Relaciones entre el metabolismo oxidativo y la obesidad Parte 2: obesidad: inercia evolutiva de los organismos y la vida moderna de los seres humanos / Oxidative metabolism and obesity Part 2: Obesity: evolutive inertia of the organisms and the modern human life

En todos los seres humanos, el crecimiento y el desarrollo, desde la condición de oocito fecundado, están predeterminados por el programa genético, incluso la acumulación de reservas energéticas en el tejido adiposo, a fin de poder sobrevivir a largos períodos invernales y de hambruna. Por lo tanto, la natural tendencia a la obesidad tiene un valor selectivo para el individuo, así como para la especie, lo que es válido desde épocas prehistóricas hasta la actualidad. Sin embargo, en los tiempos modernos, la excesiva oferta de toda clase de alimentos, y la vida sedentaria, ha alterado dramáticamente el balance entre la oferta de kilocalorías de los diversos alimentos y los requerimientos metabólicos de cada organismo, tanto en reposo como en actividad muscular. La ausencia de un control ponderal periódico, durante la vida de cada individuo, y la estrecha vigilancia de los hábitos anormales en cuanto a la alimentación y la actividad física, dan origen a un círculo vicioso, que se origina en la primera infancia y termina con una obesidad patológica, que muchas veces es refractaria a todo tratamiento racional. Finalmente, se analiza el concepto de “epidemia”, en relación con el problema de la obesidad en nuestros días.

In all human beings, both growth and development, beginning from the condition of a fertilized egg-cell, are predetermined by the genetic program, inclusively the accumulation of energy reserves within the adipose tissue, with the aim to be able to survive during long winter periods or of prolonged famines. In consequence, the natural tendency to get obesity has a selective value, both for each individual or for a given species, which is valid since prehistoric times up to the present. Nevertheless, in modern times, the excessive supply of all kinds of foods and the sedentary life stile, have dramatically changed the proper balance between the supply of kilocalories of different foods and the metabolic requirements of each organism, both during rest and muscular activity. The absence of a periodic weight control during the whole life of each human being and the close vigilance of abnormal behaviors, particularly with regard to nutrition and exercise, will originate a vicious circle which appear in the first childhood and ends with a pathological obesity, which often is refractory to any kind of therapy. Finally, the recent concept of obesity as an “epidemic” is discussed.

Relaciones entre el metabolismo oxidativo y la obesidad Parte 1: Alometría: el álgebra de la vida / Oxidative metabolism and obesity Part 1: Allometry: algebra of the life

El análisis cuantitativo de la relación entre la intensidad metabólica y eltamaño del cuerpo de los mamíferos terrestres se fundamenta en someterlos datos empíricos a una transformación logarítmica, con el propósito de obtener una relación lineal entre estas variables. El análisis de regresión permite obtener los parámetros de la ecuación alométrica de Huxley, los que pueden ser comparados con aquellos obtenidos de la teoría de similitud biológica, que se basa en el análisis dimensional de la Física. La clásica ley de la superficie de Rubner relaciona superficies y volúmenes de diversos cuerpos geométricos y no puede ser aplicada directamente a la investigación clínica. Es costumbre expresar la intensidad metabólica exclusivamente en condiciones basales en la Fisiología Comparada como en la práctica clínica, en tanto que en todos los organismos el metabolismo puede variar en un rango de 1 a 10 cuando se compara la condición reposo con la de ejercicio máximo.

The quantitative analysis of the relationship between metabolic rate and body size in terrestrial mammals is based in the log-log transformation of the experimental data in order to obtain a linear correlation. The regression analysis allows obtaining the two characteristic parameters of Huxley’s allometric equation, which can be compared with those obtained from dimensional analysis and biological, similarity theories. Rubner’s classic surface law deals only with surfaces and volumes of geometric bodies, which are not applicable in clinical research. It is customary in Comparative Physiology and clinical practice to deal exclusively with the basal metabolic rate, whereas in all organisms oxidative metabolism comprises a range which is 1:10 when resting conditions and maximal oxygen consumption during exercise are compared.

Allometric scaling of biological rhythms in mammals.

A wide spectrum of cyclic functions in terrestrial mammals of different size, from the 3-gram shrew to the 3-ton elephant, yields an allometric exponent around 0.25, which is correlated--as a kind of common denominator--with the specific metabolic rate. Furthermore, the applicability of these empirical findings could be extrapolated to chronological events in the sub-cellular realm. On the other hand, the succession of growth periods (T98%) until sexual maturity is reached also follows the 1/4 power rule. By means of Verhulst's logistic equation, it has been possible to simulate three different biological conditions, which means that by modifying the numerical value of only one parameter, revertible physiological and pathological states can be obtained, as for instance isostasis, homeostasis and heterostasis.

Two alternative models concerning the perialveolar microcirculation in mammalian lungs.

Despite the fact that the concept of sheet-flow in the pulmonary microcirculation of mammals was introduced more than three decades ago, the capillary circulatory model still prevails in the physiological literature. Since cardiac output is identical in the systemic and in pulmonary circulations, it is noteworthy that in the former, the resulting arterial pressure is five times higher than that of the latter, which means that the corresponding microcirculations must be radically different. The present study addresses this problem from both morphological and physiological perspectives.

[Homeostatic range of the oxidative metabolism: 60 years of integrative fisiometry]. / Rango homeostático del metabolismo oxidativo: 60 años de fisiometría integrativa.

The energetic metabolism and its relationship with body weight generated a vivid controversy, since the Rubner's surface law was introduced into biology. Recently, the multifactor theory (Darveau et al) has caused again a revival of this polemic topic. Moreover, the investigations concerning metabolism and body weight include all terrestrial mammals, from the shrew (3 grams) to the elephant (three tons). The corresponding allometric exponent for standard metabolic rate, both theoretical and empirical, fluctuates around an average value of 0.75, in contrast with the surface law, which postulated a value of 0.67. The "metabolic range" (rest vs maximal exercise) does vary from 1 to 10, due to the prevalent influence of the skeletal muscle activity. Recent investigations have emphasized the fact that the allometric exponent is not unique (0.75), but it should be subjected to statistical variability, both in standard and in maximal exercise.

Allometric scaling of biological rhythms in mammals

A wide spectrum of cyclic functions in terrestrial mammals of different size, from the 3-gram shrew to the 3-ton elephant, yields an allometric exponent around 0.25, which is correlated - as a kind of common denominator - with the specific metabolic rate. Furthermore, the applicability of these empirical findings could be extrapolated to chronological events in the sub-cellular realm. On the other hand, the succession of growth periods (T98 percent) until sexual maturity is reached also follows the 1/4 power rule. By means of Verhulst's logistic equation, it has been possible to simulate three different biological conditions, which means that by modifying the numerical value of only one parameter, revertible physiological and pathological states can be obtained, as for instance isostasis, homeostasis and heterostasis.

Two alternative models concerning the perialveolar microcirculation in mammalian lungs

Despite the fact that the concept of sheet-flow in the pulmonary microcirculation of mammals was introduced more than three decades ago, the capillary circulatory model still prevails in the physiological literature. Since cardiac output is identical in the systemic and in pulmonary circulations, it is noteworthy that in the former, the resulting arterial pressure is five times higher than that of the latter, which means that the corresponding microcirculations must be radically different. The present study addresses this problem from both morphological and physiological perspectives.

Time in physics and biology.

In contrast with classical physics, particularly with Sir Isaac Newton, where time is a continuous function, generally valid, eternally and evenly flowing as an absolute time dimension, in the biological sciences, time is in essence of cyclical nature (physiological periodicities), where future passes to past through an infinitely thin boundary, the present. In addition, the duration of the present (DP) leads to the so-called 'granulation of time' in living beings, so that by the fusion of two successive pictures of the world, which are not entirely similar, they attain the perception of 'movement,' both in the real world as well as in the sham-movement in the mass media (TV).

Wavelet and Fourier analysis of ventricular and main arteries pulsations in anesthetized dogs.

The purpose of this study was to characterize time-frequency behavior using the Continuous Wavelet Transform (CWT) and Fast Fourier Transform (FFT) to analyze ventricular and arterial pressure signals from anesthetized mongrel dogs. Both ventricular and arterial pressure pulsations were recorded using catheter-tip manometers and the CWT was applied to these signals to obtain module coefficients, associated contours, and the 3-D representation of these modules. FFT was applied to obtain the Fourier spectrum. The mathematical analysis of the cardiovascular pressure pulsations permitted the identification of the evolution of the frequency components for the aortic and pulmonary valve functions as well as the intra-ventricular and respiratory influences on the cardiovascular dynamics. The CWT is a very sensitive and reliable procedure for determining the three-dimensional (time-frequency-amplitude) of the oscillatory phenomena during each cardiac cycle, providing more, although complementary, information than the spectral analysis obtained with the FFT. Thanks to the FFT, exact values in Hz could be found for the different events produced in each cycle, and thus the information provided by CWT could be related to the information provided by FFT. The combination of both mathematical methodologies permitted identification of each component of the analyzed signals. The 3D representation allowed an easy comparison of the relative importance of the complex magnitudes in frequency for the different components of the pulsatile waves.

Wavelet and Fourier analysis of ventricular and main arteries pulsations in anesthetized dogs

The purpose of this study was to characterize time-frequency behavior using the Continuous Wavelet Transform (CWT) and Fast Fourier Transform (FFT) to analyze ventricular and arterial pressure signals from anesthetized mongrel dogs. Both ventricular and arterial pressure pulsations were recorded using catheter-tip manometers and the CWT was applied to these signals to obtain module coefficients, associated contours, and the 3-D representation of these modules. FFT was applied to obtain the Fourier spectrum. The mathematical analysis of the cardiovascular pressure pulsations permitted the identification of the evolution of the frequency components for the aortic and pulmonary valve functions as well as the intra-ventricular and respiratory influences on the cardiovascular dynamics. The CWT is a very sensitive and reliable procedure for determining the three-dimensional (time-frequency-amplitude) of the oscillatory phenomena during each cardiac cycle, providing more, although complementary, information than the spectral analysis obtained with the FFT. Thanks to the FFT, exact values in Hz could be found for the different events produced in each cycle, and thus the information provided by CWT could be related to the information provided by FFT. The combination of both mathematical methodologies permitted identification of each component of the analyzed signals. The 3D representation allowed an easy comparison of the relative importance of the complex magnitudes in frequency for the different components of the pulsatile waves.

Una controversia vigente: ¿ph o ch? / A standing controversy: ¿ph or ch?

La constancia de la concentración de iones hidrógeno (cH+) en el medio interno de todos los endotermos y su perfecta regulación en condiciones fisiológicas aseguran que las reacciones químicas intracelulares se verifi quen en régimen estacionario. Sin embargo, este importante parámetro biológico se define en unidades de pH (potencial de hidrógeno), que corresponde al logaritmo del valor inverso de la concentración de los iones hidrógeno, y por lo tanto esta escala de pH no se correlaciona en forma lineal (proporcional) con la concentración de iones hidrógeno. En el presente artículo se analiza la conveniencia de utilizar la expresión de concentración “nanomoles de H+/lt” en vez de pH,ya que ella permite trabajar con valores en el rango fisiológico que son fáciles de recordar y además evita el uso de una escala no lineal inversa para la concentración de estos.

Time in physics and biology

In contrast with classical physics, particularly with Sir Isaac Newton, where time is a continuous function, generally valid, eternally and evenly flowing as an absolute time dimension, in the biological sciences, time is in essence of cyclical nature (physiological periodicities), where future passes to past through an infinitely thin boundary, the present. In addition, the duration of the present (DP) leads to the so-called 'granulation of time' in living beings, so that by the fusion of two successive pictures of the world, which are not entirely similar, they attain the perception of 'movement,' both in the real world as well as in the sham-movement in the mass media (TV).

Dimensional analysis revisited.

The applicability of dimensional analysis (DA) is discussed in relation to the metabolic scaling laws. The evolution of different theories of biological similarity has shown that the calculated reduced exponents (b) of Huxley's allometric equation are closely correlated with the numerical values obtained from the statistical analysis of empirical data. Body mass and body weight are not equivalent as biological reference systems, since in accordance to Newton's second law, the former has a dimension of a mass, while the latter should be dimensionally considered as a force (W = MLT-2). This distinction affects the coefficients of the mass exponent (alpha). This difference is of paramount importance in microgravity conditions (spaceflight) and of buoyancy during the fetal life in mammals. Furthermore, the coefficients (beta) of the length dimension, and (gamma) of the time dimension do not vary when mass or weight are utilized as reference systems. Consequently, the "specific metabolic time," that results from the ratio of basal oxygen consumption and body mass or body weight yields the "biological meaning" of the time dimension, which is of fractal nature.

Homeostasis and heterostasis: from invariant to dimensionless numbers.

In the present paper we have examined the applicability of dimensionless and invariant numbers (DN & IN) to the analysis of the cardiovascular system of mammals, whose functions were measured at standard metabolic conditions. The calculated IN did not change when we compared these figures with those obtained in dogs while they were submitted to graded exercise on a treadmill. In both instances, rest and exercise, the constancy of the IN prevailed, in accordance with Cannon's principle of "homeostasis" (1929). On the contrary, when dogs were examined during a standardized hypovolemic shock, we observed a breakdown of the IN, and the resulting DN evolved as a reliable index of the condition of "heterostasis" as defined by H. Selye. The robustness of the homeostatic regulations is based on high-gain integral feedback mechanisms, while "heterostasis" could be associated with low-gain integral feedback processes, when organisms are submitted to unitary step disturbances or to changes of the set-point at the entrance of the feedback loop.

Homeostasis and Heterostasis: from invariant to dimensionless numbers

In the present paper we have examined the applicability of dimensionless and invariant numbers (DN & IN) to the analysis of the cardiovascular system of mammals, whose functions were measured at standard metabolic conditions. The calculated IN did not change when we compared these figures with those obtained in dogs while they were submitted to graded exercise on a treadmill. In both instances, rest and exercise, the constancy of the IN prevailed, in accordance with Cannon's principle of "homeostasis" (1929). On the contrary, when dogs were examined during a standardized hypovolemic shock, we observed a breakdown of the IN, and the resulting DN evolved as a reliable index of the condition of "heterostasis" as defined by H. Selye. The robustness of the homeostatic regulations is based on high-gain integral feedback mechanisms, while "heterostasis" could be associated with low-gain integral feedback processes, when organisms are submitted to unitary step disturbances or to changes of the set-point at the entrance of the feedback loop

Dimensional analysis revisited

The applicability of dimensional analysis (DA) is discussed in relation to the metabolic scaling laws. The evolution of different theories of biological similarity has shown that the calculated reduced exponents (b) of Huxley's allometric equation are closely correlated with the numerical values obtained from the statistical analysis of empirical data. Body mass and body weight are not equivalent as biological reference systems, since in accordance to Newton's second law, the former has a dimension of a mass, while the latter should be dimensionally considered as a force (W = MLT-2). This distinction affects the coefficients of the mass exponent (alpha). This difference is of paramount importance in microgravity conditions (spaceflight) and of buoyancy during the fetal life in mammals. Furthermore, the coefficients (beta) of the length dimension, and (gamma) of the time dimension do not vary when mass or weight are utilized as reference systems. Consequently, the specific metabolic time, that results from the ratio of basal oxygen consumption and body mass or body weight yields the biological meaning of the time dimension, which is of fractal nature.

An invariant number of the respiratory system of mammals: newborn and adult.

From four empirical allometric equations concerning the dynamics of the respiratory functions of mammals, it has been possible to obtain an invariant and dimensionless number after applying Buckingham's pi-theorem. In the present study, this invariant number (IN(R)), whose origin was interspecies comparisons in mammals of different sizes, was assayed with the aim to compare in a quantitative manner the possible difference between newborn and adult mammals. The results were compared with the predicted values from two theories of biological similarity, one mass-dependent, valid for newborns, and the other, weight-dependent, valid for adult mammals. Finally, we utilized Stahl's residual mass exponents (RME) to test the validity of the empirical and theoretical approaches.

[Prediction of the length of stay in Intensive Care Units using artificial neural networks]. / Identificación de los determinantes de la estadía en Unidades de Cuidados Intensivos usando redes neuronales artificiales.

BACKGROUND: The prediction of the length of stay at the moment of hospital admission is of utmost importance. Many studies have used lineal models to predict this variable, but there are inherent limitations to these models. The use of non lineal models has been scarce. AIM: To develop a non lineal model to predict length of stay in intensive care units. MATERIAL AND METHODS: Retrospective analysis of 294 patients admitted to two intensive care units in Santiago, Chile. The severity of the disease motivating the admission was nominally quantified. This and other physiological variables were included in the model. The length of stay was modeled using Artificial Neural Networks. RESULTS: The model yielded an error of 8.7% (3.6 +/- 0.4 days, CI 95%) and a correlation coefficient of 0.9 (p < 0.001) for the prediction of length of stay. Using net sensitivity analysis, the model determined that gastrointestinal diseases, infections and respiratory problems were the main causes of prolongation of intensive care unit stay. CONCLUSIONS: Intensive care units should have, in the future, computer systems that gather vital information to predict length of stay.