On the genetic determinants of hypovitaminosis D.

Hypovitaminosis D, defined by low serum levels of 25(OH)D, is a recognized worldwide public health problem. The most accepted definition considers that deficiency occurs with serum levels fall below 12 ng/ml of 25(OH)D. Long term vitamin D deficiency results in decreased bone mineralization, secondary hyperparathyroidism, increased cortical bone loss (pathogenesis of osteoporosis and hip fractures), differentiation and division of various cell types, muscle strength, diabetes type 2, blood pressure, etc. Twin- and family-based studies indicate that genetic factors influence serum 25(OH)D levels. Genetic studies have shown single-nucleotide polymorphisms (SNPs) are linked to low serum 25(OH)D concentrations through changes in the activity of the enzymes of the 1a,25(OH)2D metabolic pathway. Carriers of high genetic risk scores would need a h igher amount of vitamin D supplementation to achieve adequate serum 25(OH)D concentrations. Clinicians would not need to indicate studies to identify patients with vitamin D insufficiency of genetic origin. They should instruct their patients on their own care, to control the intake of vitamin D and the serum 25(OH)D levels until the latter are adequate. Overall, the literature reveals that the consequences of hypovitaminosis D on bone health are observed in old and infrequently in young subjects. A probable explanation for the latter is: if the rate of bone remodeling allows it, bone tissue has endogenous (genetics, hormones) and exogenous determinants (diet, physical activity) that may compensate the variables of bone health. The consequences of vitamin D deficit on bone health, has not been completely uncovered.

La hipovitaminosis D, definida por bajos niveles séricos de 25(OH)D (<12 ng/ml), es un reconocido problema de salud pública mundial. La deficiencia de vitamina D a largo plazo resulta en una disminución de la mi neralización ósea, hiperparatiroidismo secundario, pérdida de hueso cortical (patogénesis de la osteoporosis y fracturas de cadera), diferenciación y división de varios tipos de células, fuerza muscular, diabetes tipo 2, pres ión arterial, etc. Estudios genéticos han demostrado que algunos "polimorfismos de un solo nucleótido" (SNP) están relacionados con bajas concentraciones séricas de 25(OH)D a través de reducción en la actividad de las enzimas implicadas en la síntesis de 1a,25(OH)2D. Los médicos no necesitan indicar un estudio genético para identificar a la insuficiencia de vitamina D de causa genética. Bastará con instruir a los pacientes sobre su propio cuidado y controlar la ingesta de vitamina D y los niveles séricos de 25(OH)D hasta que estos últimos sean adecuados. En general, la literatura revela que las consecuencias de la hipovitaminosis D sobre la salud ósea se observan en las personas añosas y con poca frecuencia en sujetos jóvenes. Una explicación probable para esta situación es: si la tasa de remodelación ósea lo permite, el tejido óseo tiene factores endógenos (genéticos, hormonales) y exógenos (dieta, actividad física) que pueden compensar las variables de la salud ósea. Las consecuencias del déficit de vitamina D sobre la salud ósea aún no se conocen completamente.

On the genetic determinants of hypovitaminosis D

Hypovitaminosis D, defined by low serum levels of 25(OH)D, is a recognized worldwide public health problem. The most accepted definition considers that deficiency occurs with serum levels fall below 12 ng/ml of 25(OH)D. Long term vitamin D deficiency results in decreased bone mineralization, secondary hyperparathyroidism, increased cortical bone loss (pathogenesis of osteoporosis and hip fractures), differentiation and division of various cell types, muscle strength, diabetes type 2, blood pressure, etc. Twin- and family-based studies indicate that genetic factors influence serum 25(OH)D levels. Genetic studies have shown single-nucleotide polymorphisms (SNPs) are linked to low serum 25(OH)D concentrations through changes in the activity of the enzymes of the 1α,25(OH)2D metabolic pathway. Carriers of high genetic risk scores would need a h igher amount of vitamin D supplementation to achieve adequate serum 25(OH)D concentrations. Clinicians would not need to indicate studies to identify patients with vitamin D insufficiency of genetic origin. They should instruct their patients on their own care, to control the intake of vitamin D and the serum 25(OH)D levels until the latter are adequate. Overall, the literature reveals that the consequences of hypovitaminosis D on bone health are observed in old and infrequently in young subjects. A probable explanation for the latter is: if the rate of bone remodeling allows it, bone tissue has endogenous (genetics, hormones) and exogenous determinants (diet, physical activity) that may compensate the variables of bone health. The consequences of vitamin D deficit on bone health, has not been completely uncovered.

La hipovitaminosis D, definida por bajos niveles séricos de 25(OH)D (<12 ng/ml), es un reconocido problema de salud pública mundial. La deficiencia de vitamina D a largo plazo resulta en una disminución de la mi neralización ósea, hiperparatiroidismo secundario, pérdida de hueso cortical (patogénesis de la osteoporosis y fracturas de cadera), diferenciación y división de varios tipos de células, fuerza muscular, diabetes tipo 2, pres ión arterial, etc. Estudios genéticos han demostrado que algunos "polimorfismos de un solo nucleótido" (SNP) están relacionados con bajas concentraciones séricas de 25(OH)D a través de reducción en la actividad de las enzimas implicadas en la síntesis de 1α,25(OH)2D. Los médicos no necesitan indicar un estudio genético para identificar a la insuficiencia de vitamina D de causa genética. Bastará con instruir a los pacientes sobre su propio cuidado y controlar la ingesta de vitamina D y los niveles séricos de 25(OH)D hasta que estos últimos sean adecuados. En general, la literatura revela que las consecuencias de la hipovitaminosis D sobre la salud ósea se observan en las personas añosas y con poca frecuencia en sujetos jóvenes. Una explicación probable para esta situación es: si la tasa de remodelación ósea lo permite, el tejido óseo tiene factores endógenos (genéticos, hormonales) y exógenos (dieta, actividad física) que pueden compensar las variables de la salud ósea. Las consecuencias del déficit de vitamina D sobre la salud ósea aún no se conocen completamente.

On the synthesis of vitamin d in the darkness / Sobre la síntesis de vitamina D en la oscuridad

Published evidence reports the existence of two routes for the transformation of 7-dehydrocholecalciferol into previtamin D3: a photochemical route with the participation of UVB photons and another route that occurs in the darkness. Several reports appears to support the presence of these two routes in some mammals, birds, nonvascular plants (e.g.: mosses), vascular plants (e.g.: angiosperms) and lichens. The reviewed evidence suggests that in the darkness, the synthesis of vitamin D3 follows the same scheme of the photochemical pathway, but at a reduced rate respect to the synthesis under UVB radiation. The process of vitamin D synthesis in the dark, then, may be taken as an insurance for survival, at least for mammals and birds. The low rate of the synthesis of vitamin D3 in the absence of light produce low concentrations of vitamin D3 metabolites in plasma. Long term survival under these circumstances might be possible through upregulation of vitamin D receptors (VDRs). In mole rats (South African rodents that live in the dark in underground tunnels), the reduced rate of vitamin D3 synthesis produce low levels of plasma vitamin D3 and their metabolites 25(OH) D3 and 1α,25OH2 D3 . The fact that Kd and ßmax of the complex 1α,25(OH)2 D3 -VDR from the intestinal mucosa, kidneys and the Harderian glands of the mole rat Heterocephalus glaber are significantly different in each one of these tissues, is interpreted as an indicator that the VDRs are, in each tissue, adapted to the maintenance of normal physiological functions. (AU)

Varios trabajos publicados han informado que existen dos mecanismos para la transformación de 7-dehidrocolecalciferol en previtamina D3 : uno iniciado con el auxilio de fotones UVB y un segundo que ocurre en la oscuridad, sin el auxilio de radiación ultravioleta. Una serie de publicaciones contienen información que apoya la presencia de estos dos mecanismos en mamíferos, pájaros, plantas no vasculares (musgos), vasculares (angiospermas) y líquenes. La evidencia revisada sugiere que, en la oscuridad, la síntesis de vitamina D3 sigue el mismo esquema que la ruta fotoquímica y generalmente ocurre a una tasa reducida respecto de la síntesis bajo irradiación ultravioleta. La operación de la síntesis de vitamina D3 en la oscuridad, por lo menos para mamíferos y pájaros, puede tomarse como un reaseguro de sobrevida. La reducida tasa de síntesis de vitamina D en ausencia de luz produce bajas concentraciones en plasma de los metabolitos de la vitamina. La sobrevida saludable en estas condiciones sería posible mediante upregulation de los receptores. En las ratas topo Heterocephalus glaber (roedores sudafricanos que viven en permanente oscuridad, en túneles subterráneos), la reducida tasa de síntesis de vitamina D3 es la causa de los bajos niveles plasmáticos de la vitamina y sus metabolitos: 25(OH)D3 y 1α,25OH2 D3 . El hecho de que el Kd y ßmax del complejo 1α,25(OH)2 D3 -Vitamina-D-Receptor del intestino, riñón y glándulas de Harder de Heterocephalus glaber sean significativamente diferentes entre sí indicaría que los receptores se han modificado para mantener funciones fisiológicas normales en cada tejido. (AU)

Normal physiological functions in two animal species with highly different vitamin d status compared to that of humans / Funciones fisiológicas normales en dos especies animales con estatus de vitamina d muy diferentes del actual en seres humanos

Mole rats live in permanent darkness, in networks of underground tunnels (which extend up to 1 km in the subsoil), excavated with their incisors, in warm and semi-arid areas of South Africa. Mole rats have an unusually impoverished vitamin D3 status with undetectable and low plasma concentrations of 25- hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3, respectively. They express 25-hydroxylase in the liver and 1-hydroxylase and 24-hydroxylase in their kidneys. The presence of specific receptors (VDR) was confirmed in the intestine, kidney, Harderʼs glands and skin. In spite of their poor vitamin D3 status, the apparent fractional intestinal absorption of calcium, magnesium and phosphate was high, always greater than 90%. Oral supplementation with cholecalciferol to mole rats did not improve the efficiency of gastrointestinal absorption of these minerals. Mole ratsdo not display the typical lesion of rickets: hypertrophic and radiolucent growth cartilages. Histological studies reported normal parameters of trabecular and cortical bone quality. Marmosets (monkeys of the New World) are not hypercalcaemic, eventhough they exhibit much higher levels of 25-hydroxyvitamin D3, 1α,25-dihydroxyvitamin D3 and parathyroid hormonethan that of rhesus monkeys and humans. Fed a high vitamin D3 intake (110 IU/day/100 g of body weight), a fraction of the experimental group was found to display osteomalacic changes in their bones: distinct increases in osteoid surface, relative osteoid volume, and active osteoclastic bone resorption. These findings suggest that some marmosets appears to suffer vitamin D-dependent rickets, type II. The maximum binding capacity of the VDR or the dissociation constant of VDR1α,25(OH)2D3 complex of mole rats and New World monkeys are distinctly different of VDR isolated from human cells. Health status of those species appears to be adaptations to the mutations of their VDR. Though rare, as mutations may occur at any time in any patient, the overall message of this review to clinicians may be: recent clinical studies strongly suggests that the normality of physiological functions might be a better indicator of the health status than the serum levels of vitamin D metabolites. (AU)

Las ratas topo viven en la oscuridad permanente, en redes de túneles subterráneos excavadas con sus incisivos (que se extienden hasta 1 km en el subsuelo), en áreas cálidas y semiáridas de Sudáfrica. Las ratas topo tienen un estatus de vitamina D3 inusualmente empobrecido con concentraciones plasmáticas indetectables de 25-hidroxivitamina D3 y bajas de 1α, 25-dihidroxivitamina D3. Poseen 25-hidroxilasa en el hígado y 1-hidroxilasa y 24-hidroxilasa en sus riñones. La presencia de receptores específicos (VDR) ha sido confirmada en el intestino, el riñón, las glándulas de Harder y la piel. A pesar de su pobre estatus de vitamina D3,la absorción fraccional intestinal aparente de calcio, magnesio y fosfato fue alta, siempre superior al 90%. La suplementación oral con colecalciferol a las ratas topo no mejoró la eficacia de la absorción gastrointestinal de estos minerales. No muestran la lesión típica del raquitismo: cartílagos de crecimiento hipertróficos y radiolúcidos. Varios estudios histológicos confirman los hallazgos radiológicos y se informan parámetros normales de la calidad ósea trabecular y cortical. Los titíes (monos del Nuevo Mundo) exhiben calcemias normales con niveles más elevados de 25-hidroxivitamina D3, 1α,25-dihidroxivitamina D3 y hormona paratiroidea que los monos rhesus y los seres humanos. Un tercio de un grupo de titíes alimentados con una alta ingesta de vitamina D3 (110 I/día/100 g de peso corporal) exhibió cambios osteomalácicos en sus huesos: aumento en la superficie osteoide, volumen osteoide y activa reabsorción osteoclástica. Estos hallazgos sugieren que una fracción de la población de titíes padece raquitismo dependiente de vitamina D, tipo II. Debido a mutaciones ocurridas hace millones de años, las máximas capacidades de ligamiento del VDR o los valores de la constante de disociación del complejo VDR-1α,25(OH)2D3 de las ratas topo o monos del Nuevo Mundo son muy diferentes de los verificables en receptores aislados de células humanas actuales. El mensaje de esta revisión a los médicos clínicos podría ser: varios estudios clínicos recientes indican que la normalidad de las funciones fisiológicas de un paciente es un mejor indicador de su salud que los niveles séricos de los metabolitos de la vitamina D. (AU)

Investigation on the biological effect of fluorine present on the surface of titanium implants: analysis of the reaction fluoride-titanium oxide / Investigación del efecto del fluoruro sobre la superficie de implantes de titanio: análisis de la reacción fluoruro-óxido de titanio

The aim of this work was to investigate the state of fluoride at the surface of fluoridemodified titanium implants, and to provide information to support or discard the hypothesis that fluoride ion participates in the osseointegration of implants. Titanium is coated with a 2-10 nm thick layer of stable and adherent TiO2, which reacts with fluoride as a function of the anion concentration. Under present experimental conditions, the half-life of the reaction is about 2 minutes at 17 °C. The stoichiometry of the reaction Ti:F is 0.46 ± 0.03, which do not differs significantly from 0.5, the ratio inferred from the reaction between sodium fluoride and TiO2: 3 TiO2 + 6 NaF Na2 TiF6 + 2 Na2 TiO3 . The reaction proceeds as a function of the fraction of anionic fluoride concentration, which increases from a minimum at pH 1 to a maximum close to pH 6. The number of fluoride mmoles that react with TiO2 grows exponentially as a function of fluoride concentration, towards a maximum at 0.24 M fluoride. According to literature reports, potassium hexafluorotitanate is insoluble in water and it decomposes by heating at 780 °C, indicating a high formation constant. It is concluded that the hexafluorotitanate would not ionize to provide fluoride ion to the implant-bone environment and to promote growth and differentiation of osteoblasts. The effect of fluoride on the surface of titanium sheet was investigated under SEM, showing that the titanium sheet surface is roughened and electron dispersive spectroscopic microanalysis indicated that fluorine is included in the TiO2 layer. (AU)

El objetivo de este trabajo fue investigar el estado del flúor en la superficie de implantes de titanio tratados con fluoruro de sodio y obtener información para descartar o apoyar la hipótesis de su participación en el proceso de osteo-integración. El titanio está recubierto con una capa estable y adherente de TiO2, de 2-10 nm de espesor, que reacciona con el fluoruro en función de la concentración del anión. En las condiciones experimentales utilizadas el tiempo de vida media de la reacción es de 2 minutos at 17 ºC, pH 5,5. La reacción procede en función de la fracción de fluoruro iónico de la concentración total de fluoruro, que aumenta de un mínimo a pH 1 a un máximo a pH 6. El número de µmoles de fluoruro que reaccionan con TiO2 crece exponencialmente en función de la concentración del anión, hacia un máximo a 0,244 M. La relación estequiométrica de la reacción Ti:F es 0.46 ± 0.03 no difiere significativamente de 0.5; relación inferida de la reacción: 3 TiO2 + 6 NaF Na2 TiF6 + 2 Na2 TiO3. Como el hexafluorurotitanato de potasio es insoluble en agua y tiene una elevada constante de formación (se descompone por calentamiento a 780 ºC), se concluye que no se disociará para proveer fluoruro a las células óseas en contacto con el implante. La observación al microscopio electrónico de barrido y el análisis por espectroscopía de dispersión de rayos X de la superficie de un trozo de hoja de titanio tratado con solución de NaF a pH 3.5, indicaron aumento de la rugosidad y presencia de flúor en la capa de TiO2. (AU)

Osseointegration of titanium implants anodized with and without fluoride in the electrolyte: a study in rats / Osteo-integración de implantes de titanio anodizado con y sin agregado de fluoruro en el electrolito: estudio en la rata

Based on the hypothesis that fluoride acts as a bone anabolic agent, the aim of this study was to measure in rats the osseointegration of implants (grade II titanium wire, 1 mm diameter, 4 mm long) submitted to anodic oxidation in 2 M phosphoric acid solution (control implants) or b) in 2 M phosphoric acid solution plus 0.2 M NaF (F-modified implants). Chemical composition of the implants surface was assessed by energy-dispersive X-ray spectroscopy. The surface of F-modified implants contained a 2.57% fluorine in weight. Adult male Sprague Dawley rats (300-350 g body weight) received two implants (in the femur and in the tibia, close to the knee) in each hind limb. Control and F-modified implants were inserted in the left and right hind limbs, respectively. Three weeks after surgery, the animals were sacrificed. The undecalcified bones were embedded in methylmetacrylate. Sections were obtained to measure two histomorphometric magnitudes: bone-toimplant contact (BIC) and bone volume in a defined volume of tissue around the implant (BV/TV). BIC was significantly increased on F-modified implants with respect to their controls (57.2%±3.3%, vs. 47.9±3.4, p<0.05). BV/TV did not differ significantly between F-modified and control implants (24.5±2.2% vs. 22.9±1.4, p=0.30). Profiles of the average gray pixel levels of pseudo3D images showed a greater roughness of F-modified implants respect to their controls (p<0.05). The relative contributions of surface roughness and its fluorine content to the osseointegration process requires further research. (AU)

Con la hipótesis de que el ión fluoruro actúa como anabólico sobre las células óseas, el objetivo de este trabajo fue determinar el grado de osteo-integración (en la rata) de implantes (alambre de titanio II, 1 mm de diámetro, 4 mm de largo) anodizados en solución de ácido fosfórico 2 M + NaF 0,2 M (implantes-F) comparados con implantes controles, anodizados en solución de ácido fosfórico 2 M. La composición química de la superficie de los implantes fue evaluada mediante el espectro de dispersión de rayos X producidos durante la observación en el microscopio electrónico de barrido. La superficie de los implantes-F contiene 2.57% de flúor. Ratas macho Sprague-Dawley recibieron dos implantes (en el fémur y en tibia, próximos a la rodilla). Los implantes-F y controles se insertaron en las patas izquierda y derecha respectivamente. En los cortes de hueso sin decalcificación previa se midió el contacto hueso-implante (BIC) y volumen óseo en un volumen definido de tejido (BV/TV). BIC fue significativamente mayor con los Implantes-F respecto de los controles (57,2±3,3% vs. 47,9±3,4, p<0,05). BV/TV no exhibió diferencias significativas entre implantes-F y controles (24,5±2,2% vs. 22,9±1,4, p=0,30). Los perfiles de los niveles de grises de los imágenes pseudo3D de las superficies de los implantes pusieron en evidencia la mayor rugosidad de los implantes-F respecto de los controles (p<0,05). Las contribuciones relativas de la rugosidad y del flúor en el proceso de osteo-integración requieren investigación adicional. (AU)

El crecimiento exponencial del conocimiento médico y la actualización permanente de nuestros graduados / The exponential growth of medical knowledge and the continuous updating of our graduates

Esta nota toca tres asuntos que pueden tratarse separadamentepara el análisis pero que requierenuna solución que las englobe (que se propone).Los asuntos son: a) velocidad del crecimiento de la informacióncientífica, b) actualización continua despuésde la graduación y c) calidad de la información recibidaen ciencias básicas para satisfacer el factor anterior.En esta nota y para simplificar su lectura, la expresión“ciencias básicas” alude a los contenidos de unaserie de disciplinas: biología celular y molecular, bioquí-mica, biofísica, matemáticas, genética, estadística, etc.,de los ciclos Promoción de la Salud y Prevención de laEnfermedad del corriente plan de estudios.

[On the prevalence of hypovitaminosis D in Argentina]. / Sobre la prevalencia de hipovitaminosis D en Argentina.

Between 1987 and the date of the present issue, 10 reports have been published on the prevalence of the vitamin D deficit in Argentina. These studies were done investigating new born babies, children, adolescents, and healthy and institutionalized adults, living in southern, middle or northern cities of Argentina. The weighed prevalence of vitamin D deficit in those reports was 43.3% (436/1007). This figure may be lower than reality because it is not known whether the stratification (age and location of residence) of the sum of samples agree with that of the national population. Taking into account the obvious difficulties in carrying out such a research two areas for further research are suggested: a) an investigation on the solar exposure in summer needed to obviate (or not) the oral supplementation of vitamin D in winter, b) to determine the success of the schema of administration taking into account the current controversy between dose and optimum plasma levels of 25(HO)D3. In both instances, the end point should include some of the physiological functions alluded to in this editorial.

Sobre la prevalencia de hipovitaminosis D en Argentina

Entre 1987 e inicios del corriente año, se han publicado 10 trabajos informando la prevalencia del déficit de vitamina D en nuestro país. Los trabajos incluyeron personas de ambos sexos, neonatos, niños, adultos jóvenes, adultos mayores sanos y adultos institucionalizados, residentes en el sur, centro y norte del país. El promedio ponderado de prevalencia del déficit de 25(HO)D3 en esos trabajos es de 43.3% (436/1007 personas). La prevalencia anotada podría ser menor que la real ya que es desconocido si el millar de personas estudiadas tienen una estratificación etaria y de lugar de residencia, representativa de la población nacional. Ante las evidentes dificultades para la realización de un estudio de esa extensión, se sugiere que los futuros trabajos de investigación establezcan cuál es la magnitud de la exposición solar en verano suficiente como para obviar (o no) la suplementación oral en invierno y definir el éxito de los esquemas de administración, teniendo en cuenta la controversia corriente entre dosificación y nivel plasmático óptimo. En ambos casos, se sugiere tomar como punto final alguna de las funciones fisiológicas afectadas por la hormona, aludidas en este artículo.

Between 1987 and the date of the present issue, 10 reports have been published on the prevalence of the vitamin D deficit in Argentina. These studies were done investigating new born babies, children, adolescents, and healthy and institutionalized adults, living in southern, middle or northern cities of Argentina. The weighed prevalence of vitamin D deficit in those reports was 43.3% (436/1007). This figure may be lower than reality because it is not known whether the stratification (age and location of residence) of the sum of samples agree with that of the national population. Taking into account the obvious difficulties in carrying out such a research two areas for further research are suggested: a) an investigation on the solar exposure in summer needed to obviate (or not) the oral supplementation of vitamin D in winter, b) to determine the success of the schema of administration taking into account the current controversy between dose and optimum plasma levels of 25(HO)D3. In both instances, the end point should include some of the physiological functions alluded to in this editorial.

Sobre la prevalencia de hipovitaminosis D en Argentina

Entre 1987 e inicios del corriente año, se han publicado 10 trabajos informando la prevalencia del déficit de vitamina D en nuestro país. Los trabajos incluyeron personas de ambos sexos, neonatos, niños, adultos jóvenes, adultos mayores sanos y adultos institucionalizados, residentes en el sur, centro y norte del país. El promedio ponderado de prevalencia del déficit de 25(HO)D3 en esos trabajos es de 43.3% (436/1007 personas). La prevalencia anotada podría ser menor que la real ya que es desconocido si el millar de personas estudiadas tienen una estratificación etaria y de lugar de residencia, representativa de la población nacional. Ante las evidentes dificultades para la realización de un estudio de esa extensión, se sugiere que los futuros trabajos de investigación establezcan cuál es la magnitud de la exposición solar en verano suficiente como para obviar (o no) la suplementación oral en invierno y definir el éxito de los esquemas de administración, teniendo en cuenta la controversia corriente entre dosificación y nivel plasmático óptimo. En ambos casos, se sugiere tomar como punto final alguna de las funciones fisiológicas afectadas por la hormona, aludidas en este artículo.(AU)

Between 1987 and the date of the present issue, 10 reports have been published on the prevalence of the vitamin D deficit in Argentina. These studies were done investigating new born babies, children, adolescents, and healthy and institutionalized adults, living in southern, middle or northern cities of Argentina. The weighed prevalence of vitamin D deficit in those reports was 43.3% (436/1007). This figure may be lower than reality because it is not known whether the stratification (age and location of residence) of the sum of samples agree with that of the national population. Taking into account the obvious difficulties in carrying out such a research two areas for further research are suggested: a) an investigation on the solar exposure in summer needed to obviate (or not) the oral supplementation of vitamin D in winter, b) to determine the success of the schema of administration taking into account the current controversy between dose and optimum plasma levels of 25(HO)D3. In both instances, the end point should include some of the physiological functions alluded to in this editorial.(AU)

[Impact factor, its variants and its influence in academic promotion]. / El factor de impacto, sus variantes y su influencia en la promoción académica.

Bibliometrics is a set of methods used to study or measure texts and information. While bibliometric methods are most often used in the field of library and information science, bibliometrics variables have wide applications in other areas. One popular bibliometric variable is Garfield's Impact Factor (IF). IF is used to explore the impact of a given field, the impact of a set of researchers, or the impact of a particular paper. This variable is used to assess academic output and it is believed to affect adversely the traditional approach and assessment of scientific research. In our country, the members of the evaluation committees of intensive research institutions, e.g. the National Scientific and Technical Research Council (CONICET) use IF to assess the quality of research. This article revises the exponential growth of bibliometrics and attempts to expose the overall dissatisfaction with the analytical quality of IF. Such dissatisfaction is expressed in the number of investigations attempting to obtain a better variable of improved analytical quality.

El factor de impacto, sus variantes y su influencia en la promoción académica / Impact factor, its variants and its influence in academic promotion

La bibliometría refiere a un conjunto de métodos de análisis o medición de la información. Aunque estos métodos pertenecen a la bibliotecología y ciencias de la información, algunas variables bibliométricas son muy frecuentemente utilizadas en áreas afines. Una de las más populares es el Factor de Impacto (FI). El FI es utilizado para determinar el impacto de un área en una determinada disciplina, el impacto de un grupo de investigadores o el de un trabajo en particular. Esta variable es usada en la evaluación cuantitativa de la producción académica y estaría amenazando el curso de la metodología tradicional y la evaluación de la investigación científica. En nuestro medio, los miembros de las comisiones evaluadoras de instituciones de investigación intensiva como el Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), utilizan el FI para calificar el trabajo de los investigadores. Este artículo revisa el crecimiento exponencial de la bibliometría e intenta exponer la insatisfacción general sobre la calidad analítica del FI. La insatisfacción mencionada es evidente al observar el número de investigaciones en curso que intentan obtener una nueva variable de calidad analítica perfeccionada.

Bibliometrics is a set of methods used to study or measure texts and information. While bibliometric methods are most often used in the field of library and information science, bibliometrics variables have wide applications in other areas. One popular bibliometric variable is Garfield´s Impact Factor (IF). IF is used to explore the impact of a given field, the impact of a set of researchers, or the impact of a particular paper. This variable is used to assess academic output and it is believed to affect adversely the traditional approach and assessment of scientific research. In our country, the members of the evaluation committees of intensive research institutions, e.g. the National Scientific and Technical Research Council (CONICET) use IF to assess the quality of research. This article revises the exponential growth of bibliometrics and attempts to expose the overall dissatisfaction with the analytical quality of IF. Such dissatisfaction is expressed in the number of investigations attempting to obtain a better variable of improved analytical quality.

Effect of rhGH on the synthesis and secretion of VLDL to lymph and plasma from the intestine of the female rat.

The intravenous administration of rhGH (recombinant human Growth Hormone) to fasting female rats causes an increase in the rate of synthesis and secretion of VLDL (very low density lipoproteins). This phenomenon has three striking characteristics: (1) the demonstration of an unexpected lipogenic effect of rhGH, (2) its rapid occurrence after intravenous injection of the hormone and (3) the apparent dependence on the levels of circulating estrogens, as deduced by the lack of effect of rhGH on males and castrated females. The target tissue for the lipogenic effect was traced to the intestine by means of perfusion experiments of isolated duodenal loops. Impairment of liver blood supply discarded this tissue as the source of VLDL induced by rhGH. After a single dose of rhGH (T(1/2)=16min), the increase in plasma TAG (triacylglycerides) levels followed a positive exponential course that lasted ca. 3h. The same phenomenon (with no significant differences in kinetic parameters) was observed in three other experimental circumstances: fasting intact virgin female rats with impaired hepatic circulation, perfusion of isolated duodenum and sampling of mesenteric lymph. It is assumed that rhGH stimulates the synthesis of TAG and VLDL by the physiological mechanisms already present in enterocytes. Because increased plasma levels of VLDL and GH have been demonstrated in the last week of rat pregnancy, we believe that the reported phenomenon has physiological implications, hypothetically associated with fetal lung maturation. As an hypothesis, we suggest that the effect of growth hormone (of pituitary or placental origin) on the synthesis and secretion of VLDL by enterocytes uses a nongenomic pathway.

Growth-associated changes in the periodontal bone and molar teeth of male rats.

Here we report quantitative data associating periodontal bone variables of young conventional rats with the growth process. The hemimandibles of male rats (IIM/Fm stock, 2 to 15 wk of age.) were excised and submitted to conventional morphologic, radiologic, and histologic evaluation. The length, area, or X-ray absorbance of various regions or structures was measured on digital images of radiographs by using an image-analysis program. The sum of periodontal bone areas undergoing resorption (interproximal + intraradicular) increased until 9 or 10 wk of age and decreased thereafter. Mineral accretion rates and mineral density asymptotes were not significantly different among molars. The mineral density of resorption areas in alveolar bone fitted sinusoidal kinetics, indicative of the 'instability' of the tissue due to its high metabolic activity. Mineral accretion rates and mineral density asymptotes were not significantly different among molars. The proportion of root length within alveolar bone exhibited a biphasic curve (minimum at 5 wk of age), due to differences in the growth rates of variables involved in its calculation (distance between the cementoenamel junction to the apex and height of the resorption areas). The distance between the cementoenamel junction and alveolar bone crest over time fitted a sigmoidal function with a point of inflection that did not differ significantly from that of body or mandible dry weight. In summary, the growth process appears to affect periodontal bone support and the distance between the cementoenamel junction and alveolar bone crest in male rats.

Effect of calcium on rat intestinal alkaline phosphatase activity and molecular aggregation.

Two fractions of rat intestinal alkaline phosphatase (IAP) were detected by Western blot: 168 +/- 6 and 475 +/- 45 kDa. The low molecular weight fraction constitutes 43% of the isolated proteins exhibiting 82% of the enzymatic activity, and a heavier fraction constitutes 57% of the isolated proteins and has 18% of the enzymatic activity. Calcium produced an increase of the 475-kDa form to the detriment of the 168-kDa form. This work also describes the kinetic and structural changes of IAP as a function of calcium concentration. With [Ca2+] < 10 mmole/L, the Ca(2+)-IAP interaction fitted a binding model with 7.8 +/- 4.4 moles of Ca2+ /mole of protein, affinity constant = 19.1 +/- 8.4 L/mmole, and enzymatic activity increased as a linear function of [Ca2+] (r = 0.946 p < 0.01). On the other hand, with [Ca2+] > 10 mmole/L the data did not fit this model and, the enzymatic activity decreased as a function of [Ca2+] (r = - 0.703 p < 0.05).

[Body mass index and the reasoning of an astronomer]. / El indice de masa corporal y los razonamientos de un astrónomo.

This article traces the story of the Body Mass Index, also called Quetelet's Index or the ratio between weight (in kilograms) divided by height (in meters) squared. The Index is used extensively in clinical practice to characterize overweight. Based on literature reports, probable answers are furnished for the following questions: Which were Quetelet's objectives at associating weight with height? Why did he choose to select Weight/(Height)2? When did the index begin to be applied in modern clinical medicine? Which were the experimental studies which associated the ratio Weight/ (Height)2 with the body fat content? Which are the limitations of the ratio?

Effect of fluoride on the secretion of insulin in the rat.

Sodium fluoride (CAS 7681-49-4) 5-20 micromol/L in the extracellular space inhibited insulin secretion by isolated Langerhans islets stimulated with glucose. Insulin secretion followed a negative exponential function. This phenomenon is rapidly reversible. Perfusion of pancreatic tissue (rat) in vivo with stimulatory levels of glucose revealed that 20 micromol/L fluoride in the perfusion fluid inhibited the initial and sustained phases of insulin secretion to 15% of that of controls. The stimulatory effects of the ionophore A23187, phorbol-ester and forskolin on the secretion of insulin of isolated rat Langerhans islets in vitro were inhibited by 20 micromol/L fluoride. The results suggested that fluoride affects some stage of insulin secretion situated below the cascade of events that include the participation of calmodulin, protein-kinase C and cyclic AMP.