Importancia de la leche y sus potenciales efectos en la salud humana / Importance of milk and its potential efects on human health

El Código Alimentario Argentino establece: "Con la denomi-nación de leche sin calificativo alguno, se entiende el producto obtenido por el ordeño total e ininterrumpido, en condiciones de higiene, de la vaca lechera en buen estado de salud y ali-mentación, proveniente de tambos inscriptos y habilitados por la Autoridad Sanitaria Bromatológica Jurisdiccional y sin aditivos de ninguna especie"1. La leche de vaca es un componente cuantitativamente útil en la alimentación humana en gran parte debido al acceso generali-zado a partir de su industrialización y comercialización. Su com-posición la hace de interés para adaptar su uso y prescripción en distintos momentos de la vida y en la promoción de la salud.Según estudios de investigación, los efectos no se limitarían exclu-sivamente a su valor nutricional, sino que sumarían otros poten-ciales en determinadas patologías como la enfermedad cardiovas-cular, algunos tipos de cáncer, hipertensión arterial, en patología ósea o dental y en la lucha frente al sobrepeso y la obesidad.Por este motivo, el Grupo de Trabajo Alimentos de la Sociedad Argentina de Nutrición realizó esta revisión sobre los potenciales efectos de la leche: virtuosos o adversos.

Resveratrol inhibits Ca

BACKGROUND@#Resveratrol has been shown to inhibit platelet aggregation. However, the mechanism for this action of resveratrol remains to be clarified. The purpose of this study was to elucidate the Ca@*METHODS@#Ca@*RESULTS@#Thapsigargin-induced Ca@*CONCLUSIONS@#The results suggest that resveratrol inhibits thrombin-induced platelet aggregation through decreasing Ca

Cardiac function and intracellular Ca2+ handling proteins are not impaired by high-saturated-fat diet-induced obesity

Obesity is often associated with changes in cardiac function; however, the mechanisms responsible for functional abnormalities have not yet been fully clarified. Considering the lack of information regarding high-saturated-fat diet-induced obesity, heart function, and the proteins involved in myocardial calcium (Ca2+) handling, the aim of this study was to test the hypothesis that this dietary model of obesity leads to cardiac dysfunction resulting from alterations in the regulatory proteins of intracellular Ca2+ homeostasis. Male Wistar rats were distributed into two groups: control (C, n=18; standard diet) and obese (Ob, n=19; high-saturated-fat diet), which were fed for 33 weeks. Cardiac structure and function were evaluated using echocardiographic and isolated papillary muscle analyses. Myocardial protein expressions of sarcoplasmic reticulum Ca2+-ATPase, phospholamban (PLB), PLB serine-16 phosphorylation, PLB threonine-17 phosphorylation, ryanodine receptor, calsequestrin, Na+/Ca2+ exchanger, and L-type Ca2+ channel were assessed by western blot. Obese rats presented 104% increase in the adiposity index (C: 4.5±1.4 vs Ob: 9.2±1.5%) and obesity-related comorbidities compared to control rats. The left atrium diameter (C: 5.0±0.4 vs Ob: 5.5±0.5 mm) and posterior wall shortening velocity (C: 36.7±3.4 vs Ob: 41.8±3.8 mm/s) were higher in the obese group than in the control. The papillary muscle function was similar between the groups at baseline and after inotropic and lusitropic maneuvers. Obesity did not lead to changes in myocardial Ca2+ handling proteins expression. In conclusion, the hypothesis was not confirmed, since the high-saturated-fat diet-induced obese rats did not present cardiac dysfunction or impaired intracellular Ca2+ handling proteins.

Disfunção cardíaca induzida por obesidade genética e dietética: modulação pelo trânsito de cálcio / Cardiac dysfunction induced by genetic and dietetic obesity: modulation by calcium handling

Introdução: A obesidade é considerada importante problema de saúde pública e fator de risco para o desenvolvimento de doenças cardiovasculares. Estudos apontam que o trânsito de cálcio (Ca+2) intracelular e extracelular, mecanismo essencial no acoplamento excitação-contração-relaxamento cardíaco, está envolvido nesse processo patológico. Enquanto o influxo de Ca+2 promove aumento da concentração de Ca+2 livre no citosol na fase de contração, a recaptura e a extrusão do Ca+2 são importantes para a diminuição do Ca+2 intracelular durante o relaxamento. Objetivo: Identificar, baseado na literatura científica, a modulação da disfunção cardíaca pelo trânsito de cálcio em modelos de obesidade genética e dietética. Métodos: A busca de artigos em bases de dados eletrônicas foi realizada com palavras-chaves e seus correspondentes em inglês. Resultados: Inicialmente os artigos que apresentassem uma das palavras-chaves no título foram selecionados. Após processo de triagem, foram identificados 23 artigos para leitura na íntegra. Foram selecionados ao debate na seção "Discussão" apenas 18 artigos, visto que apresentaram conteúdo satisfatório sobre o tema abordado. Conclusão: A literatura mostra que a obesidade, genética ou dietética, promove disfunções cardíacas moduladas por diversas alterações no trânsito de Ca+2 intracelular e em suas proteínas regulatórias.

Introduction: Obesity is considered an important public that presents increasing prevalence on a global scene. Obese individuals have greater susceptibility to the development of cardiac disease. Studies show that calcium (Ca2+) handling, essential mechanism in the process contraction-relaxation of the cardiac muscle, is associated with cardiac dysfunction in obesity models. While Ca2+ influx promotes elevation of free Ca2 + concentration in the cytosol in the contraction period, the recapture and extrusion Ca2 + are important to Ca2+ reduction during the relaxation. Objective: To identify, based on scientific literature, modulation of cardiac function by calcium handling impairments in models of genetic and dietetic obesity. Methods: The search for articles in electronic databases was performed with key words. Results: Initially studies that showed in title one of the key words were selected for analysis. 23 articles were obtained for reading in full. Then, 18 relevant articles were identified on cardiac dysfunction in obesity, both genetic and dietary and participation of the intracellular calcium handling. Conclusion: The literature presents that both genetic and dietetic obesity promotes cardiac dysfunction modulated by various changes in traffic intracellular Ca2+ and its regulators protein.

Use of otolith strontium: calcium and zinc:calcium ratios as an indicator of the habitat of Percophis brasiliensis Quoy & Gaimard, 1825 in the southwestern Atlantic Ocean

We evaluate the simultaneous use of Sr: Ca and Zn: Ca ratios of the sagitta otolith as a potential indicator of the habitat of Percophis brasiliensis along a latitudinal gradient in the southwestern Atlantic Ocean (34-42ºS and 51-67ºW), in order to reliably identify fish stocks. Fish were collected in three sampling sites: Argentine-Uruguayan Common Fishing Zone (AUCFZ), El Rincón (ER) and San Matías Gulf (SMG). The otolith Sr:Ca and Zn:Ca ratios were determined by ICP-OES and EDTA volumetric method. The otolith Sr:Ca ratio was similar in the three sampling sites, while the Zn:Ca ratio was significantly higher in AUCFZ than in ER and SMG for all age groups. The discriminant analysis showed an association between the otolith Sr:Ca and Zn:Ca ratios from ER and SMG. Present results suggest the potential occurrence of two fish stocks of P. brasiliensis in the study area.

Evaluamos el uso simultáneo de las relaciones Sr:Ca y Zn:Ca de los otolitos sagittae como un potencial indicador de hábitat de Percophis brasiliensis a lo largo de un gradiente longitudinal el Atlántico sudoccidental (34-42ºS - 51-67ºW) con el fin de contribuir a la identificación de los stocks pesqueros. Los peces fueron capturados en tres sitios de muestreo: Zona Común de Pesca Argentina-Uruguaya (ZCPAU), El Rincón (ER) y el Golfo San Matías (GSM). Las relaciones Sr:Ca y Zn:Ca se determinaron por ICP-OES y por titulación con EDTA. La relación Sr:Ca fue similar en los tres sitios de muestreo. La relación Zn:Ca fue mayor en la ZCPAU que en las demás areas (ER y GSM) para todos los rangos de edad. El análisis discriminante mostró una asociación entre las relaciones Sr:Ca y Zn:Ca de ER y GSM. Los resultados de este trabajo sugieren la presencia de al menos dos stocks de P. brasiliensis en el aérea de estudio.

Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

In cardiomyocytes, calcium (Ca2+) release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.

Modalidades de parada cardíaca induzida: hipercalemia e hipocalcemia - revisão de literatura / Modes of induced cardiac arrest: hyperkalemia and hypocalcemia - Literature review

A entrada de sódio e cálcio desempenham efeito chave no miócito submetido à parada cardíaca por hiperpotassemia. Eles provocam edema celular, acidose, consumo de trifosfato de adenosina e desencadeiam processo de morte celular programada. A parada cardíaca provocada por hipocalcemia mantém os níveis intracelulares de trifosfato de adenosina, melhora o rendimento diastólico e reduz o consumo de oxigênio, o que pode ser traduzido em melhor proteção do miócito às lesões provocadas pela parada cardíaca induzida.

The entry of sodium and calcium play a key effect on myocyte subjected to cardiac arrest by hyperkalemia. They cause cell swelling, acidosis, consumption of adenosine triphosphate and trigger programmed cell death. Cardiac arrest caused by hypocalcemia maintains intracellular adenosine triphosphate levels, improves diastolic performance and reduces oxygen consumption, which can be translated into better protection to myocyte injury induced by cardiac arrest.

Receptor de rianodina, fuga de calcio y arritmias / Ryanodine receptor, calcium leak and arrhythmias

La participación del canal de Ca2+/receptor de rianodina en el acoplamiento excitación-contracción cardiaco se conoce desde finales de los años ochenta, cuando en varios trabajos trascendentales se comunicó por primera vez su purificación y se encontró que correspondía a las estructuras conocidas como «pies¼ localizadas en las cisternas terminales del retículo sarcoplásmico. Adicionalmente a su papel como canal responsable del aumento global y transitorio de Ca2+ que activa a la maquinaria contráctil durante el ciclo cardiaco, el receptor de rianodina también libera Ca2+ durante la fase de relajación, dando lugar a la fuga de Ca2+ en la diástole que en condiciones fisiológicas regula el nivel de Ca2+ luminal, pero cuando se encuentra alterada participa en la generación de arritmias adquiridas o hereditarias. Recientemente, el esfuerzo de diversos grupos de investigación se ha enfocado en el desarrollo de herramientas farmacológicas para controlar la fuga diastólica de Ca2+ que se presenta alterada en algunas enfermedades cardiacas. En esta revisión nos enfocamos en describir la participación del receptor de rianodina cardiaco en la fuga diastólica de Ca2+ así como los diversos enfoques terapéuticos que se han implementado para controlar su actividad exacerbada en la diástole.

The participation of the ionic Ca2+ release channel/ryanodine receptor in cardiac excitation-contraction coupling is well known since the late '80s, when various seminal papers communicated its purification for the first time and its identity with the "foot" structures located at the terminal cisternae of the sarcoplasmic reticulum. In addition to its main role as the Ca2+ channel responsible for the transient Ca2+ increase that activates the contractile machinery of the cardiomyocytes, the ryanodine receptor releases Ca2+ during the relaxation phase of the cardiac cycle, giving rise to a diastolic Ca2+ leak. In normal physiological conditions, diastolic Ca2+ leak regulates the proper level of luminal Ca2+, but in pathological conditions it participates in the generation of both, acquired and hereditary arrhythmias. Very recently, several groups have focused their efforts into the development of pharmacological tools to control the altered diastolic Ca2+ leak via ryanodine receptors. In this review, we focus our interest on describing the participation of cardiac ryanodine receptor in the diastolic Ca2+ leak under physiological or pathological conditions and also on the therapeutic approaches to control its undesired exacerbated activity during diastole.

Rational use of blood calcium determinations / Uso racional da dosagem de cálcio no sangue

CONTEXT AND OBJECTIVE: This study was motivated by the recent excessive increase in requests for blood calcium determinations and laboratory tests in general, in the Hospital das Clínicas complex of Faculdade de Medicina, Universidade de São Paulo (HCFMUSP). Its aim was to suggest rules for the determination of total and ionized calcium in our intensive care units, emergency department, wards and outpatient services, thus contributing towards improving the quality of medical care and achieving more appropriate use of human and financial resources. DESIGN AND SETTING: Critical analysis on clinical and laboratory data and the pertinent scientific literature, conducted by the study group for rational clinical laboratory use, which is part of the Central Laboratory Division, HCFMUSP. METHODS: The study group reviewed scientific publications, statistics and clinical and laboratory data concerning requests for total and ionized calcium determinations in the settings of intensive care units, emergency department, wards and outpatient services. RESULTS: From this critical analysis, clinical decision flow diagrams aimed at providing guidance for ordering these tests were constructed. CONCLUSIONS: Use of the proposed flow diagrams may help to limit the numbers of inappropriate requests for ionized and total calcium determinations, with consequent reductions in the number of tests, risks to patients and unnecessary costs. .

CONTEXTO E OBJETIVO: Este trabalho foi motivado pelo recente aumento excessivo de solicitações de dosagem de cálcio no sangue, assim como de exames laboratoriais em geral, no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). Seu objetivo foi sugerir regras para a determinação de cálcio total e iônico nas nossas unidades de terapia intensiva, pronto-socorro, enfermarias e ambulatórios e contribuir para a melhoria da qualidade da assistência médica, com utilização mais adequada dos recursos humanos e financeiros. TIPO DO ESTUDO E LOCAL: Análise crítica de dados clínicos, laboratoriais e da literatura médica pertinente, realizada pelo grupo de estudos para o uso racional do laboratório clínico, vinculado à Divisão de Laboratório Central do HCFMUSP. MÉTODOS: O grupo de estudos reviu publicações científicas, estatísticas e dados clínico-laboratoriais relativos às solicitações de cálcio total e iônico nos ambientes das unidades de terapia intensiva, prontos-socorros, enfermarias e ambulatórios. RESULTADOS: A partir dessa análise crítica, foram construídos fluxogramas de decisão clínica que visam orientar a requisição desses testes. CONCLUSÕES: A utilização dos fluxogramas propostos pode ajudar a limitar a solicitação inadequada das dosagens de cálcio total e iônico, com consequente redução do número de exames, de riscos para os pacientes e de custos desnecessários. .

Effects of eugenol on resting tension of rat atria

In cardiac and skeletal muscle, eugenol (μM range) blocks excitation-contraction coupling. In skeletal muscle, however, larger doses of eugenol (mM range) induce calcium release from the sarcoplasmic reticulum. The effects of eugenol are therefore dependent on its concentration. In this study, we evaluated the effects of eugenol on the contractility of isolated, quiescent atrial trabeculae from male Wistar rats (250-300 g; n=131) and measured atrial ATP content. Eugenol (1, 3, 5, 7, and 10 mM) increased resting tension in a dose-dependent manner. Ryanodine [100 µM; a specific ryanodine receptor (RyR) blocker] and procaine (30 mM; a nonspecific RyR blocker) did not block the increased resting tension induced by eugenol regardless of whether extracellular calcium was present. The myosin-specific inhibitor 2,3-butanedione monoxime (BDM), however, reversed the increase in resting tension induced by eugenol. In Triton-skinned atrial trabeculae, in which all membranes were solubilized, eugenol did not change resting tension, maximum force produced, or the force vs pCa relationship (pCa=-log [Ca2+]). Given that eugenol reduced ATP concentration, the increase in resting tension observed in this study may have resulted from cooperative activation of cardiac thin filaments by strongly attached cross-bridges (rigor state).

Liberación de calcio de un sellador endodóntico experimental a base de trióxido mineral / Calcium release from an experimental endodontic sealer based on mineral trioxide

El objetivo de este estudio fue evaluar, en un medio acuoso, la liberación de calcio de un sellador endodóntico experimental a base de polvo de MTA Angelus mezclado con una resina polivinílica de base acuosa (polímero soluble en agua), comparativamente con el MTA Angelus. Cinco discos de sellador endodóntico experimental elaborados con polvo de MTA Angelus mezclados con con una resina de base acuosa como vehículo, fueron fabricados utilizando secciones desterilizadas de un caño de PVC de 12mm de diámetro interno y 4mm de espesor, constituyendo el grupo A. Otros 5 discos de MTA Angelus fueron elaborados según indicación del fabricante, conformando el grupo B. Todas las muestras fueron manejadas asépticamente y suspendidas en recipientes estériles conteniendo agua destilada desionizada y mantenidas a 37 grados durante 24 horas. Como control negativo se usaron dos anillos vacíos sumergidos en agua destilada estéril. Pasado ese lapso el remanente líquido fue estudiado por espectrometría de absorción atómica y generación de hidruros para determinar la concentración de calcio. El grupo A mostró una media de liberación de calcio de 0,71 g/l y el grupo B de 0,59 g/l. El grupo control no verificó concentración de calcio (0,00 g/l). A la luz de los resultados, el sellador endodóntico a base de trióxido mineral agregado presentó mayor liberación de iones de calcio comparativamente con el MTA Angelus, siendo esta diferencia estadísticamente significativa (p<0,01).

The Role of the Calcium and the Voltage Clocks in Sinoatrial Node Dysfunction

Recent evidence indicates that the voltage clock (cyclic activation and deactivation of membrane ion channels) and Ca2+ clocks (rhythmic spontaneous sarcoplasmic reticulum Ca2+ release) jointly regulate sinoatrial node (SAN) automaticity. However, the relative importance of the voltage clock and Ca2+ clock for pacemaking was not revealed in sick sinus syndrome. Previously, we mapped the intracellular calcium (Cai) and membrane potentials of the normal intact SAN simultaneously using optical mapping in Langendorff-perfused canine right atrium. We demonstrated that the sinus rate increased and the leading pacemaker shifted to the superior SAN with robust late diastolic Cai elevation (LDCAE) during beta-adrenergic stimulation. We also showed that the LDCAE was caused by spontaneous diastolic sarcoplasmic reticulum (SR) Ca2+ release and was closely related to heart rate changes. In contrast, in pacing induced canine atrial fibrillation and SAN dysfunction models, Ca2+ clock of SAN was unresponsiveness to beta-adrenergic stimulation and caffeine. Ryanodine receptor 2 (RyR2) in SAN was down-regulated. Using the prolonged low dose isoproterenol together with funny current block, we produced a tachybradycardia model. In this model, chronically elevated sympathetic tone results in abnormal pacemaking hierarchy in the right atrium, including suppression of the superior SAN and enhanced pacemaking from ectopic sites. Finally, if the LDCAE was too small to trigger an action potential, then it induced only delayed afterdepolarization (DAD)-like diastolic depolarization (DD). The failure of DAD-like DD to consistently trigger a sinus beat is a novel mechanism of atrial arrhythmogenesis. We conclude that dysfunction of both the Ca2+ clock and the voltage clock are important in sick sinus syndrome.

Dynamic analysis of Ca2+ level during bovine oocytes maturation and early embryonic development

Mammalian oocyte maturation and early embryo development processes are Ca(2+)-dependent. In this study, we used confocal microscopy to investigate the distribution pattern of Ca2+ and its dynamic changes in the processes of bovine oocytes maturation, in vitro fertilization (IVF), parthenogenetic activation (PA) and somatic cell nuclear transfer (SCNT) embryo development. During the germinal vesicle (GV) and GV breakdown stage, Ca2+ was distributed in the cortical ooplasm and throughout the oocytes from the MI to MII stage. In IVF embryos, Ca2+ was distributed in the cortical ooplasm before the formation of the pronucleus. In 4-8 cell embryos and morulas, Ca2+ was present throughout the blastomere. In PA embryos, Ca2+ was distributed throughout the blastomere at 48 h, similar to in the 4-cell and 8-cell phase and the morula. At 6 h after activation, there was almost no distribution of Ca2+ in the SCNT embryos. However, Ca2+ was distributed in the donor nucleus at 10 h and it was distributed throughout the blastomere in the 2-8 cell embryos. In this study, Ca2+ showed significant fluctuations with regularity of IVF and SCNT groups, but PA did not. Systematic investigation of the Ca2+ location and distribution changes during oocyte maturation and early embryo development processes should facilitate a better understanding of the mechanisms involved in oocyte maturation, reconstructed embryo activation and development, ultimately improving the reconstructed embryo development rate.

TNF alfa modifica la respuesta de la frecuencia de batido ciliar a la carga viscosa, asociado a alteraciones en el calcio intracelular en células ciliadas respiratorias humanas / TNF alpha modifies ciliary beat frequency in response to viscous overload, associated to changes in intracellular calcium in human respiratory ciliated cells

Introducción: Secreciones sinonasales patológicas y elevados niveles de factor de necrosis tumoral alfa (TNF alfa) se han encontrado en mucosa sin usal de pacientes con sinusitis crónica. Las células ciliadas respiratorias tienen una reserva funcional que les permite autorregular su frecuencia de batido ciliar (FBC) en respuesta a cambios en la viscosidad, modificando los niveles de calcio intraacelular [Ca+²]ic. Objetivo: Nuestro objetivo es determinóar si TNFalfa afecta el mecanismo de autorregulación y la homeostasis del calcio intraacelular frente a cambios en la viscosidad. Material y método: Cultivos primarios de explantes de tejido adenoideo. Registro de FBC mediante microfotodensitometría. Cultivos tratados con TNFalfa (10 ng/ml) o control durante 24 y 48 horas. Se in crementó la viscosidad agregando dextrano 500 al 10 por ciento y 20 por ciento. Se midió [Ca+²]ic en células cargadas con Fura 2AM. Resultados: El tratamiento con TNFalfa por 48 horas produjo una significativa disminución de la FBC a baja viscosidad, aumento significativo de [Ca+²]ic y caída mayor de FBC en cultivos tratados con tapsigargina (bloqueador bomba calcio-ATPasa retículo). in o se encontró diferencia a alta viscosidad. Conclusión: Después de 48 horas de exposición a TNFalfa se observa un efecto negativo en el mecanismo de adaptación de las células ciliadas a un medio con baja viscosidad, probablemente secundario a cambios en la homeostasis del [Ca+²]ic.

Introduction: Pathologic sinonasal secretions and elevated levels of tumor necrosis factor alpha (TNFalpha) have been in oted in sin us mucosa ofpatients with chronic sinusitis. Respiratory ciliated cells have a functional reserve that allows them to autoregulate their ciliary beat in response to the changesin viscosity, modify in g intraacellular calcium levels [Ca+²]ic. Aim: Our goal was to determinate if TNFalpha affect this autoregulation to viscosity and calcium homeostasis. Material and Method: Primary cultures from adenoid tissue expiants. Ciliary beat frequency (CBF) was recorded usin g microphotodensitometry Cultures viere treated with TNF alpha (10 ng/ml) or control during 24 and 48 hours. Viscosity was increased by add in g dextran 500 10 percent and 20 percent. [Ca+²]ic was determined in cells loaded with Fura-2AM. Results: 48 hours treatment with TNFalpha produced a significant decrease in CBF at low viscosity significant increase in [Ca+²]ic and greater decrese in CBF in cultures treated with thapsigargin (endoplasmic calcium-ATPase pump blocker). Conclusions: After 48 hours of exposure to TNF alpha a negative effect in the adaptation mechanism to a low viscous media is observed in ciliated cells, probably secondary to changesin homeostasis of [Ca+²]ic.

Synaptic vesicle pool size, release probability and synaptic depression are sensitive to Ca2+ buffering capacity in the developing rat calyx of Held

The calyx of Held, a specialized synaptic terminal in the medial nucleus of the trapezoid body, undergoes a series of changes during postnatal development that prepares this synapse for reliable high frequency firing. These changes reduce short-term synaptic depression during tetanic stimulation and thereby prevent action potential failures during a stimulus train. We measured presynaptic membrane capacitance changes in calyces from young postnatal day 5-7 (p5-7) or older (p10-12) rat pups to examine the effect of calcium buffer capacity on vesicle pool size and the efficiency of exocytosis. Vesicle pool size was sensitive to the choice and concentration of exogenous Ca2+ buffer, and this sensitivity was much stronger in younger animals. Pool size and exocytosis efficiency in p5-7 calyces were depressed by 0.2 mM EGTA to a greater extent than with 0.05 mM BAPTA, even though BAPTA is a 100-fold faster Ca2+ buffer. However, this was not the case for p10-12 calyces. With 5 mM EGTA, exocytosis efficiency was reduced to a much larger extent in young calyces compared to older calyces. Depression of exocytosis using pairs of 10-ms depolarizations was reduced by 0.2 mM EGTA compared to 0.05 mM BAPTA to a similar extent in both age groups. These results indicate a developmentally regulated heterogeneity in the sensitivity of different vesicle pools to Ca2+ buffer capacity. We propose that, during development, a population of vesicles that are tightly coupled to Ca2+ channels expands at the expense of vesicles more distant from Ca2+ channels.

New concepts in pathogenesis of renal hypophosphatemic syndromes

During the past decades, our knowledge of renal phosphate handling has advanced dramatically. This advance is primarily due to the discovery of sodium-phosphate transport channels and their regulation in health and disease. The discovery of phosphatonins, initially in patients with tumor-induced osteomalacia, has not only allowed us to develop a better understanding of several rare diseases including vitamin D-resistant rickets, but also it has expanded our knowledge of the dynamic interaction between the bone and the kidney critical to bone mineralization. In this review, the author focuses on these new developments and their importance to our understanding of phosphate homeostasis in health and disease

Role of calcium-sensing receptor in bone biology.

Bone turnover helps accomplish long-term correction of the extracellular calcium (Ca2+ o) homeostasis by the actions of osteoblasts and osteoclasts. These processes are highly regulated by the actions of hormones, most prominently parathyroid hormone (PTH), the release of which is a function of the Ca2+ o, and is regulated by the action of the Ca2+ -sensing receptor (CaR) in the parathyroid gland. Various mutations of the CaR gene give rise to gain or loss of functions leading respectively to hypo- or hypercalcaemic conditions. CaR could conceivably be a target for local changes in the Ca2+ o in the bone microenvironment thereby acting as a 'growth factor' in various cells residing in the bone marrow. This review discusses about the roles of the CaR in bone. In osteoblasts, CaR promotes its proliferation, differentiation and mineralization. In osteoclasts, CaR mediates high Ca2+ o-stimulated osteoclast differentiation as well as osteoclast apoptosis. CaR regulates localization of haematopoietic stem cells from the foetal liver to endosteal niche, the socalled homing. Although the CaR plays a key role in the defense against hypercalcaemia, its function can be aberrant in humoral hypercalcaemia of malignancy in which CaR activation stimulates secretion of parathyroid hormone-related peptide (PTHrP) secretion. Increased levels of PTHrP cause a vicious hypercalcaemic state resulting from its increased bone-resorptive and positive renal calcium reabsorbing effects give rise to hypercalcaemia. CaR mediates a variety of functions of Ca2+ o in the bone microenvironment under both normal and pathological conditions.

The physiology of vitamin D : current concepts.

The vitamin D endocrine system, besides playing pivotal roles in calcium homeostasis & bone mineral metabolism, is now recognized to subserve a wide range of fundamental biological functions in cell differentiation, inhibition of cell growth as well as immuno modulation. Vitamin D is a prohormone which is converted into its active hormonal form 1, 25 (OH)D2 D, 1, 25 (OH)D2 D activates its cellular receptor (VDR) which activate target genes to engender its biological actions. This review provides a summary of recent understanding of the complex actions of the vitamin D hormone 1, 25 (OH)2 D which is a final product of 1alpha hydroxylation in the proximal tubular cells of kidneys. Emerging evidence also indicates both 1, 25 (OH)2 D3 independent as well as depended action of vitamin D receptor (VDR). Thus, the vitamin D system action may involve more than one single receptor and legand. The presence of 1alpha hydroxylase in many target cells other than proximal renal tubular cells indicates autocrine and paracrine functions for 1, 25 (OH)2 D3 in the control of cell proliferation and differentiation. Vitamin D and related molecules belong to a elaborate endocrine system that acts on target genomic receptors in several organ systems to control cell proliferation and differentiation.

Biología molecular de la insuficiencia cardíaca / Molecular biology of heart failure

Heart failure is a complex disorder involving maladaptive responses that result in defective regulation and function of multiple biological systems. Adequate understanding of these processes is basic for the development of novel therapeutic approaches. This review, directed to the molecular biology of the heart, is divided in three sections, with some redundancy between them: hypertrophy and remodeling, molecular composition of the failing heart, and molecular mechanisms leading to heart failure.