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.

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.

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.

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.

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).

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.

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.

Roles of calcium and IP3 in impaired colon contractility of rats following multiple organ dysfunction syndrome

The purpose of the present study was to explore changes in rat colon motility, and determine the roles of calcium and inositol (1,4,5)-triphosphate (IP3) in colon dysmotility induced by multiple organ dysfunction syndrome (MODS) caused by bacteria peritonitis. The number of stools, the contractility of the muscle strips and the length of smooth muscle cells (SMC) in the colon, the concentration of calcium and IP3 in SMC, and serum nitric oxide were measured. Number of stools, fecal weight, IP3 concentration in SMC and serum nitric oxide concentration were 0.77 ± 0.52 pellets, 2.51 ± 0.39 g, 4.14 ± 2.07 pmol/tube, and 113.95 ± 37.89 mumol/L, respectively, for the MODS group (N = 11) vs 1.54 ± 0.64 pellets, 4.32 ± 0.57 g, 8.19 ± 3.11 pmol/tube, and 37.42 ± 19.56 mumol/L for the control group (N = 20; P < 0.05). After treatment with 0.1 mM acetylcholine and 0.1 M potassium chloride, the maximum contraction stress of smooth muscle strips, the length of SMC and the changes of calcium concentration were 593 ± 81 and 458 ± 69 g/cm³, 48.1 ± 11.8 and 69.2 ± 15.7 muM, 250 ± 70 and 167 ± 48 percent, respectively, for the control group vs 321 ± 53 and 284 ± 56 g/cm³, 65.1 ± 18.5 and 87.2 ± 23.7 muM, 127 ± 35 and 112 ± 35 percent for the MODS group (P < 0.05). Thus, colon contractility was decreased in MODS, a result possibly related to reduced calcium concentration and IP3 in SMC.

Efectos contráctiles dependientes del calcio intracelular inducidos por la serotonina en la arteria umbilical humana / Intracellular calcium-dependent contractile effects of serotonin in the human umbilical artery

Antecedentes: Los vasos umbilicales humanos se caracterizan por la ausencia de inervación y por consecuencia, las diferentes sustancias vasoactivas y la respuesta contráctil a través de los iones de calcio son los factores que determinan el flujo sanguíneo al espacio intervelloso en condiciones normales y patológicas, como es el caso de la preeclampsia eclampsia. Objetivo: Aportar información adicional de la respuesta contráctil de la serotonina en relación al calcio intracelular en la arteria umbilical humana. Material y métodos: Se utilizaron vasos umbilicales procedentes de mujeres con embarazo normoevolutivo, los cuales una vez disecados se cortaron en anillos de 5 mm y se montaron en cámara de órgano aislado, utilizando solución de Krebs con y sin calcio, burbujeada con carbógeno y la temperatura controlada. Se evaluó el efecto contráctil inducido por serotonina a diferentes concentraciones molares y se contrastó con verapamil, lantano y ácido ciclopiazónico, cuantificando la respuesta contráctil mediante un polígrafo biopac acoplado a un sistema computacional. Resultados: No se observaron diferencias significativas en la magnitud de la respuesta obtenida en presencia y ausencia de calcio extracelular. Se apreció el efecto contráctil a la serotonina que disminuyó significati vamente como respuesta a la estimulación repetida a la misma; así mismo, se incrementó el tono basal posterior a la adición del calcio al medio de incubación, lo que dependió del tiempo de exposición. También se observó la inhibición parcial del incremento en el tono basal con vera pamil y lantano. Finalmente, el pretratamiento con ácido ciclopiazónico no modificó la respuesta contráctil a la serotonina en un medio sin calcio. Conclusiones: La contracción inducida por serotonina en la arteria umbilical humana, depende principalmente de calcio intracelular y favorece el ingreso capacitativo de este ion, el cual se incrementa gradualmente a través del tiempo. El ingreso capacitativo del calcio secundario al vaciamiento de los depósitos intracelulares de este ion con serotonina se efectúa a través de canales tipo L y no-L, y no parecen ser sensibles al ácido ciclopiazónico.

Background: Absence of innervation is a hallmark of human umbilical vessels. Intervillous space blood flow is regulated by vasoactive substances and calcium dependent contractility, both in normal and pathological conditions such as preeclampsia eclampsia. Objective: To obtain additional information on the intracellular calcium contractile effects of serotonin in human umbilical arteries. Materials and Methods: Umbilical arteries from normal pregnancies were dissected, cut in 5 mm rings and mounted in a temperature controlled isolated organ chamber, using calciumfree Krebs solution. The contractile effects of serotonin, lantane, verapamil and cyclopiazonic acid were evaluated at different concentrations using a computer coupled biopac polygraph. Results: No differences in response were observed in the presence and absence of intracellular calcium. The positive contractile effects observed with serotonin were significantly decreased with repeated stimulation. An increase in the basal tone of the vessel was observed after calcium supplementation was added to the solution. This effect was minimized in the presence of verapamil and lantane. The contractile effects of serotonin in the calcium free solution were not affected by the presence of cyclopiazonic acid. Conclusions: Serotonin contractile effects in the human umbilical artery depend mainly on intracellular calcium levels which favor the gradual entrance of this ion over time. Calcium influx induced by serotonin is possible through L and Non-L channels apparently insensitive to cyclopiozonic acid.

Distúrbios do eixo cálcio-PTH-vitamina D nas doenças hepáticas crônicas / Disturbances of calcium-PTH-vitamin D axis in chronic liver diseases

Distúrbios no eixo cálcio-PTH-vitamina D são freqüentemente associados às doenças hepáticas crônicas (DHC). Já foi demonstrado que pacientes com DHC apresentam uma tendência à diminuição do cálcio e vitamina D, com aumento compensatório do PTH. Embora a diminuição da hidroxilação da vitamina D em 25 (OH) vitamina D fosse considerada o mecanismo principal destas alterações, estudos recentes vêm demonstrando que, mesmo nos estágios avançados de doença, o fígado ainda consegue manter níveis adequados de 25 (OH) vitamina D. Desta forma, outros fatores (ex: dieta inadequada, diminuição da exposição à luz solar) seriam os responsáveis pelas alterações no eixo cálcio-PTH-vitamina D. Além disso, o tratamento das DHC com glicocorticóides (fibrose cística) e ribavirina (Hepatite C) parece contribuir como agravante destes distúrbios. Por outro lado, parece ser a osteoporose, e não a osteomalácia ou o hiperparatireoidismo secundário, a principal alteração nas DHC. Assim, continua objeto de discussão o papel das alterações do eixo cálcio-PTH-vitamina D na osteodistrofia hepática.

To be or not to be nicotinic acid adenine dinucleotide phosphate (NAADP): a new intracellular second messenger?

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent activator of intracellular Ca2+ release in several vertebrate and invertebrate systems. The role of the NAADP system in physiological processes is being extensively investigated at the present time. The NAADP receptor and its associated Ca2+ pool have been hypothesized to be important in several physiological processes including fertilization, T cell activation, and pancreatic secretion. However, whether NAADP is a new second messenger or a tool for the discovery of a new Ca2+ channel is still an unanswered question. Research developed over the last two years has provided some important clues to whether NAADP is or not a physiological cellular messenger. In this short review, I will discuss some of these new findings that are helping us to find an answer to the important question: Is NAADP a second messenger or not?.

Mitochondrial Ca2+ homeostasis in health and disease

Although it has long been known that mitochondria possess a complex molecular repertoire for accumulating and releasing Ca2+, only in recent years has a large body of data demonstrated that these organelles promptly respond to Ca2+-mediated cell stimulations. In this contribution, we will review the principles of mitochondrial Ca2+ homeostasis and its signaling role in different physiological and pathological conditions.