TY  - GEN
A1  - Morris, Penelope J.
A1  - Salt, Carina
A1  - Raila, Jens
A1  - Brenten, Thomas
A1  - Kohn, Barbara
A1  - Schweigert, Florian J.
A1  - Zentek, Jürgen
T1  - Safety evaluation of vitamin A in growing dogs
T2  - Potsprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - The safe upper limit for inclusion of vitamin A in complete diets for growing dogs is uncertain, with the result that current recommendations range from 5.24 to 104.80 mu mol retinol (5000 to 100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable energy (ME). The aim of the present study was to determine the effect of feeding four concentrations of vitamin A to puppies from weaning until 1 year of age. A total of forty-nine puppies, of two breeds, Labrador Retriever and Miniature Schnauzer, were randomly assigned to one of four treatment groups. Following weaning at 8 weeks of age, puppies were fed a complete food supplemented with retinyl acetate diluted in vegetable oil and fed at 1ml oil/100 g diet to achieve an intake of 5.24, 13.10, 78.60 and 104.80 mu mol retinol (5000, 12 500, 75 000 and 100 000 IU vitamin A)/4184 kJ (1000 kcal) ME. Fasted blood and urine samples were collected at 8, 10, 12, 14, 16, 20, 26, 36 and 52 weeks of age and analysed for markers of vitamin A metabolism and markers of safety including haematological and biochemical variables, bone-specific alkaline phosphatase, cross-linked carboxyterminal telopeptides of type I collagen and dual-energy X-ray absorptiometry. Clinical examinations were conducted every 4 weeks. Data were analysed by means of a mixed model analysis with Bonferroni corrections for multiple endpoints. There was no effect of vitamin A concentration on any of the parameters, with the exception of total serum retinyl esters, and no effect of dose on the number, type and duration of adverse events. We therefore propose that 104.80 mu mol retinol (100 000 IU vitamin A)/4184 kJ (1000 kcal) is a suitable safe upper limit for use in the formulation of diets designed for puppy growth.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 686 
KW  - puppies
KW  - dogs
KW  - Retinol
KW  - Retinyl esters
KW  - vitamin A
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-414929
IS  - 686
ER  - 
TY  - CHAP
A1  - Espe, Katharina M.
A1  - Raila, Jens
A1  - Henze, Andrea
A1  - Blouin, Katja
A1  - Schneider, A.
A1  - Schmiedeke, D.
A1  - Krane, Vera
A1  - Schweigert, Florian J.
A1  - Hocher, Berthold
A1  - Wanner, Christoph
A1  - Drechsler, Christiane
T1  - Low vitamin E plasma levels are associated with cerebrovascular events and mortality in hemodialysis patients
T2  - Annals of nutrition & metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)
Y1  - 2012
SN  - 0250-6807
VL  - 60
IS  - 2
SP  - 137
EP  - 137
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Alter, Markus L.
A1  - Ott, Ina M.
A1  - von Websky, Karoline
A1  - Tsuprykov, Oleg
A1  - Sharkovska, Yuliya
A1  - Krause-Relle, Katharina
A1  - Raila, Jens
A1  - Henze, Andrea
A1  - Klein, Thomas
A1  - Hocher, Berthold
T1  - DPP-4 Inhibition on top of angiotensin receptor blockade offers a new therapeutic approach for diabetic nephropathy
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background: The need for an improved treatment for diabetic nephropathy is greatest in patients who do not adequately respond to angiotensin II receptor blockers (ARBs). This study investigated the effect of the novel dipeptidyl peptidase-4 inhibitor linagliptin alone and in combination with the ARB telmisartan on the progression of diabetic nephropathy in diabetic endothelial nitric oxide synthase (eNOS) knockout mice. Methods: Sixty male eNOS knockout C57BL/6J mice were divided into four groups after receiving intraperitoneal high-dose streptozotocin: telmisartan (1 mg/kg), linagliptin (3 mg/kg), linagliptin + telmisartan (3 mg/kg + 1 mg/kg) and vehicle. Fourteen mice were used as non-diabetic controls. Results: After 12 weeks, urine and blood were obtained and blood pressure measured. Glucose concentrations were increased and similar in all diabetic groups. Telmisartan alone reduced systolic blood pressure by 5.9 mmHg versus diabetic controls (111.2 +/- 2.3 mmHg vs 117.1 +/- 2.2 mmHg; mean +/- SEM; P = 0.071). Combined treatment significantly reduced albuminuria compared with diabetic controls (71.7 +/- 15.3 mu g/24 h vs 170.8 +/- 34.2 mu g/24 h; P = 0.017), whereas the effects of single treatment with either telmisartan (97.8 +/- 26.4 mu g/24 h) or linagliptin (120.8 +/- 37.7 mu g/24 h) were not statistically significant. DPP-4 inhibition, alone and in combination, led to significantly lower plasma osteopontin levels compared with telmisartan alone. Histological analysis revealed reduced glomerulosclerosis after Linagliptin alone and in combination with telmisartan in comparison to non treated diabetic animals (p < 0.01 and p < 0.05). Kidney malonaldehyde immune-reactivity, a marker of oxidative stress, was significantly lower in animals treated with linagliptin. Conclusions: DPP-4 inhibition on top of ARB treatment significantly reduced urinary albumin excretion and oxidative stress in diabetic eNOS knockout mice. Linagliptin on top of an angiotensin II receptor blocker may offer a new therapeutic approach for patients with diabetic nephropathy.
KW  - Diabetic nephropathy
KW  - DPP-4 inhibitor
KW  - Linagliptin
KW  - Renin-angiotensin system
Y1  - 2012
U6  - https://doi.org/10.1159/000341487
SN  - 1420-4096
VL  - 36
IS  - 1
SP  - 119
EP  - 130
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Raila, Jens
A1  - Enjalbert, Francis
A1  - Mothes, Ralf
A1  - Hurtienne, Andrea
A1  - Schweigert, Florian J.
T1  - Validation of a new point-of-care assay for determination of ss-carotene concentration in bovine whole blood and plasma
JF  - Veterinary clinical pathology
N2  - Background: beta-Carotene is an important precursor of vitamin A, and is associated with bovine fertility. beta-Carotene concentrations in plasma are used to optimize beta-carotene supplementation in cattle, but measurement requires specialized equipment to separate plasma and extract and measure beta-carotene, either using spectrophotometry or high performance liquid chromatography (HPLC).
 Objective: The objective of this study was to validate a new 2-step point-of-care (POC) assay for measuring beta-carotene in whole blood and plasma.
 Methods: beta-carotene concentrations in plasma from 166 cows were measured using HPLC and compared with results obtained using a POC assay, the iCheck-iEx-Carotene test kit. Whole blood samples from 23 of these cattle were also evaluated using the POC assay and compared with HPLC-plasma results from the same 23 animals. The POC assay includes an extraction vial (iEx Carotene) and hand-held photometer (iCheck Carotene).
 Results: Concentrations of beta-carotene in plasma measured using the POC assay ranged from 0.40 to 15.84 mg/L (n = 166). No differences were observed between methods for assay of plasma (mean +/- SD; n = 166): HPLC-plasma 4.23 +/- 2.35 mg/L; POC-plasma 4.49 +/- 2.36 mg/L. Similar good agreement was found when plasma analyzed using HPLC was compared with whole blood analyzed using the POC system (n = 23): HPLC-plasma 3.46 +/- 2.12 mg/L; POC-whole blood 3.67 +/- 2.29 mg/L.
 Conclusions: Concentrations of beta-carotene can be measured in blood and plasma from cattle easily and rapidly using a POC assay, and results are comparable to those obtained by the highly sophisticated HPLC method. Immediate feedback regarding beta-carotene deficiency facilitates rapid and appropriate optimization of beta-carotene supplementation in feed.
KW  - Biomarker
KW  - HPLC
KW  - method comparison
KW  - nutritional supplements
KW  - vitamin A
Y1  - 2012
U6  - https://doi.org/10.1111/j.1939-165X.2012.00400.x
SN  - 0275-6382
VL  - 41
IS  - 1
SP  - 119
EP  - 122
PB  - Wiley-Blackwell
CY  - Malden
ER  - 
TY  - JOUR
A1  - Piechotta, Marion
A1  - Raila, Jens
A1  - Rick, Markus
A1  - Beyerbach, Martin
A1  - Hoppen, Hans-Otto
T1  - Serum transthyretin concentration is decreased in dogs with nonthyroidal illness
JF  - Veterinary clinical pathology
N2  - Background: Hypothyroidism in dogs is often difficult to diagnose owing to nonspecific clinical signs and laboratory test results that can be mimicked by nonthyroidal illness (NTI). Thyroxine (T4) circulates in blood mainly bound to T4-binding globulin and, to a lesser degree, transthyretin (TTR) and albumin. The concentration of total T4 depends on the concentrations of these binding proteins.
 Objectives: We hypothesized that dogs with NTI and decreased serum total T4 concentrations would have decreased serum TTR concentrations. The objective of the study was to measure and compare serum TTR concentrations in healthy dogs, in dogs with NTI and low serum T4 concentrations, and in dogs with hypothyroidism.
 Methods: Assignment of dogs to 3 groups was based on physical examination and serum concentrations of T4 and TSH (mean +/- SD): for healthy dogs (n = 13), T4 was 24.8 +/- 3.6 nmol/L and TSH was 0.15 +/- 0.08 mu g/L; for dogs with NTI and low T4 (n = 20), T4 was 3.2 +/- 3.0 nmol/L and TSH was 0.18 +/- 0.13 mu g/L; and for hypothyroid dogs (n = 19), T4 was 5.3 +/- 4.3 nmol/L and TSH was 2.33 +/- 1.90 mu g/L). TTR concentrations in serum were determined semiquantitatively using western blot analysis.
 Results: Serum TTR concentration (mean +/- SD) was decreased in the dogs with NTI (24.8 +/- 7.9 mg/L) compared with that of hypothyroid dogs (41.1 +/- 21.4 mg/L, P = .0035). Differences were not found between TTR concentrations in clinically healthy dogs (33.3 +/- 10.1 mg/L) and hypothyroid dogs or dogs with NTI.
 Conclusions: Serum TTR concentrations were significantly decreased in dogs with NTI and low T4 compared with concentrations in hypothyroid dogs. Additional studies should be done to determine if TTR concentrations can discriminate between dogs with NTI and low T4 and dogs with primary hypothyroidism.
KW  - Euthyroid
KW  - hypothyroid
KW  - T4
KW  - thyroid-stimulating hormone
KW  - thyroxine-binding
Y1  - 2012
U6  - https://doi.org/10.1111/j.1939-165X.2011.00394.x
SN  - 0275-6382
VL  - 41
IS  - 1
SP  - 110
EP  - 113
PB  - Wiley-Blackwell
CY  - Malden
ER  - 
TY  - JOUR
A1  - Khalil, Mahmoud
A1  - Raila, Jens
A1  - Ali, Mostafa
A1  - Islam, Khan M. S.
A1  - Schenk, Regina
A1  - Krause, Jens-Peter
A1  - Schweigert, Florian J.
A1  - Rawel, Harshadrai Manilal
T1  - Stability and bioavailability of lutein ester supplements from Tagetes flower prepared under food processing conditions
JF  - Journal of functional food
N2  - Tagetes spp. belongs to the Asteraceae family. It is recognized as a major source of lutein ester (lutein esterified with fatty acids such as lauric, myristic and palmitic acids), a natural colorant belonging to the xanthophylls or oxygenated carotenoids. Four species of Tagetes flower (Tagetes tenuifolia, Tagetes erecta, Tagetes patula, and Tagetes lucida) were used to extract lutein and lutein esters with three different methods. The results showed that T. erecta, type "orangeprinz", is the richest source of lutein esters (14.4 +/- 0.234 mg/g) in comparison to other Tagetes spp. No significant differences between extractions of lutein esters with medium-chain triacylglycerols (MCT) oil, orange oil or solvent (hexane/isopropanol) could be observed. MCT oil also improved stability of lutein esters at 100 degrees C for 40 min. Emulsification of MCT oil improved the stability of lutein ester extract against UV light at 365 nm for 72 h. Finally, an emulsion was prepared under food processing conditions, spray dried and its bioavailability investigated in a preliminary human intervention study. The results show a lower resorption, but further data suggest improvements in implementation of such supplements. (c) 2012 Elsevier Ltd. All rights reserved.
KW  - Tagetes
KW  - Lutein ester
KW  - Emulsion
KW  - Stability
KW  - Whey protein
KW  - Bioavailability
Y1  - 2012
U6  - https://doi.org/10.1016/j.jff.2012.03.006
SN  - 1756-4646
VL  - 4
IS  - 3
SP  - 602
EP  - 610
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Ott, Ina M.
A1  - Alter, Markus L.
A1  - von Websky, Karoline
A1  - Kretschmer, Axel
A1  - Tsuprykov, Oleg
A1  - Sharkovska, Yuliya
A1  - Krause-Relle, Katharina
A1  - Raila, Jens
A1  - Henze, Andrea
A1  - Stasch, Johannes-Peter
A1  - Hocher, Berthold
T1  - Effects of Stimulation of Soluble Guanylate Cyclase on Diabetic
 Nephropathy in Diabetic eNOS Knockout Mice on Top of Angiotensin II
 Receptor Blockade
JF  - PLOS ONE
N2  - The prevalence of diabetes mellitus and its complications, such as diabetic nephropathy (DN), is rising worldwide and prevention and treatment are therefore becoming increasingly important. Therapy of DN is particularly important for patients who do not adequately respond to angiotensin receptor blocker (ARB) treatment. Novel approaches include the stimulation of soluble guanylate cyclase (sGC) as it is reported to have beneficial effects on cardiac and renal damage. We aimed to investigate the effects of the sGC stimulator riociguat and ARB telmisartan on kidney function and structure in a hypertensive model of diabetic nephropathy. Seventy-six diabetic male eNOS knockout C57BL/6J mice were randomly divided after having received streptozotocin: telmisartan (1 mg/kg/d), riociguat (3 mg/kg/d), riociguat+telmisartan (3+1 mg/kg/d), and vehicle. Fourteen mice were used as non-diabetic controls. Treatment duration was 11 weeks. Glucose concentrations were increased and similar in all diabetic groups. Telmisartan insignificantly reduced blood pressure by 5.9 mmHg compared with diabetic controls (111.2 +/- 2.3 mmHg vs. 117.1 +/- 2.2 mmHg; p = 0.071). Treatment with riociguat both alone and in combination with telmisartan led to a significant reduction of blood pressure towards diabetic vehicle (105.2 +/- 2.5 mmHg and 105.0 +/- 3.2 mmHg, respectively, vs. 117.1 +/- 2.2 mmHg). Combined treatment also significantly decreased albuminuria compared with diabetic controls (47.3 +/- 9.6 mu g/24 h vs. 170.8 +/- 34.2 mu g/24 h; p = 0.002) reaching levels similar to those of non-diabetic controls (34.4 +/- 10.6 mu g/24 h), whereas the reduction by single treatment with either telmisartan (97.8 +/- 26.4 mu g/24 h) or riociguat (97.1 +/- 15.7 mu g/24 h) was not statistically significant. The combination treatment led to a significant (p < 0.01) decrease of tissue immunoreactivity of malondialdehyde, as consequence of reduced oxidative stress. In conclusion, stimulation of sGC significantly reduced urinary albumin excretion in diabetic eNOS knockout mice treated already with ARB. Thus, this new drug class on top of standard ARBs administration may offer a new therapeutic approach for patients resistant to ARB treatment.
Y1  - 2012
U6  - https://doi.org/10.1371/journal.pone.0042623
SN  - 1932-6203
VL  - 7
IS  - 8
PB  - PUBLIC LIBRARY SCIENCE
CY  - SAN FRANCISCO
ER  - 
TY  - CHAP
A1  - Schupp, M.
A1  - Raila, Jens
A1  - Witte, N.
A1  - Tuvia, N.
A1  - Münzner, Matthias
T1  - RBP4 and its membrane receptor stra6 control adipogenesis by regulating cellular retinoid homeostasis
T2  - Diabetologia : journal of the European Association for the Study of Diabetes (EASD)
Y1  - 2012
SN  - 0012-186X
SN  - 1432-0428
VL  - 55
SP  - S93
EP  - S93
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Elias-Miro, Maria
A1  - Massip-Salcedo, Marta
A1  - Raila, Jens
A1  - Schweigert, Florian J.
A1  - Mendes-Braz, Mariana
A1  - Ramalho, Fernando
A1  - Jimenez-Castro, Monica B.
A1  - Casillas-Ramirez, Arani
A1  - Bermudo, Raquel
A1  - Rimola, Antoni
A1  - Rodes, Juan
A1  - Peralta, Carmen
T1  - Retinol binding protein 4 and retinol in steatotic and nonsteatotic rat livers in the setting of partial hepatectomy under ischemia/reperfusion
JF  - Liver transplantation
N2  - Steatotic livers show increased hepatic damage and impaired regeneration after partial hepatectomy (PH) under ischemia/reperfusion (I/R), which is commonly applied in clinical practice to reduce bleeding. The known function of retinol-binding protein 4 (RBP4) is to transport retinol in the circulation. We examined whether modulating RBP4 and/or retinol could protect steatotic and nonsteatotic livers in the setting of PH under I/R. Steatotic and nonsteatotic livers from Zucker rats were subjected to PH (70%) with 60 minutes of ischemia. RBP4 and retinol levels were measured and altered pharmacologically, and their effects on hepatic damage and regeneration were studied after reperfusion. Decreased RBP4 levels were observed in both liver types, whereas retinol levels were reduced only in steatotic livers. RBP4 administration exacerbated the negative consequences of liver surgery with respect to damage and liver regeneration in both liver types. RBP4 affected the mobilization of retinol from steatotic livers, and this revealed actions of RBP4 independent of simple retinol transport. The injurious effects of RBP4 were not due to changes in retinol levels. Treatment with retinol was effective only for steatotic livers. Indeed, retinol increased hepatic injury and impaired liver regeneration in nonsteatotic livers. In steatotic livers, retinol reduced damage and improved regeneration after surgery. These benefits of retinol were associated with a reduced accumulation of hepatocellular fat. Thus, strategies based on modulating RBP4 could be ineffective and possibly even harmful in both liver types in the setting of PH under I/R. In terms of clinical applications, a retinol pretreatment might open new avenues for liver surgery that specifically benefit the steatotic liver. Liver Transpl 18:1198-1208, 2012.
Y1  - 2012
U6  - https://doi.org/10.1002/lt.23489
SN  - 1527-6465
VL  - 18
IS  - 10
SP  - 1198
EP  - 1208
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Henze, Andrea
A1  - Espe, Katharina M.
A1  - Wanner, Christoph
A1  - Krane, Vera
A1  - Raila, Jens
A1  - Hocher, Berthold
A1  - Schweigert, Florian J.
A1  - Drechsler, Christiane
T1  - Transthyretin predicts cardiovascular outcome in hemodialysis patients with type 2 diabetes
JF  - Diabetes care
N2  - OBJECTIVE-BMI and albumin are commonly accepted parameters to recognize wasting in dialysis patients and are powerful predictors of morbidity and mortality. However, both parameters reveal limitations and may not cover the entire range of patients with wasting. The visceral protein transthyretin (TTR) may be helpful in overcoming the diagnostic and prognostic gap. Therefore, the aim of this study was to assess the association of TTR with morbidity and mortality in hemodialysis patients.
 RESEARCH DESIGN AND METHODS-The TTR concentration was determined in plasma samples of 1,177 hemodialysis patients with type 2 diabetes. Cox regression analyses were used to determine hazard ratios (HRs) for the risk of cardiovascular end points (CVEs) and mortality according to quartiles of TTR concentration for the total study cohort and the subgroups BMI >= 23 kg/m(2), albumin concentration >= 3.8 g/dL, and a combination of both.
 RESULTS-A low TTR concentration was associated with an increased risk for CVE for the total study cohort (HR 1.65 [95% CI 1.27-2.14]), patients with BMI >= 23 kg/m(2) (1.70 [1.22-2.37]), albumin >= 3.8 g/dL (1.68 [1.17-2.42]), and the combination of both (1.69 [1.13-2.53]). Additionally, a low TTR concentration predicted mortality for the total study cohort (1.79 [1.43-2.24]) and patients with BMI >= 23 kg/m(2) (1.46 [1.09-1.95]).
 CONCLUSIONS-The current study demonstrated that TTR is a useful predictor for cardiovascular outcome and mortality in diabetic hemodialysis patients. TTR was particularly useful in patients who were not identified to be at risk by BMI or albumin status.
Y1  - 2012
U6  - https://doi.org/10.2337/dc12-0455
SN  - 0149-5992
VL  - 35
IS  - 11
SP  - 2365
EP  - 2372
PB  - American Diabetes Association
CY  - Alexandria
ER  -