bluuebunny/crossref_metadata_2025_split huggingface dataset:
Difference of DNA Compaction Performed by Two kinds of Oncopterin-Mimic Pteridine - Polyamine Conjugates
Authors: Murata Shizuaki , Chen Ning 
Published: August 2013

Abstract
Two types of pteridine - polyamine conjugates designed on oncopterin perform different actions to DNA. The most obvious difference is their actions in DNA compaction. One of the pteridine - polyamine conjugates, PT- 2R, containing a polyamine substituent (R) on the C(2) position of pterin (PT) compacts a DNA molcculc in an all-or-none fashion without the intervention of an intermediate. The othcr (PT-4R: R exists on the c(4) position of PT) carries out the DNA compaction via partially compacted intermediates. The difference is discussed based on various interaction modes of the pteridine - polyamine conjugates to DNA.
Serial Analysis of Tryptophan Degradation and Neopterin Formation in an otherwise Healthy Individual before and during an Infectious Episode
Authors: Huber Leonhard , Winkler Christiana , Schroecksnadel Katharina , Geser Willi , Schubert Christian , Fuchs Dietmar 
Published: August 2013

Abstract
Thl-type cytokine interferon-y induces neopterin production in human monocyte-derived macrophages and it stimulates enzyme indoleamine (2,3)-dioxygenase (IDO) which converts tryptophan to kynurenine in various cells. In an integrative single-case study, a healthy, 27-year-old female had collected her entire urine in 12-hour (= I lag) intervals on 56 consecutive days. Neopterin, tryptophan, kynurenine and Creatinine concentrations were determined using HPLC. The kynurenine to tryptophan ratio (kyn/trp) was calcuiated as an index for IDO activity. Within the Observation period, the woman experienced an infection episode presenting with vomiting and headache, however, not serologically verified. During this period, strong increases in both urinary kyn/trp and neopterin to Creatinine concentrations were observed, and thcrc was a significant correlation between neopterin/creatinine and kyn/trp at the same day (rs =0.334, p <0.001). However, adjusted cross-correlational analysis revealed that accelerated tryptophan degradation preceded increases in neopterin by 24 to 36 hours (24h: r =0.185, 36h: r =0.408; both p <0.05). Our Observation confirms the dose relationship between neopterin production and tryptophan degradation under real-life conditions.
Beneficial Role of Tetrahydrobiopterin on Various Cardiovascular Diseases and Regulation of its Levels under Pathological Conditions
Authors: Shimizu Shunichi , Ishii Masakazu , Wajima Teruaki , Hagiwara Tamio , Negoro Takaharu 
Published: August 2013

Abstract
5,6,7,8-Tetrahydrobiopterin (BH4) is an csscntial cofactor for production of nitric oxide (NO) by N O synthase (NOS). Nitric oxide (NO) is an important signaling mo!ecu!e for the regulation o f vita! functions such as vascular tone, neurotransmission and immune surveiüance. Accumu!ated evidences show that although NOS mainly re!eases N O under nonnal conditions, NOS also produces Superoxide anion and hydrogen peroxide when BH4 is decreased, suggesting the possibility that NOS is a source of reactive oxygen species (ROS) under pathological conditions. In fact, supplementation of BH4 restores N O production and availability in various diseases including hyperlipidemia, diabetes, hypertension and ischemia-reperfusion. Moreover, recent studies show that administration o f BH4 protects tissues against ischemia-reperfusion injuiy in heart, stomach and liver. Oxidative stress is a common mechanism underlying the development of vascular diseases and reperfusion injury. Regulation of BH4 levels under oxidative stress is important to understand the role of BH4 on the development of vascular diseases and reperfusion injury. We recently described that oxidative stress transiently decreased BH4 levels, and then markedly increased its levels in vascular endothelial cells. Supplementation of BH4 appears to be important therapeutic strategies in vascular diseases and reperfusion injury, and induction of BH4 synthesis may endogenous defense system against oxidative stress-mediated cardiovascular diseases.
Statin Increases GTP Cyclohydrolase I mRNA and 5,6,7,8-Tetrahydrobiopterin in Vascular Endothelial Cells
Authors: Hattori Yoshiyuki , Nakanishi Nobuo 
Published: August 2013

Abstract
We investigated the effects of HMG-CoA reductase inhibitors, so-called statins, on 5,6,7,8-tctrahydrobioptcrin (BH4) metabolism in human umbilical vein endothelial cells (HUVEC). The mRNA of GTP cyclohydrolase I (GTPCH), as well as cNOS, was upregulated in HUVEC treated with cerivastatin. This increase was time- and dose-dependent. Fluvastatin was also observed to enhance GTPCH and eNOS mRNA levels. In parallel with this observation, cerivastatin increased intracellular BH4. Cerivastatin increased the stability of eNOS mRNA. However, it did not alter the stability of GTPCH mRNA but increased GTPCH gene transcription as shown by nuclear run-on assays. Preteatment of HUVEC with the selective GTPCH inhibitor, 2,4-diamino-6-hydroxypyrimidine, caused a decrease in intracellular BH4 and decreased citrulline formation following stimulation with ionomycin. Furthermore, the potentiating effect of cerivasatin was decreased by limiting the cellular availability of BH4. In addition to augmenting eNOS expression, statins potentiate GTPCH gene expression and BH4 synthesis, thereby increasing NO production and preventing relative shortages of BH4
Vitamin Β12 and Folic Acid Effects on Polyamine Metabolism in Rat Liver
Authors: Bjelakovic Gordana , Pavlovic Dusica , Jevtovic Tatjana , Stojanovic Ivana , Sokolovic Dušan , Bjelakovic Goran B. , Nikolic Jelenka , Basic Jelena 
Published: August 2013

Abstract
Polyamines, spennine, spermidine and putrescinc, small aliphatic nitrous bases, are normal constituents of microbial, plant and animal cells, where they fulfill an array of physiological roles. Metabolism of polyamines is associated with growth and differentiation of mammalian cells, spermine related to RNA and spermidine to DNA metabolism. Methyl-cobalamin, the coenzyme of methionine synthetase, catalyses the recycling of homocysteine to methionine using 5-methyltctrahydrofolate. By acceleration of methionine biosynthesis these vitamins may influence spermidine and spermine synthesis.
Liver tissue is rich in polyamines and it is the place of vitamin B12 and folic acid deposition. Polyamine oxidase (PAO, EC 1.5.3) and diamino oxidase (DAO, EC 1.4.3.6) participate in the process of degradation and interconversion of spermine, spermidine and putrescinc. The idea of our work was to examine the effccts of cobalamin and folic acid on the polyamine metabolism. We have examined the amount of spermine, spermidine and putrescine in liver tissue. At the same time we have examined the activities of PAO and DAO, the catabolic enzymes of polyamine metabolism. Our result suggest that the supplementation of experimental animals with vitamin B12 alone or together with folic acid augmentais spermidine and spermine levels in rat liver, at the same time the amount of putrescine does not change. The application of vitamin cobalamin to experimental animals alone increases PAO; the supplementation of experimental animals with vitamin Β12 together with folic acid causes opposite effect - the decrease of PAO activity. DAO activity significantly decreases under the influence of cobalamin and also with cobalamin and folic acid in combination. Our experimental results indicate the importance of cobalamin and folic acid in polyamine metabolism.
Systemic Immune Activation, Anemia and Thrombocytosis in Breast Cancer Patients Treated by Doxorubicin and Paclitaxel
Authors: Melichar Bohuslav , Solichova Dagmar , Melicharova Karolina , Urminska Hana , Ryska Ales , Cermanova Melanie 
Published: August 2013

Abstract
Increased urinary concentrations of neopterin, an indicator of systemic immune activation, have been reported only in a minority of patients with breast cancer. We determined urinary neopterin by high-performance liquid chromatography in 78 patients with breast carcinoma, including 51 patients treated by systemic administration of doxorubicin and paclitaxel. Urinary neopterin before the therapy was not statistically different in patients compared to controls. Increased neopterin concentrations were more frequent in patients with advanced disease. A statistically significant increase in urinary neopterin, gradual decrease in hemoglobin and an increase in platelet counts were observed during doxorubicin/paclitaxel chemotherapy. The concentration of urinary neopterin before the second cycle of chemotherapy has shown significant negative correlation with the concentrations of hemoglobin later in the course of chemotherapy and a positive correlation with platelet counts. In conclusion, urinary neopterin is normal in most patients with breast cancer. Increased urinary neopterin concentrations during doxorubicin/ paclitaxel chemotherapy indicate the presence of systemic immune activation that seems to be associated with chemotherapy-induced anemia and thrombocytosis.
Muscle Trauma and Immune Activation after a Downhill Marathon (Tyrolean Speed Marathon)
Authors: Schobersberger Wolfgang , Sumann Guenther , Mittermayr Markus , Griesmacher Andrea , Falkensammer Gerda , Greie Sven , Schobersberger Beatrix , Hoffmann Georg , Fuchs Dietmar , Koller Arnold 
Published: August 2013

Abstract
Prolonged physical exercise is associated with multiple changes in the immune status indicating an acute phase response and an activation of the immune system. Eccentric muscle activation (e.g. downhill running) induces micro-trauma of skeletal muscles thus inducing an inflammatory response. At present there are no data to which extent the immune system is activated after a downhill marathon run and if there arc any correlations between immune activation and markers for muscle damage or functional impairment of leg muscles. As model for severe eccentric exercise we selected the Tyrolean Speed Marathon (42 km downhill run, 795 m vertical difference). 13 volunteers (12 male, 1 female; mean running time 224 min [range 193 - 266 min.]) finished the run. Blood from antecubital veins was collected 3-4 days before (T1 ), 3-4 hrs before (T2) and immediately after the marathon (T3) as well as on the morning after the run (T4). We measured serum neopterin concentrations, white blood cell count. C-reactive protein (CRP), creatine kinase (CK), myoglobin (Mb), cardiac troponin I (cTnl) and troponin Τ (cTnT). Moreover, isokinetic muscle tests were performed. Following significant changes were found (before vs. after the run): increase in neopterin, CRP, total leukocyte count, CK. Mb, cTnl, cTnT, whereas isokinetic dynamometry showed a reduction in peak hamstring torque of both thighs after the marathon. There were no significant correlations (Spearman's rank correlation coefficient) between the observed changes in neopterin and CRP, CK, Mb. cTnT, cTnl or between neopterin concentrations and parameters of isokinetic muscle tests. We could demonstrate that a 42 km downhill marathon is associated a) with an activation of the cellular immune system, as evidenced by the increase in serum-neopterin. b) pronounced micro-skeletal muscle damage with high serum creatine kinase and myoglobin, and c) eccentric hamstring fatigue. The absolute changes in neopterin were moderate and similar to other types of exercise (flat course and bicycle marathon, mountain hiking).
Long-term Supplementation with Β Vitamins does not Change Plasma Neopterin Concentrations in Demented Patients
Authors: Schroecksnadel Katharina , Gruber Birgit , Frick Barbara , Jenny Marcel , Ledochowski Maximilian , Leblhuber Friedrich , Fuchs Dietmar 
Published: August 2013

Abstract
Inflammation and immune system activation seem to play an important role in the development and progression of dementia. Also concentrations of immune activation marker neopterin are increased in serum and cerebrospinal fluid of some patients with dementia, and a significant relationship is found between concentrations of neopterin and homocysteine. Β vitamin supplementation is able to rapidly slow-down homocysteine formation in patients. However, no change of neopterin was found within one month of such therapy. In this study, scrum concentrations of neopterin and homocysteine were investigated in 58 patients with Alzheimer's disease (n=30), vascular dementia (n=12) and mild cognitive impairment (n=16) during 1 -3 months of supplementation with Β vitamins (Beneitran compositum®)with monthly increasing dose ( 1 - 6 tablets a day). No change of neopterin concentrations was observed In the patients groups throughout the whole study period (all ρ >0.05). As was reported earlier, a rapid decline of homocysteine concentrations was achieved already within the first month of supplementation (p <0.01 ), however, no further change of homocysteine was observed later on despite accelerated dose of vitamin supplements. Β vitamin supplementation did not influence neopterin concentrations, and also the longer period of supplementation had no effect. The question remains, if solely the lowering of homocysteine concentrations by folate supplementation could have any beneficial effect to modulate the course of dementia when the immunopathogenetic mechanisms are not influenced.
Preliminary Evidence on the Direction of Effects Between Day-to-Day Changes in Cellular Immune Activation, Fatigue and Mood in a Patient with Prior Breast Cancer: A Time-Series Analysis Approach
Authors: Schubert Christian , Neises Mechthild , Fritzsche Kurt , Geser Willi , Ocana-Peinado Francisco M. , Fuchs Dietmar , Hass Ralf , Schmid-Ott Gerhard , Burbaum Christina 
Published: August 2013

Abstract
This study on a patient with prior breast cancer investigated the cause-effect relations between immune system activation, fatigue and mood under real-life conditions. The 60-year old woman (primary diagnosis 5 years ago, relapse one year ago, currently no signs of recurrence) collected her entire urine for 31 days in 12 hour intervals for the determination of immune activation marker neopterin and creatinine concentrations by HPLC. This study used only the daytime urinary neopterin concentrations (from approx. 8 a.m. to 8 p.m.) and cross-correlated them with daily data from mood (3-Skalen-EWL) and fatigue (VAS) questionnaires which the patient filled in for 31 days. Serial dependencies were controlled for by applying moving average smoothing. When averaged over the whole observation period, daily fatigue, daily mood and daily urinary neopterin (average 173 μmol per mol creatinine) were within normal limits. Cross-correlational analyses revealed that increases in urinary neopterin significantly preceded increases in fatigue by 24 hours (lag 1: r = +0.424; p <0.05). The opposite direction of effects, however, existed between mood and neopterin, i.e., decreases in mood preceded increases in neopterin by 96 hours (lag 4: r = −0.697; p <0.05). The results in this patient suggest a disturbed stress system activity where negative emotions are associated with increases instead of decreases in the degree of cellular immune activation and where cellular immune activation may trigger central nervous system symptoms such as fatigue. Despite some restrictions in data quality this study shows the feasibility of gathering evidence on naturally occurring psychoimmunological cause-effect relations based on extensive serial data collection and time series analysis.
A Basic Molecular Analysis of the Diabetic Antigen GAD by Homology Modelling. Principles of the Method and Understanding of Antigenicity and Binding Sites
Authors: Wiltgen Marco , Tilz Gernot P. 
Published: August 2013

Abstract
Functional specificity of a protein is linked to its structure. A growing section of bioinformatics deals with the prediction and visualization of protein 3D structures. In homology modelling, a protein sequence with an unknown structure is aligned with sequences of known protein structures. By exploiting structural information from the known configurations, the new structure can be predicted. In this introductory paper, we will present the principles of homology modelling and demonstrate the method used, by determining the structure of the enzyme glutamic decarboxylase (GAD 65). This protein is an autoantigen involved in several human autoimmune diseases. We will illustrate the different steps in structure prediction of GAD 65 by use of two experimentally determined structures of pig kidney DOPA decarboxylase (one structure in complex with the inhibitor carbidopa) as templates. The resulting model of GAD 65 provides detailed information about the active site of the protein and selected epitopes. By analysis of the interactions between the DOPA decarboxylase with the inhibitor carbidopa, the residues of the GAD 65 active site can be identified via the sequence alignment between DOPA and GAD 65. The locations of known epitopes in the molecule are visualized in special representations giving insights into mechanisms of antigenicity. Hydrophobicity analysis gives first hints for the adherence ability of GAD 65 to the cell membrane. Homology modelling is at present one of the most efficient techniques to provide accurate structural models of proteins. It is expected that in few years, for every new determined protein sequence, at least one member with a known structure of the same protein family will be available, which will steadily increase the importance and applicability of homology modelling.
Effects of Methanolic Extract and Commercial Oil of Nigella sativa L. on Blood Glucose and Antioxidant Capacity in Alloxan-Induced Diabetic Rats
Authors: Houcher Zahira , Boudiaf Khaouther , Benboubetra Mustapha , Houcher Bakhouche 
Published: August 2013

Abstract
Nigella sativa is a medicinal plant widely used in the Arabic and Islamic world against a number of human pathologies. In this present study the methanol extraction (85 % then 50 %) of plant seeds gave an important yield of 27 % of dry substance. The anti-hyperglycaemia effect of the crude methanolic extract and the commercial oil of these seeds were tested in alloxan-induced, intra peritoneal, diabetic rats (150 mg/kg). Effects of these two substances on other diabetes-linked factors such as the reducing power of the plasma and the osmotic fragility of erythrocytes. The daily orally administration of the crude methanolic extract (810 mg/kg/day) and the oil (2.5 ml/kg/day) for 25 days leads to a significant decrease of glycaemia, especially during the first 10 days of treatment (decreases of 58.09 and 73.27 % respectively). However, the dose of 270 mg/kg of crude methanolic extract had no effect, which is probably due to the low dose. In addition the antioxidant capacity, measured by the ferric reducing ability of plasma (FRAP) technique, increased in all diabetic rats and the introduction of either the crude methanolic extract or the oil fraction showed any improvement on this factor. However, a slight resistance, not reaching significance, against the osmotic fragility of erythrocytes was induced in diabetic rats. The antihyperglycaemic effect of both substances is not related to inhibition of intestinal glucose absorption or stimulation of insulin secretion. We suggest that the action is a result of the inhibition of enzymes involved in the neoglucogenesis pathway in the liver. As shown the stress associated with the metabolic perturbation observed in diabetes induces a physiological anti-oxidant response, which probably masks the antioxidant effect of our two substances of this medicinal plant.
Influence of Extreme Long Endurance Sports Activity on Neopterin Excretion
Authors: Moser Berthold , Schroecksnadel Katharina , Hörtnagl Helmut , Rieder Josef , Fuchs Dietmar , Gottardis Marco 
Published: August 2013

Abstract
Immune system activation has been observed during endurance exercise, but its relevance is largely unclear. We evaluated urinary neopterin excretion in an athlete competing in the Race Across America (RAAM), to determine whether neopterin excretion would indicate that immune system activation occurs during extreme endurance sport. Urinary samples were collected at the day before the race, during the whole RAAM, and, without a physical strain, seven days after the race. Neopterin normalized to creatinine concentration was determined by reversed-phase high-pressure liquid chromatography (HPLC). Data were analysed by repeated-measured analysis of variance (ANOVA). In the athlete, urinary neopterin concentration started to increase consistently after the start of the race until day four, followed by a decline thereafter, reaching values close to the starting value. The lowest average neopterin concentration was observed at day seven; this concentration was significantly lower than mean values at days 2- 6 (all p <0.05). Comparing the power output (Watt) with the neopterin concentrations at the same time point revealed a significant correlation (rs = 0.333; p <0.05). A comparison of average daily urinary neopterin excretion mean values between the test and control person showed significant differences at all time points, except for the specimen obtained at day seven. This pilot study supports the hypothesis that extreme long endurance strain at low intensities leads to an activation of the immune system. Neopterin levels could be a convenient tool to assess the immune system activation induced by training in athletes.
Gastrointestinal Permeability - a Parameter of Possible Prognostic Importance in Metastatic Colorectal Carcinoma
Authors: Melichar Bohuslav , Hyspler Radomír , Kalabova Hana , Urbanek Lubor , Krcmova Lenka , Solichova Dagmar 
Published: August 2013

Abstract
Recently, we have observed in patients with ovarian carcinoma an association between intestinal permeability and prognosis and a correlation between urinary neopterin and parameters of intestinal permeability. In order to examine prognostic significance of intestinal permeability in a different group of patients, we have retrospectively analyzed pretreatment parameters of gastrointestinal permeability and urinary neopterin in 21 consecutive patients with metastatic colorectal carcinoma treated with the combination of cetuximab, irinotecan, leucovorin and 5-fluorouracil. Neopterin was determined by high-performance liquid chromatography, and gastrointestinal permeability was assessed by measuring, using capillary gas chromatography, urinary sucrose, lactulose, xylose, mannitol and sucralose after oral challenge. Pretreatment sucrose/mannitol ratio equal or above 0.04 (median survival 10.6 vs. 18.4 months; p = 0.03), sucrose/xylose equal or above 0.02 (12.1 vs. 19 months; p = 0.04) and urinary neopterin equal or above 220 μmol/mol creatinine (10.6 vs. 18.4 months; p = 0.02) were indicative of poor survival. A significant correlation was observed between urinary neopterin and sucrose/xylose ratio (rs = 0.57, p = 0.007), while correlation between urinary neopterin and sucrose/mannitol ratio (rs = 0.38, p = 0.096) was of borderline significance. In conclusion, present data demonstrate that gastrointestinal permeability is associated with systemic immune activation and may be of prognostic significance in patients with metastatic colorectal carcinoma.