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1.
J Biol Regul Homeost Agents ; 33(1): 29-38, 2019.
Article in English | MEDLINE | ID: mdl-30734547

ABSTRACT

Since vascular calcification is considered a process regulated similar to that of bone tissue mineralization, we investigated the participation of bone formation proteins. We analyzed the correlation of serum circulating bone markers, osteoprotegerin (OPG) and receptor activator of nuclear factor ĸB ligand (RANKL) in chronic kidney disease (CKD) patients, to coronary artery calcification score. We also considered the effect of inorganic phosphate on pro- and anti-calcifying tissue factors. We confirmed that circulating OPG is an independent calcium score predictor with its high serum concentration favoring high coronary artery calcification. In tissue samples of non-diseased human renal arteries, the expression of OPG and receptor activator of nuclear factor ĸB (RANK) was positive, while expression of RANKL was absent. In atherosclerotic specimens and arteries with medial calcification, the most upregulated was expression of bone morphogenetic proteins, BMP-2 and BMP-7, as well as expression of RANK and RANKL. In the diseased arteries, OPG expression was present only in areas where bone structures were formed. In atherosclerotic and medial calcification arteries, loss of alpha-smooth muscle actin (α-SMA) expression was observed. These data suggest a possible regulatory role of the examined proteins, especially OPG and RANKL, in vascular calcification, as well as their possible clinical significance as circulating predictors of vascular calcification.


Subject(s)
Coronary Artery Disease/physiopathology , Osteoprotegerin/blood , RANK Ligand/blood , Vascular Calcification/physiopathology , Bone Morphogenetic Protein 2/metabolism , Bone Morphogenetic Protein 7/metabolism , Bone and Bones , Humans
2.
Med Hypotheses ; 85(2): 183-5, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25959864

ABSTRACT

Renal cell carcinoma (RCC) is the most common solid kidney tumor representing 2-3% of all cancers, with the highest frequency occurring in Western countries. There was a worldwide and European annual increase in incidence of approximately 2% although incidence has been stabilized in last few years. One third of the patients already have metastases in the time of the diagnosis with poor prognosis because RCC are radio and chemoresistant. The prognostic value of EGFR over-expression in RCC is a controversial issue that could be explained by different histological types of study tumors and non-standardized criteria for evaluation of expression. Recent evidences points to a new mode of EGFR signaling pathway in which activated EGFR undergoes nuclear translocalization and then, as transcription factor, mediates gene expression and other cellular events required for highly proliferating activities. According to our observations, the membranous expression of EGFR associates with high nuclear grade and poor differentiated tumors. On the other hand, nuclear EGFR expression was high in low nuclear graded and well differentiated tumors with good prognosis. We hypothesize that this mode of EGFR signaling characterizes still controlled proliferation retained in well differentiated RCC with Furhman nuclear grade I or II.


Subject(s)
Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Cell Nucleus/metabolism , ErbB Receptors/metabolism , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Biomarkers, Tumor/metabolism , Cell Differentiation , Cell Proliferation , Computer Simulation , Humans , Models, Biological , Neoplasm Invasiveness
3.
Transplant Proc ; 45(5): 1766-70, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23769040

ABSTRACT

BACKGROUND: Acute cellular rejection of the transplanted kidney is an important cause of impaired graft function. One of the basic characteristics of acute cellular rejection according to the latest Banff classification of renal allograft pathology is the presence of a large number of T lymphocytes in the allografted tissue. Osteoprotegerin, receptor activator of nuclear factor-kappa B (RANK) and RANK ligand (RANKL), three relatively novel members of the tumor necrosis factor superfamily, have crucial roles not only in physiologic and pathologic bone metabolism but also in immunologic processes. The aim of our study was to determine the expression of RANKL and RANK by T lymphocytes and macrophages in acute cellular kidney allograft rejection in rats. METHODS: The study included 15 male Wistar rats of 3 months old and 250-300 g as recipients and 15 male DA rats donors of 3 months old; and weight 250-300 g. When animals were sacrificed at 3 weeks to extract the transplanted kidney for pathohistologic analysis and immunoflorescence. all samples showed acute cellular rejection. Kidney sections were examined by dual-labeled immunofluorescence to detect CD4, CD8, or CD68 (red) and RANK or RANKL (green) with coexpressing cells as orange. RESULTS: RANKL-positive expression colocalized with CD4(+) and CD8(+) T lymphocytes in acutely rejected kidney tissue. There was no association between CD4(+) and CD8(+) T cells with RANK expression, which was evident by infiltrating CD68-positive macrophages in the kidney tissue interstitium. CONCLUSION: RANK and RANKL were expressed by T lymphocytes and macrophages in acute cellular kidney rejection after transplantation in rats.


Subject(s)
Graft Rejection/blood , Kidney Transplantation , Leukocytes/metabolism , RANK Ligand/blood , Animals , Fluorescent Antibody Technique , Male , Rats , Rats, Wistar
4.
Transplant Proc ; 43(7): 2505-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21911114

ABSTRACT

BACKGROUND: Deceased donor kidneys have a high incidence of delayed graft function attributable to ischemia-reperfusion injury. Although preservation solution and cold storage reduce cold ischemic injury, the depletion of cellular energy and oxidative signalling leads to cellular damage. Because bone morphogenetic protein-7 has renoprotective effect, we have hypothesized that recombinant human bone morphogenetic protein-7 (rh BMP-7) will better preserve kidney tissue exposed to prolonged cold ischemia in comparison with University of Wisconsin (UW) solution. We evaluated how the duration of cold ischemia influences the cold ischemic injury. METHODS: Levels of lipid peroxidation, protein carbonyl content, as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined in the kidneys by spectrophotometry after 6, 12, and 24 hours of cold ischemia. RESULTS: Time-dependent increases in the levels of lipid peroxidation and protein carbonyl content at all time points were significantly lower in rhBMP-7-perfused kidneys versus the UW-treated group. SOD activity after 6 hours, as well as GSH-Px activity after 24 hours of cold ischemia was significantly higher in the kidney tissue perfused by rhBMP-7 than in UW group. CONCLUSION: rhBMP-7 significantly decreases cellular damage in rat kidney versus UW preservation solution and this is attributed to lowering of cold ischemia injury and maintaining prolonged tissue antioxidant activity.


Subject(s)
Bone Morphogenetic Protein 7/therapeutic use , Kidney/blood supply , Reperfusion Injury/prevention & control , Animals , Antioxidants/metabolism , Glutathione Peroxidase/metabolism , Kidney/enzymology , Kidney/metabolism , Lipid Peroxidation , Male , Rats , Rats, Wistar , Recombinant Proteins/therapeutic use , Superoxide Dismutase/metabolism
5.
Transplant Proc ; 43(5): 2110-2, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21693338

ABSTRACT

We report a case of ureterolithiasis in a patient with an en bloc kidney transplantation, using extracorporeal shockwave lithotripsy (ESWL). The patient presented with asymptomatic macrohematuria. Computed tomography revealed a ureteral calculus just below the pyeloureteral junction with hydronephrosis of the medially positioned kidney. Took two sessions of ESWL were required for complete disintegration of the stone. At 3 years after successful treatment, the patient has an excellent functioning and stone-free graft.


Subject(s)
Kidney Transplantation , Lithotripsy , Humans , Male , Middle Aged , Tomography, X-Ray Computed
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