bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possibility of the Nonenzymatic Conversion of 6-(1'-Oxo-2'-hydroxypropyl)- Tetrahydropterin to Sepiapterin
Authors: Sawada Hiroshi , Shimura Natumi , Takikawa Shin-Ichiro , Lino Teruhiko 
Published: August 2013

Abstract
Tetrahydrobiopterin (BH4) is a cofactor for aromatic amino acid hydroxylases and nitric oxide synthase. The biosynthetic pathway of BH4 from 6-pyruvoyl-tetrahydropterin (PPH4) includes two reduction steps catalyzed by sepiapterin rcductasc (SPR). PP1I4 is reduced to 6-( 1 '-oxo-2'-hydroxypiOpyl)-tetrahydropterin (l'-OXPH4 ) or 6- ( r-hydroxy-2'-oxopropyl)-tetrahydropterin (2'-OXPH4), which is further converted to BH4. However, patients with SPR deficiency show normal urinary excretion of pterins without hyperphenylalaninemia, suggesting the existence of another BH4 biosynthetic pathway, which is not concerned with SPR in humans. Blau et al. proposed a BH4 biosynthetic salvage pathway containing nonenzymatic conversion of l'-OXPH4 to sepiapterin. In this study, the possibility of the nonenzymatic conversion of l'-OXPH4 to sepiapterin was examined by using silkworm carbonyl reductase (CR 1) and human monomeric carbonyl reductase. Since l'-OXPH4 has been suggested to be nonenzymatically converted into sepiapterin, in an incubation mixture containing PPH4 and silkworm CR I, sepiapterin was determined by its derivative as biopterin. No sepiapterin was detected in the incubation mixture when the mixture, containing 800 pmol of l'-OXPH4, was further incubated at 37°C for 2 h in darkness. This result suggests that the rate of nonenzymatic formation of sepiapterin from l'-OXPH4 is quite low. The findings obtained here indicate that the proposed pathway in which a nonenzymatic conversion of l'-OXPH4 to sepiapterin occurs may be difficult or unlikely to proceed in humans.
Neopterin Levels and Immune Activation in the Blood of Children with Down’s Syndrome
Authors: Licastro F. , Chiappelli M. , Porcellini E. , Rustica M. , Corsi M.M. 
Published: August 2013

Abstract
Patients with AD often show altered levels of some immune molecules in their peripheral blood which correlate with cognitive impairment. Downs' syndrome (DS) subjects are at high risk of developing Alzheimer's disease (AD). Here we studied immune molecules, such as interleukin-6 (IL-6), C reactive protein (CRP) and neopterin, in the blood of non demented children with DS to investigate whether altered peripheral immune phenotype could be present in this subjects without dementia, many years before the presentation of clinical signs of cognitive deterioration. Plasma levels of neopterin and IL-6 were measured by commercially available ELISA kits, whereas plasma CRP concentration was evaluated by nephelometric immunoassay technique. We studied a group of 40 patients with DS, 20 healthy controls and 100 patients w ith AD. Plasma levels of IL-6 and CRP were significantly higher in DS than in control children. The increase of IL-6 and CRP from DS children was similar to that found in elderly patients with clinical AD. In the present research we have also studied blood levels of neopterin which were in the normal range either in DS or control. Increased or normal levels of this metabolite have been found in the blood of AD patients. However, increased blood neopterin was likely to be only elevated in patients with advanced clinical stage of AD. Peripheral altered immune phenotype in healthy young subjects with DS might be an early sign of CNS alterations leading many years later to cognitive deterioration and dementia.
A Herbal Multicomponent Mixture Effective in Suppressing Biochemical Pathways in Mitogen-stimulated Human Peripheral Blood Mononuclear Cells
Authors: Neurauter Gabriele , Wirleitner Barbara , Schennach Harald , Ueberall Florian , Fuchs Dietmar 
Published: August 2013

Abstract
Extract of traditional Tibetan herbal remedy Padma 28 revealed suppressive effects on neopterin production and tryptophan degradation in mitogen-stimulated peripheral blood mononuclear cells (PBMC). One of the questions was to asses the robustness of the Tibetan way of formulating herbal multicomponent medicines. Can small changes affect the effectiveness of the formula? In this study, effect of a derivative multicomponent mixture was investigated in stimulated and unstimulated human PBMC in vitro. Neopterin production and tryptophan degradation were measured in supernatants of PBMC in the presence or absence of mitogens phytohacmagglutinin and concanavalin A. Stimulation of PBMC induced neopterin formation and tryptophan degradation, and the herbal multicomponent mixture inhibited both immunobiochemical effects in a dose-dependent way. Higher concentrations were more effective and were able to completely block the pathways induccd upon mitogenic stimulation. When comparing the results obtained with those observed earlier using Padma 28, there was no obvious difference between the two different preparations. Data allow to conclude that Padma 28 and its modified version is equally able to suppress immunobiological effects in stimulated PBMC.
Molecular Analysis of mps Operon Involved in Monapterin Syntliesis in Escherichia Coli
Authors: Ahn Chiyoung , Kim Mikyoeng , Lee Soojin , Kim Jackwang , Hwang Deogsu , Park Kyungmoon , Yim Jeongbin 
Published: August 2013

Abstract
Two genes, mpsA and mpsB, constitute an operon in the synthesis of monapterin in E. coli. Expression of mpsA, the structural gene for dihydroneopterin triphosphate 2'-epimerase, from its native promoter, required mpsB. Cotransfonnation of mpsB excludes the possibility that the MpsB is a transactivator protein for mpsA expression.
Urinary Neopterin in Patients with upper Gastrointestinal, Biliary and Pancreatic Carcinomas
Authors: Melichar Bohuslav , Solichová Dagmar , Svobodová Ivcta , Urbánek Lubor , Melicharová Karolina 
Published: August 2013

Abstract
Increased urinary neopterin has been associated with advanced disease and poor prognosis in patients with colorectal carcinoma, but less is known about urinary neopterin in other gastrointestinal tumors. We have investigated urinary neopterin in 53 patients with carcinomas of the upper gastrointestinal tract, pancreas and biliary tract. Conipared to controls, urinary neopterin was increased in patients with gastric carcinoma, pancreatic Carcinoma, cholangiocarcinoma and gallbladder carcinoma. Urinary neopterin was a significant prognostic indicator of survival in univariate as well as multivariate analyses. No significant change in urinary neopterin concentrations was observed during the short follow-up, but increased urinary neopterin concentration at the end of followup was associated with poor prognosis. In conclusion, significantly increased urinary neopterin concentrations were observed in the present cohort of patients. Urinary neopterin is an independent prognostic indicator in patients with carcinomas of the upper gastrointestinal tract, biliary tree and pancreas.
Effect of 5,6,7,8-Tetrahydrobiopterin (BH4) on γ-Ray-induced Micronucleus Frequency in RAW264.7 Cells
Authors: Hori Mayumi , Kojima Shuji 
Published: August 2013

Abstract
The effect of 5,6,7,8-tetrahydrobiopterin (BH4), an endogenous antioxidant, on γ-ray-induced micronucleus frequency was examined in RAW264.7 cells. Exogenously added BH4 reduced the γ-ray-induced micronucleus frequency. Treatment with 1 mM sepiapterin, a biosynthetic precursor of BH4, also significantly reduced the micronucleus frequency induced by 3-10 Oy y-rays, by 20-35(/o at 1 8 h post-treatment. The reducing cffect of SP on γ-ray-induced micronucleus frequency was blocked by N-acetyl-5-hydroxytryptaminc and methotrexate, which are inhibitors of BH4 biosynthesis. These results suggest that intracellular BH4 biosynthesized from sepiapterin is involved in the reducing effect of SP on γ-ray-induced micronucleus frequency. To examine possible mechanisms underlying this action, changes of intracellular BH4 concentration after sepiapterin treatment were examined. Intracellular BH4 concentration peaked at 6 h and was maintained at a high level until 24 h after sepiapterin treatment. However, the γ-ray-induced micronucleus frequency at 6 h post-treatment with sepiapterin showed no change in comparison with that after irradiation alone. These results indicate that the reducing effect of BH4 on γ-ray-induced micronucleus frequency is not necessarily due to antioxidant activity, but may involve other mechanisms.
Photoinduced Generation of H2O2 and O2•- by 6-formylpterin in Aqueous Solutions
Authors: Petroselli Gabriela , Bartsch Jonas Martin , Thomas Andrés H. 
Published: August 2013

Abstract
6-Formylpterin is one of the oxidized pterins that accumulate in the white skin patches of patients affected by vitiligo. Studies of photoinduced generation of hydrogen peroxide (H2O2 ) and superoxide anion radical (O2• ) by formylpterin in acidic and alkaline aqueous solutions at 350 nm and room temperature have been performed. The photochemical processes were followed by UV-V1S spectrophotometry and enzymatic methods for H2O2 and O2•- determination. When formylpterin is irradiated a red intermediate, that has been proposed to be 6-carboxy- 5,8-dihydropterin, is generated in an O2
-independent process. In the presence of air that intermediate reacts with O2 to yield H2O2 and 6-carboxyptcrin. In anaerobic conditions it undergoes a thermal O2-independent reaction which leads to a non-identified product without generation of H202 . The rate constants of such a process were determined to be 0.011 min 1 and 0.044 min1 at pH 5.4 and 10.5, respectively. (O2 · ), is also generated during photooxidation of formylpterin, probably as a consequence of the electron transfer from the red intermediate to O2 . The biomedical importance of photoinduced generation of H2O2 and O2• is discussed.
New Insights into Ophthalmology: Introduction of SELDI-TOF in Combination with Molecular Modelling for the Analysis of Aqueous Humour. Principle and First Results.
Authors: Tilz Gernot P. , Wiltgen Marco , Demel Ulrike , Faschinger Christoph , Scherbichler Wulf 
Published: August 2013

Abstract
We present the introduction of a new generation of techniques for early and specific diagnosis of inflammatory, immune and degenerative eye diseases. We concentrate on the applications of the SELDI-TOF (Surface enhanced laser desorption ionisation - time of flight) mass spectroscopy in combination with molecular modelling and visualization for the analysis of the aqueous humour. For our study we used aqueous humour from 25 patients undergoing cataract operation. SELDI-TOF consists on one part of an apparatus allowing the laser bombarding of molecules on a solid surface and on the other part on a system which measure the time of flight of the molecules. During the measurement the molecules are liberated from the matrix and carried to the detector. Specific proteins can be identified by the characteristic peaks of the spectrogram. Albumin and gamma-globulin were found to a considerable extend in the aqueous humour. An increased amount has been detected in inflammatory humour. The quantity may reflect some underlying complications such as inflammation and animate for further research on the spectrum of proteins and peptides released by underlying eye disorder. SELDI-TOF delivers characteristic peptide mass fingerprints, which can be used as input for the prediction of the tertiary protein structure with homology modelling. Structural deviations between a genuine protein and a mutated can be an indicator about the underlying disease, paving the way for successful diagnostic and therapy. The combination of two new technologies namely SELDI-TOF and molecular modelling may offer a broad spectrum for the differential diagnosis of some eye diseases.
In Vitro Effect of Neopterin on Splenic Mast Cell Development in Senescence Accelerated Mice (SAM)
Authors: Harada Tomonori , Tsuboi Isao , Yuda Miyuki , Wakasugi Kazunori , Aizawa Shin 
Published: August 2013

Abstract
Neopterin is produced by monocytes and is a useful biomarker of inflammatory responses. We found that neopterin enhances granulopoiesis, but suppresses B-lymphopoiesis triggered by the positive- and negative regulations of cytokines produced by stromal cells in mice. Furthermore, neopterin suppressed the colony formation of mast cell progenitor (CFU-mast) from bone marrow cells in in vitro culture system. In this study, neopterin was also found to regulate the proliferation and differentiation of splenic CFU-mast in vitro as observed in that from bone marrow, which was confirmed in the mouse model of senescent stromal-cell impairment (SCI). In non- SCI mice (=less senescent stage of SCI mice), neopterin also decreased the number of colonies of interleukin-3 (IL-3)-dependent mast-cell progenitor cells (CFU-mast) from unfractionated spleen cells, but not that from the lineage-negative (fractionated) spleen cell population without stromal cells in a semisolid in vitro culture system. In contrast, in a case of SCI mice, the treatment with neopterin did not decrease the number of colonies of IL-3- dependent mast-cell progenitor cells (CFU-mast) from unfractionated spleen cells. These results suggest that, firstly, neopterin decrease the number of colonies of IL-3-dependent CFU-mast by stimulating splenic stromal cells, and secondly, such neopterin function becomes declined during senescence because of an impaired stromalcell function.
A Modified Microbiological Method for Determination of Folate Levels in Erythrocyte and Plasma
Authors: Sipahi Hande , Baydar Terken , Ozalp Meral , Sahin Gonul 
Published: August 2013

Abstract
Pteridines are natural heterocyclic compounds and they are generally divided into two main groups which are denominated as conjugated and unconjugated pteridines. Conjugated pteridines are the folate derivatives containing p-aminobenzoate and glutamate. Folate is a normal component of the cell. Folate derivatives play a crucial role in important biochemical pathways such as purine and pyrimidine biosynthesis, conversion of serine to glycine, histidine catabolism, methionine synthesis and detoxification reactions of certain xenobiotics, in which single carbon transfer is required. Folate deficiency has been proven to play a role in the pathogenesis of certain diseases. Additionally, exposure to some xenobiotics and prolonged use of some drugs may lead to folate deficiency. Serum, plasma and especially erythrocyte folate concentrations are generally used as biomarkers of folate pool. Therefore the present study was undertaken to establish an easy applicable, economic, accurate, sensitive, specific and reproducible microbiological method by using L. rhamnosus in our laboratory. Following the establishment of the method its application was carried out in blood samples of 46 volunteers. Mean value of folate levels in erythrocyte were found 359.7 ± 133.3 ng/ml, while mean plasma folate levels were determined 27.3 ± 12.4 ng/ml. In erythrocyte, the average recovery was 103.0 ± 17.7% (mean ±SD), in plasma the average recovery was 101.0 ± 1.7% (mean ±SD) for folinic acid concentrations at 10, 25 and 50 ng/ml. The CVs were 15.1 ± 5.6% (mean ± SD) for within-run and 7.2 ± 3.9% (mean ± SD) for between-run precisions. In the present study, a modified microbiological method for folate analysis which can be applied to biological material, has been established.
Urinary Neopterin in Patients with Diabetes Mellitus and Foot Ulcers
Authors: Melicharova Karolina , Kusalova Marie , Smahelova Alena , Hyspler Radomir , Solichova Dagmar , Melichar Bohuslav 
Published: August 2013

Abstract
Increased urinary or serum concentrations of neopterin have been reported in disorders associated with systemic immune activation, e.g. viral infections, cancer, or autoimmune diseases, but the data on neopterin concentrations in patients with diabetes mellitus are limited. The aim of the present study was to investigate urinary neopterin concentrations in patients with diabetes mellitus and with or without diabetic foot. Urinary neopterin was determined by high-performance liquid chromatography in 51 patients with diabetes mellitus, including 19 patients with diabetic foot, and 18 healthy controls. Neopterin concentrations were significantly increased in patients with diabetes mellitus compared to controls (mean ± standard deviation; 221 ± 149 vs. 139 ± 66 μmol/mol creatinine; Mann-Whitney U test, p = 0.003). Urinary neopterin concentrations in patients with or without diabetic foot were identical (224 ± 113 vs. 219 ± 169 μmol/mol creatinine). No significant difference was also observed between patients with type 1 and type 2 diabetes mellitus, between patients treated with insulin compared to patients not treated with insulin, patients with or without diabetic retinopathy, with or without diabetic neuropathy, with or without diabetic nephropathy, with or without ischemic heart disease, with or without ischemic disease of lower extremities, and with or without ischemic cerebrovascular disease. Atrend of higher neopterin concentrations was observed in patients with any complication of diabetes compared to no complications (234 ± 164 vs. 176 ± 73 μmol/mol creatinine), and compared to controls, urinary neopterin was significantly increased only in patients with complications. No significant correlation was observed between urinary neopterin and glycosylated hemoglobin (rs = - 0.14, p = 0.39) or the duration of diabetes (rs = 0.25, p = 0.09). In conclusion, present results demonstrate that urinary neopterin is increased in patients with diabetes mellitus. No differences were observed in urinary neopterin concentrations based on type of diabetes, therapy or presence of diabetic foot, and urinary neopterin did not correlate with the glycosylated hemoglobin levels or duration of diabetes. Increased urinary neopterin concentrations in patients with diabetes mellitus is associated with the presence of complications and may reflect systemic immune activation associated with atherosclerosis.
Neopterin, Catalase and Superoxide Dismutase in Females with Benign and Malignant Breast Tumors
Authors: Yuksel Osman , Sahin Tevfik Tolga , Girgin Gozde , Sipahi Hande , Dikmen Kursat , Samur Ozlem , Barak Anil , Tekin Ercument , Baydar Terken 
Published: August 2013

Abstract
The aim of the present study was to evaluate the relationship between the levels of neopterin among patients with benign and malignant breast disease and the relation with the stage of the malignant process. In this study, neopterin concentrations and enzyme activities of superoxide dismutase (SOD) and catalase (CAT) were determined in malign (n=30) and benign breast tumor patients (n=30) by high performance liquid chromatographic and spectrophotometric methods, respectively. Results were compared with a healthy control group (n=20). The correlations between neopterin, CAT and SOD were also evaluated in controls and patients. Urinary neopterin level of the control group was (mean value ± S.D.) 128.6 ± 64.6 μmol/mol creatinine. Neopterin concentrations in patients with breast malignancy were 153.6 ± 71.2 μmol/mol creatinine and 107.8 ± 32.1 μmol/mol creatinine in benign disorders patients. The mean neopterin level in the benign group was found to be statistically different from the malign tumor group (p = 0.039). SOD and CAT activities in controls were found as 3.57 ± 0.84 U/mg protein and 2.19 ± 0.20 U/mg protein, respectively. In patients with malignancy, the SOD activity was 3.84 ± 0.73 U/mg protein while CAT activity was 1.03 ± 0.13 U/mg protein. Patients with benign breast disorders, SOD activity was 4.09 ± 1.00 U/mg protein and CAT activity was 1.02 ± 0.18 U/mg protein. Whereas SOD activity did not differ between the groups of patients and controls, the mean catalase level in the control group was higher than in the benign and malign tumor groups (both p <0.001). Urinary neopterin concentration seems to be an important and useful biomarker in diagnosis of breast tumors in clinical practice.
Reference Standard of Serum Neopterin Concentration in Healthy Children
Authors: Plata-Nazar Katarzyna , Luczak Grazyna , Borkowska Anna , Delinska-Galinska Anna , Kozielska Ewa , Marek Krzysztof , Korzon Maria 
Published: August 2013

Abstract
Introduction: Increased neopterin concentrations are observed in many diseases in which cell immunity is stimulated. A quick and sensitive method for monitoring the changes in immune system can be useful for understanding etiopathogenesis of the disease and choosing the appropriate treatment. There are only few known data concerning normal serum neopterin value in children, therefore the wide clinical use of this parameter is limited.
Aim: to evaluate the referential neopterin concentration in serum in healthy children according to age and gender.
Patients and methods: 105 healthy children, 47 girls and 58 boys, aged 1 month - 17.9 years were examined. Clinical examinations and laboratory test including whole blood count, serum C-reactive protein, urea, and creatinine level, were conducted. The serum neopterin level was analyzed by ELISA (BRAHMS, Hennigsdorf/Berlin, Germany). The results were used for reference standard evaluation of serum neopterin level in healthy children. Results: The serum neopterin concentrations in children were 2.87 - 14.78, mean 5.47 ± 2.58 nmol/L. No significant correlation was found between children's age and serum neopterin level. There were also no differences among serum neopterin level in different age groups: under 5, 5 to 10, and over 10 years, and between girls and boys. The estimated cut-off value 11 nmol/L of serum neopterin level for whole group of children made the 94.3% test sensitivity.
Conclusion: Serum neopterin concentration is lower than 11 nmol/L in healthy children after neonatal period, and is independent of childrens' age or gender.
Urinary Neopterin in Patients Treated with Gefitinib
Authors: Kalabova Hana , Dvorak Josef , Hyspler Radomír , Ticha Alena , Krcmova Lenka , Urbanek Lubor , Solichova Dagmar , Melichar Bohuslav 
Published: August 2013

Abstract
Inhibitors of epidermal growth factor receptor (EGFR), including low molecular weight inhibitor erlotinib and gefitinib, have been demonstrated to be active antitumor agents in patients with non-small cell lung carcinoma and head and neck carcinomas. Increased concentrations of urinary neopterin, an indicator of systemic immune activation, have also been reported in patients with lung carcinoma and head and neck carcinomas. EGFR blockade has been reported to induce immune activation. We have measured, using high performance liquid chromatography, urinary neopterin in patients with non-small cell lung carcinoma and head and neck carcinomas treated with gefitinib. Intestinal permeability was also investigated at baseline by measuring, using capillary gas chromatography, urinary xylose, mannitol and lactulose after oral challenge. Compared to controls, urinary neopterin was significantly increased in patients with non-small cell lung carcinoma. No significant change in urinary neopterin was observed during the therapy with gefitinib. A significant correlation was observed between urinary neopterin and xylose absorption (rs = -0.58, p <0.05), lactulose/mannitol (rs = 0.75, p <0.01), and lactulose/ xylose (rs = 0.62, p <0.05) ratios. In conclusion, EGFR blockade had no effect on systemic immune activation, evaluated with urinary neopterin. A significant correlation has been observed between urinary neopterin and parameters of intestinal permeability and absorption.