The Circulating Levels of Selenium, Zinc, Midkine, Some Inflammatory Cytokines, and Angiogenic Factors in Mitral Chordae Tendineae Rupture

Chordae tendineae rupture process is associated with increased production of inflammatory and angiogenesis mediators in connective tissues, which contributes to chronic inflammation and pathogenesis of degenerative chordae. A few trace elements are known to possess antioxidant, anti-inflammatory, and antiangiogenic properties. Therefore, the aim of this study was to determine whether zinc, selenium, midkine (MK), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor-A (VEGF-A), platelet-derived growth factor-BB (PDGF-BB), and reduced glutathione (GSH) levels are associated with inflammation and angiogenesis processes in the context of a potential etiology causing aggravation of mitral regurgitation and/or ruptured chordae tendineae. Seventy-one subjects comprising 34 patients with mitral chordae tendineae rupture (MCTR) and 37 healthy controls diagnosed on the basis of their clinical profile and transthoracic echocardiography were included in this study. The levels of GSH, MK, selenium, and zinc were found to be lower in the patients group when compared to control group. There were no significant difference in plasma TNF-alpha, IL-1 beta, IL-6, IL-8, VEGF-A, and PDGF-BB levels between two groups. There were positive significant correlations between MK and GSH, MK, and selenium levels in patients with MCTR. According to our data in which selenium, zinc, MK, and GSH decreased in MCTR patients, inflammatory response, oxidative stress, and trace element levels may contribute to etiopathogenesis of mitral regurgitation and/or ruptured chordae tendineae

Neurobiological trait abnormalities in bipolar disorder

Dissecting trait neurobiological abnormalities in bipolar disorder ( BD) from those characterizing episodes of mood disturbance will help elucidate the aetiopathogenesis of the illness. This selective review highlights the immunological, neuroendocrinological, molecular biological and neuroimaging abnormalities characteristic of BD, with a focus on those likely to reflect trait abnormalities by virtue of their presence in euthymic patients or in unaffected relatives of patients at high genetic liability for illness. Trait neurobiological abnormalities of BD include heightened pro-inflammatory function and hypothalamic-pituitary-adrenal axis dysfunction. Dysfunction in the intracellular signal transduction pathway is indicated by elevated protein kinase A activity and altered intracellular calcium signalling. Consistent neuroimaging abnormalities include the presence of ventricular enlargement and white matter abnormalities in patients with BD, which may represent intermediate phenotypes of illness. In addition, spectroscopy studies indicate reduced prefrontal cerebral N-acetylaspartate and phosphomonoester concentrations. Functional neuroimaging studies of euthymic patients implicate inherently impaired neural networks subserving emotional regulation, including anterior limbic, ventral and dorsal prefrontal regions. Despite heterogeneous samples and conflicting findings pervading the literature, there is accumulating evidence for the existence of neurobiological trait abnormalities in BD at various scales of investigation. The aetiopathogenesis of BD will be better elucidated by future clinical research studies, which investigate larger and more homogenous samples and employ a longitudinal design to dissect neurobiological abnormalities that are underlying traits of the illness from those related to episodes of mood exacerbation or pharmacological treatment. Molecular Psychiatry (2009) 14, 833-846; doi:10.1038/mp.2009.39; published online 19 May 200

Molecular imaging of depressive disorders

This chapter summarizes findings of a large number of molecular imaging studies in the field of unipolar and bipolar depression (BD). Brain metabolism in depressed unipolar and bipolar patients is generally hypoactive in the middle frontal gyri, the pregenual and posterior anterior cingulate, the superior temporal gyrus, the insula, and the cerebellum, while hyperactivity exists in subcortical (caudate nucleus, thalamus), limbic (amygdala, anterior hippocampus), and medial and inferior frontal regions. Interestingly, after depletion of serotonin or noradrenalin/dopamine in vulnerable (recovered) major depressive disorder (MDD) patients, a similar response pattern in metabolism occurs. Findings on the pre-and postsynaptic dopaminergic system show indications that, at least in subgroups of retarded MDD patients, presynaptic dopaminergic markers may be decreased, while postsynaptic markers may be increased. The findings regarding serotonin synthesis, pre-and postsynaptic imaging can be integrated to a presumable loss of serotonin in MDD, while this remains unclear in BD. This reduction of serotonin and dopamine in MDD was recently summarized in a revised version of the monoamine hypothesis, which focuses more on a dysfunction at the level of the MAO enzyme. This should be addressed further in future studies. Nevertheless, it should be acknowledged that the serotonergic and dopaminergic systems appear adaptive; therefore, it remains difficult to distinguish state and trait abnormalities. Therefore, future longitudinal molecular imaging studies in the same subjects at different clinical mood states (preferably with different tracers and imaging modalities) are needed to clarify whether the observed changes in transporters and receptors are compensatory reactions or reflect different, potentially causal mechanisms. Several suggestions for future developments are also provided at the end of this chapter