TY  - JOUR
A1  - Dschietzig, Thomas Bernd
A1  - Krause-Relle, Katharina
A1  - Hennequin, Maud
A1  - von Websky, Karoline
A1  - Rahnenfuhrer, Jan
A1  - Ruppert, Jana
A1  - Groena, Hans Juergen
A1  - Armbruster, Franz Paul
A1  - Bathgate, Ross A. D.
A1  - Aschenbach, Joerg R.
A1  - Forssmann, Wolf-Georg
A1  - Hocher, Berthold
T1  - Relaxin-2 does not Ameliorate Nephropathy in an experimental model of Type-1 Diabetes
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background/Aims: In diabetic nephropathy (DN), the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC), there is no specific remedy available. Relaxin-2 (Rlx) - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide - is a candidate drug for both. Methods: Low-dose (32 mu g/kg/day) and high-dose (320 mu g/kg/day) Rlx were tested against vehicle (n = 20 each) and non-diabetic controls (n = 14) for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO) mice by intraperitoneal injection of streptozotocin. Results: Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-beta pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis. Conclusions: We investigated a model showing early DN without overt tubulo-interstitial fibrosis and activation of the TGF-beta-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes.
KW  - Diabetic nephropathy
KW  - Diabetic cardiomyopathy
KW  - Fibrosis
KW  - Inflammation
KW  - Relaxin
Y1  - 2015
U6  - https://doi.org/10.1159/000368484
SN  - 1420-4096
SN  - 1423-0143
VL  - 40
IS  - 1
SP  - 77
EP  - 88
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Maschirow, Laura
A1  - Khalaf, Kinda
A1  - Al-Aubaidy, Hayder A.
A1  - Jelinek, Herbert F.
T1  - Inflammation, coagulation, endothelial dysfunction and oxidative stress in prediabetes - Biomarkers as a possible tool for early disease detection for rural screening
JF  - Clinical biochemistry : official journal of the Canadian Society of Clinical Chemists
N2  - Objectives: This study aims to increase understanding of the connection between oxidative stress and inflammation in diabetes disease progression to provide a basis for investigating improved diagnostic possibilities, treatment and prevention of prediabetes.
 Design and methods: Differences in the level of biochemical markers of oxidative stress (erythrocyte GSH/GSSG and urinary 8-isoprostane), inflammation (CRP, IL-6), endothelial dysfunction (plasma homocysteine, urinary 8-hydroxy-2-deoxy-guanosine) and coagulation/fibrinolysis (C5a, D-Dimer) were determined in prediabetes and control subjects.
 Results: While no difference was found in the 8-isoprostane levels between the two groups, the erythrocyte GSH/GSSG ratio was significantly reduced in the prediabetes group compared to control, indicating increased oxidative stress in the prediabetic state. Both urinary 8-OHdG and surprisingly also plasma homocysteine were significantly elevated in the prediabetes group, indicating endothelial dysfunction. The inflammation markers were slightly elevated in the prediabetic subjects and the same trend was found for the coagulation/fibrinolysis markers C5a and D-Dimer. These results were however not significant.
 Conclusions: The small elevation of blood glucose levels in the prediabetic state may have a detectable influence on endothelial function as indicated by changes to 8-OHdG, indicating an increased DNA-damage and homocysteine release from endothelial cells. Increased oxidative stress as indicated by the reduced GSH/GSSG ratio is likely to be the link between the moderate hyperglycaemia in prediabetes and pathological changes in endothelial function, which in the long-term may promote atherogenesis and result in the development of cardiovascular disease. Early detection of prediabetes is essential to avoid diabetes development and the associated complications like cardiovascular disease. The GSH/GSSG ratio and biomarkers like urinary 8-OHdG and plasma homocysteine offer a possible tool for the assessment of prediabetes in prevention screenings. (C) 2015 The Authors. The Canadian Society of Clinical Chemists. Published by Elsevier Inc.
KW  - Prediabetes
KW  - Oxidative stress
KW  - Inflammation
KW  - Coagulation
KW  - Endothelial dysfunction
Y1  - 2015
U6  - https://doi.org/10.1016/j.clinbiochem.2015.02.015
SN  - 0009-9120
SN  - 1873-2933
VL  - 48
IS  - 9
SP  - 581
EP  - 585
PB  - Elsevier
CY  - Oxford
ER  -