Renal cortical mitochondrial transport of calcium in chronic uremia

Renal cortical mitochondrial transport of calcium in chronic uremia. Calcium overload of tubular cells may occur in uremia, and may be the underlying functional abnormality in the continued deterioration of renal function in chronic renal failure. In order to study this question further, the effect of chronic uremia on the calcium transport properties and respiratory rates was examined in mitochondria (Mi) isolated from the cortex of the remnant kidneys of subtotally nephrectomized rats (SNX) and sham operated controls (C). Plasma calcium concentration was similar in both groups of rats, but a significant hyperphosphatemia was seen in SNX, 8.6 ± 0.6 mg%, as compared to 7.2 ± 0.2 mg% in C (P < 0.001). Mi calcium and phosphate concentrations (nmol/mg protein) were significantly elevated in SNX, 49.9 ± 7.9 and 35.1 ± 4.2, respectively, in SNX compared to C, 21.2 ± 4.2 and 21.4 ± 2.7, respectively (P < 0.01). Mi respiratory control ratio and ADP/O were similar in both experimental groups. Kinetic parameters for calcium uptake (Ca2+ concentrations in the medium of 1.25 to 16 µM) revealed initial velocities 1.5-fold higher in SNX Mi than in C. Mi retention of calcium in the presence of medium Ca2+ concentrations up to 500 µM was studied. Calcium retention was reduced in SNX: the Mi were unable to retain calcium at concentrations of 250 µM. The addition of ruthenium red to the medium substantially improved calcium retention by the uremic Mi. Chronic parathyroidectomy did not correct either the increased calcium uptake or the poor retention of uremic Mi. In conclusion: 1) Chronic uremia in rats is associated with a marked alteration in calcium transport of renal cortical Mi, which may result in Mi calcium overload. 2) The enhanced calcium uptake and poor calcium retention of uremic Mi is not PTH dependent. 3) Since Pi is known to cause a higher initial velocity of calcium uptake and to impair calcium retention of normal mitochondria, it seems that cellular accumulation of phosphate in chronic uremia may be involved in this abnormality

High circulating activin A level is associated with tumor progression and predicts poor prognosis in lung adenocarcinoma

Activin A (ActA)/follistatin (FST) signaling has been shown to be deregulated in different tumor types including lung adenocarcinoma (LADC). Here, we report that serum ActA protein levels are significantly elevated in LADC patients (n=64) as compared to controls (n=46, p=0.015). ActA levels also correlated with more advanced disease stage (p<0.0001) and T (p=0.0035) and N (p=0.0002) factors. M1 patients had significantly higher ActA levels than M0 patients (p<0.001). High serum ActA level was associated with poor overall survival (p<0.0001) and was confirmed as an independent prognostic factor (p=0.004). Serum FST levels were increased only in female LADC patients (vs. female controls, p=0.031). Two out of five LADC cell lines secreted biologically active ActA, while FST was produced in all of them. Transcripts of both type I and II ActA receptors were detected in all five LADC cell lines. In conclusion, our study does not only suggest that measuring blood ActA levels in LADC patients might improve the prediction of prognosis, but also indicates that this parameter might be a novel non-invasive biomarker for identifying LADC patients with organ metastases

Lipidna peroksidacija i aktivnost antioksidativnih enzima u eritrocitima radnika profesionalno izloženih aluminiju

Current research indicates that lipid peroxidation could have a role in aluminium toxicity. The aim of this study was to asses lipid peroxidation and antioxidative enzyme activity in erythrocytes of workers occupationally exposed to aluminium. We investigated a group of 59 workers (Al group) exposed to aluminium fumes (contamination factor F=8.07 to 13.47, national maximal allowed concentration value is 2 mg m-3). The control group (C group) consisted of 75 subjects employed in lime production who had not been occupationally exposed to aluminium or any known toxic substance. Erythrocyte aluminium concentrations were significantly higher in the exposed group than controls [Al group (8.41±3.66) µg L-1, C group (5.60±0.86) µg L-1, p<0.001]. In the Al group, erythrocyte malondialdehyde concentration was also significantly higher [Al group (189.59±81.27) µmol L-1, C group (105.21±49.62) µmol L-1, p<0.001] and antioxidative enzyme activity reduced for glucoso-6-phosphatedehydrogenase [Al group (5.05±1.70) IU g-1 Hb, C group (12.53±4.12) IU g-1 Hb, p<0.001], glutathione reductase [Al group (1.41±0.56) IU g-1 Hb, C group (1.89±0.57) IU g-1 Hb, p<0.001], glutathione peroxidase [Al group (12.37±5.76) IU g-1 Hb, C group (15.54±4.85) IU g-1 Hb, p<0.001], catalase [Al group (116.76±26.60) IU g-1 Hb, C group (158.81±71.85) IU g-1 Hb, p<0.001] and superoxide dismutase [Al group (1175.8±149.9) IU mg-1 Hb, C group (1377.9±207.5) IU mg-1 Hb, p<0.001].Rezultati suvremenih istraživanja pokazuju da lipidna peroksidacija može imati važnu ulogu u toksičnosti aluminija. Cilj istraživanja bio je da se ispita lipidna peroksidacija i aktivnost antioksidativnih enzima u eritrocitima kod radnika profesionalno izloženih aluminiju. Ispitivanjem je obuhvaćena skupina od 59 radnika (Al skupina) profesionalno izloženih aluminiju (faktor onečišćenja F=8,07 do 13,47, nacionalna maksimalno dopuštena koncentracija je 2 mg m-3). Kontrolna skupina sastojala se od 75 osoba zaposlenih u proizvodnji vapna koje nikada nisu bile profesionalno izložene aluminiju ni drugim toksičnim tvarima. U skupini izloženoj aluminiju utvrđene su statistički signifikantno više koncentracije aluminija u eritrocitima nego u kontrolnoj skupini [Al skupina (8,41±3,66) µg L-1, kontrolna skupina (5,60±0,86) µg L-1, p<0,001]. U Al skupini utvrđene su statistički značajno više koncentracije malondialdehida u eritrocitima [Al skupina (189,59±81,27) µmol L-1, kontrolna skupina (105,21±49,62) µmol L-1, p<0,001]. Također, u Al skupini utvrđene su i statistički značajno niže aktivnosti antioksidativnih enzima u eritrocitima: glukozo- 6-fosfatdehidrogenaza [Al skupina (5,05±1,70) IU g-1 Hb, kontrolna skupina (12,53±4,12) IU g-1 Hb, p<0,001], glutationreduktaza [Al skupina (1,41±0,56) IU g-1 Hb, kontrolna skupina (1,89±0,57) IU g-1 Hb, p<0,001], glutationperoksidaza [Al skupina (12,37±5,76) IU g-1 Hb, kontrolna skupina (15,54±4,85) IU g-1 Hb, p<0,001], katalaza [Al skupina (116,76±26,60) IU g-1 Hb, kontrolna skupina (158,81±71,85) IU g-1 Hb, p<0,001] i superoksiddizmutaza [Al skupina (1175,8±149,9) IU mg-1 Hb, kontrolna skupina (1377,9±207,5) IU mg-1 Hb, p<0,001]

Serum amyloid A inhibits RANKL-induced osteoclast formation

When mouse bone marrow-derived macrophages were stimulated with serum amyloid A (SAA), which is a major acute-phase protein, there was strong inhibition of osteoclast formation induced by the receptor activator of nuclear factor kappaB ligand. SAA not only markedly blocked the expression of several osteoclast-associated genes (TNF receptor-associated factor 6 and osteoclast-associated receptor) but also strongly induced the expression of negative regulators (MafB and interferon regulatory factor 8). Moreover, SAA decreased c-fms expression on the cell surface via shedding of the c-fms extracellular domain. SAA also restrained the fusion of osteoclast precursors by blocking intracellular ATP release. This inhibitory response of SAA is not mediated by the well-known SAA receptors (formyl peptide receptor 2, Toll-like receptor 2 (TLR2) or TLR4). These findings provide insight into a novel inhibitory role of SAA in osteoclastogenesis and suggest that SAA is an important endogenous modulator that regulates bone homeostasis.open

Comparative Proteomic Analysis of Serum from Patients with Systemic Sclerosis and Sclerodermatous GVHD. Evidence of Defective Function of Factor H

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by immunological and vascular abnormalities. Until now, the cause of SSc remains unclear. Sclerodermatous graft-versus-host disease (ScGVHD) is one of the most severe complications following bone marrow transplantation (BMT) for haematological disorders. Since the first cases, the similarity of ScGVHD to SSc has been reported. However, both diseases could have different etiopathogeneses. The objective of this study was to identify new serum biomarkers involved in SSc and ScGVHD. METHODOLOGY: Serum was obtained from patients with SSc and ScGVHD, patients without ScGVHD who received BMT for haematological disorders and healthy controls. Bi-dimensional electrophoresis (2D) was carried out to generate maps of serum proteins from patients and controls. The 2D maps underwent image analysis and differently expressed proteins were identified. Immuno-blot analysis and ELISA assay were used to validate the proteomic data. Hemolytic assay with sheep erythrocytes was performed to evaluate the capacity of Factor H (FH) to control complement activation on the cellular surface. FH binding to endothelial cells (ECs) was also analysed in order to assess possible dysfunctions of this protein. PRINCIPAL FINDINGS: Fourteen differentially expressed proteins were identified. We detected pneumococcal antibody cross-reacting with double stranded DNA in serum of all bone marrow transplanted patients with ScGVHD. We documented higher levels of FH in serum of SSc and ScGVHD patients compared healthy controls and increased sheep erythrocytes lysis after incubation with serum of diffuse SSc patients. In addition, we observed that FH binding to ECs was reduced when we used serum from these patients. CONCLUSIONS: The comparative proteomic analysis of serum from SSc and ScGVHD patients highlighted proteins involved in either promoting or maintaining an inflammatory state. We also found a defective function of Factor H, possibly associated with ECs damage

Hypocalcæmia and serum levels of inorganic phosphorus, magnesium parathyroid and calcitonin hormones in the last month of pregnancy in Awassi fat-tail ewes

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