bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary Neopterin Indicates Early Infection and Disease Progression: Model Studies with Simian and Human Immunodeficiency Viruses in Macaques
Authors: Stahl-Hennig Christiane , Fendrich Claudia , Lüke Wolfgang , Widner Bernhard , Hunsmann Gerhard , Fuchs Dietmar 
Published: August 2013

Abstract
The value of urinary neopterin as a predictive marker for disease progression in SIV- and HIV-2-infected rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis) was assessed by comparing pre- with postinfection data. Before infection stable baselines for neopterin were observed in both species with significantly higher concentrations in cynomolgus macaques than in rhesus macaques. After infection of cynomolgus macaques with human immunodeficiency virus type 2 (HIV-2) neopterin concentrations exceeded 1.2 - 4.2 times preinfection values, whereas rhesus monkeys infected with simian immunodeficiency virus (SIV) yielded concentrations of more than 8 times above baseline. Increased neopterin concentrations always preceded seroconversion. No rise of neopterin was observed in cynomolgus macaques remaining seronegative after inoculation with HIV-2, whereas after inoculation with SIV neopterin was slightly elevated in rhesus monkeys despite remaining seronegative. In animals with high virus replication a pronounced increase of neopterin levels was followed by signs of immunodeficiency. Therefore like in HIV-1-infected man, in macaques infected with SIV or HIV-2 the urinary neopterin concentration is an early and reliably predictive marker for AIDS disease progression and reflects pathogenicity. This parameter can be easily assessed in study protocols for drug and vaccine tests in monkeys as in man.
Neopterin, IgG, IgA, IgM, and Plasma Volume Changes During Long-distance Running
Authors: Gunga Hanns-Christian , Machotta Andreas , Schobersberger Wolfgang , Mittermayr Markus , Kirsch Karl , Koralewski Eberhard , Röcker Lothar 
Published: August 2013

Abstract
Prolonged physical exercise is associated with several immunological changes, e.g. increase in proinflammatory cytokines, changes in the white blood count etc. Great discrepancies exist with regard to the exercise- induced influence on serum immunoglobulin and neopterin values. One explanation could be the shifts in plasma volume (PV) during and after exercise which might influence plasma concentrations of these parameters. Therefore we investigated the consequences of a marathon race in a homogenous group of experienced runners on plasma volume shifts, serum Immunglobulin and neopterin concentrations. Plasma values with and without correction for plasma volume shifts were compared. PV was significantly diminished after the race (-8.4%) followed by a rise 34h after finish (+8.5%). Serum immunoglobulin IgG, IgA and IgM were increased within the first hours postmarathon and normalized in the recovery period. When chages in PV were considered, only IgA rose significantly. Serum neopterin remained unchanged after the marathon independently whether corrected for PV changes or not. We conclude that the increase in immunoglobulins in our study was mainly the consequence of plasma volume changes. Since neopterin was unchanged we have at least in our study no evidence for exercise-induced activation of the cellular immune system.
Immunologic Alterations in Schizophrenia: Neopterin, L-Kynurenine, Tryptophan and T-Cell Subsets in the Acute Stage of Illness
Authors: Sperner-Unterweger Barbara , Miller Carl , Holzner Bernhard , Laich Andreas , Widner Bernhard , Fleischhacker Wolfgang W. , Fuchs Dietmar 
Published: August 2013

Abstract
It is well established now that in diseases with activated cell-mediated immunity increased formation of neopterin and degradation of tryptophan is an indication of endogenous production of interferon-γ in patients. Therefore increased neopterin levels are associated with increased kynuremne levels and decreased tryptophan in patients suffering from virus infections, malignant diseases or autoimmunity. To investigate cell-mediated immunity m schizophrenia, neopterin, L-kynurenine, L-tryptophan and T-cell-subsets were measured in 10 chronic schizophrenic patients, addmitted to hospital due to acute psychiatric relapse. Low neopterin concentrations were found at the beginning of hospitalisation and followed by a significant increase at the time of discharge (p = 0.02). Mean neopterin values were still within the 95th percentile of healthy controls. Kynuremne levels showed a similar development (p = 0.03) as neopterin whereas tryptophan values were low at admission without any significant changes thereafter. CD3 + and CD4+-cells presented with highest numbers at admission, followed by a continuous decrease and NK-cells were found lowest on day 0 with a gradual increase by day 7. These findings argue against acute virus infection in acutely ill schizophrenic patients because this would be associated with incerased neopterin fromation and tryptophan dagradation, rather the data would be in line with a shift from TH-1 to TH-2-type immune reaction which which is common in chronic infections.
A New Functional Role of 5,6,7,8-tetrahydrobiopterin (BH4) as an Inhibitor of γ-glutamylcysteine Synthetase (γ-GCS) mRNA Expression
Authors: Kojima Shuji , Kurozumi Risa , Tuchiya Maiko 
Published: August 2013

Abstract
The effect of the intracellular 5,6,7,8-tetrahydrobiopterin (BH4) on the increased γ-glutamylcysteine synthetase (γ-GCS) mRNA expression induced by nitric oxide (NO) was investigated in RAW264.7 cells. Low doses of nitroprusside (SNP), ranging from 0.1 mM to 0.5 mM, significantly increased the intracellular glutathione levels along with the expression of mRNA for γ-GCS, a rate limiting enzyme of de novo glutathione synthesis. The increased expression was not abolished by exogenously added BH4 itself, but by sepiapterin, a precursor of BH4 synthesis, in a dose-dependent manner. The blockage by sepiapterin was ineffective in the presence of N-acetyl serotonin (NAS), an inhibitor of sepiapterin reductase. The increased γ-GCS mRNA expression was also inhibited by catalase, a scavenger of hydrogen peroxide. Evidence was further provided that BH4 effectively scavenged hydrogen peroxide. These results suggest that intracellular BH4 may play a role as an inhibitor of glutathione synthesis induced by NO via scavenging hydrogen peroxide, a mediator of the gene expression for the de novo glutathione synthesis pathway.
Differential Inhibition of Constitutive and Inducible Nitric Oxide Synthase in Vascular Endothelial Cells by Analogues of Tetrahydrobiopterin
Authors: Mueller Nicolas J , Walter Roland Β , Linscheid Philippe , Schaffner Andreas , Schoedon Gabriele 
Published: August 2013

Abstract
In the vasculature, a physiologic production of nitric oxide (NO) is maintained by endothelial nitric oxide synthase (eNOS). Induction of inducible nitric oxide synthase (ÍNOS) under inflammatory conditions (e.g. septic shock) resulting in high levels of nitric oxide (NO) is believed to be partly responsible for the pathophysiologic changes in the vascular system that occur under inflammatory conditions (e.g. septic shock). Both NOS isoforms are dependent on the obligatory cofactor tetrahydrobiopterin (BH4). We investigated the selectivity and potency of the BH4 analogues 4-amino-BH4 and 5-methyl-BH4 in inhibiting eNOS and iNOS in a murine vascular endothelial cell (MVEC) model expressing either eNOS or iNOS under physiologic and inflammatory conditions, respectively. Exogenous BH4 and its precursor sepiapterin both enhanced physiologic eNOS activity in resting MVEC, while 4-amino-BH4 slightly inhibited eNOS. 5-methyl-BH4 did not have any effect on eNOS. BH4, sepi - apterin, and 5-methyi-BH4 had no effect on iNOS in inflammatory activated MVEC. In contrast, 4-amino-BH4 selectively inhibited iNOS with a potency comparable to the unselective NOS inhibitor Νω-monomethyl-L-argimne (L-NMMA). The present study demonstrates that 4-amino-BH4 selectively and potently inhibits iNOS in vascular endothelial cells, while its effect on eNOS is minimal. The selective inhibition of iNOS is a promising strategy for the treatment of inflammatory conditions with high output of NO. Further in vivo studies are required to determine whether inhibition of NO production by analogues of BH4 offers any advantage compared to inhibition by L-arginine analogues.
Tryptophan Metabolites as Scavengers of Reactive Oxygen and Chlorine Species
Authors: Weiss Günter , Diez-Ruiz Antonio , Murr Christian , Theur Igor , Fuchs Dietmar 
Published: August 2013

Abstract
Upon stimulation with interferon-γ, a typical Thl cell-derived cytokine, human monocyte-dertved macrophages produce neopterin derivatives and in parallel degrade the essential amino acid L-tryptophan to L-kynurenine and subsequently to 3-hydroxyanthramlic acid and anthramlic acid. In parallel, stimulated macrophages produce reactive oxygen species such as hydrogen peroxide and hypochlorous acid. Earlier, neopterin and 7.8-dihydroneoptenn were found to enhance or decrease effects of reactive oxygen species in vitro, depending on concentration and on environmental condition. In this study, we investigated the ability of tryptophan and its metabolites to interfere with radicals in vitro by means of a chemiluminiseence-based assay system. When using hydrogen peroxide or chloramine Τ as source for radical formation. L-tryptophan and its catabolites reduced chennluminescence according to a dose-response relationship, 3-hydroxvanthranilic acid being the most efficient compound. Apart from L-kynurenme the scavenging effects of tryptophan and its metabolites were not affected by changes m pH from 5.5 to 7.5. Our data indicate that tryptophan degradation produces metabolites with a high scavenging ability for reactive oxygen and chlorine species, thereby establishing a self-regulatory mechanism to limit the tissue damage by reactive radicals produced by macrophages.
Urinary Neopterin Concentrations in Healthy Individuals with Household Contact
Authors: Winkler Christiana , Wirleitner Barbara , Werner Ernst R. , Fuchs Dietmar 
Published: August 2013

Abstract
Increased neopterin concentrations in serum and urine indicate activation of cell-mediated immunity. In this study, urinary neopterin concentrations of a family consisting of 1 child (aged 5 years), her parents, and her grandparents were determined over a one year period and the course of neopterin levels was compared. Urine specimens were taken every second week during 1 year beginning in June. All 5 individuals lived in the same house, child and her parents separated by one floor from the grandparents. Neopterin concentrations were determined by high Performance liquid chromatography. In adults, neopterin concentrations were very stable throughout the year and peak increases occurred only rarely. In contrast, 5 sharp peaks of urinary neopterin concentrations were observed in the child, all occurring during the period when she was attending the kindergarten. Comparing the course of neopterin concentrations between the persons tested, several corresponding elevations of urinary neopterin were detected in the child and her relatives. The best association was detected between the child and her father (3 peaks of neopterin concentrations were observed, 1 of which coinciding with a peak in the child and two peaks with two weeks delay in the father). Between the child and her mother 1 corresponding neopterin peak was observed. One highly increased urinary neopterin concentration was observed in the grandmother which corresponded to a peak in the child with two weeks delay, a similar Observation was made between the child and her grandfather. In summary, high degree of correspondence in neopterin peaks was detected between child and adults. The data render it likely that the child was transmitting infectious diseases which she acquired at the kindergarten to her relatives, and the data are in line with the assumption that a dose family contact between individuals increases the risk of infectious disease transmission via household contact.
Neopterin Profile to Evaluate the Effectiveness of Treatment in Aggressive Periodontitis
Authors: Bodur Aysen , Baydar Terken , Ozmeric Nurdan , Engin Ayse Basak , Uraz Ahu , Eren Kaya , Sahin Gonul 
Published: August 2013

Abstract
Periodontal disease results from the interaction of the host defence mechanisms with the microbial dental plaque. Analysis of gingival crevicular Huid (GCF) provides a non-invasive means of evaluating the role of the host response in periodontal disease. Based on our previous study, demonstrating increased levels of neopterin in GCF and saliva from patients with aggressive periodontitis (AgP), the aim of this study was to evaluate the effect of periodontal treatment on the levels of neopterin in GCF, saliva and urine of patients with AgP.
Pre-treatment values of neopterin in GCF were 4.04 ± 0.86 nmol/ml for the AgP group (n=8) and 2.68 ± 0.90 nmol/ml fyr the control group (n=8; difference not significant). After periodontal treatment, the level of ncoptei in was found 2.38 ± 0.72 nmol/ml in the patient group which did not differ f r om pre-treatment levels. The salivary neopterin concentration was higher in both AgP groups (14.14 ± 2.85 nmol/1 and 8.02 ± 3.12 nmol/1, before and after periodontal treatment) than in controls (2.58 ± 0.3 nmol/1; both p<0.05). No significant difference in salivary neopterin level was observed in patients before and after periodontal treatment.
Concentrations of urine neopterin in patients before treatment were 188.5 ± 30.98 μηιοί neopterin/mol creatinine and 168.1 + 20.21 μηιοί in controls (difference not significant). Following periodontal treatment, the urinary neopterin levels (310.1 ± 39.82 μηιοί neopterin/mol creatinine) were higher when compared to the baseline levels and to controls (p<0.05).
Our results suggest that neopterin in saliva and GCF might be associated with the periodontal diseases process.
On the Mechanisms of the Neopterin-induced Suppression of Renal Erythropoietin Production
Authors: Pagel Horst , Hoffmann Georg , Fuchs Dietmar , Schobersberger Wolfgang 
Published: August 2013

Abstract
Earlier neopterin was demonstrated to inhibit hypoxia-induced erythropoietin synthesis in isolated perfused rat kidneys. The present experiments were performed to gain further insight into the mode of action underlying this effect. Numerous studies provided evidence of a link between neopterin and oxidative stress as well as intraccllular calcium concentrations. Thus, neopterin (200 μM) NQS added into the perfusion medium together with either the caclium Channel blocker Verapamil (5 μM) or the anti-oxidant N-acetylcysteine (200 μM). The addition of neopterin as a Single stimulus resulted in a significant decrease in the rate of hypoxia-induced eryihropoietin release accompanied by an augmented renal vascular resistance and a reduced perfusion flow rate. Although these data point towards an involvement of calcium and/or reactive oxygen species, verapamil or Nacetyleysteine were able to abrogate the suppression of erythropoietin generation which was induced by neopterin. Therefore, the mechanisms responsible for the impact of neopterin on the production of this growih lactor in the kidney remain to be elucidated.
Clinical Application of Cerebrospinal Fluid Neopterin Concentrations in HIV Infection
Authors: Hagberg Lars , Andersson Lars-Magnus , Abdulle Sahra , Gisslén Magnus 
Published: August 2013

Abstract
HIV-1 infects the central nervous system (CNS) and may cause AIDS dementia complex (ADC) and other neurologic complications. The cerebrospinal fluid (CSF) virus load is usually 0,5 -1 log lower than in blood, but in some patients the CSF quantitative HIV-1 RNA values exceed the paired blood samples. CSF neopterin concentrations are increased in all stages of HIV-1 infection, with the highest concentrations in AIDS patients and patients with CNS opportunistic infections. CD4 cell count and quantitative HIV RNA PCR tests in peripheral blood are used in clinical practice to monitor the HIV-1 infection and the anti-retroviral treatment effect. In most patients the anti-retroviral treatment response is similar in the cerebrospinal fluid (CSF) compare to the peripheral blood and the CSF viral load and neopterin concentrations are markedly reduced following treatment. ADC has become a rare complication. In spite of virological effective treatment many patients have a low grade intrathecal immunoactivation, measured as CSF neopterin concentrations above the 95% confidence interval found in IIIV-1 negative controls, after such a long time as after 2 years of anti-retroviral treatment.
The risk of long term intrathecal immunoactivation and which anti-retroviral combination treatment has the best effect on CSF parameters is not known. CSF neopterin concentrations are at present not used in clinical practice but may add valuable information.
Linkage of Pteridine Metabolism to Iron Homeostasis
Authors: Weiss Günter 
Published: August 2013

Abstract
Iron is an essential growth factor for the proliferation and differentiation of all living cells in being centrally involved in oxygen transport by hemoglobin and myoglobin, in electron transport during mitochondrial respiration as being a part of complex I and II enzymes or in the regulation of transcription via its role as central component of ribonucelotid reductase (1,2). Moroever, iron plays a critical role in macrophage mediated cytotoxicity by contributing to the production of highly toxic hydroxy radical species needed for host defense (3). In addition, radicals formed by the catalytic action of by iron can modulate the binding affinities of several transcription factors to their target promoter region, such as hypoxia inducible factor -1 or nuclear factor-kB, thus affecting transcription of stress inducible genes (4-6).
Interferon-y-Induced Growth Inhibition of Neuroblastoma Cells is Independent of Induction of Nitric Oxide Synthase and Indoleamine 2,3-dioxygenase
Authors: Leitner Stephan , Golderer Georg , Winkler Christiana , Fuchs Dietmar , Werner-Felmayer Gabriele , Werner Ernst R. 
Published: August 2013

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.
Modulation of Free Radical Formation by Pterin Derivatives
Authors: Karl Oettl , Greilberger Joachim , Reibnegger Gilbert 
Published: August 2013

Abstract
All classes of pterins, fully reduced tetrahydropterins, aromatic pterins and dihydropterins have been investigated upon their effects on radical mediated reactions. Meanwhile all these classes were shown to act as both, proand antioxidants by a number of different methods including chemical, biochemical and biological systems. From reduced pterins radicals including oxygen-, nitrogen- and pterin-radicals arc formed enzymatically and non-enzymatically, reduced pterins react with free radicals and serve as reductive agents. All classes of pterins may interfere with enzymes involved in radical formation. Upon the diversity of possibilities the net effect of a particular compound is a question of the experimental settings and the physiological relevant role often remains obscure.
Modulation of Folate Dependent DNA Methyltransferase 1 (dnmt1) Activity in Whole Body γ-irradiated Mice.
Authors: Batra Vipen , Kesavan Vellapan , Mishra Kaushal P. 
Published: August 2013

Abstract
The methylation pattern of DNA is established during embryogenesis and is subsequently maintained by maintenance methylation activity of the enzyme DNA methyltransferase 1 (dnmtl). The modulation of nuclear dnmtl activity in nuclear and post-nuclear supernatant fractions was studied after various time intervals in 1, 3. 5 and 7 Gy whole body γ-irradiated mice. Significant changes in enzyme activity were observed in nuclear fraction of liver at various stages after irradiation. Our results show a dose-dependent increase in nuclear dnmtl activity after 24 hours al 1 to 5 Gy, with the maximum increase in activity at 7 Gy. An attenuation of enzyme activity was observed after 48 hours, which was continued at 96 hours post-iradiation, where the activity approached subnormal levels at higher doses. The dnmtl activity was less conspicuous in supernatant fraction and no significant change in activity was observed 24 hours after irradiation. Present studies suggest the possible role of radiation as a stressor in modulating the folate dependent dnmtl activity, which in turn may affect global DNA methylation pattern.
Increased Neopterin Concentration in Older Age Coincides with Decline of CD28+CD45RA+ T-cells
Authors: Murr Christian , Hainz Ursula , Asch Ester , Berger Peter , Jenewein Brigitte , Saurwein-Teissl Maria , Grubeck-Loebenstein Beatrix , Fuchs Dietmar 
Published: August 2013

Abstract
Neopterin is produced from human monocyte-derived macrophages and dendritic cells upon Stimulation with interferon-y, and increased neopterin concentrations thus indicate cell-mediated immune activation. In healthy individuals increasing neopterin concentrations are found with increasing age, which is also evident from the agedependency of reference values of serum neopterin concentrations. Increase of neopterin concentrations in the elderly may relate to, e.g., altered T lymphocyte differentiation with age. In this study, serum neopterin concentrations of 138 persons (median age: 34 years; interquartile range 29.0 - 67.8 years) were investigated and compared to age and to the percentage of CD28+CD45RA+ or CD28+CD45RO+ subsets among CD8+ T cells. With increasing age, the percentage of CD28+CD45RA+ in CD8+ T-cells decreased (Spearman's rank correlation coefficient: rs = -0.561; p < 0.0001) accompanied by an increase of the percentage of CD28+CD45RO+ in CD8+ T-cells (rs = +0.221; p < 0.01). Serum neopterin concentrations increased with age (rs = -+0.541; p < 0.0001). This increase of neopterin concentration was accompanied by a decreased percentage of CD28+CD45RA+ in CD8+ T-cells (r+ = -0.287; p < 0.001). Multivariate analyses revealed that the inverse relationship between the percentage of CD28+CD45RA+ in CD8+ T-cells and neopterin concentrations was at least partly independent from age. Thus, investigation allows to conclude that an increase of neopterin concentrations with older age is accompanied by a loss of naive CD28+CD45RA+ CD8+ T-cells. Data suggest that the subset of CD28+CD8+ T-cells, which is developing in states of sustained immune activation, is important for a chronic production of interferon-γ which in turn gives rise to increased neopterin concentrations.