bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neopterin, soluble receptors for interleukin-2 and tumor necrosis factor in viral cirrhosis and alcoholic cirrhosis
Authors: Gonzalez-Calvin Jorge , Tilz Gernot P. , Gallego-Rojo Francisco , Torres-Almendros Marina , Widner Bernhard , Diez-Ruiz Antonio , Rico-Irles José , Fuchs Dietmar 
Published: August 2013

Abstract
Alcoholic cirrhosis and viral cirrhosis are associated with alterations of immune system function and cytokine production. Our aim was to investigate whether serum concentrations of soluble receptors for interleukin-2 (sIL- 2 R) and tumor necrosis factor (55kD-type, sTNFR-55), and serum neopterin can be used as markers to establish differences in etiology and severity in liver cirrhosis and to determine whether they correlate with laboratory and clinical parameters. Thirty three patients with alcoholic and 15 with viral cirrhosis (classified according to the Child-Pugh score of severity of liver disease) and 43 healthy controls were studied. Serum concentrations of sIL2-R, sTNFR-55 and neopterin were significantly raised in patients. No significant differences between alcoholic and viral cirrhosis were found. The concentrations of sIL-2 Rand sTNFR-55 were significantly higher in patients with more severe disease. There existed correlations b<!tween sIL-2R and sTNFR-55 (rs = 0.50, P < 0.001) and between both soluble receptors and the Child-Pugh score (sTNF-R55: rs = 0.70, p < 0.001; sIL-2R: rs = 0.33, p < 0.05) and serum albumin. The results are likely to reflect that the monocyte-macrophage and T-cell functions are stimulated in patients with liver cirrhosis independently of the etiology of the disease, and the persistent activation of the immune system occurs in cirrhosis even at the end stage of the disease. Chronic immune activation might have deletereous consequences on the evolution of cirrhosis.
Peripheral Immune Activation in Alzheimer's Disease
Authors: Leblhuber Friedrich , Walli Johannes , Tilz Gernot P. , Demel Ulrike , Widner Bernhard , Fuchs Dietmar 
Published: August 2013

Abstract
In fifty-four patients with Alzheimer's disease [AD (14 males, 40 females, age 77.1 2: 7.4 years)], free of any infection and twenty-two age-matched healthy controls with normal mental status (9 males, 13 females, age 74.9 ± 9.0 years) serum concentrations of soluble parameters of immune activation including neopterin, 55 kDa-type soluble tumor necrosis factor receptor (sTNF-RSS), soluble interleukin-2 receptor (sIL-2R), immunoglobulins A, M and G, complement components C3 and C4, circulating immune complexes, and soluble CD23 as well as a panel of routine laboratory tests were determined. Compared to controls, significantly higher concentrations of sIL-2R (p < 0.01), neopterin (p < 0.01), sTNF-R55. sCD23 and IgA (all p < O.OS) were found in AD patients. Patients with greater cognitive impairment had higher concentrations of neopterin and sTNF-R55. An inverse correlation was seen between mini mental state (MMS) and sTNF-R55 (r = -0.43S; P < 0.01) and neopterin (rs = -0.289; P < 0.05). Our data show increased serum concentrations of immune activation markers in patients with AD correlating with the severity of dementia. Increased neopterin concentrations together with increased slNF-R55 and sIL-2R imply a chronic state of peripheral immune activation in the course of AD. Our data underscore previous reports on the effect of anti-inflammatory drugs in therapy and prevention of AD.
Dihydroneopterin and the generation of superoxide from iron ions
Authors: Oettl Karl , Greilberger Joachim , Reibnegger Gilbert 
Published: August 2013

Abstract
We describe the impact of dihydroneopterin on the formation of superoxide radicals. As radical source ferrous iron in air-saturated aequeous solution was used. Detection of superoxide was achieved using reduction of nitroblue tetrazolium to formazan. Dihydroneopterin decreases formazan formation when high concentrations of ferrous iron are used which induce a rapid superoxide formation within minutes. On the other hand, when low concentrations of ferrous iron are used, addition of dihydroneopterin to the assay mixture leads to an increase ir. formazan formation for several hours of incubation. We therefore conclude that the radical promoting activity of dihydroneopterin is physiologically more relevant compared to its radical scavenging properties.
Variations in Folate Metabolism in Whole Body γ-Irradiated Mice
Authors: Kesavan V. , Pote M.S. , Anand R. , Viswanathan G. 
Published: August 2013

Abstract
Folate metabolism has been studied in 7 Gy whole body y-irradiated mice. Considerable changes in the formyl and methyl tetrahydrofolate derivatives were observed in the liver at various stages after irradiation. Methyltetrahydrofolate polyglutamate cofactors were reduced to a considerable extent in the irradiated group. Significant levels of oxidized folates such as pteroyl mono-, di-, and tetra- glutamyl forms were found only in the irradiated liver indicative of oxidative changes. Methylenetetrahydrofolate reductase, the enzyme synthesizing methyltetrahydrofolates was impaired 35-40% in irradiated animals possibly leading to an impairment in methyltetrahydrofolate synthesis. Folylpolyglutamate hydrolase which hydrolyzes polyglutamylfolates to simpler forms, showed an immediate spurt in the activity but returned to normal values, 48-72 h after irradiation. An increased lysosomal membrane damage as assessed by higher free-amino acid pool was observed in irradiated mice.
Protective Effect of Tetrahydrobiopterin Against Reactive Oxygen Species- and Nitric Oxide-induced Vascular Endothelial Cell Injury
Authors: Shimizu Shunichi 
Published: August 2013

Abstract
Vascular endothelial cells are one of the major biological targets of reactive oxygen species (ROS) in ischemiareperfusion, diabetes, hypercholesterolemia and inflammation. Accumulated evidence has shown that tetrahydrobiopterin (BH4), which is an essential cefactor for nitric oxide synthase (NOS) activity, protected the cells against ROS and nitric oxide (NO) toxicities. Although NOS releases NO, which regulates vascular tone and immune surveillance under normal conditions, NOS also produces superoxide anion and hydrogen peroxide when BH4 is decreased, suggesting the possibility that NOS is a source of ROS under pathological conditions. Since BH4 is easily oxidized by ROS, oxidative stress may induce ROS release from NOS by the decomposition of BH4. BH4 also has an antioxidative activity and scavenging activity for ROS. In this review, the r o l e of BH4 in the function of' NOS, and the mechanisms underlying the protective effect of BH4 against ROS- and/or NO-induced endothelial cell injury will be discussed.
Comparing the sensitivity of pyridoxal-5-phosphate, homocysteine and neopterin in coronary heart disease
Authors: Rudzite Vera , Jurika Edite , Kalnins Uldis , Erglis Andrejs , Trusinskis Karlis , Jegere Sanda , Frick Barbara , Fuchs Dietmar 
Published: August 2013

Abstract
Blood serum pyridoxal-5-phosphate, homocysteine and neopterin concentrations have been examined in 30 healthy individuals and 87 patients with coronary heart disease, verified by coronary angiography. Patients have been observed before percutaneus transluminal coronary angioplasty (31 patients with one-artery disease, 30 with two- or three-artery disease, 26 with restenosis). Results suggest that lowered serum pyridoxal-5-phosphate concentrations were an earlier indicator of coronary heart disease than increase of serum homocysteine concentration above 15 μmοΙ/L. An increase of serum neopterin concentration appears to be a marker of coronary disease activity rather than a marker of the presence of coronary heart disease.
Synthesis and Properties of Condensed Lumazine-Ringsystems
Authors: Abou-Hadeed Khaled , Pfleiderer Wolfgang 
Published: August 2013

Abstract
1,3-Dimethyllumazine-6,7-diamine (1) and its monomethyl -(3,4) and monophenylamino (5) derivates are interesting starting materials for the synthesis of imidazo[4,5-g] (6-22) and pyrazino[2,3-g]lumazines (23-26). Ringclosure proceeds under relative drastic conditions and the resulting reaction products are highly fluorescent. Methylation of 5,7-dimethyll-imidazo[4,5-g)lumazine (6) led to an isomeric mixture of the 1- (17) and 3-methyl derivatives (7) which could be separated chromatographically. Their structural assignment was based on unambiguous syntheses heating 4 and 3, respectively, with formamide under reflux for ringclosure. The newly synthesized compounds have been characterized by 1H-NMR and UV-spectra as well as elemental analyses.
Theory of Measuring the Selfsame Single Fluorescent Molecule in Solution Suited for Studying Individual Molecular Interactions by SPSM-FCS
Authors: Földes-Papp Zeno 
Published: August 2013

Abstract
Three exact criteria are first derived for the probabilities that determine single molecule sensitivity in single-phases, for example in solutions or membranes. It is shown how the criteria can be used to decide whether single molecule sensitivity is obtained. Most straightforwardly, all we require is that we experimentally determine the Poisson probability for the absolute number of fluorescent molecules in the volume of observation. This is achieved by fluorescence correlation spectroscopy and allows identifying the selfsame, one single fluorescent molecule in single-phases. Further, we first provide the new and powerful analytical capability to fluorescencetagged inidividual molecules and reactions in in-vitro and living systems to follow their molecular interactions and function by means of spatial stochastic behavior. This fully stochastic modeling is derived which describes the influence of spatial separation on the reaction coordinate of one single individual molecule in single-phases within the observation volume. The theoretical concept is applied to experimental data 'at the single-molecule level' of photosensitive riboflavin and riboflavin-containing blue fluorescence protein. The data were taken from the literature. As simulation results of the elucidative examples, experiments are suggested that would measure individual, single molecules of flavins and flavoproteins m solution. They are of importance for experimentalists.
Stimulation of Tetrahydrobiopterin Synthesis by Cyclosporin A during Lipopolysaccharide Treatment in Vascular Endothelial Cells
Authors: Ishii Masakazu , Shimizu Shunichi , Shiota Kazuhiro , Yamamoto Shinichiro , Kiuchi Yuji , Yamamoto Toshinori 
Published: August 2013

Abstract
We examined the effect of immunosuppressant cyclosporin A (CsA) on the synthesis of tetrahydrobiopterin (BH4), which is a cofactor for nitric oxide synthase (NOS), during treatment with lipopolysaccharide (LPS) in mouse brain microvascular endothelial cells. Addition of LPS to the endothelial cells increased the BH4 content and the mRNA level of GTP-cyclohydrolase I (GTPCH), the rate-limiting enzyme of BH4 synthesis, and the LPSínduced increases in both the BH4 content and expression of GTPCH mRNA were further stimulated by the cotreatment with CsA. 2,4-Diamino-6-hydroxypyrimidine, an inhibitor of GTPCH, blocked the increase in BH4 content induced by CsA during the LPS treatment. Moreover. CsA stimulated the expression of inducible NOS (iNOS) mRNA during the LPS treatment. These findings suggest that CsA stimulates LPS-induced BH4 synthesis through the induction of GTPCH, and iNOS expression. CsA may increase NO production during LPS treatment in brain microvascular endothelial cells.
Influence of 7,8 Dihydroneopterin and Hyperoxia on Neurite Growth and Tyrosine Hydroxylase Activity of PC 12 Cells
Authors: Vrecko Karoline , Reibnegger Gilbert 
Published: August 2013

Abstract
The influence of dihydroneopterin on tyrosine hydroxylase activity in PC 12 cells was investigated under normoxic and hyperoxic conditions, and with or without iron ions in the incubation medium. Low dihydroneopterin concentrations as well as hyperoxia increase tyrosine hydroxylase activity. Due to a too vigorous radical formation, high dihydroneopterin concentrations lead to a decrease of tyrosine hydroxylation in normoxic state and even more strongly in hyperoxic state. Similar depression of tyrosine hydroxylase activity was seen after addition of iron ions, which can form hydroxyl radicals by a Fenton type reaction. As higher iron concentrations in combination with dihydroneopterin do not suppress tyrosine hydroxylase activity completely, we conclude that dihydroneopterin and iron ions react with each other resulting in neutralisation of their effects. In conclusion, 7,8 dihydroneopterin can modulate tyrosine hydroxylase activity and its effects are dependent on concentration of oxygen as well as presence or absence of iron ions.
Folate Supplementation in Rats: Does it Cause Behavioural and Electrophysiological Changes?
Authors: Baydar Terken , Papp Andras , Nagymajtényr Laszlo , Schulz Horst , Sahin Gonul 
Published: August 2013

Abstract
Folate supplementation is becoming increasingly popular not only to decrease homocystein, a long with the finding that moderate hyperhomocysteinaemia is a cardiovascular risk factor but also diminish some other risks related to folate depletion. The aim of the study was to investigate whether folic acid supplementation leads to behavioural and electrophysiological changes in rats. Therefore, 30 male Wistar rats were divided to three groups. Each of animal groups was consisted of 10 animals. Folic acid was applied to rats by gavage for 8 weeks. Group I as a control group was taking folic acid-free water by gavage throughout the duration of the experiment. Groups II and III were treated with 2.0 mg/kg/day and 20.0 mg/kg/day of folic acid, respectively. Behavioural effects were evaluated by open field motor activity and by acoustic startle response. Electrophysiological examination was done by recording spontaneous activity and sensory evoked potentials from the visual, somatosensory, as weil as auditory cortex. No significant effects on motor activity or acoustic startle response were observed. Both doses of folic acid shortened the latency of the visual cortical evoked potential (p<0.05) and caused a slightly but nonsignificant change in the relative refractory period of a peripheral nerve. There was no effect on the electrocorticograms or on the other evoked potentials. Among the investigated organs, significant differences were observed in relative weight of kidneys and adrenal glands among the folic acid treatment at both the doses and the control groups (p<0.05).
Neopterin, Dihydroneopterin, Tetrahydroneopterin: Different Structures-Increasing Capacity Cleaving the Porphyrin in Heme Proteins
Authors: Horejsi Renate , Möller Reinhard , Tafeit Erwin , Reibnegger Gilbert 
Published: August 2013

Abstract
Neopterin, 7,8-dihydroneopterin and 5,6,7,8-terahydroneopterm are secreted by human macrophages after activation by interferon-γ. The biological stability of the reduced pterins is less than one hour and therefore distinctly lower than that of neopterin. Ptendme derivatives are known to act as enhancers as well as scavengers of radical mediated processes. The effects of the three pteridines were investigated on hemoglobin and myoglobin, biomolecules that generate reactive oxygen species themselves. The amounts of liberated carbon monoxide and non heme iron stemming from the cleaved porphyrin were quantified. Iron and carbon monoxide were yielded at equimolar concentrations with a con-elation coefficients greater 0.9. Dihydroneopterin and tetrahydroneopterin were assumed to reduce the heme iron in intact heme molecules creating the conditions for adducting carbon monoxide and additionally the subsequent generation of hydroxide radicals via autooxidation. The effect of neopterin under these experimental concentrations was rather weak.
Moderate Hyperhomocysteinemia in Patients with Huntington's Disease
Authors: Laich Andreas , Leblhuber Friedrich , Widner Bernhard , Frick Barbara , Jellinger Kurt , Fuchs Dietmar 
Published: August 2013

Abstract
Hyperhomocysteinemia is considered to be an independent risk factor for cardiovascular diseases and atherosclerosis. Also patients with dementia, either of Alzheimer's or of vascular type, may present with elevated homocysteine levels. All these disorders are linked with older age and since hyperhomocysteinemia is also frequent in the healthy elderly, we were interested to determine homocysteine concentrations in a younger population of demented patients suffering from Huntington's disease. In 15 patients with Huntington's disease and in a control group of similar age, serum homocysteine concentrations were measured and changes were compared to concentrations of folate and neopterin, the latter being an indicator of immune activation. A subgroup of patients with Huntington's disease presented with elevated homocysteine concentrations compared to healthy controls of similar age. Moderate hyperhomocysteinemia was related to lower folate concentrations and also to higher neopterin levels which indicate increased immune activation. The correlation of homocysteine with neopterin concentrations points to a possible relationship between the development of hyperhomocysteinemia and immune activation in the patient
Plasma Levels of Neopterin and Biopterin in the Umbilical Vessels and the Maternal Vein
Authors: Iwanaga Naoko , Yamamasu Seiichi , Tachibana Daisuke , Nishio Junko , Nakai Yuichiro , Shintaku Haruo , Imanaka Motoharu , Yamano Tsunekazu , Ishiko Osamu 
Published: August 2013

Abstract
Tetrahydrobiopterin (BH4) is a highly bioactive pterin required for nitric oxide synthase and monooxygenases of aromatic amino acids, and is involved in the synthesis of nitric oxide, catecholamines and Serotonin. Although these functions imply that pterin metabolism plays critical roles in human development, the intrauterine metabolism is unclear. To elucidate the pterin metabolism in the human feto-placental unit, blood was obtained from the umbilical artery and vein, and the maternal vein, and plasma biopterin and neopterin concentrations were analyzed by the high-performance liquid chromatography method. To clarify the effect of labor, data was also compared between the transvaginal delivery (TV) and the caesarean delivery (CS). The levels of biopterin and the neopterin, and neopterin/biopterin ratio were higher in the fetal plasma than in the maternal plasma. Biopterin levels in the umbilical artery were higher than those in the umbilical vein. There were significant correlations in either biopterin or neopterin between the fetal plasma and the maternal plasma. There was no significant difference in the fetal pterin levels between TV and CS. The results suggest the stimulated BH4 synthesis in the fetoplacental unit, the independent homeostasis of the fetal pterin metabolism, and the possibility of dynamic movements of pterins among the fetus, the placenta and the mother.
Molecular Mechanisms of Endothelial Dysfunction in the Insulin-Resistant State: the Roles of Abnormal Pteridine Metabolism
Authors: Shinozaki Kazuya , Kashiwagi Atsunori , Masada Masahiro , Okamura Tomio 
Published: August 2013

Abstract
Although abnormalities in endothelial function are described in various insulin-resistant conditions, including obesity, diabetes, and hypertension in both humans and animal models, the underlying mechanisms are poorly understood. Experimental evidence suggests that (6R)-5,6,7,8-tetrahydrobiopterin (BH4), the natural and essential cofactor of NO synthases (NOS), plays a crucial role not only in increasing the rate of NO generation by NOS bat also in Controlling the formation of superoxide anion (O2 ) in endothelial cells. Under insulin-resistant conditions where BH4 levels are suboptimal, the production of O2 by NO synthase leads to endothelial dysfunction. Furthermore, oral supplementation of BH4 (10 mg/kg/day) for 8 weeks restores endothelial function and relieved oxidative tissue damage, at least in part, through activation of eNOS in the aorta of insulin-resistant rats. These results suggest that abnormal pteridine metabolism contributes to causing endothelial dysfunction and the enhancement of vascular oxidative stress in the insulin-resistant State.
The Intracellular Distribution of Folate Derivatives in Pea Leaves
Authors: Chan Sherwin Y. , Cossins Edwin A. 
Published: August 2013

Abstract
After hydrolysis of polyglutamate derivatives, leaf extracts of pea (Pisum sativum L.) seedlings were examined for individual folates using high Performance liquid chromatography and microbiological assays employing Lactobacillus rhamnosus and Pediococcus acidilactici. 14-day seedlings contained 0.17±0.01 nmol folate mg-1 protein that was predominantly methylated and associated with the cytosolic fraction. Percoll gradient-purified mitochondria and chloroplasts contained 11.0±2.3% and 8.4±0.6% of cellular folate, respectively. Mitochondrial folates (0.47±0.11 nmol folate mg-1 protein) were predominately (90%) formylated and unsubstituted. In contrast, chloroplasts contained a less concentrated (0.02±0.001 nmol folate mg-1 protein) folate pool consisting of approximately 30% methylated folate. The total folate content of pea leaves increased by 40% when dark-grown (etiolated) 9-day seedlings were exposed to light for 48 hours. During this light treatment, the mitochondrial folate pool, on a per mg protein basis, increased 10-fold. This light treatment also changed the composition of the mitochondrial folate pool with a shift occurring from methylated to formylated and unsubstituted derivatives. These changes in the folates of greening tissues are discussed in relation to the metabolism of glycine and serine that accompanies photorespiration in leaf tissues.
Assessment of Folate Status: Measurement of Homocysteine versus Vitamin B12 and Folate
Authors: Houcher Bakhouche , Candito Mirande , Gibelin Pierre , Caramella Anne , Poitier De Courcy Genevieve , Naimi Dalila , Lefebvre Jean-Claude , Van Obberghen Emmanuel 
Published: August 2013

Abstract
This study was based on 63 subjects (mean age 50 ± 9) including 41 patients with clinical and objective investigational evidence of vascular disease (age 30-66 years) and 22 control subjects (age 26-54 years). Dietary intake of folate was estimated from a food questionnaire of folate (Q.folate). There was no statistically significant difference between controls and patients for dietary folate. Also the plasma folate level did did noly slightly differ between the controls and patients (6.68 ± 2.52 ng/mL versus 5.62 +4.16 ng/mL, not significant). Patients had higher average homocysteine concentrations than control subjects (12.93 ± 8.79 vs 9.07 ± 3.08 μmol/l, p<0.05). A significant relationship was observed in controls between plasma folate concentrations and the homocysteine levels (rs = - 0.538; p<0.01), and the folate questionnaire (rs = 0.697; p<0.001). We found in controls significant positive correlation between vitamin B12 and vitamin B6 (rs = 0.475, p<0.05). By contrast, no association v/as found in patients between folate and homocysteine concentrations and the dietary nutrient intake of folate. On the other hand vitamin B12 is inversely associated with homocysteine (rs = -0.333, p<0.05). These data provide further evidence that plasma homocysteine is an independent risk factor for myocardial infraction. Homocysteine is a valuable functional index of micronutrient status and intakes for people, which can assist the development of the public health. In our population, folate was the most important determinant of plasma homocysteine, even in subjects with apparently adequate nutritional status of this vitamin.