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  • 1
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    Online Resource
    AMAS (Austrian Moderate Altitude Study)-2000: Effects of Hiking Holidays at Moderate Altitude on Immune System Markers in Persons with Metabolic Syndrome.
    Walter de Gruyter GmbH ; 2004
    In:  pteridines Vol. 15, No. 4 ( 2004-11), p. 149-154
    Details
    In: pteridines, Walter de Gruyter GmbH, Vol. 15, No. 4 ( 2004-11), p. 149-154
    Abstract: Recent studies have shown a strong association between indices of inflammation and metabolic Syndrome. Proinflammatory mediators like tumor necrosis factor-α may act as a trigger for insulin insensitivity. Therefore, patients with metabolic Syndrome might be at higher risk of insulin resistance when confronted with additional Stimuli of the immune system. These Stimuli are not restricted to the presence of pathogens but include environmental factors like physical exercise and hypoxemia as well. With respect to these interdependencies, one may assume higher risk for patients with metabolic Syndrome who perform physical exercise in alpine regions. We investigated the effects of a 3-weeks holiday with moderate sporting activities at moderate altitude (1700 m) on the conceiitrations of neopterin, tumor necrosis factor-α, serum soluble 75kD type TNF receptor (sTNF-R75), and interleukin-6 in vacationers with metabolic Syndrome. Only serum neopterin and sTNF-R75 concentrations transiently increased during the stay at moderate altitude compared to pre-altitude levels (P 〈 0.05). Interestingly, after return to 500 m sea-level neopterin concentrations dropped beyond baseline concentrations (p 〈 0.05). However, the variations in neopterin concentrations might not be of clinical relevance since they did not exceed the threshold indicating significant activation of the cellular immune system. We conclude that a 3-week sojourn at moderate altitude including individually adapted physical exercise does not represent accumulated risk factors in subjects with metabolic Syndrome.
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines.2004.15.4.149
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2004
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  • 2
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    Dynamic regulation of phenylalanine hydroxylase
    Walter de Gruyter GmbH ; 2014
    In:  Pteridines Vol. 25, No. 2 ( 2014-7-1), p. 33-39
    Details
    In: Pteridines, Walter de Gruyter GmbH, Vol. 25, No. 2 ( 2014-7-1), p. 33-39
    Abstract: Phenylalanine hydroxylase (PAH) is the key enzyme in phenylalanine metabolism, catalyzing its oxidative breakdown to tyrosine. Its function in the committed step of amino acid metabolism requires strict regulation. Thus, several regulatory mechanisms are central for an understanding of PAH at the atomistic level. The enzyme is activated by incubation with phenylalanine and inhibited by tetrahydrobiopterin binding. Furthermore, phosphorylation of Ser-16 in the regulatory domain influences enzyme turnover. All major regulatory processes in PAH are connected to the conformational changes within a protein and its oligomeric assembly. The underlying dynamic processes in the enzyme are tackled by a variety of experimental and computational approaches. We especially emphasize the computational approaches, aiming to unravel the changes in the molecular dynamics of PAH that govern allosteric regulation. State-of-the-art molecular dynamics simulations provide access to the conformational transitions in biological macromolecules at the microsecond time scale and beyond. Thus, in silico strategies are promising for the identification of the complex allosteric mechanisms governing PAH activity in vivo .
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines-2014-0006
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2014
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  • 3
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    Online Resource
    Interferon-γ-Induced Degradation of Tryptophan by Human Cells in vitro
    Walter de Gruyter GmbH ; 1987
    In:  Biological Chemistry Hoppe-Seyler Vol. 368, No. 2 ( 1987-01), p. 1407-1412
    Details
    In: Biological Chemistry Hoppe-Seyler, Walter de Gruyter GmbH, Vol. 368, No. 2 ( 1987-01), p. 1407-1412
    Type of Medium: Online Resource
    ISSN: 0177-3593
    URL: Article
    DOI: 10.1515/bchm3.1987.368.2.1407
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 1987
    detail.hit.zdb_id: 1466062-3
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  • 4
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    Online Resource
    Pteridines and Lipid Metabolism
    Walter de Gruyter GmbH ; 1998
    In:  Pteridines Vol. 9, No. 2 ( 1998-05), p. 103-112
    Details
    In: Pteridines, Walter de Gruyter GmbH, Vol. 9, No. 2 ( 1998-05), p. 103-112
    Abstract: The effect of 9 different pteridines on fatty acid incorporation into phospholipids as well as on cholesterol and phospholipid content was compared in vitro using rat liver homogenate, Krebs-Ringer phosphate buffer containing 0.3 % albumin (pH=7.4), fatty acid mixture and glycerol. D-neopterin (5-30 pmol/g) induced an increase of saturated, a decrease of unsaturated fatty acids incorporation into phospholipids and elevated the cholesterol content in samples. The phospholipid amount in samples remained unchanged. Sepiapterin, 7,8-dihydrobiopterin, 5,6,7,8-tetrahydrobiopterin, biopterin, monapterin and 7,8-dihydroneopterin addition to samples induced an inverse relationship: a decrease of saturated, an increase of unsaturated fatty acid, especially arachidonic acid, incorporation into phospholipids and the decrease of cholesterol content in samples. The phospholipid amount in samples remained unchanged or increased. Lipid metabolism was not altered after addition of xanthopterin and isoxanthopterin to samples. It was suggested that neopterin decreased membrane fluidity, prevented cell cycle, induced cell dystrophy and apoptosis, and promoted the cholesterol precipitation while tetrahydrobiopterin, its precursors, biopterin, monapterin and dihydroneopterin increased membrane fluidity, stimulated cell cycle, prevented cholesterol precipitation. The data point to a potential role of increased neopterin concentrations in vivo to support atherosclerosis development and progression whereas the other pteridines may have a protective effect. Moreover, these pteridines can also promote cell transformation.
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines.1998.9.2.103
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 1998
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  • 5
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    Online Resource
    Neopterin and Cellular Immune Activation in Active Gynaecological Cancer: Significant Correlation Between Neopterin and Circulating Number of HLA-DR Expressing Lymphocytes
    Walter de Gruyter GmbH ; 1990
    In:  Pteridines Vol. 2, No. 1 ( 1990-01), p. 17-21
    Details
    In: Pteridines, Walter de Gruyter GmbH, Vol. 2, No. 1 ( 1990-01), p. 17-21
    Abstract: Urine concentrations of neopterin, a marker for the activation of cellular immunity, were determined concomitantly with a large panel of hematological and immunological variables on 24 women with gynaecological cancers (12 uterine cervix, 5 endometrium, 7 ovary). There were 14 women investigated at first diagnosis of carcinoma, and 10 women were studied during follow-up (evidence of disease, only palliative treatment during the preceding three months). A statistically significant correlation was found between neopterin concentrations and number of circulating non-B lymphocytes expressing HLA-DR antigen. Neopterin concentrations, numbers of HLA-DR positive cells, and numbers of circulating leukocytes were significantly higher in women studied during follow-up, when compared with women freshly diagnosed. In contrast. numbers of CD4 +, CD3 +, CD19 + lymphocytes and of total lymphocytes in peripheral blood were significantly lower in women studied during follow-up. The results suggest that high neopterin levels in tumor patients indicate activation of early steps of cellular immune mechanisms.
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines.1990.2.1.17
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 1990
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  • 6
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    Online Resource
    Neopterin in Autoimmune Rheumatic Diseases
    Walter de Gruyter GmbH ; 1999
    In:  pteridines Vol. 10, No. 3 ( 1999-08), p. 119-124
    Details
    In: pteridines, Walter de Gruyter GmbH, Vol. 10, No. 3 ( 1999-08), p. 119-124
    Abstract: Neopterin concentrations in body fluids allow to monitor the activation status of the cellular ( =Thl-type) llnmune system in an easy but also sensitive way. Autoimmune disease result from deterioration of almost .1,1 immune system compartments. Rheumatic disorders comprise an important group of diseases featuring several aspects of autoimmune disorders. Already several years ago increased neopterin concentrations were Jemonstrated in patients with rheumatoid arthritis and later on in patients with systemic lupus erythemarosus. Neopterin concentrations were fowld to correlate with the activity of the diseases and to conveniently indicate effects of therapy. Similar data were obtained in patients with acute rheumatic fever, and more recently, the utility of neopterin determination was also demonstrated in patients with Wegeners granulomatosis and with polymytositis/dermatomyositis. In this article we intend to summarize the current knowledge about the usefulness of neopterin measurements in patients with rheumatic diseases.
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines.1999.10.3.119
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 1999
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  • 7
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    Impairment of Lipid Metabolism Due to Deficiency of Pyridoxal-5-phosphate and/or Activated Immune system: its Interpretation
    Walter de Gruyter GmbH ; 2000
    In:  pteridines Vol. 11, No. 4 ( 2000-11), p. 107-120
    Details
    In: pteridines, Walter de Gruyter GmbH, Vol. 11, No. 4 ( 2000-11), p. 107-120
    Abstract: Impairment of lipid metabolism due to excess metabolite accumulation induced by pyridoxal-5-phosphate (P-5-P)-deficiency and/or stimulated immune system has been studied and interpreted. Decreased amounts of phospholipids as well as deviations in phospholipid classes and fatty acid composition of phospholipids have been demonstrated due to kynurenine accumulation in the blood of P-5-P-deficient cardiovascular patients and white rats as well as in cardiovascular patients with activated immune system identified by an increased neopterin concentration in the blood (dilated cardiomyopathy). The addition of P-5-P to the incubation medium for phospholipid biosynthesis in vitro did not change fatty acid incorporation into phospholipids, whereas it normalised fatty acid incorporation into phospholipids in liver homogenates received from P-5-P-deficient rats: The addition of kynurenine, neopterin and noradrenalin (accumulated m isolated heart tissue after addition of kynurenine and neopterin to incubation medium for isolated heart) to incubation medium for phospholipid biosynthesis in vitro induced an increase of saturated and a decrease of polyunsaturated fatty acid incorporation into phospholipids. These changes in fatty acid incorporation into phospholipids were followed by increased cholesterol concentrations in samples and an increased cholesterol/phospholipid ratio. Our results suggest that these changes in lipids are characteristic for decreased membrane fluidity, depressed cell cycle and lowered possibility of phospholipids to keep cholesterol in solution. P-5-P-deficiency is also accompanied with excess accumulation of homocysteine in the blood. The addition of L-homocysteine to the incubation medium for phospholipid biosynthesis in vitro was followed by inverse changes in fatty acid incorporation into phospholipids when compared with kynurenine, neopterin and noradrenalin. L-homocysteine induced a decrease of saturated and an increase of polyunsaturated fatty acid incorporation into phospholipids. The cholesterol concentration decreased in samples and the cholesterol/ phospholipid ratio decreased, too . These findings suggest that changes in lipids induced by L-homocysteine are characteristic for increased membrane fluidity and stimulated cell cycle. In this study, we have observed a similar effect to L-homocysteine effect when L-homocysteine, L-tryptophan and 5,6,7,8-tetrahydrobiopterin were added to the incubation medium for phospholipid biosynthesis in vitro. The comparison of our results with data from the literature allows to suggest that excess metabolite accumulation due to activated formation and inactivated catabolism of it plays a significant role in quantitative and qualitative changes of lipids, especially phospholipids, and therefore participates in the regulation of membrane fluidity, cell cycle of normal and malignant cells as well as in keeping cholesterol in the state of solution.
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines.2000.11.4.107
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2000
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  • 8
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    Online Resource
    Interferon-y-Induced Growth Inhibition of Neuroblastoma Cells is Independent of Induction of Nitric Oxide Synthase and Indoleamine 2,3-dioxygenase
    Walter de Gruyter GmbH ; 2004
    In:  pteridines Vol. 15, No. 3 ( 2004-08), p. 91-96
    Details
    In: pteridines, Walter de Gruyter GmbH, Vol. 15, No. 3 ( 2004-08), p. 91-96
    Abstract: We investigated a possible involvement of nitric oxide formed by inducible nitric oxide synthase (iNOS) in the signaling cascade leading to growth inhibition and differentiation in the human neuroblastoma cell line SK-NSII. Treatment of SK-N-SH with interferon-γ (IFN-γ) plus interleukin-lß (IL-lß) led to induction of iNOS, growth inhibition and an altered cell shape. However two inhibitors of iNOS were not able to prevent cytokine induced changes. In addition, IFN-γ alone led to growth inhibition in absence of iNOS induction. Inhibition of the induced indoleamine 2,3-dioxygenase (IDO) activity also did not prevent growth inhibition. Our findings show that mechanisms other than NO and IDO can control interferon-y-induced growth inhibition of SK-N-SH cells.
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines.2004.15.3.91
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2004
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  • 9
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    Influence of Extreme Long Endurance Sports Activity on Neopterin Excretion
    Walter de Gruyter GmbH ; 2008
    In:  pteridines Vol. 19, No. 1 ( 2008-02), p. 114-119
    Details
    In: pteridines, Walter de Gruyter GmbH, Vol. 19, No. 1 ( 2008-02), p. 114-119
    Abstract: Immune system activation has been observed during endurance exercise, but its relevance is largely unclear. We evaluated urinary neopterin excretion in an athlete competing in the Race Across America (RAAM), to determine whether neopterin excretion would indicate that immune system activation occurs during extreme endurance sport. Urinary samples were collected at the day before the race, during the whole RAAM, and, without a physical strain, seven days after the race. Neopterin normalized to creatinine concentration was determined by reversed-phase high-pressure liquid chromatography (HPLC). Data were analysed by repeated-measured analysis of variance (ANOVA). In the athlete, urinary neopterin concentration started to increase consistently after the start of the race until day four, followed by a decline thereafter, reaching values close to the starting value. The lowest average neopterin concentration was observed at day seven; this concentration was significantly lower than mean values at days 2- 6 (all p 〈 0.05). Comparing the power output (Watt) with the neopterin concentrations at the same time point revealed a significant correlation (r s = 0.333; p 〈 0.05). A comparison of average daily urinary neopterin excretion mean values between the test and control person showed significant differences at all time points, except for the specimen obtained at day seven. This pilot study supports the hypothesis that extreme long endurance strain at low intensities leads to an activation of the immune system. Neopterin levels could be a convenient tool to assess the immune system activation induced by training in athletes.
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines.2008.19.1.114
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2008
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  • 10
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    Evaluation of Serum and Urinary Levels of some Pteridine Pathway Components in Healthy Turkish Children
    Walter de Gruyter GmbH ; 2012
    In:  pteridines Vol. 23, No. 1 ( 2012-02), p. 90-95
    Details
    In: pteridines, Walter de Gruyter GmbH, Vol. 23, No. 1 ( 2012-02), p. 90-95
    Abstract: Neopterin, as a non-conjugated pteridine, is synthesized from guanosine triphosphate and its production is upregulated upon the activation of cellular immune response. Alterations of pteridines in body fluids are known to correlate well with existing diseases and stages, prognosis, clinical outcomes and survival data. It is of advantage to have a pteridine database of healthy volunteers to determine normal values. Thereby, especially in children there is no detailed study on pteridine levels. The aim of this study is to initiate the establishment of pteridine database of healthy children in our country. Serum neopterin levels were analysed by enzyme-linked immunosorbent assay. Urinary neopterin and biopterin levels and serum kynurenine, tryptophan levels and kynurenine/tryptophan ratio as an estimate of tryptophan breakdown were assessed with high-pressure liquid chromatography in serum and urine samples of 55 children aged between 3 months and 10 years. The results were evaluated within the subgroups of different ages and sex. Pteridine pathway components were found to be higher in children compared to adults. Higher levels of pteridine pathway components observed within the first years of life may reflect the rapid maturation of the immune system, and environmental adaptation and/or insufficiency of defence systems. On the other hand, it may also relate to a higher frequency of infections not (yet) manifested clinically.
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines.2012.23.1.90
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2012
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