@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{SchweigertBatheChenetal.2004, author = {Schweigert, Florian J. and Bathe, Katharina and Chen, Frank and B{\"u}scher, Ulrich and Dudenhausen, Joachim W.}, title = {Effect of the stage of lactation in humans on carotenoid levels in milk, blood plasma and plasma lipoprotein fractions}, year = {2004}, abstract = {In mammals the composition of milk changes during early lactation, with a rapid decline of fat-soluble vitamins and a continuous increase in total lipids. The mechanisms underlying this phenomenon are not well understood, but might involve selective mechanisms related to mammary uptake or secretion into the milk. Since carotenoids are specifically distributed among the lipoprotein fractions in plasma, the simultaneous determination of carotenoids in plasma, lipoprotein fractions and milk might offer an opportunity to gain insight into this phenomenon. In 21 healthy mothers carotenoids in plasma and lipoprotein fractions were investigated at day 2 and 19 and milk on day 4 and 19 after delivery. Plasma levels of alpha-tocopherol and cholesterol as well as lutein, zeaxanthin and cryptoxanthin were significantly lower later in lactation (day 19) than shortly after birth (P < 0.01). The stage of lactation had no effect on the distribution of carotenoids and -tocopherol among the plasma lipoprotein fractions. In milk, triacylglycerol increased (P < 0.01). In contrast, levels of carotenoids, alpha- tocopherol and vitamin A were highest in colostrum and declined (P < 0.01). Because the magnitude of decrease was not the same in all carotenoids, the carotenoid pattern changed substantially. In colostrum the carotenoid pattern resembled those of plasma and the low- density lipoprotein fraction. In mature milk it was similar to the pattern found in the high density lipoprotein fraction. Based on these observations a selective mechanism might be responsible for the transfer of these components in milk involving different lipoprotein fractions at specific times of lactation}, language = {en} } @article{RuehlSczechLandesetal.2004, author = {R{\"u}hl, Ralph and Sczech, Ronny and Landes, Nico and Pfluger, Paul Thomas and Kluth, Dirk and Schweigert, Florian J.}, title = {Carotenoids and their metabolites are naturally occurring activators of gene expression via the pregnane X receptor}, year = {2004}, abstract = {Carotenoids are important micronutrients in the human diet and are present in human serum at micromolar concentrations. In addition to their antioxidant potential, carotenoids obtain physiologically relevant properties such as influencing cellular signal pathways, gene expression or induction of detoxifying enzymes. In this study, we determined the transactivation of PXR by cotransfection with the full-length receptor and a PXR-responsive reporter gene. Carotenoids and retinol revealed a 5-6-fold reporter gene activity in HepG2 cells in comparison to a 7-fold induction by the well known PXR agonist rifampicin whereas apo-carotenals and lycopene exerted less or no activation potential. The inductive efficacy was hereby concentration-dependent. In addition, carotenoid or retinol mediated gene expression of PXR responsive genes like CYP3A4/CYP3A7, CYP3A5, MDR-1 and MRP-2 has been determined in HepG2 cells by RT- PCR with upregulative properties of beta-carotene or retinol being comparable or even higher than that of rifampicin. In conclusion, PXR-mediated upregulation of CYP3A4/CYP3A7 and CYP3A5 as well as MDR1 and MRP2 by carotenoids points to a potential interference on the metabolism of xenobiotic and endogenous relevant compounds}, language = {en} } @article{RuehlHamscherGarciaetal.2004, author = {R{\"u}hl, Ralph and Hamscher, Gerd and Garcia, Ada and Nau, Heinz and Schweigert, Florian J.}, title = {Identification of 14-hydroxy-retro-retinol and 4-hydroxy-retinol as endogenous retinoids in rats throughout neonatal development}, issn = {0024-3205}, year = {2004}, abstract = {14-Hydroxy-retro-retinol was previously described as an in vivo and in vitro metabolite of retinol. Furthermore, the retinoid 4-hydroxy-retinol was identified as an endogenous occurring retinoid in the amphibian organism and an in vitro metabolite of retinol. We describe in the present study that 14-hydroxy-retro-retinol and 4-hydroxy- retinol are present in normal neonatal rat serum as endogenous occurring retinoids in normal non-vitamin A supplemented mammals (rats). Both retinoids were detected in serum and liver of neonatal rats at days 3 and 11 after birth. The respective concentrations at day 11 after birth were 41.8 +/- 2.8 ng/ml (serum)/ 104 +/- 6 ng/g (liver) for 4-hydroxy- retinol and 23 +/- 4.6 ng/ml (serum)/ 285 +/- 5 ng/g (liver) for 14-hydroxy-retro-retinol. Both retinoids could not be detected in adult rat serum and liver. From our experiments important physiological functions of these retinoids during postnatal development could be postulated. (C) 2004 Elsevier Inc. All rights reserved}, language = {en} } @article{RuehlGarciaSchweigertetal.2004, author = {R{\"u}hl, Ralph and Garcia, Ada and Schweigert, Florian J. and Worm, Margitta}, title = {Modulation of cytokine production by low and high retinoid diet in ovalbumin-sensitized mice}, year = {2004}, abstract = {Retinoids modulate many physiological processes such as the differentiation and growth of different cell types. including cells from the immune system. We have previously shown that retinoids modulate IgE production in vitro and in vivo. In the present study we investigated the effects of retinoids in non-sensitized and ovalbumin-sensitized mice that were fed for 11 weeks with three different vitamin A (VA) diets: a) VA-deficiency diet, b) base diet, and c) base diet supplemented with 0.5\% all-trans-retinoic acid (ATRA). Phorbol-myristate-acetate (PMA)/ionomycin-stimulated SMC (splenic mononuclear cells) from mice fed with ATRA and the vitamin A-deficient diet group showed increased interleukin-4 (IL-4) responses in non-sensitized mice. After ovalbumin sensitization in the VA-deficient and the ATRA supplementation diet groups, no significant effects on IL-4 production were observed. By contrast, gamma interferon (IFN-gamma production from PMA/ionomycin-stimulated SMC was enhanced in the VA-deficient diet group in ovalbumin-sensitized mice, and also in non-sensitized mice compared to the base and the ATRA-supplemented diet group. The data indicate that VA and retinoid content in a diet influences the cytokine response in non-sensitized and also ovalbumin-sensitized mice. Therefore these molecules may serve as active modulators of cytokine production in vivo that are responsible for the induction and persistence of atopic diseases}, 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} } @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{LoehrkeVierguthKanitzetal.2004, author = {L{\"o}hrke, B. and Vierguth, T. and Kanitz, W. and G{\"o}llnitz, K. and Becker, F. and Hurtienne, Andrea and Schweigert, Florian J.}, title = {High milk yield in dairy cows associated with oxidant stress}, issn = {1328-925X}, year = {2004}, language = {en} } @article{GerickeKoebnickReimannetal.2004, author = {Gericke, Beate and Koebnick, Corinna and Reimann, Manja and Forterre, Simone and Zunft, Hans-Joachim Franz and Schweigert, Florian J.}, title = {Influence of hormone replacement therapy on proteomic pattern in serum of postmenopausal women}, year = {2004}, abstract = {Objectives: Proteomics approaches to cardiovascular biology and disease hold the promise of identifying specific proteins and peptides or modification thereof to assist in the identification of novel biomarkers. Method: By using surface-enhanced laser desorption and ionization time of flight mass spectroscopy (SELDI-TOF-MS) serum peptide and protein patterns were detected enabling to discriminate between postmenopausal women with and without hormone replacement therapy (HRT). Results: Serum of 13 HRT and 27 control subjects was analyzed and 42 peptides and proteins could be tentatively identified based on their molecular weight and binding characteristics on the chip surface. By using decision tree-based Biomarker Patterns (TM) Software classification and regression analysis a discriminatory function was developed allowing to distinguish between HRT women and controls correctly and, thus, yielding a sensitivity of 100\% and a specificity of 100\%. The results show that peptide and protein patterns have the potential to deliver novel biomarkers as well as pinpointing targets for improved treatment. The biomarkers obtained represent a promising tool to discriminate between HRT users and non-users. Conclusion: According to a tentative identification of the markers by their molecular weight and binding characteristics, most of them appear to be part of the inflammation induced acute-phase response. (c) 2004 Elsevier Ireland Ltd. All rights reserved}, 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{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} }