TY  - JOUR
A1  - Espe, Katharina M.
A1  - Raila, Jens
A1  - Henze, Andrea
A1  - Krane, Vera
A1  - Schweigert, Florian J.
A1  - Hocher, Berthold
A1  - Wanner, Christoph
A1  - Drechsler, Christiane
T1  - Impact of vitamin A on clinical outcomes in haemodialysis patients
JF  - Nephrology, dialysis, transplantation
N2  - Background. Patients on maintenance haemodialysis treatment experience an excessive risk of cardiovascular disease and mortality. The vitamin A concentration is known to be higher in these patients compared to the general population where elevated vitamin A concentrations are associated with adverse outcome. The impact of vitamin A on morbidity and mortality in end-stage renal disease patients is controversial and is the topic of this study.
 Methods. We analysed plasma retinol and retinol-binding protein 4 (RBP4) in 1177 diabetic haemodialysis patients, who participated in the German Diabetes and Dialysis Study (median follow-up 4 years). By Cox regression analyses hazard ratios (HRs) were determined for pre-specified, adjudicated end points according to baseline concentrations.
 Results. Patients had a mean age of 66 +/- 8 years, mean retinol and RBP4 concentrations of 3.28 (0.71-7.44) and 4.02 (1.28-10.1) mu mol/L, respectively. Patients with retinol concentrations in the first quartile (<2.6 mu mol/L) had an almost 2-fold increased risk of all-cause mortality compared to patients of the fourth quartile [>3.9 mu mol/L; HR 1.81, 95% confidence interval (CI) 1.43-2.30]. There was a strong association between low retinol and the risk of sudden cardiac death (SCD, HR 2.22, 95% CI 1.41-3.50) and fatal infection (HR 2.19, 95% CI 1.26-3.82). Patients with RBP4 concentrations in the lowest quartile (<3.0 mu mol/L) were more likely to die of any cause (HR 1.43, 95% CI 1.14-1.80), experience SCD (HR 1.97, 95% CI 1.28-3.03) and cardiovascular events (HR 1.43, 95% CI 1.10-1.85).
 Conclusion. This large cohort study shows a strong association of low retinol and RBP4 concentrations with SCD and all-cause mortality in diabetic haemodialysis patients.
KW  - haemodialysis
KW  - mortality
KW  - retinol
KW  - retinol-binding protein 4
KW  - sudden death
Y1  - 2011
U6  - https://doi.org/10.1093/ndt/gfr171
SN  - 0931-0509
VL  - 26
IS  - 12
SP  - 4054
EP  - U583
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Nitezki, Tina
A1  - Kleuser, Burkhard
A1  - Krämer, Stephanie
T1  - Fatal gastric distension in a gold thioglucose mouse model of obesity
JF  - Laboratory Animals
N2  - This case report addresses the problem of underreporting negative results and adverse side effects in animal testing. We present our findings regarding a hyperphagic mouse model associated with unforeseen high mortality. The results outline the necessity of reporting detailed information in the literature to avoid duplication. Obese mouse models are essential in the study of obesity, metabolic syndrome and diabetes mellitus. An experimental model of obesity can be induced by the administration of gold thioglucose (GTG). After transcending the blood-brain barrier, the GTG molecule interacts with regions of the ventromedial hypothalamus, thereby primarily targeting glucose-sensitive neurons. When these neurons are impaired, mice become insensitive to the satiety effects of glucose and develop hyperphagia. In a pilot study for optimising dosage and body weight development, C57BL/6 mice were treated with GTG (0.5 mg/g body weight) or saline, respectively. Animals were provided a physiological amount of standard diet (5 g per animal) for the first 24 hours after treatment to prevent gastric dilatation. Within 24 hours after GTG injection, all GTG-treated animals died of gastric overload and subsequent circulatory shock. Animals developed severe attacks of hyperphagia, and as the amount of provided chow was restricted, mice exhibited unforeseen pica and ingested bedding material. These observations strongly suggest that restricted feeding is contraindicated concerning GTG application. Presumably, the impulse of excessive food intake was a strong driving force. Therefore, the actual degree of suffering in the GTG-induced model of hyperphagia should be revised from moderate to severe.
KW  - appetite
KW  - distress
KW  - refinement
KW  - mortality
Y1  - 2018
U6  - https://doi.org/10.1177/0023677218803384
SN  - 0023-6772
SN  - 1758-1117
VL  - 53
IS  - 1
SP  - 89
EP  - 94
PB  - Sage Publ.
CY  - Thousand Oaks
ER  -