This study evaluates bone mineral density (BMD) and trabecular bone score (TBS) in relationship with new markers of chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23), and klotho. The ...patients in this cross-sectional study were divided as follows: group A -patients in stages G1-3; group B -patients in stages G4 - 5 according to KDIGO. Plasma levels of soluble klotho and FGF23 were determined by ELISA. Bone mineral density (BMD) and trabecular bone score (TBS) were measured. 74 patients with CKD (mean age 68.8 years) were included in the study. Higher levels of FGF23 were observed in group B (N=15) compared to group A (N=59; p=0.001) were observed. FGF23 was higher in group A compared to group B. Significant difference in TBS within the first 3 stages of CKD was observed (mean TBS in G1=1.375 vs. G2=1.340 vs. G3a=1.24; p<0.05) and negative correlation of FGF23 and TBS (R=-0.33; p=0.05) and positive correlation between klotho and TBS (R=0.419; p=0.04) was observed. This study confirmed that FGF23 and klotho are associated with TBS, but TBS reflects a decrease in kidney function only in the first 3 stages of CKD. Thus, FGF23 and klotho together with TBS are promising markers of early trabecular bone impairment in CKD.
Patients with chronic kidney disease (CKD) have an increased risk of premature mortality, mainly due to cardiovascular causes. The association between hemodialysis and accelerated atherosclerosis has ...long been described. The ankle-brachial index (ABI) is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. The clinical implications of ABI cut-points are not well defined in patients with CKD. Echocardiography is the most widely used imaging method for cardiac evaluation. Structural and functional myocardial abnormalities are common in patients with CKD due to pressure and volume overload as well as non-hemodynamic factors associated with CKD. Our study aimed to identify markers of subclinical cardiovascular risk assessed using ABI and 2D and 3D echocardiographic parameters evaluating left ventricular (LV) structure and function in patients with end-stage renal disease (ESRD) (patients undergoing dialysis), patients after kidney transplantation and non-ESRD patients (control). In ESRD, particularly in hemodialysis patients, changes in cardiac structure, rather than function, seems to be more pronounced. 3D echocardiography appears to be more sensitive than 2D echocardiography in the assessment of myocardial structure and function in CKD patients. Particularly 3D derived end-diastolic volume and 3D derived LV mass indexed for body surface appears to deteriorate in dialyzed and transplanted patients. In 2D echocardiography, myocardial mass represented by left ventricular mass/body surface area index (LVMI) appears to be a more sensitive marker of cardiac structural changes, compared to relative wall thickness (RWT), left ventricle and diastolic diameter index (LVEDDI) and left atrial volume index (LAVI). We observed a generally favorable impact of kidney transplantation on cardiac structure and function; however, the differences were non-significant. The improvement seems to be more pronounced in cardiac function parameters, peak early diastolic velocity/average peak early diastolic velocity of mitral valve annulus (E/e´), 3D left ventricle ejection fraction (LV EF) and global longitudinal strain (GLS). We conclude that ABI is not an appropriate screening test to determine the cardiovascular risk in patients with ESRD.
•Five Fallopia clones were cultivated for 3yr in the field.•Rhizomes and roots contain more stilbenes and emodin than shoots.•F. japonica produced most stilbenes per gram and hexaploid hybrids most ...biomass.•Knotweed yielded 0.7, 4, 6 and 0.6kg/ha of resveratrol, resveratroloside, piceid and emodin, respectively.
Most people consider knotweeds to be dangerous, invasive weeds. These plants produce useful secondary metabolites, stilbenes and emodin. We conducted a 3-yr field experiment with two parental species Fallopia japonica and Fallopia sachalinensis, and three clones of their hybrid, F.×bohemica. Knotweed biomass and resveratrol, resveratroloside, piceid and emodin contents were assessed three times per year. Their biomasses (in descending order) are as follows: the two hexaploid hybrid clones, the octoploid hybrid clone, and the two parental clones. Although more energy is needed to harvest rhizomes and roots from knotweed, these produce more resveratrol, piceid and emodin than shoots. Out of the five clones tested, F. japonica contained the greatest amounts of resveratrol, resveratroloside, piceid and emodin, in its belowground biomass. The optimal harvest of rhizomes and roots from productive clones was in the autumn of the second year of cultivation.
Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement in different physiological and pathophysiological processes. However, the ...functional role of ORs in the human heart is still unclear. Here, we firstly report the functional characterization of an OR in the human heart. Initial next-generation sequencing analysis revealed the OR expression pattern in the adult and fetal human heart and identified the fatty acid-sensing OR51E1 as the most highly expressed OR in both cardiac development stages. An extensive characterization of the OR51E1 ligand profile by luciferase reporter gene activation assay identified 2-ethylhexanoic acid as a receptor antagonist and various structurally related fatty acids as novel OR51E1 ligands, some of which were detected at receptor-activating concentrations in plasma and epicardial adipose tissue. Functional investigation of the endogenous receptor was carried out by Ca
2+
imaging of human stem cell-derived cardiomyocytes. Application of OR51E1 ligands induced negative chronotropic effects that depended on activation of the OR. OR51E1 activation also provoked a negative inotropic action in cardiac trabeculae and slice preparations of human explanted ventricles. These findings indicate that OR51E1 may play a role as metabolic regulator of cardiac function.
Tetramethylammonium (TMA) chloride, dimethyl sulfoxide and formamide are known to increase, under certain conditions, the specificity and efficiency of the polymerase chain reaction (PCR). We ...compared the ability of several TMA derivatives and some other reagents to increase the specificity of PCR and to improve the yield of amplification. A novel combination of the enhancer TMA and oxalate as anion is demonstrated to be a powerful enhancer of PCR. Addition of 2 mM TMA oxalate to the PCR mixture decreases the formation of non-specific DNA fragments and increases the yield of specific PCR products.
The first step in immunoreceptor signaling is represented by ligand-dependent receptor aggregation, followed by receptor phosphorylation mediated by tyrosine kinases of the Src family. Recently, ...sphingolipid- and cholesterol-rich plasma membrane microdomains, called lipid rafts, have been identified and proposed to function as platforms where signal transduction molecules may interact with the aggregated immunoreceptors. Here we show that aggregation of the receptors with high affinity for immunoglobulin E (Fc epsilon RI) in mast cells is accompanied by a co-redistribution of the Src family kinase Lyn. The co-redistribution requires Lyn dual fatty acylation, Src homology 2 (SH2) and/or SH3 domains, and Lyn kinase activity, in cis or in trans. Palmitoylation site-mutated Lyn, which is anchored to the plasma membrane but exhibits reduced sublocalization into lipid rafts, initiates the tyrosine phosphorylation of Fc epsilon RI subunits, Syk protein tyrosine kinase, and the linker for activation of T cells, along with an increase in the concentration of intracellular Ca super(2+). However, Lyn mutated in both the palmitoylation and myristoylation sites does not anchor to the plasma membrane and is incapable of initiating Fc epsilon RI phosphorylation and early signaling events. These data, together with our finding that a constitutively tyrosine-phosphorylated Fc epsilon RI does not exhibit an increased association with lipid rafts, suggest that Fc epsilon RI phosphorylation and early activation events can be initiated outside of lipid rafts.
Cite this as: J. M. Cyphert, M. Kovarova and B. H. Koller, Clinical & Experimental Allergy, 2011 (41) 260–269.
Summary
Background
Studies in both human and mouse indicate that mediators released by ...mast cells can lead to bronchoconstriction, and thus these are important effector cells in lifethreatening anaphylaxis. Much of our understanding of the various functions of mast cells emanates from the study of mice lacking these cells, particularly mice carrying mutations in the tyrosine kinase gene Kit. Definitive evidence for the role of mast cells in the altered immune response requires the demonstration that this response can be normalized by reconstitution of the mice with cultured bone marrow‐derived mast cells (BMMCs). While many mast cell niches can be restored with BMMCs, this has not been demonstrated for mast cells present in the airways of the lung, cells poised to mediate bronchoconstriction during allergic responses.
Objective
To determine if mast cell‐deficient KitWsh/Wsh reconstituted lines are an appropriate model for the study of the role of these cells in bronchoconstriction associated with allergic responses.
Methods
KitWsh/Wsh mice were reconstituted with either whole bone marrow (WBM) or BMMCs and responses to IgE‐mediated mast cell activation were determined; including systemic hypothermia, mediator release, and bronchoconstriction in anaesthetized, mechanically ventilated animals.
Results
Engraftment of KitWsh/Wsh mice with WBM and BMMCs results in reconstitution of the central airways with mast cells. While the treatment of the two groups of animals resulted in systemic changes when challenged with IgE/Ag in a model of passive anaphylaxis, bronchoconstriction was observed only in KitWsh/Wsh animals, which had received a bone marrow transplant.
Conclusions
While BMMCs can populate the lung, they cannot restore IgE/Ag‐mediated bronchoconstriction to mast cell‐deficient animals. This suggests that the mast cell population, which mediates this function, may be unique, and to fill this niche in the lung cells must undergo a specific developmental programme, one that is no longer available to cultured mast cells.
Lateral cross‐linking of transmembrane high‐affinity IgE receptors (FcϵRI) or glycosylphosphatidylinositol‐anchored Thy‐1 glycoproteins on the surface of rat mast cells and rat basophilic leukemia ...(RBL) cells triggers the signaling pathways that lead to the release of allergy mediators. Although both of these pathways are initiated by an increased activity of Lyn kinase, the exact mechanism by which Lyn kinase interacts with aggregated FcϵRI and Thy‐1 is not completely understood. Here we demonstrate that pretreatment of RBL cells with methyl‐β‐cyclodextrin (MBCD) resulted in a dose‐ and time‐dependent decrease in cellular cholesterol, increased detergent solubilization of Thy‐1 and Lyn kinase, and a transient increase in tyrosine phosphorylation of several proteins. Acute lowering of cholesterol suppressed the activation through Thy‐1, as determined by tyrosine phosphorylation of Syk kinase and some other proteins, and modulation of free cytoplasmic calcium. In contrast, the FcϵRI‐mediated activation events were more resistant. Thy‐1 and FcϵRI in MBCD‐pretreated cells also differed in the extent of aggregation after cross‐linking: Thy‐1 formed large caps, whereas FcϵRI accumulated in small patches. MBCD treatment induced an increased release of secretory components in both Thy‐1‐ and FcϵRI‐activated cells. The combined data indicate that cholesterol depletion does not merely block receptor signaling but has more complex consequences.
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