@article{UngruBlueherCoenenetal.2012, author = {Ungru, J. and Bl{\"u}her, M. and C{\"o}nen, M. and Raila, Jens and Boston, R. and Vervuert, I.}, title = {Effects of body weight reduction on blood adipokines and subcutaneous adipose tissue adipokine mRNA expression profiles in obese ponies}, series = {The veterinary record}, volume = {171}, journal = {The veterinary record}, number = {21}, publisher = {British Veterinary Association}, address = {London}, issn = {0042-4900}, doi = {10.1136/vr.100911}, pages = {528 -- +}, year = {2012}, abstract = {Fifteen obese ponies were used in a body weight (BW) reduction programme (BWRP, daily energy intake: 7.0-8.4 MJ/100 kg BW). A frequently sampled intravenous glucose tolerance test was used to assess insulin sensitivity. Subcutaneous adipose tissue biopsies of the tail head were obtained for mRNA gene expression profiles of adiponectin, retinol-binding protein 4 (RBP4), interleukin 6 (IL-6) and macrophage activation marker (CD68) before and after BWRP. Blood samples were analysed for serum leptin, serum RBP4 and plasma adiponectin. Significant BW losses occurred with 7 MJ DE/100 kg BW. Serum leptin and RBP4 were initially similar between insulin-resistant (IR) and insulin-sensitive (IS) ponies, and both significantly decreased during BWRP. Compared with IS ponies, IR ponies initially had significantly lower plasma adiponectin levels. At the beginning of BWRP, mRNA expression of RBP4, adiponectin, IL-6 and CD68 was similar between IR and IS ponies. Plasma adiponectin was strongly related to IR, whereas serum leptin and RBP4 were closely linked to adiposity, independent of insulin sensitivity. Adipose tissue mRNA expression profiles did not clearly reflect these differences. However, the role of subcutaneous adipose tissue in IR remains open.}, language = {en} } @article{ThawnashomTungtrongchitrChanchayetal.2011, author = {Thawnashom, Kittisak and Tungtrongchitr, Rungsunn and Chanchay, Siriporn and Tungtrongchitr, Anchalee and Raila, Jens and Henze, Andrea and Schweigert, Florian J.}, title = {Association between Retinol-Binding protein and renal function among Asian subjects with type 2 diabetes mellitus a cross-sectiona{\"o} study}, series = {The Southeast Asian journal of tropical medicine and public health : official publication of the SEAMEO Regional Tropical Medicine and Public Health Project (TROPMED)}, volume = {42}, journal = {The Southeast Asian journal of tropical medicine and public health : official publication of the SEAMEO Regional Tropical Medicine and Public Health Project (TROPMED)}, number = {4}, publisher = {SEAMEO}, address = {Bangkok}, issn = {0125-1562}, pages = {936 -- 945}, year = {2011}, abstract = {Retinol-binding protein 4 (RBP4) has been suggested as new adipokine, possibly linking obesity to type 2 diabetes mellitus (T2DM). Since the kidneys are the main site of RBP4 degradation and since renal failure is a frequent co-morbid condition with diabetes mellitus, we evaluated the association among RBP4, renal function and T2DM in an Asian population. RBP4 serum levels were analyzed in 110 subjects (50 with T2DM) using an enzyme-linked immunosorbent assay (ELISA). Based on a cut-off estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m(2) (calculated according the abbreviated MDRD formula which uses serum creatinine level, age and gender) and on the T2DM status, subjects were assigned to four subgroups: Group A - controls with an eGFR > 60 ml/min per 1.73 m(2), Group B - controls with an eGFR < 60 ml/min per 1.73 m(2), Group C- T2DM subjects with an eGFR>60 ml/min per 1.73 m(2), and Group D - T2DM subjects with an eGFR <60 ml/ mm per 1.73 m(2). In both the T2DM and control groups, RBP4 levels were higher in subjects with an eGFR < 60 ml/min per 1.73 m(2) than in subjects with an eGFR >60 ml/min per 1.73 m(2). However, the difference was only significant between the control groups (p <0.05). After adjusting for age, gender, BMI, eGFR and the presence of T2DM, eGFR, not T2DM, was associated with plasma RBP4 levels (p<0.05). These results suggest among Asians the eGFR, but not the presence of T2DM, is a major determinant of RBP4 serum levels. The eGFR should be taken into account when evaluating the role of RBP4 in the pathogenesis of insulin resistance and T2DM.}, language = {en} } @article{StarzonekRoscherBlitheretal.2019, author = {Starzonek, Janine and Roscher, Katja and Blither, Matthias and Blaue, Dominique and Schedlbauer, Carola and Hire, Manuela and Raila, Jens and Vervuert, Ingrid}, title = {Effects of a blend of green tea and curcuma extract supplementation on lipopolysaccharide-induced inflammation in horses and ponies}, series = {PeerJ}, volume = {7}, journal = {PeerJ}, publisher = {PeerJ Inc.}, address = {London}, issn = {2167-8359}, doi = {10.7717/peerj.8053}, pages = {17}, year = {2019}, abstract = {Background. In horses and ponies numerous medical conditions are known to be linked with inflammation in different tissues, especially in the liver. Besides affecting other metabolic pathways such as the expression of certain interleukins (IL), inflammation is associated with stress of the endoplasmic reticulum (ER). In particular, ER stress leads to adaptive stress response and can be measured by several markers of inflammatory and stress signalling pathways, like nuclear factor kappa B (NF-kB). Objectives. To investigate lipopolysaccharide (LPS)-induced inflammatory reactions and their modulation in horses and ponies by feeding a polyphenol-rich supplement consisting of green tea and curcuma. Methods. In a cross-over study, 11 animals were allocated to either a placebo or a supplement group and supplemented with 10 g of a blend of green tea and curcuma extract (GCE) or a placebo (calcium carbonate) once daily. After 21 days of supplementation, all animals underwent a LPS challenge to induce moderate systemic inflammation. Blood samples and liver biopsies were taken at standardized time points: 24 hours before and 12 hours after LPS challenge. Inflammatory blood parameters such as serum amyloid A (SAA), haptoglobin and retinol binding protein 4 (RBP4) were measured in serum. Hepatic mRNA levels of selected markers of inflammation such as haptoglobin, tumor necrosis factor alpha (TNF-alpha), IL-1 beta, IL-6, cluster of differentiation 68 (CD68), fibroblast growth factor 21 (FGF-21), NF-kappa B, activating transcription factor 4 (ATF4) were quantified by RT-qPCR. In addition, liver biopsies were examined histologically for inflammatory alterations. Results. Blood markers of acute inflammatory response increased after LPS challenge. In the liver, the proinflammatory cytokine IL-1 beta showed significantly lower mRNA levels after LPS challenge in the supplemented group (P = 0.04) compared to the placebo group. Levels of the hepatic CD68 mRNA increased significantly in the placebo group (P = 0.04). There were no significant differences between supplemented and placebo groups concerning other markers of inflammation and markers of ER stress within the liver. The number of hepatic macrophages were not different after LPS challenge in both feeding groups. Conclusion. LPS was able to induce inflammation but seemed less suitable to induce ER stress in the horses and ponies. The polyphenol-rich supplement showed some potential to reduce inflammatory responses. Nevertheless, the supplementation did not exert an overall anti-inflammatory effect in horses and ponies.}, language = {en} } @article{ShahidManchiSlunskyetal.2017, author = {Shahid, Muhammad and Manchi, G. and Slunsky, Pavel and Naseer, O. and Fatima, A. and Leo, B. and Raila, Jens}, title = {A systemic review of existing serological possibilities to diagnose canine osteoarthritis with a particular focus on extracellular matrix proteoglycans and protein}, series = {Polish journal of veterinary sciences : PJVS : the journal of Committee of Veterinary Sciences of Polish Academy of Sciences and University of Warmia and Mazury in Olsztyn}, volume = {20}, journal = {Polish journal of veterinary sciences : PJVS : the journal of Committee of Veterinary Sciences of Polish Academy of Sciences and University of Warmia and Mazury in Olsztyn}, number = {1}, publisher = {De Gruyter}, address = {Berlin}, issn = {1505-1773}, doi = {10.1515/pjvs-2017-0024}, pages = {189 -- 201}, year = {2017}, abstract = {Extra-cellular matrix (ECM) components are important and their stabilization is significant in maintaining normal healthy joint environment. In osteoarthritis (OA), ECM components are altered and indicate disease progression. The joint ECM is composed of proteoglycans (aggrecan, perlecan,inter α-trypsin inhibitor), glycoproteins (fibronectin, lubricin, COMP) and collagen types (most abundantly collagen type II) which represent structural and functional transformation during disease advancement. ECM investigation revealed significant biomarkers of OA that could be used as a diagnostic and therapeutic tool in different canine orthopedic diseases. This review deliberates our current findings of how the components of ECM change at the molecular level during disease progression in canine OA.}, language = {en} } @article{SchweigertWirthRaila2004, author = {Schweigert, Florian J. and Wirth, Kerstin and Raila, Jens}, title = {Characterization of the microheterogeneity of transthyretin in plasma and urine using SELDI-TOF-MS immunoassay}, year = {2004}, language = {en} } @article{SchweigertRailaSehoulietal.2004, author = {Schweigert, Florian J. and Raila, Jens and Sehouli, Jalid and B{\"u}scher, Ulrich}, title = {Accumulation of Selected Carotenoids, alpha-tocopherol and Retinol in Human Ovarian Carcinoma Ascitic Fluid}, issn = {1421-9697}, year = {2004}, abstract = {Background: Patients with severe forms of cancer are reported to have reduced concentrations of micronutrients in plasma due to the chronic reduction of food intake and an increased metabolism of these components. The purpose of this study was to evaluate if an accumulation of carotenoids, alpha-tocopherol and retinol in malignant ascitic fluid in women with ovarian cancer might contribute to a loss of these components from plasma. Methods: Blood and ascitic fluid samples obtained from 21 women with ovarian carcinomas and 17 healthy controls were analyzed for retinol, retinol- binding protein (RBP), alpha-tocopherol and carotenoids. Results: Plasma concentrations of all micronutrients were lower in cancer patients compared to controls. Ascitic fluid concentration of all investigated components was comparable (73- 110\%) to plasma. While the mean concentration of retinol in malignant ascites represented 73\% of that in plasma, the concentration of RBP was less than 10\% resulting in an increased mean molar ratio of retinol to RBP from 1.18 to 10.5. Conclusions: The results suggest that lower plasma concentrations of micronutrients in women suffering from ovarian carcinoma are not only caused by a cachexia-induced decrease of food intake and a higher rate of metabolic utilization, but also by a substantial yet not considered transfer from plasma into ascitic fluid possibly associated with plasma lipoproteins. This raises questions with regard to the protective function of these plasma components in ascitic fluid, the consequences of paracentesis on an additional supplementation and finally the possibility to use one or a combination of these components as an additional marker to discriminate between benign and malignant ascites. Copyright (C) 2004 S. Karger AG, Basel}, language = {en} } @article{SchweigertRailaHaebel1998, author = {Schweigert, Florian J. and Raila, Jens and Haebel, Sophie}, title = {Vitamin A excreted in the urine of canines is associated with a Tamm-Horsfall-like Glycoprotein}, year = {1998}, language = {en} } @article{SchweigertRailaEisenachetal.1997, author = {Schweigert, Florian J. and Raila, Jens and Eisenach, C. and Buchholz, Ingeborg}, title = {Distribution of vitamin A and retinol-binding-protein (RBP) in plasma, urine and various tissues of canines}, year = {1997}, language = {en} } @article{SchweigertRaila2005, author = {Schweigert, Florian J. and Raila, Jens}, title = {Inadequate attempts to measure the microheterogeneity of transthyretin by low-resolution mass spectrometry : Response}, issn = {0009-9147}, year = {2005}, language = {en} } @inproceedings{SchuppRailaWitteetal.2012, author = {Schupp, M. and Raila, Jens and Witte, N. and Tuvia, N. and M{\"u}nzner, Matthias}, title = {RBP4 and its membrane receptor stra6 control adipogenesis by regulating cellular retinoid homeostasis}, series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, volume = {55}, booktitle = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, publisher = {Springer}, address = {New York}, issn = {0012-186X}, pages = {S93 -- S93}, year = {2012}, language = {en} } @article{SchmiedchenLongardtLouietal.2016, author = {Schmiedchen, Bettina and Longardt, Ann Carolin and Loui, Andrea and Buehrer, Christoph and Raila, Jens and Schweigert, Florian J.}, title = {Effect of vitamin A supplementation on the urinary retinol excretion in very low birth weight infants}, series = {European journal of pediatrics : official organ of the Belgian Pediatric Association}, volume = {175}, journal = {European journal of pediatrics : official organ of the Belgian Pediatric Association}, publisher = {Springer}, address = {New York}, issn = {0340-6199}, doi = {10.1007/s00431-015-2647-9}, pages = {365 -- 372}, year = {2016}, abstract = {Despite high-dose vitamin A supplementation of very low birth weight infants (VLBW, <1500 g), their vitamin A status does not improve substantially. Unknown is the impact of urinary retinol excretion on the serum retinol concentration in these infants. Therefore, the effect of high-dose vitamin A supplementation on the urinary vitamin A excretion in VLBW infants was investigated. Sixty-three VLBW infants were treated with vitamin A (5000 IU intramuscular, 3 times/week for 4 weeks); 38 untreated infants were classified as control group. On days 3 and 28 of life, retinol, retinol-binding protein 4 (RBP4), glomerular filtration rate, proteinuria, and Tamm-Horsfall protein were quantified in urine. On day 3 of life, substantial retinol and RBP4 losses were found in both groups, which significantly decreased until day 28. Notwithstanding, the retinol excretion was higher (P<0.01) under vitamin A supplementation as compared to infants of the control group. On day 28 of life, the urinary retinol concentrations were predictive for serum retinol concentrations in the vitamin A treated (P<0.01), but not in the control group (P=0.570). Conclusion: High urinary retinol excretion may limit the vitamin A supplementation efficacy in VLBW infants. Advanced age and thus postnatal kidney maturation seems to be an important contributor in the prevention of urinary retinol losses.}, language = {en} } @misc{SchmiedchenLongardtBuehreretal.2017, author = {Schmiedchen, Bettina and Longardt, Ann Carolin and B{\"u}hrer, Christoph and Raila, Jens and Loui, Andrea and Schweigert, Florian J.}, title = {The Relative Dose Response Test Based on Retinol-Binding Protein 4 Is Not Suitable to Assess Vitamin A Status in Very Low Birth Weight Infants}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-399853}, pages = {6}, year = {2017}, abstract = {Background: The relative dose response (RDR) test, which quantifies the increase in serum retinol after vitamin A administration, is a qualitative measure of liver vitamin A stores. Particularly in preterm infants, the feasibility of the RDR test involving blood is critically dependent on small sample volumes. Objectives: This study aimed to assess whether the RDR calculated with retinol-binding protein 4 (RBP4) might be a substitute for the classical retinol-based RDR test for assessing vitamin A status in very preterm infants. Methods: This study included preterm infants with a birth weight below 1,500 g (n = 63, median birth weight 985 g, median gestational age 27.4 weeks) who were treated with 5,000 IU retinyl palmitate intramuscularly 3 times a week for 4 weeks. On day 3 (first vitamin A injection) and day 28 of life (last vitamin A injection), the RDR was calculated and compared using serum retinol and RBP4 concentrations. Results: The concentrations of retinol (p < 0.001) and RBP4 (p < 0.01) increased significantly from day 3 to day 28. On day 3, the median (IQR) retinol-RDR was 27\% (8.4-42.5) and the median RBP4-RDR was 8.4\% (-3.4 to 27.9), compared to 7.5\% (-10.6 to 20.8) and -0.61\% (-19.7 to 15.3) on day 28. The results for retinol-RDR and RBP4-RDR revealed no significant correlation. The agreement between retinol-RDR and RBP4-RDR was poor (day 3: Cohen's κ = 0.12; day 28: Cohen's κ = 0.18). Conclusion: The RDR test based on circulating RBP4 is unlikely to reflect the hepatic vitamin A status in preterm infants.}, language = {en} } @article{SchedlbauerBlaueRailaetal.2020, author = {Schedlbauer, Carola and Blaue, Dominique and Raila, Jens and Vervuert, Ingrid}, title = {Alterations of serum vitamin E and vitamin A concentrations of ponies and horses during experimentally induced obesity}, series = {Journal of animal physiology and animal nutrition}, volume = {104}, journal = {Journal of animal physiology and animal nutrition}, number = {5}, publisher = {Wiley}, address = {Hoboken}, issn = {0931-2439}, doi = {10.1111/jpn.13385}, pages = {1501 -- 1508}, year = {2020}, abstract = {Vitamin A, vitamin E and retinol-binding protein 4 (RBP4) are a focus of current obesity research in humans. The impact of body weight (BW) gain on fat-soluble vitamins and its associated parameters in equines has not been previously reported. Ten Shetland ponies and 9 Warmblood horses, all adult geldings, non-obese and healthy, were fed an excessive energy diet for 20 months to induce BW gain. Serum alpha-tocopherol (vitamin E), retinol (vitamin A), retinol-binding protein 4 (RBP4) and retinol/RBP4 ratio were analysed before BW gain induction and at six timepoints during the BW gaining period. The mean (+/- SD) \% BW gain achieved during two years of excess energy intake was 29.9 +/- 19.4\% for ponies and 17 +/- 6.74\% for horses. Serum alpha-tocopherol increased significantly in ponies and horses during excess energy intake and circulating alpha-tocopherol levels correlated positively with alpha-tocopherol intake (r = .6; p < .001). Serum retinol concentrations showed variations during the study but without relation to intake. Serum RBP4 decreased at the end of the study. The retinol/RBP4 ratio increased with BW gain without differences between ponies and horses. In comparison with human research, the increase in the retinol/RBP4 ratio was unexpected and needs further elucidation.}, language = {en} } @misc{SchedlbauerBlaueRailaetal.2020, author = {Schedlbauer, Carola and Blaue, Dominique and Raila, Jens and Vervuert, Ingrid}, title = {Alterations of serum vitamin E and vitamin A concentrations of ponies and horses during experimentally induced obesity}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {5}, issn = {1866-8372}, doi = {10.25932/publishup-51951}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-519515}, pages = {10}, year = {2020}, abstract = {Vitamin A, vitamin E and retinol-binding protein 4 (RBP4) are a focus of current obesity research in humans. The impact of body weight (BW) gain on fat-soluble vitamins and its associated parameters in equines has not been previously reported. Ten Shetland ponies and 9 Warmblood horses, all adult geldings, non-obese and healthy, were fed an excessive energy diet for 20 months to induce BW gain. Serum alpha-tocopherol (vitamin E), retinol (vitamin A), retinol-binding protein 4 (RBP4) and retinol/RBP4 ratio were analysed before BW gain induction and at six timepoints during the BW gaining period. The mean (+/- SD) \% BW gain achieved during two years of excess energy intake was 29.9 +/- 19.4\% for ponies and 17 +/- 6.74\% for horses. Serum alpha-tocopherol increased significantly in ponies and horses during excess energy intake and circulating alpha-tocopherol levels correlated positively with alpha-tocopherol intake (r = .6; p < .001). Serum retinol concentrations showed variations during the study but without relation to intake. Serum RBP4 decreased at the end of the study. The retinol/RBP4 ratio increased with BW gain without differences between ponies and horses. In comparison with human research, the increase in the retinol/RBP4 ratio was unexpected and needs further elucidation.}, language = {en} } @article{RailaWirthChenetal.2004, author = {Raila, Jens and Wirth, Kerstin and Chen, Frank and B{\"u}scer, Ulrich and Dudenhausen, Joachim W. and Schweigert, Florian J.}, title = {Excretion of vitamin A in urine of women during Normal pregnancy and pregnancy complications}, issn = {0250-6807}, year = {2004}, abstract = {Background/Aims: The renal function, including the excretion of low-molecular-weight proteins, changes during pregnancy and may cause a urinary excretion of retinol-binding protein (RBP). Whether it is accompanied by a substantial loss of vitamin A ( retinol) has not been established yet. We therefore determined the excretion of retinol and RBP in urine of pregnant women. Methods: The study involved analyses of urine samples from 40 healthy pregnant women and 29 women with pregnancy complications during the third trimester. Analyses of plasma and urine of 7 healthy women and 5 women with pregnancy complications were also carried out 6 weeks antepartum, at time of delivery and 1 week postpartum. Results: Urinary retinol was higher in women who suffered from pregnancy disorders with an influence on maternal metabolism ( p < 0.01). RBP was excreted at substantial concentrations in the urine of all 69 women, but there were no differences between the groups. Women with a concomitant excretion of retinol had higher levels of urinary RBP than those without a retinol excretion ( p < 0.05). Differences in plasma retinol and RBP were not significant. Conclusion: The excretion of urinary retinol may increase significantly during pregnancy complications, which needs further clarification to which extent this condition may negatively affect the vitamin A status in such women. Copyright (C) 2004 S. Karger AG, Basel}, language = {en} } @book{RailaWirthBuescheretal.2001, author = {Raila, Jens and Wirth, Kerstin and B{\"u}scher, Ulrich and Dudenhausen, Joachim W. and Schweigert, Florian J.}, title = {Einfluss normaler und pathologischer Schwangerschaftsverl{\"a}ufe auf die renale Ausscheidung von Vitamin A und Retinol-Bindungsprotein}, year = {2001}, language = {de} } @article{RailaWillnowSchweigert2005, author = {Raila, Jens and Willnow, T. E. and Schweigert, Florian J.}, title = {Megalin-mediated reuptake of retinol in the kidneys of mice is essential for vitamin A homeostasis}, issn = {0022-3166}, year = {2005}, abstract = {The reuptake of retinol (ROH) and retinol-binding protein (RBP) in the kidneys is mediated by the endocytic receptor megalin, suggesting an important role for this receptor in vitamin A (VA) metabolism. We examined the extent to which megalin deficiency may affect urinary ROH excretion, levels of ROH and RBP in plasma, as well as storage of VA in liver and kidney. For this purpose, mice with a kidney-specific megalin gene defect (megalin(lox/lox):; apoE(Cre)) and control mice (megalin(lox/lox)) were fed either a basal diet containing 4500 retinol equivalents (RE)/kg diet or a diet without VA during experimental periods of 42 and 84 d. Urinary ROH excretion was observed only in megalin(lox/lox); apoE(Cre) mice (P < 0.0001, 2-way ANOVA) and not in the controls. Plasma ROH and RBP differed only by diet (P < 0.05), but not genotype (P = 0.615). A major effect of megalin deficiency, however, was evident in retinyl ester levels in the liver (P < 0.05), which were similar to 37\% lower than those in megalin(lox/lox) controls (P < 0.05, Student's t test) during the 84-d period of dietary VA deprivation. Kidney levels of VA were not affected by the receptor gene defect. The findings demonstrate that urinary ROH excretion caused by megalin deficiency requires accelerated mobilization of hepatic VA stores to maintain normal plasma ROH levels, which suggests that megalin plays an essential role in systemic VA homeostasis}, language = {en} } @article{RailaStohrerForterreetal.2004, author = {Raila, Jens and Stohrer, M. and Forterre, Simone and Stangassinger, M. and Schweigert, Florian J.}, title = {Effect of exercise on the mobilization of retinol and retinyl esters in plasma of sled dogs}, year = {2004}, abstract = {Fasting dogs do transport vitamin A (VA) in plasma not only as retinol but predominantly as retinyl esters. Contrary to retinol, nothing is known concerning the effects of athletic performance on plasma retinyl ester concentrations. The aim of this study was therefore to examine whether physical stress because of exercise and modification of the oxidative stress by supplementation of alpha-tocopherol influences the concentrations of retinol and retinyl esters in plasma of sled dogs. The study was carried out on 41 trained adult sled dogs, which were randomly assigned into two groups. One group (19 dogs) was daily substituted with 50 mg DL-alpha-tocopheryl acetate per kilogram body weight and the control group (22 dogs) was maintained on a basal diet during 3 months prior to exercise. The plasma concentrations of retinol, retinyl esters, alpha-tocopherol and triglycerides were measured immediately before, directly after and 24 h after exercise. The supplementation of alpha-tocopheryl acetate had no effect on plasma retinol and retinyl ester concentrations at any measurement time point. However, retinyl ester levels doubled in the non- supplemented group immediately after the race (p < 0.001), whereas in the supplemented group similar high levels were observed not until 24 h post-racing (p < 0.001). The high levels of retinyl esters were paralleled to some extent by an increase in plasma triglyceride concentrations, which were significantly higher 24 h post-racing than immediately before (p < 0.001) and after exercise (p < 0.001) in both groups. The increase in retinyl ester concentrations might be indicative of their mobilization from liver and adipose tissue. Whether plasma retinyl esters can be used as an indicator for the extent of nutrient mobilization during and post-exercise in sled dogs remains to be elucidated}, language = {en} } @article{RailaSchweigertStanitznigetal.2017, author = {Raila, Jens and Schweigert, Florian J. and Stanitznig, A. and Lambacher, B. and Franz, S. and Baldermann, Susanne and Wittek, T.}, title = {No detectable carotenoid concentrations in serum of llamas and alpacas}, series = {Journal of animal physiology and animal nutrition}, volume = {101}, journal = {Journal of animal physiology and animal nutrition}, publisher = {Wiley}, address = {Hoboken}, issn = {0931-2439}, doi = {10.1111/jpn.12638}, pages = {629 -- 634}, year = {2017}, abstract = {Carotenoids are lipid-soluble pigments and important for a variety of physiological functions. They are major dietary vitamin A precursors and act as lipophilic antioxidants in a variety of tissues and are associated with important health benefits in humans and animals. All animals must acquire carotenoids from their diet, but to our knowledge, there are no studies investigating the intestinal carotenoid absorption and their blood concentrations in New World camelids. The present study aimed to assess the serum concentrations of selected carotenoids in llamas (n=13) and alpacas (n=27). Serum carotenoids as well as retinol (vitamin A) and -tocopherol (vitamin E) were determined by high-performance liquid chromatography coupled with mass spectrometry and these were unable to detect any carotenoids (- and -carotene, - and -cryptoxanthin, lutein, zeaxanthin, lycopene) in the samples. The concentrations of retinol in alpacas (2.89 +/- 1.13mol/l; mean +/- SD) were higher (p=0.024) than those found in llamas (2.05 +/- 0.87mol/l); however, the concentrations of -tocopherol were not significantly (p=0.166) different (llamas: 3.98 +/- 1.83mol/l; alpacas: 4.95 +/- 2.14mol/l). The results show that both llamas and alpacas are not able to absorb intact carotenoids, but efficiently convert provitamin A carotenoids to retinol.}, language = {en} } @article{RailaSchweigertKohn2011, author = {Raila, Jens and Schweigert, Florian J. and Kohn, Barbara}, title = {C-reactive protein concentrations in serum of dogs with naturally occurring renal disease}, series = {Journal of veterinary diagnostic investigation}, volume = {23}, journal = {Journal of veterinary diagnostic investigation}, number = {4}, publisher = {Sage Publ.}, address = {Thousand Oaks}, issn = {1040-6387}, doi = {10.1177/1040638711407896}, pages = {710 -- 715}, year = {2011}, abstract = {The current study was undertaken to investigate the relation between serum C-reactive protein (CRP) concentrations and parameters of renal function in dogs with naturally occurring renal disease. Dogs were assigned to groups according to plasma creatinine concentration, urinary protein-to-creatinine ratio (UP/UC), and exogenous plasma creatinine clearance (P-Cl(Cr)) rates. Group A (healthy control dogs; n = 8): non-azotemic (plasma creatinine <125 mu mol/l) and nonproteinuric (UP/UC <0.2), with P-Cl(Cr) rates >90 ml/min/m(2); group B (n = 11): non-azotemic, nonproteinuric dogs with reduced P-Cl(Cr) rates (50-89 ml/min/m(2)); group C (n = 7): azotemic, borderline proteinuric dogs (P-Cl(Cr) rates: 22-67 ml/min/m(2)); and group D (n = 6): uremic, proteinuric dogs (not tested for P-Cl(Cr)). The serum CRP concentrations were measured via commercial enzyme-linked immunosorbent assay. The CRP concentrations in the clinically healthy dogs (group A) ranged from 2.09 mg/l to 8.60 mg/l (median: 3.21 mg/l). In comparison with dogs of group A, median CRP concentrations were significantly (P < 0.01) elevated in dogs of group B (17.6 mg/l, range: 17.0-19.2 mg/l), group C (24.8 mg/l, range: 18.0-32.5 mg/l), and group D (59.7 mg/l, range: 17.7-123 mg/l). Serum CRP was significantly related to P-Cl(Cr) (r = -0.83; P < 0.001), plasma creatinine (r = 0.81; P < 0.001), UP/UC (r = 0.70; P < 0.001), and leukocytes (r = 0.49; P < 0.01). The significant relations between serum CRP concentrations and biochemical parameters of kidney function in plasma and urine suggest that a stimulation of the acute phase response is implicated in the pathogenesis of canine renal disease.}, language = {en} } @article{RailaSchweigertKohn2014, author = {Raila, Jens and Schweigert, Florian J. and Kohn, Barbara}, title = {Relationship between urinary Tamm-Horsfall protein excretion and renal function in dogs with naturally occurring renal disease}, series = {Veterinary clinical pathology}, volume = {43}, journal = {Veterinary clinical pathology}, number = {2}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0275-6382}, doi = {10.1111/vcp.12143}, pages = {261 -- 265}, year = {2014}, abstract = {Background Tamm-Horsfall protein (THP) is physiologically excreted in urine, but little is known about the role of THP in the diagnosis of renal disease in dogs. Objective The aim of this study was to evaluate to which extent naturally occurring renal disease affects the urinary excretion of THP. Methods Dogs were divided into 5 groups according to plasma creatinine concentration, urinary protein-to-creatinine ratio (UP/UC), and exogenous plasma creatinine clearance (P-ClCr) rates: Group A (healthy control dogs; n=8), nonazotemic and nonproteinuric dogs, with P-ClCr rates > 90mL/min/m2; group B (n=25), nonazotemic and nonproteinuric dogs with reduced P-ClCr rates (51-89mL/min/m2); group C (n=7), nonazotemic but proteinuric dogs with P-ClCr rates 53-98mL/min/m2; group D (n=8), azotemic and borderline proteinuric dogs (P-ClCr rates: 22-45mL/min/m2); and group E (n=15), azotemic and proteinuric dogs (not tested for P-ClCr). THP was measured by quantitative Western blot analysis, and the ratio of THP-to-urinary creatinine (THP/UC) was calculated. Results The THP/UC concentrations were not different among dogs of groups A-D, but were reduced in dogs of group E (P<.001). THP/UC correlated negatively with serum creatinine (P<.01) and UP/UC (P<.01), but was not significantly associated with P-ClCr. Conclusions Decreased levels of THP/UC were present in moderately to severely azotemic and proteinuric dogs. This suggests tubular injury in these dogs and that THP might be useful as urinary marker to study the pathogenesis of renal disease.}, language = {en} } @misc{RailaSchweigertKohn2017, author = {Raila, Jens and Schweigert, Florian J. and Kohn, Barbara}, title = {C-reactive protein concentrations in serum of dogs with naturally occurring renal disease}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-402942}, pages = {6}, year = {2017}, abstract = {The current study was undertaken to investigate the relation between serum C-reactive protein (CRP) concentrations and parameters of renal function in dogs with naturally occurring renal disease. Dogs were assigned to groups according to plasma creatinine concentration, urinary protein-to-creatinine ratio (UP/UC), and exogenous plasma creatinine clearance (P-Cl(Cr)) rates. Group A (healthy control dogs; n = 8): non-azotemic (plasma creatinine <125 mu mol/l) and nonproteinuric (UP/UC <0.2), with P-Cl(Cr) rates >90 ml/min/m(2); group B (n = 11): non-azotemic, nonproteinuric dogs with reduced P-Cl(Cr) rates (50-89 ml/min/m(2)); group C (n = 7): azotemic, borderline proteinuric dogs (P-Cl(Cr) rates: 22-67 ml/min/m(2)); and group D (n = 6): uremic, proteinuric dogs (not tested for P-Cl(Cr)). The serum CRP concentrations were measured via commercial enzyme-linked immunosorbent assay. The CRP concentrations in the clinically healthy dogs (group A) ranged from 2.09 mg/l to 8.60 mg/l (median: 3.21 mg/l). In comparison with dogs of group A, median CRP concentrations were significantly (P < 0.01) elevated in dogs of group B (17.6 mg/l, range: 17.0-19.2 mg/l), group C (24.8 mg/l, range: 18.0-32.5 mg/l), and group D (59.7 mg/l, range: 17.7-123 mg/l). Serum CRP was significantly related to P-Cl(Cr) (r = -0.83; P < 0.001), plasma creatinine (r = 0.81; P < 0.001), UP/UC (r = 0.70; P < 0.001), and leukocytes (r = 0.49; P < 0.01). The significant relations between serum CRP concentrations and biochemical parameters of kidney function in plasma and urine suggest that a stimulation of the acute phase response is implicated in the pathogenesis of canine renal disease.}, language = {en} } @article{RailaSchweigert2001, author = {Raila, Jens and Schweigert, Florian J.}, title = {Zur Bedeutung der Nieren im Vitamin-Stoffwechsel}, year = {2001}, language = {de} } @article{RailaRohnSchweigertetal.2011, author = {Raila, Jens and Rohn, Sascha and Schweigert, Florian J. and Abraham, Getu}, title = {Increased antioxidant capacity in the plasma of dogs after a single oral dosage of tocotrienols}, series = {The British journal of nutrition : an international journal devoted to the science of human and animal nutrition}, volume = {106}, journal = {The British journal of nutrition : an international journal devoted to the science of human and animal nutrition}, number = {7}, publisher = {Cambridge Univ. Press}, address = {Cambridge}, issn = {0007-1145}, doi = {10.1017/S0007114511000511}, pages = {S116 -- S119}, year = {2011}, abstract = {The intestinal absorption of tocotrienols (TCT) in dogs is, to our knowledge, so far unknown. Adult Beagle dogs (n 8) were administered a single oral dosage of a TCT-rich fraction (TRF; 40 mg/kg body weight) containing 32\% alpha-TCT, 2\% beta-TCT, 27\% gamma-TCT, 14\% delta-TCT and 25\% alpha-tocopherol (alpha-TCP). Blood was sampled at baseline (fasted), 1, 2, 3, 4, 5, 6, 8 and 12 h after supplementation. Plasma and chylomicron concentrations of TCT and alpha-TCP were measured at each time point. Plasma TAG were measured enzymatically, and plasma antioxidant capacity was assessed by the Trolox equivalent antioxidant capacity assay. In fasted dogs, levels of TCT were 0.07 (SD 0.03) mu mol/l. Following the administration of the TRF, total plasma TCT peaked at 2 h (7.16 (SD 3.88) mu mol/l; P<0.01) and remained above baseline levels (0.67 (SD 0.44) mu mol/l; P, 0.01) at 12 h. The TCT response in chylomicrons paralleled the increase in TCT in plasma with a maximum peak (3.49 (SD 2.06) mu mol/l; P, 0.01) at 2 h post-dosage. alpha-TCP was the major vitamin E detected in plasma and unaffected by TRF supplementation. The Trolox equivalent values increased from 2 h (776 (SD 51.2) mu mol/l) to a maximum at 12 h (1130 (SD 7.72) mmol/l; P<0.01). The results show that TCT are detected in postprandial plasma of dogs. The increase in antioxidant capacity suggests a potential beneficial role of TCT supplementation in the prevention or treatment of several diseases in dogs.}, language = {en} } @article{RailaNeumannSchweigert2003, author = {Raila, Jens and Neumann, U. and Schweigert, Florian J.}, title = {Immunochemical Localization of Megalin, Retinol-binding protein and Tamm-Horsfall Glycoprotein in the Kidneys of Dogs}, year = {2003}, language = {en} } @article{RailaMathewsSchweigert2001, author = {Raila, Jens and Mathews, U. and Schweigert, Florian J.}, title = {Plasma transport and tissue distribution of ß-carotene, vitamin A and retinol-binding protein in domestic cats}, year = {2001}, language = {en} } @misc{RailaKawashimaSauerweinetal.2017, author = {Raila, Jens and Kawashima, Chiho and Sauerwein, Helga and H{\"u}lsmann, Nadine and Knorr, Christoph and Myamoto, Akio and Schweigert, Florian J.}, title = {Validation of blood vitamin A concentrations in cattle: comparison of a new cow-side test (iCheck™ FLUORO) with high-performance liquid chromatography (HPLC)}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-401978}, pages = {6}, year = {2017}, abstract = {Background: Plasma concentration of retinol is an accepted indicator to assess the vitamin A (retinol) status in cattle. However, the determination of vitamin A requires a time consuming multi-step procedure, which needs specific equipment to perform extraction, centrifugation or saponification prior to high-performance liquid chromatography (HPLC). Methods: The concentrations of retinol in whole blood (n = 10), plasma (n = 132) and serum (n = 61) were measured by a new rapid cow-side test (iCheck™ FLUORO) and compared with those by HPLC in two independent laboratories in Germany (DE) and Japan (JP). Results: Retinol concentrations in plasma ranged from 0.033 to 0.532 mg/L, and in serum from 0.043 to 0.360 mg/L (HPLC method). No significant differences in retinol levels were observed between the new rapid cow-side test and HPLC performed in different laboratories (HPLC vs. iCheck™ FLUORO: 0.320 ± 0.047 mg/L vs. 0.333 ± 0.044 mg/L, and 0.240 ± 0.096 mg/L vs. 0.241 ± 0.069 mg/L, lab DE and lab JP, respectively). A similar comparability was observed when whole blood was used (HPLC vs. iCheck™ FLUORO: 0.353 ± 0.084 mg/L vs. 0.341 ± 0.064 mg/L). Results showed a good agreement between both methods based on correlation coefficients of r2 = 0.87 (P < 0.001) and Bland-Altman blots revealed no significant bias for all comparison. Conclusions: With the new rapid cow-side test (iCheck™ FLUORO) retinol concentrations in cattle can be reliably assessed within a few minutes and directly in the barn using even whole blood without the necessity of prior centrifugation. The ease of the application of the new rapid cow-side test and its portability can improve the diagnostic of vitamin A status and will help to control vitamin A supplementation in specific vitamin A feeding regimes such as used to optimize health status in calves or meat marbling in Japanese Black cattle.}, language = {en} } @article{RailaKawashimaSauerweinetal.2017, author = {Raila, Jens and Kawashima, Chiho and Sauerwein, Helga and H{\"u}lsmann, Nadine and Knorr, Christoph and Myamoto, Akio and Schweigert, Florian J.}, title = {Validation of blood vitamin A concentrations in cattle: comparison of a new cow-side test (iCheck™ FLUORO) with high-performance liquid chromatography (HPLC)}, series = {BMC veterinary research}, volume = {13}, journal = {BMC veterinary research}, publisher = {BioMed Central}, address = {London}, doi = {10.1186/s12917-017-1042-3}, year = {2017}, abstract = {Background: Plasma concentration of retinol is an accepted indicator to assess the vitamin A (retinol) status in cattle. However, the determination of vitamin A requires a time consuming multi-step procedure, which needs specific equipment to perform extraction, centrifugation or saponification prior to high-performance liquid chromatography (HPLC). Methods: The concentrations of retinol in whole blood (n = 10), plasma (n = 132) and serum (n = 61) were measured by a new rapid cow-side test (iCheck™ FLUORO) and compared with those by HPLC in two independent laboratories in Germany (DE) and Japan (JP). Results: Retinol concentrations in plasma ranged from 0.033 to 0.532 mg/L, and in serum from 0.043 to 0.360 mg/L (HPLC method). No significant differences in retinol levels were observed between the new rapid cow-side test and HPLC performed in different laboratories (HPLC vs. iCheck™ FLUORO: 0.320 ± 0.047 mg/L vs. 0.333 ± 0.044 mg/L, and 0.240 ± 0.096 mg/L vs. 0.241 ± 0.069 mg/L, lab DE and lab JP, respectively). A similar comparability was observed when whole blood was used (HPLC vs. iCheck™ FLUORO: 0.353 ± 0.084 mg/L vs. 0.341 ± 0.064 mg/L). Results showed a good agreement between both methods based on correlation coefficients of r2 = 0.87 (P < 0.001) and Bland-Altman blots revealed no significant bias for all comparison. Conclusions: With the new rapid cow-side test (iCheck™ FLUORO) retinol concentrations in cattle can be reliably assessed within a few minutes and directly in the barn using even whole blood without the necessity of prior centrifugation. The ease of the application of the new rapid cow-side test and its portability can improve the diagnostic of vitamin A status and will help to control vitamin A supplementation in specific vitamin A feeding regimes such as used to optimize health status in calves or meat marbling in Japanese Black cattle.}, language = {en} } @article{RailaForterreSchweigert2005, author = {Raila, Jens and Forterre, Simone and Schweigert, Florian J.}, title = {Markerproteine im Harn von Hunden}, isbn = {3-8304-1051-4}, year = {2005}, language = {de} } @article{RailaForterreSchweigert2005, author = {Raila, Jens and Forterre, Simone and Schweigert, Florian J.}, title = {Physiologische und pathophysiologische Grundlagen der Proteinurie : eine {\"U}bersicht}, year = {2005}, language = {de} } @article{RailaForterreSchweigert2005, author = {Raila, Jens and Forterre, Simone and Schweigert, Florian J.}, title = {Physiology and pathophysiology of proteinuria : a review}, issn = {0005-9366}, year = {2005}, abstract = {The term proteinuria is taken to mean abnormally high protein excretion in the urine. Proteinuria is the consequence of glomerular filtration of plasma proteins, their subsequent reabsorption by the proximal tubular cells and secretion of protein by the tubular cells and distal urinary tract. In physiological conditions, the structural integry of the glomerular filtration barrier prevents the abnormal passage of albumin (molecular mass 66 kDa) and high-molecular- weight proteins (> 66 kDa),whereas the passage of low-molecular-weight proteins (< 66 kDa) is almost completely unrestricted. Proteins that arrive the tubular lumen are reabsorbed by endocytosis after binding to the megalin-cubilin complex. An increased load of proteins in the tubular lumen leads to the saturation of the reabsorptive mechanism and higher urinary protein excretion. Proteinuria can originate from prerenal, renal and postrenal causes. Elevated tubular protein concentrations have been recognized to be toxic to tubular cells and associated with the progression of chronic renal disease. Therefore, the quantitative and qualitative evaluation of proteinuria is important for the diagnosis of renal disease}, language = {en} } @article{RailaForterreSchweigert2003, author = {Raila, Jens and Forterre, Simone and Schweigert, Florian J.}, title = {Die Bedeutung von Megalin in der Pathogenese der tubul{\"a}ren Proteinurie des Hundes}, isbn = {3-936815-65-8}, year = {2003}, language = {de} } @article{RailaForterreSchweigert2003, author = {Raila, Jens and Forterre, Simone and Schweigert, Florian J.}, title = {Levels of retinol and retinyl esters in plasma and urine of dogs with urolithiasis}, year = {2003}, language = {en} } @article{RailaEnjalbertMothesetal.2012, author = {Raila, Jens and Enjalbert, Francis and Mothes, Ralf and Hurtienne, Andrea and Schweigert, Florian J.}, title = {Validation of a new point-of-care assay for determination of ss-carotene concentration in bovine whole blood and plasma}, series = {Veterinary clinical pathology}, volume = {41}, journal = {Veterinary clinical pathology}, number = {1}, publisher = {Wiley-Blackwell}, address = {Malden}, issn = {0275-6382}, doi = {10.1111/j.1939-165X.2012.00400.x}, pages = {119 -- 122}, year = {2012}, abstract = {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.}, language = {en} } @article{RailaEisenachBuchholzetal.1997, author = {Raila, Jens and Eisenach, C. and Buchholz, Ingeborg and Schweigert, Florian J.}, title = {Verteilung von Vitamin A und Retinol-Bindungs-Protein (RBP) in verschiedenen Geweben von Caniden}, year = {1997}, language = {de} } @article{RailaEisenachBuchholzetal.1997, author = {Raila, Jens and Eisenach, C. and Buchholz, Ingeborg and Schweigert, Florian J.}, title = {Distribution of vitamin A and retinol-binding-protein (RBP) in various tissue of dogs and reccoon dogs}, year = {1997}, language = {en} } @article{RailaBuchholzSchweigert1997, author = {Raila, Jens and Buchholz, Ingeborg and Schweigert, Florian J.}, title = {Untersuchungen zur Vitamin-A-Bindung im Harn von Hunden}, year = {1997}, language = {de} } @article{RailaBuchholzAupperleetal.2000, author = {Raila, Jens and Buchholz, Ingeborg and Aupperle, Heike and Raila, Jens and Schoon, Heinz-Adolf and Schweigert, Florian J.}, title = {The distribution of vitamin A and retinol-binding protein (RBP) in the blood plasma, urine, liver and kidney of carnivores}, year = {2000}, language = {en} } @article{RailaBokBuchholzetal.1997, author = {Raila, Jens and Bok, V. and Buchholz, Ingeborg and Schweigert, Florian J.}, title = {Untersuchungen zum Vitamin-A-Stoffwechsel der Niere des Hundes}, year = {1997}, language = {de} } @article{RailaBokBuchholzetal.1997, author = {Raila, Jens and Bok, V. and Buchholz, Ingeborg and Schweigert, Florian J.}, title = {Investigations on the excretion of vitamin A as retinol and retinyl esters bound to a high molecular complex}, year = {1997}, language = {en} } @article{PasslackSchmiedchenRailaetal.2016, author = {Passlack, Nadine and Schmiedchen, Bettina and Raila, Jens and Schweigert, Florian J. and Stumpff, Friederike and Kohn, Barbara and Neumann, Konrad and Zentek, Juergen}, title = {Impact of Increasing Dietary Calcium Levels on Calcium Excretion and Vitamin D Metabolites in the Blood of Healthy Adult Cats}, series = {PLoS one}, volume = {11}, journal = {PLoS one}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0149190}, pages = {47 -- 67}, year = {2016}, abstract = {Background Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken. Results Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D-2 and 25(OH)D-3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001). Conclusions In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P.}, language = {en} } @article{NaglLouiRailaetal.2009, author = {Nagl, Britta and Loui, Andrea and Raila, Jens and Felderhoff-Mueser, Ursula and Obladen, Michael and Schweigert, Florian J.}, title = {Urinary vitamin A excretion in very low birth weight infants}, issn = {0931-041X}, doi = {10.1007/s00467-008-0965-0}, year = {2009}, abstract = {Vitamin A (VA) deficiency in very low birth weight (VLBW) infants is associated with an increased risk for disorders related to kidney and lung maturation and function. VA losses through increased urinary retinol (ROH) excretion might contribute to this deficiency risk. The mechanism accounting for ROH loss in the urine has not yet been clarified. The aim of this study was to assess the excretion of ROH, retinol-binding protein 4 (RBP4) and transthyretin (TTR) in urine from VLBW infants in comparison with that in term infants in relation to kidney function. Urine specimens were collected from 15 VLBW infants (birth weight < 1,500 g) as well as from 20 term infants during the first 2 days after birth. ROH in urine was detectable in 14 of the 15 VLBW infants at a median concentration of 234 nmol/g creatinine. In the group of term infants, 17 of the 20 excreted ROH, but at an approximately five-times lower concentration (P<0.001). Excretion of RBP4 and TTR was also much higher in VLBW infants (both P<0.001). The urinary ROH excretion in VLBW infants may be related to the impaired tubular handling of its carrier proteins RBP4 and TTR. Thus, ROH excretion might contribute to an increased risk of VA deficiency, especially in VLBW infants.}, language = {en} } @article{MuenznerTuviaDeutschmannetal.2013, author = {M{\"u}nzner, Matthias and Tuvia, Neta and Deutschmann, Claudia and Witte, Nicole and Tolkachov, Alexander and Valai, Atijeh and Henze, Andrea and Sander, Leif E. and Raila, Jens and Schupp, Michael}, title = {Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by regulating cellular retinoid homeostasis and retinoic acid receptor alpha activity}, series = {Molecular and cellular biology}, volume = {33}, journal = {Molecular and cellular biology}, number = {20}, publisher = {American Society for Microbiology}, address = {Washington}, issn = {0270-7306}, doi = {10.1128/MCB.00221-13}, pages = {4068 -- 4082}, year = {2013}, abstract = {Retinoids are vitamin A (retinol) derivatives and complex regulators of adipogenesis by activating specific nuclear receptors, including the retinoic acid receptor (RAR) and retinoid X receptor (RXR). Circulating retinol-binding protein 4 (RBP4) and its membrane receptor STRA6 coordinate cellular retinol uptake. It is unknown whether retinol levels and the activity of RAR and RXR in adipocyte precursors are linked via RBP4/STRA6. Here, we show that STRA6 is expressed in precursor cells and, dictated by the apo-and holo-RBP4 isoforms, mediates bidirectional retinol transport that controls RAR alpha activity and subsequent adipocyte differentiation. Mobilization of retinoid stores in mice by inducing RBP4 secretion from the liver activated RAR alpha signaling in the precursor cell containing the stromal-vascular fraction of adipose tissue. Retinol-loaded holo-RBP4 blocked adipocyte differentiation of cultured precursors by activating RAR alpha. Remarkably, retinol-free apo-RBP4 triggered retinol efflux that reduced cellular retinoids, RAR alpha activity, and target gene expression and enhanced adipogenesis synergistically with ectopic STRA6. Thus, STRA6 in adipocyte precursor cells links nuclear RAR alpha activity to the circulating RBP4 isoforms, whose ratio in obese mice was shifted toward limiting the adipogenic potential of their precursors. This novel cross talk identifies a retinoldependent metabolic function of RBP4 that may have important implications for the treatment of obesity.}, language = {en} } @article{MuellerAltenkampRailaetal.2011, author = {M{\"u}ller, Kerstin E. and Altenkamp, Rainer and Raila, Jens and Schmidt, Daniel and Dietrich, Robert and Hurtienne, Andrea and Wink, Michael and Krone, Oliver and Brunnberg, Leo and Schweigert, Florian J.}, title = {Plasma concentration of alpha-tocopherol in different free-ranging birds of prey}, series = {European journal of wildlife research}, volume = {57}, journal = {European journal of wildlife research}, number = {5}, publisher = {Springer}, address = {New York}, issn = {1612-4642}, doi = {10.1007/s10344-011-0516-z}, pages = {1043 -- 1049}, year = {2011}, abstract = {In this study, we investigated the alpha-tocopherol plasma concentrations in healthy free-ranging nestlings of the white-tailed sea eagle (Haliaeetus albicilla) (n=32), osprey (Pandion haliaetus) (n=39), northern goshawk (Accipiter gentilis) (n=25), common buzzard (Buteo buteo) (n=31), and honey buzzard (Pernis apivorus) (n=18) as well as of free-ranging adults of the white-tailed sea eagle (n=10), osprey (n=31), and northern goshawk (n=45). alpha-Tocopherol plasma concentrations were determined by reverse-phase high-performance liquid chromatography. alpha-Tocopherol plasma concentrations in nestlings of osprey, white-tailed sea eagle, and northern goshawk did not differ significantly amongst the species, but the common buzzard and honey buzzard nestlings had significantly lower alpha-tocopherol plasma concentrations than nestlings of the other species (both P<0.001). Adult male ospreys and white-tailed sea eagles had significantly higher alpha-tocopherol concentrations compared to adult females (both P<0.005). Adult ospreys and northern goshawks had significantly higher alpha-tocopherol plasma concentrations compared to their nestlings (both P<0.001). In adult female northern goshawks, plasma concentrations of alpha-tocopherol increased significantly before egg laying (P<0.001). These results demonstrate alpha-tocopherol plasma concentrations in birds of prey to be species specific and influenced by age and reproductive status.}, language = {en} } @article{MuellerRailaAltenkampetal.2012, author = {Mueller, K. and Raila, Jens and Altenkamp, Rainer and Schmidt, D. and Dietrich, R. and Hurtienne, Andrea and Wink, M. and Krone, O. and Brunnberg, Leo and Schweigert, Florian J.}, title = {Concentrations of retinol, 3,4-didehydroretinol, and retinyl esters in plasma of free-ranging birds of prey}, series = {Journal of animal physiology and animal nutrition}, volume = {96}, journal = {Journal of animal physiology and animal nutrition}, number = {6}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0931-2439}, doi = {10.1111/j.1439-0396.2011.01219.x}, pages = {1044 -- 1053}, year = {2012}, abstract = {This study investigated vitamin A compounds in the plasma of healthy free-ranging Central European raptors with different feeding strategies. Plasma samples of nestlings of white-tailed sea eagle [white-tailed sea eagle (WTSE), Haliaeetus albicilla) (n = 32), osprey (Pandion haliaetus) (n = 39), northern goshawk (Accipiter gentilis) (n = 25), common buzzard (Buteo buteo) (n = 31), and honey buzzard (Pernis apivorus) (n = 18) and adults of WTSE (n = 10), osprey (n = 31), and northern goshawk (n = 45) were investigated with reversed-phase-high-performance liquid chromatography (RP-HPLC). In WTSE, northern goshawks and common buzzards retinol were the main plasma component of vitamin A, whilst in ospreys and honey buzzards, 3,4-didehydroretinol predominated. The median of the retinol plasma concentration in the nestlings group ranged from 0.12 to 3.80 mu M and in the adult group from 0.15 to 6.13 mu M. Median plasma concentrations of 3,4-didehydroretinol in nestlings ranged from 0.06 to 3.55 mu M. In adults, northern goshawks had the lowest plasma concentration of 3,4-didehydroretinol followed by WTSE and ospreys. The plasma of all investigated species contained retinyl esters (palmitate, oleate, and stearate). The results show considerable species-specific differences in the vitamin A plasma concentrations that might be caused by different nutrition strategies.}, language = {en} } @article{LongardtSchmiedchenRailaetal.2014, author = {Longardt, Ann Carolin and Schmiedchen, B. and Raila, Jens and Schweigert, Florian J. and Obladen, M. and Buehrer, Christoph and Loui, A.}, title = {Characterization of the vitamin A transport in preterm infants after repeated high-dose vitamin A injections}, series = {European journal of clinical nutrition}, volume = {68}, journal = {European journal of clinical nutrition}, number = {12}, publisher = {Nature Publ. Group}, address = {London}, issn = {0954-3007}, doi = {10.1038/ejcn.2014.202}, pages = {1300 -- 1304}, year = {2014}, abstract = {BACKGROUND/OBJECTIVES: Preterm infants have low vitamin A stores at birth, and parenteral administration of high-dose vitamin A reduces pulmonary morbidity. The aim was to characterize vitamin A transport and status. SUBJECTS/METHODS: Prospective study of 69 preterm infants (median birth weight 995 g, gestational age 28 weeks), in which 51 received 5000 IU vitamin A three times per week intramuscular (i.m.) for 4 weeks and 18 infants without i.m. vitamin A served as controls. Serum retinol, retinyl palmitate, total retinol-binding protein 4 (RBP4), retinol-unbound RBP4 (apo-RBP4) and transthyretin concentrations were determined at days 3 (D3) and 28 (D28) of life. RESULTS: D3 retinol concentrations were low for the entire group (382 (285/531) nmol/l; median/interquartile range) and unrelated to gestational age. D28 retinol was unchanged in controls (382 (280/471) nmol/l), but increased in the vitamin A group (596 (480/825) nmol/l; P < 0.001). A similar pattern was observed for RBP4. The calculated retinol-to-RBP4 ratio rose in vitamin A infants (D3: 0.81 (0.57/0.94), D28: 0.98 (0.77/1.26); P < 0.01) but not in controls. In the vitamin A group, the retinol-to-RBP4 ratio was 41 in 15\% of all infants on D3 and in 45\% of infants on D28, but was <= 1 in all, but one, controls on D28. CONCLUSIONS: In preterm infants receiving a 4-week course of high-dose i. m. vitamin A, serum retinol concentrations increased by 55\%, with molar concentrations of retinol exceeding those of RBP4 in 45\% of the infants suggesting transport mechanisms other than RBP4.}, language = {en} } @inproceedings{KhalilIsalmRailaetal.2011, author = {Khalil, Mahomound and Isalm, K. Shaiful and Raila, Jens and Schenk, R. and Rawel, Harshadrai Manilal and Schweigert, Florian J.}, title = {Content of lutein and lutein ester in tagetes and improvement of their stability}, series = {Annals of nutrition \& metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)}, volume = {58}, booktitle = {Annals of nutrition \& metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)}, number = {3}, publisher = {Karger}, address = {Basel}, issn = {0250-6807}, pages = {16 -- 16}, year = {2011}, language = {en} } @article{KhalilRailaAlietal.2012, author = {Khalil, Mahmoud and Raila, Jens and Ali, Mostafa and Islam, Khan M. S. and Schenk, Regina and Krause, Jens-Peter and Schweigert, Florian J. and Rawel, Harshadrai Manilal}, title = {Stability and bioavailability of lutein ester supplements from Tagetes flower prepared under food processing conditions}, series = {Journal of functional food}, volume = {4}, journal = {Journal of functional food}, number = {3}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1756-4646}, doi = {10.1016/j.jff.2012.03.006}, pages = {602 -- 610}, year = {2012}, abstract = {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.}, language = {en} } @article{IslamKhalilMaenneretal.2016, author = {Islam, Khan Shaiful and Khalil, Mahmoud and M{\"a}nner, K. and Raila, Jens and Rawel, Harshadrai Manilal and Zentek, J. and Schweigert, Florian J.}, title = {Effect of dietary alpha-tocopherol on the bioavailability of lutein in laying hen}, series = {Journal of animal physiology and animal nutrition}, volume = {100}, journal = {Journal of animal physiology and animal nutrition}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0931-2439}, doi = {10.1111/jpn.12464}, pages = {868 -- 875}, year = {2016}, abstract = {Lutein and its isomer zeaxanthin have gained considerable interest as possible nutritional ingredient in the prevention of age-related macular degeneration (AMD) in humans. Egg yolk is a rich source of these carotenoids. As an oxidative sensitive component, antioxidants such as -tocopherol (T) might contribute to an improved accumulation in egg yolk. To test this, chickens were fed lutein esters (LE) with and without -tocopherol as an antioxidant. After depletion on a wheat-soya bean-based lutein-poor diet for 21days, laying hens (n=42) were equally divided into three groups and fed the following diets for 21days: control (basal diet), a LE group (40mg LE/kg feed) and LE+T group (40mg LE plus 100mg T/kg feed). Eggs and blood were collected periodically. Carotenoids and -tocopherol in yolk and blood plasma were determined by HPLC. Egg yolk was also analysed for total carotenoids using a one-step spectrophotometric method (iCheck(())). Lutein, zeaxanthin, -tocopherol and total carotenoids in egg yolk were highest after 14days of feeding and decreased slightly afterwards. At the end of the trial, eggs of LE+T group contained higher amount of lutein (13.72), zeaxanthin (0.65), -tocopherol (297.40) and total carotenoids (21.6) compared to the LE group (10.96, 0.55, 205.20 and 18.0mg/kg, respectively, p<0.05). Blood plasma values of LE+T group contain higher lutein (1.3), zeaxanthin (0.06) and tocopherol (20.1) compared to LE group (1.02, 0.04 and 14.90mg/l, respectively, p<0.05). In conclusion, dietary -tocopherol enhances bioavailability of lutein reflecting higher content in egg yolk and blood plasma. Improved bioavailability might be due to increased absorption of lutein in the presence of tocopherol and/or a greater stability of lutein/zeaxanthin due to the presence of -tocopherol as an antioxidant.}, language = {en} } @article{IslamKhalilMaenneretal.2017, author = {Islam, Khan M. S. and Khalil, Mahmoud Abd Elhamid and Maenner, Klaus and Raila, Jens and Rawel, Harshadrai Manilal and Zentek, J{\"u}rgen and Schweigert, Florian J.}, title = {Lutein Specific Relationships among Some Spectrophotometric and Colorimetric Parameters of Chicken Egg Yolk}, series = {The journal of poultry science}, volume = {54}, journal = {The journal of poultry science}, publisher = {Japan Poultry Science Association}, address = {Tsukuba}, issn = {1346-7395}, doi = {10.2141/jpsa.0160065}, pages = {271 -- 277}, year = {2017}, abstract = {Lutein is an essential dietary carotenoid with health benefits and is inter alia responsible for the colouration of egg yolk. The relationship between lutein accumulation and egg yolk colouration was therefore studied in more detail. After feeding a low-luteine diet for 21 days, 14 birds (Lohmann brown hens aged 20 weeks) were fed a diet containing marigold (80 mg lutein/kg feed) and 14 other birds were fed a diet containing oleoresin (45 mg lutein/kg feed) for 21 days; for both groups of birds, this feeding period was followed by withdrawal for 21 days. The Roche Yolk Colour Fan (RYCF) score (0 to 15, where higher values denote greater colour intensity; R-2=0.87; P<0.01) and redness (R-2=0.89; P<0.01) increased with increasing lutein content of egg yolk. Total carotenoid content had a poor relationship with lightness (R-2=0.13; P>0.05) and yellowness (R-2=0.12; P>0.05) of the yolk. It may be concluded that increased lutein is potentially responsible for an increased RYCF score and redness (a*), but decreased yellowness (b*) and lightness (L*), of egg yolk.}, language = {en} } @inproceedings{HenzeRailaScholzeetal.2013, author = {Henze, Andrea and Raila, Jens and Scholze, Alexandra and Schweigert, Florian J. and Tepel, Martin}, title = {Administration of N-Acetylcyteine causes beneficial posttranslationalmodifications of transthyretin in hemodialysis patients}, series = {Nephrology, dialysis, transplantation}, volume = {28}, booktitle = {Nephrology, dialysis, transplantation}, number = {2}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0931-0509}, pages = {164 -- 164}, year = {2013}, language = {en} } @article{HenzeRailaKempfetal.2011, author = {Henze, Andrea and Raila, Jens and Kempf, Caroline and Reinke, Petra and Sefrin, Anett and Querfeld, Uwe and Schweigert, Florian J.}, title = {Vitamin A metabolism is changed in donors after living-kidney transplantation an observational study}, series = {Lipids in health and disease}, volume = {10}, journal = {Lipids in health and disease}, number = {23}, publisher = {BioMed Central}, address = {London}, issn = {1476-511X}, doi = {10.1186/1476-511X-10-231}, pages = {7}, year = {2011}, abstract = {Background: The kidneys are essential for the metabolism of vitamin A (retinol) and its transport proteins retinol-binding protein 4 (RBP4) and transthyretin. Little is known about changes in serum concentration after living donor kidney transplantation (LDKT) as a consequence of unilateral nephrectomy; although an association of these parameters with the risk of cardiovascular diseases and insulin resistance has been suggested. Therefore we analyzed the concentration of retinol, RBP4, apoRBP4 and transthyretin in serum of 20 living-kidney donors and respective recipients at baseline as well as 6 weeks and 6 months after LDKT. Results: As a consequence of LDKT, the kidney function of recipients was improved while the kidney function of donors was moderately reduced within 6 weeks after LDKT. With regard to vitamin A metabolism, the recipients revealed higher levels of retinol, RBP4, transthyretin and apoRBP4 before LDKT in comparison to donors. After LDKT, the levels of all four parameters decreased in serum of the recipients, while retinol, RBP4 as well as apoRBP4 serum levels of donors increased and remained increased during the follow-up period of 6 months. Conclusion: LDKT is generally regarded as beneficial for allograft recipients and not particularly detrimental for the donors. However, it could be demonstrated in this study that a moderate reduction of kidney function by unilateral nephrectomy, resulted in an imbalance of components of vitamin A metabolism with a significant increase of retinol and RBP4 and apoRBP4 concentration in serum of donors.}, language = {en} } @misc{HenzeRailaKempfetal.2017, author = {Henze, Andrea and Raila, Jens and Kempf, Caroline and Reinke, Petra and Sefrin, Anett and Querfeld, Uwe and Schweigert, Florian J.}, title = {Vitamin A metabolism is changed in donors after living-kidney transplantation}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-400942}, pages = {7}, year = {2017}, abstract = {Background The kidneys are essential for the metabolism of vitamin A (retinol) and its transport proteins retinol-binding protein 4 (RBP4) and transthyretin. Little is known about changes in serum concentration after living donor kidney transplantation (LDKT) as a consequence of unilateral nephrectomy; although an association of these parameters with the risk of cardiovascular diseases and insulin resistance has been suggested. Therefore we analyzed the concentration of retinol, RBP4, apoRBP4 and transthyretin in serum of 20 living-kidney donors and respective recipients at baseline as well as 6 weeks and 6 months after LDKT. Results As a consequence of LDKT, the kidney function of recipients was improved while the kidney function of donors was moderately reduced within 6 weeks after LDKT. With regard to vitamin A metabolism, the recipients revealed higher levels of retinol, RBP4, transthyretin and apoRBP4 before LDKT in comparison to donors. After LDKT, the levels of all four parameters decreased in serum of the recipients, while retinol, RBP4 as well as apoRBP4 serum levels of donors increased and remained increased during the follow-up period of 6 months. Conclusion LDKT is generally regarded as beneficial for allograft recipients and not particularly detrimental for the donors. However, it could be demonstrated in this study that a moderate reduction of kidney function by unilateral nephrectomy, resulted in an imbalance of components of vitamin A metabolism with a significant increase of retinol and RBP4 and apoRBP4 concentration in serum of donors.}, language = {en} } @article{HenzeFreyRailaetal.2010, author = {Henze, Andrea and Frey, Simone K. and Raila, Jens and Scholze, Alexandra and Spranger, Joachim and Weickert, Martin O. and Tepel, Martin and Zidek, Walter and Schweigert, Florian J.}, title = {Alterations of retinol-binding protein 4 species in patients with different stages of chronic kidney disease and their relation to lipid parameters}, issn = {0006-291X}, doi = {10.1016/j.bbrc.2010.01.082}, year = {2010}, abstract = {Retinol-binding protein 4 (RBP4) is elevated in patients with chronic kidney disease (CKD) and has been discussed as marker of kidney function. In addition to an elevated concentration, the existence of truncated RBP4 species, RBP4-L (truncated at last C-terminal leucine) and RBP4-LL (truncated at both C-terminal leucines), has been reported in serum of hemodialysis patients. Since little is known about the occurrence of RBP4 species during the progression of CKD it was the aim of this study to analyse this possible association. The presence of RBP4, RBP4-L, RBP4- LL and transthyretin (TTR) was assessed in serum of 45 healthy controls and 52 patients with stage 2-5 of CKD using ELISA and RBP4 immunoprecipitation with subsequent MALDI-TOF-MS analysis. A reduction of glomerular filtration rate was accompanied by a gradual elevation of RBP4 serum levels and relative amounts of RBP4-LL. Correlation analysis revealed a strong association of the RBP4-TTR ratio with parameters of lipid metabolism and with diabetes-related factors. In conclusion, RBP4 serum concentration and the appearance of RBP4-LL seem to be influenced by kidney function. Furthermore, the RBP4-TTR ratio may provide diagnostic potential with regard to metabolic complications in CKD patients.}, language = {en} } @article{HenzeEspeWanneretal.2012, author = {Henze, Andrea and Espe, Katharina M. and Wanner, Christoph and Krane, Vera and Raila, Jens and Hocher, Berthold and Schweigert, Florian J. and Drechsler, Christiane}, title = {Transthyretin predicts cardiovascular outcome in hemodialysis patients with type 2 diabetes}, series = {Diabetes care}, volume = {35}, journal = {Diabetes care}, number = {11}, publisher = {American Diabetes Association}, address = {Alexandria}, issn = {0149-5992}, doi = {10.2337/dc12-0455}, pages = {2365 -- 2372}, year = {2012}, abstract = {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.}, language = {en} } @article{HenzeAumerGrabneretal.2011, author = {Henze, Andrea and Aumer, Franziska and Grabner, Arthur and Raila, Jens and Schweigert, Florian J.}, title = {Genetic differences in the serum proteome of horses, donkeys and mules are detectable by protein profiling}, series = {The British journal of nutrition : an international journal devoted to the science of human and animal nutrition}, volume = {106}, journal = {The British journal of nutrition : an international journal devoted to the science of human and animal nutrition}, publisher = {Cambridge Univ. Press}, address = {Cambridge}, issn = {0007-1145}, doi = {10.1017/S0007114511000845}, pages = {S170 -- S173}, year = {2011}, abstract = {Although horses and donkeys belong to the same genus, their genetic characteristics probably result in specific proteomes and post-translational modifications (PTM) of proteins. Since PTM can alter protein properties, specific PTM may contribute to species-specific characteristics. Therefore, the aim of the present study was to analyse differences in serum protein profiles of horses and donkeys as well as mules, which combine the genetic backgrounds of both species. Additionally, changes in PTM of the protein transthyretin (TTR) were analysed. Serum protein profiles of each species (five animals per species) were determined using strong anion exchanger ProteinChips (R) (Bio-Rad, Munich, Germany) in combination with surface-enhanced laser desorption ionisation-time of flight MS. The PTM of TTR were analysed subsequently by immunoprecipitation in combination with matrix-assisted laser desorption ionisation-time of flight MS. Protein profiling revealed species-specific differences in the proteome, with some protein peaks present in all three species as well as protein peaks that were unique for donkeys and mules, horses and mules or for horses alone. The molecular weight of TTR of horses and donkeys differed by 30Da, and both species revealed several modified forms of TTR besides the native form. The mass spectra of mules represented a merging of TTR spectra of horses and donkeys. In summary, the present study indicated that there are substantial differences in the proteome of horses and donkeys. Additionally, the results probably indicate that the proteome of mules reveal a higher similarity to donkeys than to horses.}, language = {en} } @article{HammesAndreassenSpoelgenetal.2005, author = {Hammes, Annette and Andreassen, Thomas K. and Spoelgen, Robert and Raila, Jens and Hubner, Norbert and Schulz, Herbert and Metzger, Jochen and Schweigert, Florian J. and Luppa, Peter B. and Nykjaer, Andreas and Willnow, Thomas E.}, title = {Role of endocytosis in cellular uptake of sex steroids}, issn = {0092-8674}, year = {2005}, abstract = {Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists. Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs}, language = {en} } @article{GriebschArndtRailaetal.2009, author = {Griebsch, Christine and Arndt, Gisela and Raila, Jens and Schweigert, Florian J. and Kohn, Barbara}, title = {C-reactive protein concentration in dogs with primary immune-mediated hemolytic anemia}, issn = {0275-6382}, doi = {10.1111/j.1939-165X.2009.00146.x}, year = {2009}, abstract = {Background Canine primary immune-mediated hemolytic anemia (IMHA) is associated with a high-mortality rate. C- reactive protein (CRP) is the most important acute-phase protein in dogs and may have value as a marker of prognosis or response to treatment in IMHA. Objective The objectives of this study were to evaluate serum CRP concentration in dogs with primary IMHA at presentation and during treatment, to assess potential differences based on survival time, and to compare CRP with other laboratory parameters of inflammation and prognosis. Methods Inclusion criteria for primary IMHA were anemia (PCV < 0.30 L/L), a positive Coombs' test or persistent autoagglutination of erythrocytes, and the exclusion of underlying diseases by other diagnostic tests. Dogs were divided into 2 groups based on survival: dogs that were still alive 14 days after start of treatment (group 1) and dogs that died or were euthanized before day 14 (group 2). Serum CRP concentration, a CBC, and a biochemistry profile were performed on days 0, 3, 8, and 14. Serum CRP also was determined in 25 clinically healthy dogs. Results CRP concentration in the 25 clinically healthy dogs ranged from 0- 8.9 mu g/mL (median 2.2 mu g/mL). Thirty dogs were diagnosed with primary IMHA, 24 in group 1 and 6 in group 2. On day 0, CRP concentration in dogs in both groups (median 224 mu g/mL) was increased above the reference interval. In group 1 dogs, median CRP concentration was 242 mu g/mL on day 0, 69 mu g/mL on day 3, 35 mu g/mL on day 8, and 2 mu g/mL on day 14. In group 2 dogs, median CRP concentration was 194 mu g/mL on day 0, 119 mu g/mL on day 3, and 41 mu g/mL on day 8; only 1 dog in group 2 survived to day 8. There was a significant correlation between CRP and total WBC concentrations on days 0 and 3 (r=-.598, P=.003). Conclusions Serum CRP concentration was markedly increased in dogs with primary IMHA. CRP concentration did not differ based on patient survival, but might be a marker for long-term monitoring of these patients.}, language = {en} } @article{GrafRailaSchweigertetal.2012, author = {Graf, Christine and Raila, Jens and Schweigert, Florian J. and Kohn, Barbara}, title = {Effect of leukoreduction treatment on vascular endothelial growth factor concentration in stored canine blood transfusion products}, series = {American journal of veterinary research}, volume = {73}, journal = {American journal of veterinary research}, number = {12}, publisher = {American Veterinary Medical Association}, address = {Schaumburg}, issn = {0002-9645}, pages = {2001 -- 2006}, year = {2012}, abstract = {Objective-To evaluate vascular endothelial growth factor (VEGF) concentrations in canine blood products treated with or without a leukoreduction filter. Sample-10 canine blood donors. Procedures-Dogs underwent blood collection. Five of 10 units were leukoreduced prior to separation into packed RBCs and fresh frozen plasma (FFP). Concentrations of VEGF were measured by ELISA in plasma supernatants from aliquots of packed RBCs obtained immediately after separation and on days 7, 14, and 21 of storage. Fresh frozen plasma samples of 2 filtered and 2 nonfiltered units were examined after storage. Results-RBC counts in whole blood before and after leukoreduction did not differ significantly, but WBCs and platelets were removed effectively. The VEGF concentration was lower than the detection limit (9 pg/mL) in 9 of 10 plasma samples and in all packed RBC and FFP units immediately after separation. The median VEGF concentrations in 5 nonfiltered packed RBC units were 37, 164, and 110 pg/mL on days 7, 14, and 21 of storage, respectively. In 5 filtered packed RBC and all FFP units, VEGF concentrations remained lower than the detection limit. Conclusions and Clinical Relevance-Leukoreduction filters were effective in preventing the release of VEGF during storage of canine RBC products.}, language = {en} } @article{GiengRailaRosales2005, author = {Gieng, S. H. and Raila, Jens and Rosales, F. J.}, title = {Accumulation of retinol in the liver after prolonged hyporetinolemia in the vitamin A-sufficient rat}, issn = {0022-2275}, year = {2005}, abstract = {We assessed the effects of prolonged reduction of plasma retinol concentrations (hyporetinolemia) on the distribution of tissue vitamin A (VA) and of its active compounds using a model of continuous recombinant human interleukin-6 (rhIL-6) infusion via osmotic minipumps in VA-sufficient male rats. Plasma retinol and retinol-binding protein (RBP) concentrations remained decreased and lower in rhIL-6- treated rats compared with controls from 7.5 h throughout 7 days of infusion (P < 0.001). This reduction was accompanied by a 68\% increase in hepatic retinol concentration by 7 days (P < 0.05). Hepatic and renal retinyl palmitate and retinoic acid concentrations did not change, and renal megalin content remained unchanged; hepatic RBP concentrations were 41\% lower in rhIL-6-treated rats compared with controls (P < 0.05). These results indicate that instead of being lost, retinol accumulated in the liver during inflammation and that hyporetinolemia was attributable to a decrease in the availability of hepatic RBP. A plausible consequence of the effect of rhIL-6-induced hyporetinolemia is that by 7 days tissues that are dependent on plasma retinol may become deprived of VA. These results have important implications in understanding the mechanism by which measles infection induces hyporetinolemia and VA deficiency of extrahepatic tissues}, language = {en} } @article{GerickeRailaSehoulietal.2005, author = {Gericke, Beate and Raila, Jens and Sehouli, Jalid and Haebel, Sophie and Konsgen, D. and Mustea, A. and Schweigert, Florian J.}, title = {Microheterogeneity of transthyretin in serum and ascitic fluid of ovarian cancer patients}, issn = {1471-2407}, year = {2005}, abstract = {Background: Transthyretin (TTR), a traditional biomarker for nutritional and inflammatory status exists in different molecular variants of yet unknown importance. A truncated form of TTR has recently been described to be part of a set of biomarkers for the diagnosis of ovarian cancer. The main aim of the study was therefore to characterize differences in microheterogeneity between ascitic fluid and plasma of women affected with ovarian cancer and to evaluate the tumor site as the possible source of TTR. Methods: Subjects were 48 women with primary invasive epithelial ovarian cancer or recurrent ovarian carcinoma. The control group consisted of 20 postmenopausal women. TTR and retinol-binding protein (RBP) levels were measured by enzyme-linked immunoassay ( ELISA) and C-reactive protein (CRP) levels by a high- sensitivity latex particle turbidimetric assay. The molecular heterogeneity of TTR was analysed using immunoprecipitation and matrix-associated laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Presence of TTR in tumor tissue was determined with indirect peroxidase immunostaining. Results: TTR and RBP (mu g/ml) levels in serum were 148.5 +/- 96.7 and 22.5 +/- 14.8 in affected women compared to 363.3 +/- 105.5 and 55.8 +/- 9.3 in healthy postmenopausal women ( p < 0.01). In ascitic fluid, levels were 1.02 +/- 0.24 and 4.63 +/- 1.57 mu g/ml, respectively. The mean levels of TTR and RBP in serum showed a tendency to decrease with the severity of the disease and were lower in affected women whose CRP levels were > 40 mg/ml ( p = 0.08 for TTR; p < 0.05 for RBP). No differences in TTR microheterogeneity were observed between TTR isolated from serum of affected and healthy women or from ascitic fluid. TTR occurred rather consistently in four variants. Mass signals were at 13758 +/- 7, 13876 +/- 13 ( greatest intensity), 13924 +/- 21 and 14062 +/- 24 Da, representing native, S-cysteinylated, S-cysteinglycinylated and glutathionylated TTR, respectively. Serum of healthy and affected women as well as ascitic fluid contained the truncated fragment of TTR ( 12828 +/- 11 Da). No immunoreactive TTR was observed in the tumor sites. Conclusion: The severity of the cancer associated catabolism as well as the inflammation status affect serum TTR and RBP levels. Neither TTR nor its truncated form originates from tumor tissue and its occurrence in ascites may well reflect the filtration from blood into ascitic fluid}, language = {en} } @article{GarciaRailaKoebnicketal.2006, author = {Garcia, Ada Lizbeth and Raila, Jens and Koebnick, Corinna and Eulenberger, Klaus and Schweigert, Florian J.}, title = {Great apes show highly selective plasma carotenoids and have physiologically high plasma retinyl esters compared to humans}, series = {American journal of physical anthropology}, volume = {131}, journal = {American journal of physical anthropology}, number = {2}, publisher = {Wiley}, address = {Hoboken}, issn = {0002-9483}, doi = {10.1002/ajpa.20428}, pages = {236 -- 242}, year = {2006}, abstract = {Great apes are the closest living relatives of humans. Physiological similarities between great apes and humans provide clues to identify which biological features in humans are primitive or derived from great apes. Vitamin A (VA) and carotenoid metabolism have been only partially studied in great apes, and comparisons between great apes and humans are not available. We aimed to investigate VA and carotenoid intake and plasma concentrations in great apes living in captivity, and to compare them to healthy humans. Dietary intakes of humans (n = 20) and, among the great apes, chimpanzees (n = 15) and orangutans (n = 5) were calculated. Plasma retinol (ROH), retinol-binding protein (RBP), retinyl esters, and major carotenoids were analyzed. The great ape diet was higher in VA than in humans, due to high intake of provitamin A carotenoids. Plasma ROH concentrations in great apes were similar to those in humans, but retinyl esters were higher in great apes than in humans. Differences in plasma carotenoid concentrations were observed between great apes and humans. Lutein was the main carotenoid in great apes, while P-carotene was the main carotenoid for humans. RBP concentrations did not differ between great apes and humans. The molar ratio of ROH to RBP was close to 1.0 in both great apes and humans. In conclusion, great apes show homeostatic ROH regulation, with high but physiological retinyl esters circulating in plasma. Furthermore, great apes show great selectivity in their plasmatic carotenoid concentration, which is not explained by dietary intake.}, language = {en} } @article{FruscalzoLonderoDriuletal.2015, author = {Fruscalzo, Arrigo and Londero, Ambrogio P. and Driul, Lorenza and Henze, Andrea and Tonutti, Laura and Ceraudo, Maria and Zanotti, Giuseppe and Berni, Rodolfo and Schweigert, Florian J. and Raila, Jens}, title = {First trimester concentrations of the TTR-RBP4-retinol complex components as early markers of insulin-treated gestational diabetes mellitus}, series = {Clinical chemistry and laboratory medicine : journal of the Forum of the European Societies of Clinical Chemistry - the European Branch of the International Federation of Clinical Chemistry and Laboratory Medicine}, volume = {53}, journal = {Clinical chemistry and laboratory medicine : journal of the Forum of the European Societies of Clinical Chemistry - the European Branch of the International Federation of Clinical Chemistry and Laboratory Medicine}, number = {10}, publisher = {De Gruyter}, address = {Berlin}, issn = {1434-6621}, doi = {10.1515/cclm-2014-0929}, pages = {1643 -- 1651}, year = {2015}, abstract = {Background: The objective of the study was to investigate the relationship between first trimester maternal serum levels of the TTR-RBP4-ROH complex components and the later insurgence of an altered glucose metabolism during pregnancy. Methods: Retrospective case control study including 96 patients between the 12th and 14th week of gestation, 32 that developed gestational diabetes mellitus (GDM), respectively, 21 non-insulin-treated (dGDM) and 11 insulin-treated (iGDM), 20 large for gestational age fetuses (LGA) without GDM and 44 patients with normal outcome as control. Serum concentrations of RBP4 and TTR were assessed by ELISA; serum concentration of ROH by reverse-phase high performance liquid chromatography (rpHPLC). The molecular heterogeneity of TTR and RBP4 was analyzed after immunoprecipitation by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Results: iGDM patients were characterized by reduced TTR, RBP4 and ROH compared to controls (respectively, iGDM vs. controls, mean +/- SD: TTR 3.96 +/- 0.89 mu mol/L vs. 4.68 +/- 1.21 mu mol/L, RBP4 1.13 +/- 0.25 mu mol/L vs. 1.33 +/- 0.38 mu mol/L and ROH 1.33 +/- 0.17 mu mol/L vs. 1.62 +/- 0.29 mu mol/L, p < 0.05). TTR containing Gly10 in place of Cys10 was lower in the iGDM group (p < 0.05) compared to controls. In the final logistic regression model ROH significantly predicted the diagnosis of iGDM (OR 0.93, 95\% CI 0.87-0.98, p < 0.05). Conclusions: First trimester maternal serum ROH, RBP4 and TTR represent potential biomarkers associated with the development of iGDM.}, language = {en} } @article{FruscalzoFrommerLonderoetal.2017, author = {Fruscalzo, Arrigo and Frommer, Julia-Marie and Londero, Ambrogio P. and Henze, Andrea and Schweigert, Florian J. and Nofer, Jerzy-Roch and Steinhard, Johannes and Klockenbusch, Walter and Schmitz, Ralf and Raila, Jens}, title = {First trimester TTR-RBP4-ROH complex and angiogenic factors in the prediction of small for gestational age infant's outcome}, series = {Archives of gynecology and obstetrics}, volume = {295}, journal = {Archives of gynecology and obstetrics}, publisher = {Springer}, address = {Heidelberg}, issn = {0932-0067}, doi = {10.1007/s00404-017-4338-4}, pages = {1157 -- 1165}, year = {2017}, abstract = {To study the role of the TTR-RBP4-ROH complex components (transthyretin, serum retinol binding protein, retinol) and of angiogenic factors PlGF (placental growth factor) and sFlt-1 (soluble fms-like tyrosine kinase-1) in pregnancies complicated by small for gestational age infants (SGA). Case control study conducted on maternal serum collected between 11 + 0 to 13 + 6 weeks of gestation. TTR, RBP4, ROH, PlGF and sFlt-1 were measured in SGA patients (birth weight < 10\%) who delivered at term (n = 37) and before 37 weeks of gestation (n = 17) and in a matched control group with uneventful pregnancies (n = 37). We found decreased RBP4 in SGA patients that delivered fetuses < 3\% and in fetuses delivered after the 37 weeks of gestation compared to controls [1.50 (95\% CI 1.40-1.75) vs 1.62 (95\% CI 1.47-1.98), p < 0.05]. Further, we found lower PlGF and sFlt-1 concentrations in SGA that delivered before 37 weeks of gestation compared to controls (respectively, PIGF and sFlt-1: 39.7 pg/ml (95\% CI 32.3-66.3) vs 62.9 pg/ml (95\% CI 45.2-78.4) and 906 pg/ml (95\% CI 727-1626) vs 1610 pg/ml (95\% CI 1088-212), p < 0.05). First trimester maternal serum RBP4 and angiogenic factors PlGF and sFlt-1 can differently predict the timing of delivery of pregnancies complicated by SGA fetuses.}, language = {en} } @article{FreySprangerHenzeetal.2009, author = {Frey, Simone K. and Spranger, Joachim and Henze, Andrea and Pfeiffer, Andreas F. H. and Schweigert, Florian J. and Raila, Jens}, title = {Factors that influence retinol-binding protein 4-transthyretin interaction are not altered in overweight subjects and overweight subjects with type 2 diabetes mellitus}, issn = {0026-0495}, doi = {10.1016/j.metabol.2009.05.003}, year = {2009}, abstract = {Retinol-binding protein 4 (RBP4) is an adipokine bound in plasma to transthyretin (TTR), which prevents its glomerular filtration and subsequent catabolism in the kidney. Alterations of this interaction have been Suggested to be implicated in the elevation of RBP4 that are thought to contribute to the development Of insulin resistance associated with obesity and type 2 diabetes mellitus (T2DM). However, the factors linking RBP4 to TTR in humans are not clear. Therefore, this Study evaluated parameters influencing the RBP4-TTR interaction and their relation to obesity and T2DM. The RBP4 and TTR levels were quantified in plasma of 16 lean controls, 28 overweight controls, and 14 overweight T2DM patients by enzyme-linked immunosorbent assay. Transthyretin isoforms involved in RBP4 binding were determined by linear matrix-assisted laser desorption/ionization-time of flight-mass spectrometry after RBP4 coimmunoprecipitation. Holo-RBP4 (retinol-bound) and apo-RBP4 (retinol-free) were assessed by immunoblotting using nondenaturating polyacrylamide gel electrophoresis. Plasma levels of both RBP4 and TTR did not differ among the groups of lean controls, overweight controls, and overweight T2DM subjects. Using RBP4 immunoprecipitation, 4 mass signals were observed for TTR representing native, S-cysteinylated, S-cysteinglycinylated, and S-glutathionylated TTR. No differences in peak intensity of TTR isoforms were observed among the groups. Moreover, no differences in the ratio of holo- and apo-RBP4 were evident. The results suggest that circulating RBP4 and TTR were not affected by human obesity or T2DM, which might be attributed to the absence of alterations of TTR isoforms and the ratio of holo- and apo-RBP4 that might modify the TTR-RBP4 interaction.}, language = {en} } @article{FreyHenzeNagletal.2009, author = {Frey, Simone K. and Henze, Andrea and Nagl, Britta and Raila, Jens and Scholze, Alexandra and Tepel, Martin and Schweigert, Florian J. and Zidek, Walter}, title = {Effect of renal replacement therapy on retinol-binding protein 4 isoforms}, issn = {0009-8981}, doi = {10.1016/j.cca.2008.11.008}, year = {2009}, abstract = {Background: Retinol-binding protein 4 (RBP4) levels are elevated in the serum of patients with kidney dysfunction. We recently showed that RBP4 isoforms including apo-RBP4 (RBP4 not bound to retinol) and RBP4 truncated at the C-terminus (RBP4-L, RBP4-LL) are increased in the serum of patients with kidney diseases but not in serum of patients with various liver diseases. The aim of this study was to investigate the effect of renal replacement therapy on RBP4 isoforms. Methods: We investigated serum levels of RBP4, apo-RBP4, holo-RBP4, RBP4-L, RBP4-LL, retinol and transthyretin (TTR) in 18 hemodialysis (HD) patients, 30 patients after renal transplantation (RTx) and in 35 healthy controls. RBP4 and TTR levels were measured by enzyme-linked immunosorbent assay, apo- and holo-RBP4 by native electrophoresis, retinol by high performance liquid chromatography and RBP4-L and RBP4-LL were analyzed by mass spectrometry. Results: HD and RTx patients had elevated RBP4, apo-RBP4 and RBP4-LL levels compared to controls. RTx patients had elevated amounts of RBP4-L compared to controls and elevated RBP4 and apo-RBP4 levels compared to HD patients. Conclusion: The results demonstrate a strong correlation between kidney function and RBP4 isoforms and provide data for investigating the relation of RBP4 and insulin resistance in these patients.}, language = {en} } @article{ForterreRailaSchweigert2004, author = {Forterre, Simone and Raila, Jens and Schweigert, Florian J.}, title = {Protein profiling of urine from dogs with renal disease using ProteinChip analysis}, year = {2004}, abstract = {Measurement of total urinary proteins in individuals that tested positive by urinary dipstick is a typical method for assessing the presence of potentially serious renal disorders. In the absence of such overt proteinuria, however, measurement of specific urinary proteins may be useful in the diagnosis of nephropathies and may provide greater insight into the pathogenesis. The urine of 28 dogs (16 with renal disease and 12 healthy) was evaluated to determine whether specific low-molecular-weight proteins or the pattern of protein excretion could also be used as a marker of tubular dysfunction in dogs. Specific proteins were assessed by immunological methods, whereas protein profiles were determined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (MS). In particular, changes in the excretion of retinol-binding protein (RBP) and Tamm-Horsfall protein (THP) appear to be of clinical relevance in the diagnosis of canine kidney diseases. The pattern of urinary protein and peptides revealed specific changes in abundance in dogs with renal disease at molecular masses (kD) of 11.58, 12.41, 12.60, 14.58, 20.95 (RBP), 27.85, and 65.69 (albumin). In conclusion, comparable proteins as in humans might be used as urinary markers for proximal (RBP) and distal (THP) tubular dysfunction in dogs. Surface-enhanced laser desorption/ionization time-of-flight MS is a promising tool for the study of kidney physiology and pathophysiology and might aid in the discovery of new biomarkers of renal disease}, language = {en} } @article{ForterreRailaKohnetal.2006, author = {Forterre, Simone and Raila, Jens and Kohn, Barbara and Brunnberg, Leo and Schweigert, Florian J.}, title = {Protein profiling of organic stone matrix and urine from dogs with urolithiasis}, issn = {0931-2439}, doi = {10.1111/j.1439-0396.2005.00590.x}, year = {2006}, abstract = {Two-thirds of the organic matrix in urinary stones consists of proteins. Their relationship to calculogenesis remains controversial with regard to their effect as inhibitors or promoters during stone formation. The purpose of the present study was to determine the differences in peptide and protein pattern between the urine of stone formers (n = 23) and control dogs (n = 12), as well as between organic matrix of different urinary stones (struvite n = 11, calcium oxalate n = 8, uric acid n = 4) using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Specific differences in protein and peptide profiles were found in the organic matrix of different mineral compositions. Characteristic differences were also found in urinary peptide and protein pattern especially in molecular masses below 20 kDa between affected and healthy dogs. Based on the obtained molecular masses they were in some cases tentatively identified as proteins that are known to be involved in stone formation in humans. The study shows that in dogs, specific-urinary peptides and proteins might be associated with urolithiasis. It indicates the importance to further characterize those proteins for possible diagnostic purposes in prognosis and therapy}, language = {en} } @article{ForterreRailaForterreetal.2006, author = {Forterre, Simone and Raila, Jens and Forterre, Franck and Brunnberg, Leo and Schweigert, Florian J.}, title = {Characterisation of transthyretin and retinol-binding protein in plasma and cerebrospinal fluid of dogs}, issn = {1090-0233}, doi = {10.1016/j.tvjl.2004.11.017}, year = {2006}, abstract = {The aim of this study was to investigate differences in concentrations of vitamin A, transthyretin (TTR) and retinol-binding protein (RBP) between plasma and cerebrospinal fluid (CSF) in dogs. RBP was detected using ELISA, and both RBP and TTR by Western blot analysis after separation on SDS-PAGE. Vitamin A was determined by high performance liquid chromatography. RBP and TTR as well as vitamin A were detected in all samples but at substantially lower concentrations in CSF compared to plasma. RBP in dog plasma showed a similar molecular mass to that of humans, whereas canine TTR had a lower molecular mass. Comparison between plasma and CSF showed that both RBP and TTR were of lower molecular mass in CSF. In CSF, RBP and retinol were present at 10-100-fold lower concentrations compared to plasma. Retinyl esters were present only in minute amounts in 5/17 samples. In conclusion, the CSF of dogs compared to humans is significantly different in terms of both quality and quantity of transport proteins for vitamin A.}, language = {en} } @article{ForeterreRailaForterreetal.2004, author = {Foreterre, Simone and Raila, Jens and Forterre, Franck and Brunnberg, Leo and Schweigert, Florian J.}, title = {Characterisation of transthyretin and retinol-binding protein in plasma and cerebrospinal fluid of dogs}, year = {2004}, language = {en} } @article{EspeRailaHenzeetal.2011, author = {Espe, Katharina M. and Raila, Jens and Henze, Andrea and Krane, Vera and Schweigert, Florian J. and Hocher, Berthold and Wanner, Christoph and Drechsler, Christiane}, title = {Impact of vitamin A on clinical outcomes in haemodialysis patients}, series = {Nephrology, dialysis, transplantation}, volume = {26}, journal = {Nephrology, dialysis, transplantation}, number = {12}, publisher = {Oxford Univ. Press}, address = {Oxford}, organization = {German Diabetes \& Dialysis Study I}, issn = {0931-0509}, doi = {10.1093/ndt/gfr171}, pages = {4054 -- U583}, year = {2011}, abstract = {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.}, language = {en} } @article{EspeRailaHenzeetal.2013, author = {Espe, Katharina M. and Raila, Jens and Henze, Andrea and Blouin, Katja and Schneider, Andreas and Schmiedeke, Daniel and Krane, Vera and Pilz, Stefan and Schweigert, Florian J. and Hocher, Berthold and Wanner, Christoph and Drechsler, Christiane}, title = {Low plasma alpha-tocopherol concentrations and adverse clinical outcomes in diabetic hemodialysis patients}, series = {Clinical journal of the American Society of Nephrology}, volume = {8}, journal = {Clinical journal of the American Society of Nephrology}, number = {3}, publisher = {American Society of Nephrology}, address = {Washington}, organization = {German Diabet \& Dialysis Study Inv}, issn = {1555-9041}, doi = {10.2215/CJN.04880511}, pages = {452 -- 458}, year = {2013}, abstract = {Background and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of alpha-tocopherol and specific clinical outcomes in diabetic hemodialysis patients. Design, settings, participants, \& measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), alpha-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma alpha-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508). Results Patients had a mean age of 66 8 years, and mean plasma alpha-tocopherol level was 22.8+/-9.6 mu mol/L. Levels of alpha-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest alpha-tocopherol quartile had (in unadjusted analyses) a 79\% higher risk of stroke and a 31\% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratio(stroke)=1.56, 95\% confidence interval=0.75-3.25; hazard ratio(mortality)=1.22, 95\% confidence interval=0.89-1.69, respectively). There was no association between alpha-tocopherol and myocardial infarction, sudden death, or infectious death. Conclusions Plasma alpha-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients.}, language = {en} } @inproceedings{EspeRailaHenzeetal.2012, author = {Espe, Katharina M. and Raila, Jens and Henze, Andrea and Blouin, Katja and Schneider, A. and Schmiedeke, D. and Krane, Vera and Schweigert, Florian J. and Hocher, Berthold and Wanner, Christoph and Drechsler, Christiane}, title = {Low vitamin E plasma levels are associated with cerebrovascular events and mortality in hemodialysis patients}, series = {Annals of nutrition \& metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)}, volume = {60}, booktitle = {Annals of nutrition \& metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)}, number = {2}, publisher = {Karger}, address = {Basel}, issn = {0250-6807}, pages = {137 -- 137}, year = {2012}, language = {en} } @article{EliasMiroMassipSalcedoRailaetal.2012, author = {Elias-Miro, Maria and Massip-Salcedo, Marta and Raila, Jens and Schweigert, Florian J. and Mendes-Braz, Mariana and Ramalho, Fernando and Jimenez-Castro, Monica B. and Casillas-Ramirez, Arani and Bermudo, Raquel and Rimola, Antoni and Rodes, Juan and Peralta, Carmen}, title = {Retinol binding protein 4 and retinol in steatotic and nonsteatotic rat livers in the setting of partial hepatectomy under ischemia/reperfusion}, series = {Liver transplantation}, volume = {18}, journal = {Liver transplantation}, number = {10}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1527-6465}, doi = {10.1002/lt.23489}, pages = {1198 -- 1208}, year = {2012}, abstract = {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.}, language = {en} } @article{DanquahDobruckyFranketal.2015, author = {Danquah, Ina and Dobrucky, C. Lydia and Frank, Laura K. and Henze, Andrea and Amoako, Yaw A. and Bedu-Addo, George and Raila, Jens and Schulze, Matthias Bernd and Mockenhaupt, Frank P. and Schweigert, Florian J.}, title = {Vitamin A: potential misclassification of vitamin A status among patients with type 2 diabetes and hypertension in urban Ghana}, series = {The American journal of clinical nutrition : a publication of the American Society for Nutrition, Inc.}, volume = {102}, journal = {The American journal of clinical nutrition : a publication of the American Society for Nutrition, Inc.}, number = {1}, publisher = {American Society for Nutrition, Inc.}, address = {Bethesda}, issn = {0002-9165}, doi = {10.3945/ajcn.114.101345}, pages = {207 -- 214}, year = {2015}, abstract = {Background: Sub-Saharan Africa is facing a double burden of malnutrition: vitamin A deficiency (VAD) prevails, whereas the nutrition-related chronic conditions type 2 diabetes (T2D) and hypertension are emerging. Serum retinol a VAD marker increases in kidney disease and decreases in inflammation, which can partly be attributed to alterations in the vitamin A transport proteins retinol-binding protein 4 (RBP4) and prealbumin. Kidney dysfunction and inflammation commonly accompany T2D and hypertension. Objective: Among urban Ghanaians, we investigated the associations of T2D and hypertension with serum retinol as well as the importance of kidney function and inflammation in this regard. Design: A hospital-based, case-control study in individuals for risk factors of T2D, hypertension, or both was conducted in Kumasi, Ghana (328 controls, 197 with T2D, 354 with hypertension, and 340 with T2D plus hypertension). In 1219 blood samples, serum retinol, RBP4, and prealbumin were measured. Urinary albumin and estimated glomerular filtration rate (eGFR) defined kidney function. C-reactive protein (CRP) >5 mg/L indicated inflammation. We identified associations of T2D and hypertension with retinol by linear regression and calculated the contribution of RBP4, prealbumin, urinary albumin, eGFR, and CRP to these associations as the percentages of the explained variance of retinol. Results: VAD (retinol <1.05 mu mol/L) was present in 10\% of this predominantly female, middle-aged, overweight, and deprived population. Hypertension, but not T2D, was positively associated with retinol (beta: 0.12; 95\% CI: 0.08, 0,17), adjusted for age, sex, socioeconomic factors, anthropometric measurements, and lifestyle. In addition to RBP4 (72\%) and prealbumin (22\%), the effect of increased retinol on individuals with hypertension was mainly attributed to impaired kidney function (eGFR: 30\%; urinary albumin: 5\%) but not to inflammation. Conclusions: In patients with hypertension, VAD might be underestimated because of increased serum retinol in the context of kidney dysfunction. Thus, the interpretation of serum retinol in sub-Saharan Africa should account for hypertension status.}, language = {en} } @article{BrentenMorrisSaltetal.2014, author = {Brenten, Thomas and Morris, Penelope J. and Salt, Carina and Raila, Jens and Kohn, Barbara and Brunnberg, Leo and Schweigert, Florian J. and Zentek, Juergen}, title = {Energy intake, growth rate and body composition of young Labrador Retrievers and Miniature Schnauzers fed different dietary levels of vitamin A}, series = {The British journal of nutrition : an international journal devoted to the science of human and animal nutrition}, volume = {111}, journal = {The British journal of nutrition : an international journal devoted to the science of human and animal nutrition}, number = {12}, publisher = {Cambridge Univ. Press}, address = {Cambridge}, issn = {0007-1145}, doi = {10.1017/S0007114514000543}, pages = {2104 -- 2111}, year = {2014}, abstract = {Research in rodents has shown that dietary vitamin A reduces body fat by enhancing fat mobilisation and energy utilisation; however, their effects in growing dogs remain unclear. In the present study, we evaluated the development of body weight and body composition and compared observed energy intake with predicted energy intake in forty-nine puppies from two breeds (twenty-four Labrador Retriever (LAB) and twenty-five Miniature Schnauzer (MS)). A total of four different diets with increasing vitamin A content between 5.24 and 104.80 mu mol retinol (5000-100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable energy were fed from the age of 8 weeks up to 52 (MS) and 78 weeks (LAB). The daily energy intake was recorded throughout the experimental period. The body condition score was evaluated weekly using a seven-category system, and food allowances were adjusted to maintain optimal body condition. Body composition was assessed at the age of 26 and 52 weeks for both breeds and at the age of 78 weeks for the LAB breed only using dual-energy X-ray absorptiometry. The growth curves of the dogs followed a breed-specific pattern. However, data on energy intake showed considerable variability between the two breeds as well as when compared with predicted energy intake. In conclusion, the data show that energy intakes of puppies particularly during early growth are highly variable; however, the growth pattern and body composition of the LAB and MS breeds are not affected by the intake of vitamin A at levels up to 104.80 mu mol retinol (100 000 IU vitamin A)/4184 kJ (1000 kcal).}, language = {en} } @article{BobbertRailaSchwarzetal.2010, author = {Bobbert, Thomas and Raila, Jens and Schwarz, Franziska and Mai, Knut and Henze, Andrea and Pfeiffer, Andreas F. H. and Schweigert, Florian J. and Spranger, Joachim}, title = {Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness}, issn = {0021-9150}, doi = {10.1016/j.atherosclerosis.2010.07.063}, year = {2010}, abstract = {Objective: Retinol is transported in a complex with retinol-binding protein 4 (RBP4) and transthyretin (TTR) in the circulation. While retinol is associated with various cardiovascular risk factors, the relation between retinol, RBP4, TTR and carotid intima media thickness (IMT) has not been analysed yet. Methods: Retinol, RBP4 and TTR were measured in 96 individuals and their relation to mean and maximal IMT was determined. Results: Mean IMT correlated with RBP4 (r = 0.335, p < 0.001), retinol (r = -0.241, p = 0.043), RBP/TTR ratio (r = 0.254, p = 0.025) and retinol/RBP4 ratio (r = -0.549, p < 0.001). Adjustment for age, sex, BMI, blood pressure, HDL/total cholesterol ratio, triglyceride, diabetes and smoking revealed that the retinol/RBP4 ratio was strongly and independently associated with mean IMT. Similar results were found for maximal IMT, which included the measurement of plaques. Conclusion: The data support that the transport complex of vitamin A is associated with the IMT, an established parameter of atherosclerosis. Changes in RBP4 saturation with retinol may link renal dysfunction and insulin resistance to atherosclerosis.}, language = {en} } @article{AuyyuenyongHenzeUngruetal.2017, author = {Auyyuenyong, Ratchada and Henze, Andrea and Ungru, Julia and Schweigert, Florian Johannes and Raila, Jens and Vervuert, Ingrid}, title = {Determination of lipid profiles in serum of obese ponies before and after weight reduction by using multi-one-dimensional thin-layer chromatography}, series = {Research in veterinary science}, volume = {117}, journal = {Research in veterinary science}, publisher = {Elsevier}, address = {Oxford}, issn = {0034-5288}, doi = {10.1016/j.rvsc.2017.11.013}, pages = {111 -- 117}, year = {2017}, abstract = {Obesity is a key component of equine metabolic syndrome, which is highly associated with laminitis. Feed restriction and/or exercise are known to alleviate the detrimental effects of insulin resistance in obese ponies. However, little is known about changes in the serum lipid patterns due to weight reduction and its association with disease outcomes. Therefore, the lipid patterns in the serum of 14 mature ponies before and after a 14-week body weight reduction program (BWRP) were investigated by multi-one-dimensional thin-layer chromatography (MOD-TLC). Additionally, sensitivity to insulin (SI), body condition scores (BCS) and cresty neck scores (CNS) were measured. A BWRP resulted in a significant loss of body weight (P < 0.001), which was associated with beneficial decreases in BCS and CNS (both, P < 0.001). Serum lipid compositions revealed significantly increased free fatty acid (FFA), sphingomyelin (SM; both P < 0.001), total cholesterol (C) and cholesterol ester (CE) (both P < 0.01) and triacylglycerol (TG; P < 0.05) densities. Improvement of SI after the BWRP was associated with increases in neutral lipids (C, CE and TG, all P < 0.01), FFA and the phospholipid SM (both, P < 0.001). The results show that a BWRP in obese ponies was effective and associated with changes in the concentrations of neutral lipids and the phospholipid SM, indicating that SM may play a role in insulin signaling pathways and thus in the pathogenesis of insulin resistance and the progression of metabolic syndrome in obese ponies.}, language = {en} } @article{AlterOttvonWebskyetal.2012, author = {Alter, Markus L. and Ott, Ina M. and von Websky, Karoline and Tsuprykov, Oleg and Sharkovska, Yuliya and Krause-Relle, Katharina and Raila, Jens and Henze, Andrea and Klein, Thomas and Hocher, Berthold}, title = {DPP-4 Inhibition on top of angiotensin receptor blockade offers a new therapeutic approach for diabetic nephropathy}, series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, volume = {36}, journal = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, number = {1}, publisher = {Karger}, address = {Basel}, issn = {1420-4096}, doi = {10.1159/000341487}, pages = {119 -- 130}, year = {2012}, abstract = {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.}, language = {en} }