bluuebunny/crossref_metadata_2025 huggingface dataset:
Periodate oxidation and macromolecular compaction of hyaluronan
Authors: Kristiansen Kåre A. , Dalheim Marianne Ø. , Christensen Bjørn E.
Published: August 2013

Partial periodate oxidation of hyaluronan (HA) leads to ring opening of the 4-linked D-glucuronate (GlcA) residues, providing a particularly flexible element within otherwise semi-flexible chains. This leads to compaction of the chains as demonstrated by a pronounced decrease in the intrinsic persistence length, which was determined on the basis of the molecular weight dependence of radius of gyration (R
G) and the intrinsic viscosity. These parameters were readily obtained using size-exclusion chromatography (SEC) with an online multi-angle laser light scattering (MALLS) detector, a viscosity detector, and a concentration-sensitive detector. The electrostatic contribution to the total persistence length increased with increasing degree of oxidation. Compared to alginates and chitosans, HA becomes less degraded during the oxidation, which is attributed to a protective effect of periodate-resistant N-acetyl-D-glucosamine (GlcNAc) residues adjacent to periodate-sensitive GlcA residues in HA.
Properties of molding plates made with various matrices impregnated with PF and liquefied wood-based PF resins
Authors: Lee Yun-Yun , Lee Wen-Jau , Hsu Ling-Ying , Hsieh Han-Min
Published: August 2013

Phenol (P) and phenol-liquefied wood (LW; Cryptomeria japonica, Japanese cedar) have been reacted with formalin and ammonium hydroxide as a catalyst to prepare alcohol-soluble phenol-formaldehyde (PF) resins named PF and LWPF, respectively. The resins prepared were dehydrated, diluted with ethanol, and impregnated into wood powders, filter papers, and cloths. The PF resin-impregnated matrix materials were then hot-pressed to form molding plates (MP) and their properties were tested. Differential scanning calorimetric (DSC) analysis shows that both PF and LWPF behave as hot-melting resins and are able to further condensation reactions to form a set resin. However, the maximal temperatures of LWPF are shifted to a higher temperature range compared with PF. MPs made with LWPF-impregnated materials have poorer performance than that of PF. However, the bending strength of MP with filter paper is 96.8 MPa, which fits the request of CNS 10559. The MPs made of filter papers have the best mechanical properties followed by MPs with wood powders and cloths.
Selective purification of bleached spruce TMP process water by induced air flotation (IAF)
Authors: Zasadowski Dariusz , Strand Anders , Sundberg Anna , Edlund Håkan , Norgren Magnus
Published: August 2013

The environmentally benign closure of water systems in paper mills leads to the problem of accumulation of dissolved and colloidal wood substances (DCS) in process water. Notably, pitch affects the pulp and paper production negatively and increases the demand for additional treatment of the process water. In the present article, the purification of thermomechanical pulping process water from the alkaline peroxide bleaching stage has been investigated, with the induced air flotation (IAF) in focus. The following parameters were considered concerning the IAF efficiency to remove detrimental substances: concentration of cationic foaming agent, pH value, calcium concentration, and temperature. The amounts and characteristics of residual DCS were determined by gas chromatography and turbidity measurements. Residual concentrations of the foaming agent dodecyltrimetylammonium chloride were determined by electrospray ionization mass spectrometry. Up to 90% of pitch was removed, whereas hemicelluloses, which are important in preventing pitch problems, remained in the waters. Up to 70% of the pectic acids accounted for the high cationic demand of the process waters were removed by optimization of the IAF parameters. The presented separation process gives new opportunities to a selective purification of the process waters.
Synthesis of alcohol-soluble phenol-formaldehyde resins from pyrolysis oil of Cunninghamia lanceolata wood and properties of molding plates made of resin-impregnated materials
Authors: Lee Wen-Jau , Tseng I-Min , Kao Yu-Pin , Lee Yun-Yun , Hu Ming-Shan
Published: August 2013

Fast pyrolysis oil (Py-oil) from Cunninghamia lanceolata wood was the starting material in preparing alcohol-soluble phenol-formaldehyde (PF) resins. For this purpose, phenol (Ph) and Py-oils were mixed in weight ratios of 50/50, 40/60, and 30/70. The molecular weight distribution, thermal setting behavior, and heat resistance of the set resins were investigated. Albizia falcataria wood powder and cotton paper were impregnated with the resin mixture, and molding plates were produced by hot pressing; their physical, mechanical, and thermal properties were evaluated. The results show that Py-oil blended with Ph is a suitable raw material for preparing alcohol-soluble PF resins, which possess the characteristics of thermal melting and setting. The properties of the molding plates were satisfactory. The static bending strength (>100 MPa) and elastic modulus of the cotton paper-based products fulfill the requirements of CNS 10559 standard. The initial temperature of the thermal degradation of molding plates is >345°C. The performance of the molding plates decreased with increasing ratios of Py-oil.
Neopterin and other indicators of HIV progression in Zambian adults
Authors: Hosp M , Quigley M , Mwinga Am , Godfrey-Faussett P , Porter Jdh , McAdam Kpw , Fuchs Oj
Published: August 2013

In this study, we assessed a possible correlation of CD4 counts with the low-cost progression markers neopterin, 132-microglobulin (B2M), total lymphocyte count (TLC) and hemoglobin, and we investigated associations between progression :narkers and clinical parameters in HIV -1 seropositive Zambians. Of 147 HIV- 1 seropositive patients presenting to an outpatient clinic in Lusaka, blood was taken for CD4 counts, serum progression markers and full blood count. A detailed clinical history and medical examination was taken at that point, and the patients were seen 3··monthly over the following 12 months. Further CD4 counts were taken after 6 and 12 months. Neopterin, B2M: lymphocyte count, and hemoglobin showed a strong correlation with CD4 count. Of the serum progression markers, neopterin was more sensitive than B2M to detect HIV related symptoms and to predict weight loss and death in the follow-up period. Lymphocyte count and hemoglobin were significantly lower in patients with oral candidiasis and those falling sick or dying in the follow-up period. Hemoglobin was also associated with past diarrhoea. When stratified by sex, the associations of hemoglobin were very strong in males, but weaker in females . In conclusion, neopterin and B2M correlate well with CD 4 counts in this African population. Neopterin appears to be more sensitive for the clinical evaluation o: the patients in this study. Hemoglobin might only be useful as a progression marker in male individuals .
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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.
Correlation between Neopterin, Biopterin and Nitrite/Nitrate in Cerebrospinal Fluid in Child Patients with Neurological Diseases
Authors: Kawakami Yasuhiko , Sakamoto Mayuko , Shimada Ken-ichi , Noguchi Eiji , Kuwabara Kentaro , Fukui-Kobayashi Tomoko , Shirota Kazuhiko , Ogawa Ko-ichi , Fujita Takehisa , Fujino Osamu , Kojima Shuji , Fukunaga Yoshitaka
Published: August 2013

Cerebrospinal fluid (CSF) neopterin been previously reported in various diseases. In this study CSF neopterin, biopterin, and nitrite/nitrate (NOx) Contents were measured and the correlation between them in child patients with various kinds of neurological diseases were investigated. Changes in the CSF neopterin levels in patients with bacterial meningitis were similar to those previously reported for those with bacterial meningitis; on the 2th hospital day they were significantly higher than on admission, and on the 6th hospital day they were tapered. The CSF biopterin levels and CSF NOx content in patients with bacterial meningitis on admission were significantly higher than those with other categories and were decreased gradually. Although patients with high levels of CSF neopterin tended to have high CSF biopterin levels in any categories, there was no significant correlation between CSF neopterin and biopterin levels. The CSF biopterin and NOx levels in patients with convulsions were higher than those with aseptic meningitis. Since the neuro-protective or anticonvulsant role for NO was previously reported, high CSF biopterin and NOx levels in patients having epilepsy or febrile convulsions may be regarded as one of the endogenous mechanisms for recovery from an overexcitatory brain in patients with convulsive diseases.
Follow-up of Urinary Neopterin Concentrations in two Healthy Children until Adolescence
Authors: Winkler Christiana , Frick Barbara , Schroecksnadel Katharina , Wirleitner Barbara , Fuchs Dietmar
Published: August 2013

Neopterin is a sensitive marker of the activated cellular (= Thl-type) immune response. Neopterin concentrations in healthy children are higher compared with those of adults and are declining with increasing age. In this study, we present a follow-up of urinary neopterin to creatinine concentrations in two healthy children until adolescence. Data were available from one female (7 - 23 years) and her brother (0 - 18 years), of whom early morning urine specimens were collected on an irregular basis throughout 18 years. In total, neopterin and creatinine concentrations were measured by high pressure liquid chromatography (HPLC) in 343 urinary specimens. In both children, concentrations of urinary neopterin were highest at study entry. With increasing age neopterin concentrations decreased continuously to reach rather constant levels around the age of fifteen years. On several occasions at which individuals presented with common sickness, mostly of infectious origin, neopterin concentrations were found highly increased. In the absence of such infectious episodes, neopterin/creatinine measurements of both individuals fit well to previously established normal ranges. However this was true only for specimens collcctcd when children were older than 10 years, before that age concentrations of neopterin were frequently found to be higher than the established upper limits of the normal range.
The Intracellular Distribution of Folate Derivatives in Pea Leaves
Authors: Chan Sherwin Y. , Cossins Edwin A.
Published: August 2013

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. Percoli gradient-purified mitochondria and chloroplasls contained 11,0±2.3% and 8.4±0.6% of cellular folate, respectively. Mitochondrial folates (0.47+0.11 nmol folate mg"' protein) were predominately (90%) formylatcd and unsubstituted. In contrast, chloroplasts contained a less concentrated (0.02±0.001 nmol folate mg"' 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 itssues.
Neopterin and Oxidation Products in the Blood of Patients with Various Forms of Dementia
Authors: Frick Barbara , Neurauter Gabriele , Diez-Ruiz Antonio , Schroecksnadel Katharina , Wirleitner Barbara , Leblhuber Friedrich , Fuchs Dietmar
Published: August 2013

Human monocyte-derived macrophages and dendritic cells produce increased amounts of neopterin derivatives upon stimulation with interferon-γ (IFN-γ). In parallel, such stimulated cells release a record of oxidizing specics as part of their cytocidal repertoire. Production of reactive oxygen species by stimulated immunocompetent cells may be the reason for the depletion of antioxidant vitamins and the development of oxidative stress during diseases with stimulated immune system. Noteworthy also neopterin derivatives are able to interfere with reactive oxygen, chlorine, and nitrogen species, and neopterin itself could contribute to oxidative stress. In vivo, neopterin concentrations thus allow not only to monitor cell-mediated immune response, they also allow to estimate the extent of oxidative stress which emerges during immune response. In certain diseases associations between higher neopterin levels and markers of oxidative stress have been reported. In neurodegenerative diseases, neopterin concentrations in scrum and cerebrospinal fluid also correlate with the cognitive decline in patients. In this studv we compared serum concentrations of neopterin with serum concentrations of peroxides and homocysteine in patients with various forms of dementia and in 5 healthy elderly controls. In patients of either form of dementia serum concentrations of peroxides and neopterin were increased compared to controls. There existed a positive correlation between age and concentrations of peroxides, neopterin and homocysteine. The data further supportile view that increased neopterin concentrations are associated with oxidative stress which could underlie c¡r increased demand of antioxidants in neurodegenerative disorders. It appears important that such changes can h> detected in the blood of patients with dementia, albeit its pathogenesis is considered to be confined to the brain The results further suggest that aging is associated with immune system activation which may lead to the increased production of peroxides.
Effects of Carnosine on the Toxicity of Doxorubicin in Rabbits and Mice
Authors: Zieba Remigiusz , Czarnecka Elzbieta , Wągrowska-Danilewicz Małgorzata , Dzielska-Olczak Malgorzata , Graczyk Julita
Published: August 2013

The aim of this study was to establish the effect of naturally occurring antioxidant - carnosine - on the doxorubicin induced cardiotoxicity in a rabbit model. For this purpose we evaluated the influence of doxorubicin administration alone and in a combined therapy with carnosine on the haemodynamic parameters and on the degree of cardiac muscle cells alterations in rabbits. The rabbits were divided into four groups. One group of rabbits was injccted with doxorubicin in a dose of 2 mg kg-1 weekly for 7 weeks to induce congestive heart failure. Another group of rabbits received the same doses of doxorubicin simultaneously with carnosine in a dose of 100 mg kg1 p.o. daily for 9 weeks. Administration of carnosine was started 1 week prior to the first dose of doxorubicin and was ended one week after the administration of the last dose of doxorubicin. The control groups of animals received 0.9% NaCl and carnosine alone. The following haemodynamic parameters were estimated: heart rate, mean arterial pressure, cardiac index, stroke index and total peripheral resistance. Registration of the haemodynamic parameters in rabbits was performed by Doppler method. Carnosine normalised the values of mean arterial pressure in rabbits receiving doxorubicin, and increased the values of cardiac index and stroke index. The influence of carnosine on total peripheral resistance was not statistically significant, but there was a decreasing tendency. The degree of cardiac muscle cell alterations was examined by light microscopy using Mean Total Score technique. The histopathological studies revealed smaller damage of cardiac muscle in rabbits which received doxorubicin and carnosine, in comparison to animals receiving doxorubicin alone. Carnosine seems to be car dioprotective during doxorubicin administration
Wine and Grape Juice Modulate Interferon-y-induced Neopterin Production and Tryptophan Degradation in Human PBMC
Authors: Neurauter Gabriele , Wirleitner Barbara , Schroecksnadel Katharina , Schennach Harald , Fuchs Dietmar
Published: August 2013

Population-based studies suggest moderate and regular consumption of alcoholic beverages and especially of red wine to reduce morbidity and mortality from coronary heart disease. These beverages may interfere with immune activation cascades crucial in the pathogenesis of coronary heart diseases. Neopterin concentrations in human body tluids were found to increase in the course of coronary heart disease indicating the activity of the atherogenetic process. In this study, human peripheral blood mononuclear cells (PBMC) stimulated with mitogens phytohaemagglutinin and concanavalin A were exposed to red and white wines, to ethanol and to grape juice as a non-alcoholic control in vitro. Neopterin production and tryptophan degradation were measured in supcrnalants. Both biochemical effects are induced by Th 1-type cytokine interferon-y and allow monitoring of immune actnation. In stimulated PBMC increased production of neopterin and degradation of tryptophan was observed Red and white wines, as well as grape juice inhibited these stimulation-induced effects, higher concentrations being more cffective. Ethanol had comparably small if any effect, Red and white wines as well as grape juice down regulate cytokine-mediated effects in PBMC. Most likely, antioxidant ingredients of wine and grape juice such as resveratrol are capable of interfering with immunologic pathways which appear to be of relevance, e g.. in the pathogenesis of cardiovascular disease.
Aldol-type and Claisen Condensation Reactions of 1,3,6- and 1,3,7-Trimethyllumazines
Authors: Muranishi Shuichi , Soyka Rainer , Pfleiderer Wolfgang
Published: August 2013

Various side-chain modifications of 6- and 7-substituted 1,3-dimethyl-lumazines are described. Wittig reactions with 1.3-dimelhyllumazin-6- (13) and 1,3-dimethyllumazin-7-yl-methyltriphenyIphosphonium bromide (10) Icad to styryl derivates (8, 9, 14) as well as a variety of structural analoges 15 - 27. Compound 10 could be converted by DBU in the stable 1,3-dimethyllumazin-7-yl-triphenylphosphoniumylide (11). 1,3.6-Trimethyl- (1) and 6-benzyl 1,3-dimethyllumazine (29) have been subject for Claisen-condensations with etbyl Oxalate to give 28 and 30 1,3-Dimethyllumazme-6-carbonylchloride (33) reacted well with the ethoxy-magnesium salt of ethyl malonatc. ethyl cyanoacctate, ethyl acetacetate and malononitrilc to form elongated side-chains (34 - 37).
Comparative Assessment of the Diagnostic Value of Neopterin and Acute Phase Proteins in Angiographically Assessed Stahle Coronary Artery Disease
Authors: Gülmen Bahar , Turgan Nevbahar , Kayikçioglu Meral , Özmen Dilek , Ersöz Biltan , Kültürsay Hakan
Published: August 2013

Assessment of markers of systemic inflammation, such as acute-phase reactants C-reactive protein (CRP), fibrinogen and ceruloplasmin, sialic acid, a major component of these proteins and neopterin, a specific marker of cellular immune activation, in clinically stable coronary artery disease, may contribute to Staging and risk stratification. These markers were measured in 225 consecutive stable coronary artery disease patients before undergoing coronary angiography. According to their angiographic scores 32 patients were designated as having minor, 34 moderate and 96 severe coronary artery disease. 63 patients with negative angiograms were taken as the angiographic controls. High sensitive-CRP (hs-CRP) and fibrinogen were found to be higher in patients with angiographically established coronary artery disease, than in angiographic controls (p<0.05) and correlated with the severity and extent of disease. Ceruloplasmin and sialic acid concentrations did not differ between patients with and without angiographically cstablished coronary artery disease. Serum neopterin levels were sigificantly higher in patients undergoing coronary angiography than in healthy controls. Neopterin levels were similar between the different subgroups of coronary artery disease, suggesting that neopterin determinations do not contribute to the assessment of the presence and severity of disease in clinically stable patients. In stable angina, serum hs-CRP and plasma fibrinogen levels proved to be more effective than ceruloplasmin, sialic acid and neopterin in discriminating between patients with positive and negative angiograms and various degrees of coronary artery disease, thus in pointing out to increased risk. Our results, do not support the inclusion of neopterin in risk assessment of stable coronary artery disease.
Neopterin: a Mediator of the Cellular Immune System
Authors: Hoffmann Georg , Schobersberger Wolfgang
Published: August 2013

In this review, we will summarize our investigations on the potential biochemical, physiological, and pathophysiological effects of neopterin in the course of infection and inflammation. In a number of in v/'iro-studies wc could show that the pteridine compound neopterin manifested distinct biochemical properties via interfering with cellular redox mechanisms. Among the observed actions of neopterin are the stimulation of inducible nitric oxide synthase gene expression and nitric oxide release, the activation of the transcription factor nuclear factor-κΒ, the induction of apoptotic ccll death, the inhibition of erythropoietin synthesis and release, and the stimulation of tumor necrosis factor-α generation in different cell culture as well as organic models. By these means, neopterin may represent a part of the host-defence reactions. In addition, an excessive or continous release of neopterin due to a chronically activated cellular immune system may contribute to the deleterious events commonly observed in progressive infectious or inflammatory diseases. Our data are supported by the findings of a strong correlation between raised levels of neopterin and the severity and the outcome of these disorders.
Synthesis of 7-Acyl-2,4-disubstituted Pteridines by Radical Nucleophilic Substitution and Displacement Reactions
Authors: Döring Thomas , Boruah Romesh C. , Pfleiderer Wolfgang
Published: August 2013

2,4-Disubstituted pteridine derivatives (1-3) react with acyl radicals very selectively in position 7 by a nucleophilic Substitution mechanism (4-10). Oxidation of the 2-methylthio group proceeds with m-chloroperbenzoic acid in good yields to the corresponding 7-acyl-2-methylsulfonyl-4-aminopteridines (11-16). The methylsulfonyl group can easily been displaced by nucleophiles such as aliphatic amines (27, 29, 32-42, 45), cyclic amines (56-
61), aromatic amines (30, 31) and amino acids (43-54). Oxygen nucleophiles lead to 7-acyl-isopterin derivatives (62-66). The acyl side-chain is also prone to structural modifications leading to the corresponding secondary alcohols on NaBH4 reduction (74-77) or to imino derivatives on reactions with amines (67-73) which can analogously been reduced to 2,4-disubstituted 7-( l-aminoalkyl)pteridines (80-85). An interesting H-shift was observed during heating of 32, 78 and 79 with benzylamine leading not to the benzylimines but the isomeric benzylideneamino derivatives 86-88. Various acetylations by acetic anhydride (AC2O) gave 89-93 and reduction of the pyrazine moiety to the 5,6,7,8-tetrahydro-pteridine derivatives 94-96 proceeded in the expected manner. The characterization of ther newly synthesized pteridine derivatives was performed by 1H-NMR spectra, UV-spectra and elemental analyses. Measurements of the basic pKa values of a selection of 2,4,7-trisubstituted pteridines were pteridines to characterize the dication, monocation and the neutral species by their UV-spectra.