC-III had much less LCAT (19.8, 12.2 and 8.37% of plasma LCAT respectively for E + C-, E-C+ and E + C+). LCAT mass was lower in E + C- HDL relative to E-C- HDL, but LCAT activity was similar in both fractions, signaling a greater activity-to-mass ratio associated with the presence of apoE. Both CETP mass and CETP activity showed only slight variations across HDL subspecies. There was an inverse correlation between plasma LCAT activity and concentrations of both E-C+ pre-beta HDL (r = - 0.55, P = 0.017) and E-C- alpha 1 HDL (r = - 0.49, P = 0.041). Conversely, there was a direct correlation between plasma CETP activity and concentrations of E-C+ alpha 1 HDL (r = 0.52, P = 0.025). CONCLUSIONS: The presence of apoE in small HDL is correlated with increased LCAT activity and esterification of plasma cholesterol. These results favor an interpretation that LCAT and apoE interact to enhance anti-atherogenic pathways of HDL.

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Resumen Introducción: Previamente se desarrolló una nueva metodología de ayuda diagnóstica para los registros Holter fundamentada en los sistemas dinámicos y la teoría de probabilidad, a partir de la información registrada en 21 horas. Objetivo: Evaluar la capacidad diagnóstica de esta metodología durante 19 horas, comparándola con los resultados convencionales del Holter y con los resultados del método matemático aplicado en 21 horas. Materiales y Métodos: fueron evaluados 80 casos de pacientes mayores a 20 años, 10 con registro Holter normal y 70 diagnosticados de forma convencional con diferentes patologías cardíacas. Se establecieron los rangos para las frecuencias cardíacas y de número de latidos por hora en 21 y 19 horas; luego, se calculó la probabilidad de ocurrencia de estos, lo que permitió diferenciar estados de normalidad y enfermedad aguda a partir de tres parámetros. Se comparó el diagnóstico físico-matemático con el diagnóstico convencional, tomado como Gold Standard. Resultados: De los casos normales, dos presentaron probabilidad menor o igual a 0,217 y ocho probabilidades mayores o igual a 0,304; ningún caso de enfermedad aguda presentó valores con probabilidad menor o igual a 0,217, mientras que todos presentaron valores mayores o iguales a 0,304, tanto para los registros Holter evaluados en 21 como en 19 horas. Conclusiones: Se confirmó la utilidad clínica de la metodología ante una reducción del tiempo de evaluación a 19 horas, obteniendo diagnósticos objetivos con base en la auto-organización matemática del fenómeno.

Abstract Background: a new method to help evaluate 21-hour holter recordings based on dynamic systems and the theory of probability was previously developed Aim: to evaluate the diagnostic value of this methodology in the analysis of 19 hr compared to conventional holter analysis over a 21-hr recording. Methods: the holter recordings of 80 subjects aged over 20 years old were analyzed. Ten subjects had a normal holter and 70 conventionally diagnosed as abnormal. Ranges for heart rate and number of beats in 21 or 19 hours were determined. The probability of their occurrence was calculated using 3 parameters. The mathematically derived diagnosis was compared to the clinical diagnosis, considered a gold standard. Results: Among normal cases the calculated probability was ≤ 0.217 in 2 cases and ≥0.304 in 8. No case with acute disease presented probability values ≤0.217; all had probability values ≥0.304, both in 21 and 19 hour recordings. Conclusion: the mathematical methodology described was clinically useful allowing a reduction in recording time from 21 to 19 hr. Clinical diagnosis may be inferred from the mathematical organization of a holter recording.

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Antecedentes: Con conceptos provenientes de la teoría de sistemas dinámicos y la geometría fractal, se ha logrado caracterizar el comportamiento de la dinámica cardíaca, dando resultados objetivos y estableciendo distinciones entre estados de normalidad y enfermedad. Objetivo: Aplicar una ley matemática exponencial de la dinámica cardíaca, inscrita en el contexto de los sistemas dinámicos y la geometría fractal, para evidenciar su utilidad diagnóstica en 16 horas. Materiales y métodos: Fueron empleados 200 Holters y registros electrocardiográficos continuos, entre normales y con diferentes alteraciones cardíacas. Se simuló una secuencia de frecuencias cardíacas en 16 y 21 horas, con la cual se construyó el atractor de cada dinámica. También se calculó la dimensión fractal y la ocupación de los atractores en el espacio fractal. Se estableció el diagnóstico físico-matemático en 16 y 21 horas y la subsecuente validación estadística. Resultados: Fueron obtenidos valores en la rejilla Kp entre 44 y 198 para estados patológicos y entre 221 y 377 para estados de normalidad en 16 horas, la sensibilidad y especificidad fue del 100% y el coeficiente Kappa de 1. Conclusión: Se logró diferenciar de manera adecuada estados normales de patológicos mediante la ley exponencial aplicada en registros de 16 horas

Background: With concepts derived from dynamical systems theory and fractal geometry, it has been possible to characterize the behavior of the cardiac dynamics, giving objective results and estabishing distinctions between states of normality and disease. Objective: To apply an exponential mathematical law of cardiac dynamics, inscribed in the context of dynamical systems and fractal geometry, to demonstrate its diagnostic utility in the context of a reduction in the evaluation time, originally of 21 hours. Materials and methods: There were used 200 Holters and cotinuous electrocardiographic records, between normal and with different cardiac alterations. A sequence of heart rates was simulated in 16 and 21 hours, with which the attractor of each dynamic was constructed. There were also calculated the fractal dimension and the occupation of the attractors in the fractal space. The physical-mathematical diagnosis was establishd at 16 and 21 hours, and the staqtistical validation was performed. Results: Values obtained in the Kp grid were between 44 y 198 for pathological sttes, and between 221 and 377 for normal states in 16 hours. The sensitivity and specificity was 100% and the Kappa coefficient was 1. Conclusion: It was possible to differentiate adequately normal states of pathological by means fo the exponential law applied in registers of 16 hours

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BACKGROUND: Myokines are a group of protein mediators produced by skeletal muscle under stress or physical exertion. Even though their discovery and effects in cell culture and animal models of disease have elicited great enthusiasm, very little is known about their role in human metabolism. We assessed whether plasma concentrations of three known myokines [myonectin, myostatin, and fibroblast-derived growth factor 21 (FGF-21)] would be associated with direct and indirect indicators of insulin resistance (IR) in individuals who did not have a diagnosis of diabetes. METHODS: We studied 81 adults of both sexes comprising a wide range of body adiposity and insulin sensitivity. All participants underwent a thorough clinical assessment and a 5-point oral glucose tolerance test with calculation of multiple IR and insulin sensitivity indices. Twenty-one of them additionally underwent a hyperinsulinemic-euglycemic clamp with determination of steady-state whole-body insulin-stimulated glucose disposal ("M"). We compared plasma myokine concentrations across quartiles of IR indices and clinical IR surrogates, and explored the correlation of each myokine with the M-value. RESULTS: Plasma myonectin levels increased monotonically across quartiles of the incremental area under the insulin curve (higher values indicate more IR) (p-trend = 0.021) and decreased monotonically across quartiles of the insulin sensitivity index (ISI - higher values indicate less IR) (p-trend = 0.012). After multivariate adjustment for other relevant determinants of IR (body mass index, age, and sex), the negative association of myonectin with ISI persisted (standardized beta = -0.235, p = 0.023). Myostatin was not associated with any clinical IR indicator or direct IR index measure. In multivariate analyses, FGF-21 showed a trend toward a positive correlation with glucose disposal that did not reach statistical significance (standardized beta = 0.476, p = 0.091). CONCLUSION: The secretion of myonectin may constitute an attempt at a compensatory mechanism against IR in humans.

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BACKGROUND: Plasma concentrations of some lysophospholipids correlate with metabolic alterations in humans, but their potential as biomarkers of insulin resistance (IR) is insufficiently known. We aimed to explore the association between plasma linoleoylglycerophosphocholine (LGPC) and objective measures of IR in adults with different metabolic profiles. METHODS: We studied 62 men and women, ages 30 to 69 years, (29% normal weight, 59% overweight, 12% obese). Participants underwent a 5-point oral glucose tolerance test (5p-OGTT) from which we calculated multiple indices of IR and insulin secretion. Fifteen participants additionally underwent a hyperinsulinemic-euglycemic clamp for estimation of insulin-stimulated glucose disposal. Plasma LGPC was determined using high performance liquid chromatography/time-of-flight mass spectrometry. Plasma LGPC was compared across quartiles defined by the IR indices. RESULTS: Mean LGPC was 15.4±7.6 ng/mL in women and 14.1±7.3 ng/mL in men. LGPC did not correlate with body mass in-dex, percent body fat, waist circumference, blood pressure, glycosylated hemoglobin, log-triglycerides, or high density lipoprotein cholesterol. Plasma LGPC concentrations was not systematically associated with any of the studied 5p-OGTT-derived IR indices. However, LGPC exhibited a significant negative correlation with glucose disposal in the clamp (Spearman r=-0.56, P=0.029). Despite not being diabetic, participants with higher plasma LGPC exhibited significantly higher post-challenge plasma glucose excursions in the 5p-OGTT (P trend=0.021 for the increase in glucose area under the curve across quartiles of plasma LGPC). CONCLUSION: In our sample of Latino adults without known diabetes, LGPC showed potential as a biomarker of IR and impaired glucose metabolism.

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Type 2 diabetes mellitus (T2DM) is characterized by oxidative stress that could lead to chronic micro- and macrovascular complications. We hypothesized that some of the target organ damage is mediated by oxidative alterations in epigenetic mechanisms involving DNA methylation (5mC) and DNA hydroxymethylation (5hmC). We analyzed global DNA methylation and hydroxymethylation in peripheral blood cells in well-controlled and poorly controlled patients with T2DM and compared them with healthy controls. We also analyzed microarrays of DNA methylation and gene expression of other important tissues in the context of diabetes from the GEO database repository and then compared these results with our experimental gene expression data. DNA methylation and, more importantly, DNA hydroxymethylation levels were increased in poorly controlled patients compared to well-controlled and healthy individuals. Both 5mC and 5hmC measurements were correlated with the percentage of glycated hemoglobin, indicating a direct impact of hyperglycemia on changes over the epigenome. The analysis of methylation microarrays was concordant, and 5mC levels were increased in the peripheral blood of T2DM patients. However, the DNA methylation levels were the opposite of those in other tissues, such as the pancreas, adipose tissue and skeletal muscle. We hypothesize that a process of DNA oxidation associated with hyperglycemia may explain the DNA demethylation in which the activity of ten-eleven translocation (TET) proteins is not sufficient to complete the process. High levels of glucose lead to cellular oxidation, which triggers the process of DNA demethylation aided by TET enzymes, resulting in epigenetic dysregulation of the damaged tissues.

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Aunque no es una intoxicación frecuente, las intoxicaciones por sulfato de Talio en nuestro medio tienen una incidencia que amerita su estudio, máximo cuando muchas de ellas suceden en la población infantil y de manera accidental, y otras tantas son de manera voluntaria y un tercer grupo, bajo en frecuencia, padece la intoxicación por fines delictivos. Queremos entonces presentar la sintomatología aguda y crónica producida por el sulfato de Talio y los diferentes esquemas de manejo.

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Con este artículo se pretende interesar al médico sobre las diferentes situaciones de emergencia en toxicología y la manera como se deben abordar. Para esto, se hace un análisis de las formas más frecuentes de intoxicación en nuestro medio y presento un esquema de atención al paciente intoxicado agudo, en orden secuencial, enfocándolo en medidas a favor del enfermo y en contra de la sustancia tóxica; haciéndose énfasis en que cada uno de los pasos enumerados se deben realizar simultáneamente, por el personal del servicio de urgencias.

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