@article{DollGerickeDanickeetal.2005,
  author    = {Doll, S. and Gericke, S. and Danicke, S. and Raila, Jens and Ueberschar, K. H. and Valenta, H. and Schnurrbusch, U. and Schweigert, Florian G. and Flachowsky, G.},
  title     = {The efficacy of a modified aluminosilicate as a detoxifying agent in Fusarium toxin contaminated maize containing diets for piglets},
  year      = {2005},
  abstract  = {Two feeding experiments with female weaned piglets were carried out applying a complete two by two factorial design to investigate the effects of the dietary inclusion of 500 g/kg Fusarium toxin contaminated maize (8.6 mg/kg deoxynivalenol (DON); 1.2 mg/kg zearalenone (ZON)) and of 4 g/kg aluminosilicate (AS) as a detoxifying agent. The resulting four diets were fed ad libitum to a total of 80 piglets (20 piglets per group, allotted to a total of 20 pens) covering a live weight range of 10.5 +/- 1.3 to 27.5 +/- 4.4 kg in experiment 1, and to a total of 48 piglets (12 piglets per group, allotted to 12 pens) covering a live weight range of 9.7 +/- 1.8 to 21.4 +/- 4.8 kg in experiment 2. The animals of experiment 1 were slaughtered on days 34-36 of feeding the experimental diets. The mycotoxin analyses revealed that the control maize also contained considerable concentrations of Fusarium toxins, but the differences in DON and ZON concentrations between control and contaminated diets were sufficiently high to demonstrate both dose- related toxin effects. Voluntary feed intake and live weight gain of the animals were significantly reduced by the inclusion of Fusarium toxin contaminated maize into the diets in both experiments, while a significantly decreased feed to gain ratio was found in experiment 1. Furthermore, the relative weight of the uterus, stomach and heart of the animals fed the contaminated maize containing diets were significantly increased. Serum albumin concentrations and the activity of GLDH were significantly reduced by the inclusion of the contaminated maize. The addition of AS to the Fusarium toxin contaminated diets did not prevent or alleviate any of the mentioned effects. Moreover, the feed intake tended to be decreased by this supplementation in both experiments, while a significantly decreased feed to gain ratio was indicated for this factor in experiment one as well. The serum concentration of albumin and the activities of ASAT and gamma GT were significantly increased if AS was present in the diets while serum concentration of cholesterol and alpha-tocopherol were decreased significantly or in tendency, respectively. The concentrations of retinol and retinyl esters in liver and serum were not altered by the treatments. The analysed concentrations of zearalenone (ZON) and its metabolites in the bile fluid clearly indicated the differences in dietary ZON concentrations and showed that AS was ineffective in preventing the absorption of the toxin from the gastrointestinal tract. Also, serum concentrations of DON reflected the DON intake prior to sampling. However, there were no differences between groups fed diets with or without AS which also suggests the inefficacy of the tested AS in preventing the DON absorption. The present investigations failed to demonstrate a detoxifying capacity of the tested additive and emphasize the general necessity for a critical verification of detoxifying agents in vivo},
  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{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{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{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{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{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}
}