Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice

Objective: This study was undertaken to investigate the mechanism of altered contractility in hearts from transgenic mice overexpressing the sarcoplasmic reticulum (SR) Ca²⁺ ATPase (SERCA2a). In particular, we sought to determine whether the reported increase in contractility is freqnency-dependent, as might be expected if attributable to changes in SR Ca²⁺ loading. Methods: Intracellular [Ca²⁺] and contractile force were measured at room temperature (22 °C) simultaneously in fura-2-loaded isometrically-contracting trabeculae dissected from the hearts of FVB/N control (n=6) or SERCA2a transgenic (n=6) mice. Results: SERCA transgenics exhibit a positive force-frequency relationship, but this was flat in age- and strain-matched controls. SERCA transgenics exhibit a sizable increase in calcium transient amplitude relative to controls, with a concomitant increase in force generation at higher frequencies of stimulation. Amplitudes of Ca²⁺ transients (transgenics: 1.56 ± 0.09 μmol/l, controls: 1.21 ± 0.14) and twitches (transgenics: 21.71 ± 0.91 mN/mm², controls: 13.74 ± 1.67) were significantly different at 2.0 Hz stimulation (P < 0.05). Conclusion: An increase in SERCA expression increases the ability of the sarcoplasmic reticulum to store calcium, such that more calcium is available to be released during each heartbeat at higher stimulation rates.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculare

Quantification of (–)-Epigallocatechin-3-gallate Inhibition of Anaplastic Thyroid Cancer Cell Line Adhesion and Proliferation Using Real-time Cell Analysis

Anaplastic thyroid cancer (ATC) has a poor prognosis because of immediate metastasis. Several studies in humans and animals have suggested that the ingestion of green tea or its active ingredient (–)-epigallocatechin-3-gallate (EGCG) may decrease the risk of cancer. Using a recently developed real-time cell analysis (RTCA) system, we have shown previously that EGCG inhibits cell migration and the invasion of oral cavity cancers by suppressing matrix metalloproteinases. In the present study we used RTCA to investigate the effects of EGCG on cell adhesion to fibronectin-coated plates using three cancer cell lines: one ATC cell line (TCO-1) and two poorly differentiated oral squamous cell carcinomas (OSCCs) cell lines (SAS and HO-1-u-1; originating from the tongue and floor of the mouth, respectively). EGCG (50µM) inhibited the adhesion of all three cell lines. In addition to its effects on cell adhesion, 50µM EGCG inhibited the cell proliferation of TCO-1 cells. Furthermore, EGCG decreased αV integrin (ITGAV) mRNA levels in all three cell lines, suggesting that EGCG inhibits the cell adhesion and proliferation of OSCC and ATC cells via suppression of integrin expression. Therefore, EGCG represents a useful dietary constituent or a lead compound for counteracting metastasis of oral cavity cancers and thyroid cancers

Lack of association between XBP1 genotype and calcium signaling in the platelets of healthy subjects

Dysregulations of calcium (Ca) homeostasis may be involved in the pathophysiology of bipolar disorder. Enhanced Ca response to various agonists in peripheral blood cells is one of a few confirmed biological markers for bipolar disorder. Recently, a polymorphism of XBP1, a pivotal gene in the endoplasmic reticulum (ER) stress response, was shown to contribute to the genetic risk factor for bipolar disorder. Thus, in this study, we examined the relationship between the XBP1 gene polymorphism and the Ca signaling in the platelets of healthy controls. The present results suggest no significant difference in the basal Ca level or 5-HT-induced Ca mobilization among normal subjects with -116C/C, C/G and G/G genotypes. Further investigations are necessary to examine the relationship in the different peripheral blood cells and/or in larger samples from patients with bipolar disorder.http://www.sciencedirect.com/science/journal/0304394

Relationship between XBP1 genotype and personality traits assessed by TCI and NEO-FFI

There have been several researches on the role of personality in the pathophysiology of bipolar disorder. Recently, a polymorphism of XBP1, a pivotal gene in the endoplasmic reticulum (ER) stress response, was shown to contribute to the genetic risk factor for bipolar disorder. Therefore, in this study, we examined the relationship between the XBP1 gene polymorphism and the personality traits assessed by two self-rating scales, a shortened version of Temperament and Character Inventory (TCI) and NEO-Five Factor Inventory (NEO-FFI) in healthy subjects. The present results suggested that the XBP1 gene polymorphism was associated with the NEO-FFI score of neuroticism in female subjects. However, no significant differences in the other personality scale scores of both assessments were observed among normal subjects with -116C/C, C/G and G/G genotypes. Further investigations are necessary to examine the relationship in patients with bipolar disorder, or use full version of various self-rating personality assessments

LUMBAR CORSETS CAN DECREASE LUMBAR MOTION IN GOLF SWING

Swinging a golf club includes the rotation and extension of the lumbar spine. Golf-related low back pain has been associated with degeneration of the lumbar facet and intervertebral discs, and with spondylolysis. Reflective markers were placed directly onto the skin of 11young male amateur golfers without a previous history of back pain. Using a VICON system (Oxford Metrics, U.K.), full golf swings were monitored without a corset (WOC), with a soft corset (SC), and with a hard corset (HC), with each subject taking 3 swings. Changes in the angle between the pelvis and the thorax (maximum range of motion and angular velocity) in 3 dimensions (lumbar rotation, flexion-extension, and lateral tilt) were analyzed, as was rotation of the hip joint. Peak changes in lumbar extension and rotation occurred just after impact with the ball. The extension angle of the lumbar spine at finish was significantly lower under SC (38°) or HC (28°) than under WOC (44°) conditions (p < 0.05). The maximum angular velocity after impact was significantly smaller under HC (94°/sec) than under SC (177°/sec) and WOC (191° /sec) conditions, as were the lumbar rotation angles at top and finish. In contrast, right hip rotation angles at top showed a compensatory increase under HC conditions. Wearing a lumbar corset while swinging a golf club can effectively decrease lumbar extension and rotation angles from impact until the end of the swing. These effects were significantly enhanced while wearing an H