bluuebunny/crossref_metadata_2025 huggingface dataset:
AMAS (Austrian Moderate Altitude Study)-2000: Effects of Hiking Holidays at Moderate Altitude on Immune System Markers in Persons with Metabolic Syndrome.
Authors: Schobersberger Wolfgang , Hoffmann Georg , Fries Dietmar , Gunga Hanns-Christian , Greie Sven , Fuchs Dietmar , Klingler Anton , Humpeler Egon
Published: August 2013

Recent studies have shown a strong association between indices of inflammation and metabolic Syndrome. Proinflammatory mediators like tumor necrosis factor-α may act as a trigger for insulin insensitivity. Therefore, patients with metabolic Syndrome might be at higher risk of insulin resistance when confronted with additional Stimuli of the immune system. These Stimuli are not restricted to the presence of pathogens but include environmental factors like physical exercise and hypoxemia as well. With respect to these interdependencies, one may assume higher risk for patients with metabolic Syndrome who perform physical exercise in alpine regions. We investigated the effects of a 3-weeks holiday with moderate sporting activities at moderate altitude (1700 m) on the conceiitrations of neopterin, tumor necrosis factor-α, serum soluble 75kD type TNF receptor (sTNF-R75), and interleukin-6 in vacationers with metabolic Syndrome. Only serum neopterin and sTNF-R75 concentrations transiently increased during the stay at moderate altitude compared to pre-altitude levels (P<0.05). Interestingly, after return to 500 m sea-level neopterin concentrations dropped beyond baseline concentrations (p<0.05). However, the variations in neopterin concentrations might not be of clinical relevance since they did not exceed the threshold indicating significant activation of the cellular immune system. We conclude that a 3-week sojourn at moderate altitude including individually adapted physical exercise does not represent accumulated risk factors in subjects with metabolic Syndrome.
Increase in Tetrahydrobiopterin Release from PC 12 Cells under Hypotonic Culture Conditions is Inhibited by HgCl2
Authors: Nakanishi Nobuo , Kurihara Kinji , Tomomura Akito , Tonosaki Keiichi , Hattori Yoshiyuki , Oguro Kazuya , Hasegawa Hiroyuki
Published: August 2013

Tetrahydrobiopterin (BH4) was released from PC 12 cells to the extracellular fluid. We found that the BH4 outward flow from the cells placed in Hanks medium was increased when NaCl concentration of the medium was decreased. Increase in the BH4 out flow was not observed when NaCl in the Hanks medium was substituted with sodium glutamate (0.14 M), choline chloride (0.14 M) or sucrosc (0.25 M). HgCl2, an inhibitor of water channel, aquaporin, prevented the increase in BH4 out flow caused by the hypotonic medium. The results suggested the presence of a site in BH4 transport which was stimulated by osmotic pressure and/or water influx.
Intestinal Uptake of 6(R)-L-erythro-Tetrahydrobiopterin is Distinct from the Liver-Type MTX-Sensitive Accumulation Process
Authors: Sawabe Keiko , Suetake Yasuko , Wakasugi Kazunori Osuke , Hasegawa Hiroyuki
Published: August 2013

In order to increase the tissue level of tetrahydrobiopterin (BH4 ) , supplementation with 6R-tetrahydrobiopterin (6RBH4) has been widely employed. In this work, the profile of BH4 accumulation was compared between the liver and the small intestine after feeding with 10mg/kg of 6RBH4 or 7,8-dihydrobiopterin (7,8BH2 ). Endogenous BH4 was 7.20 ± 0.28 and 1.59 ± 0.13 nmol/g in the liver and the intestine, respectively. BH4 levels rose to 12.5 ± 1.35 (1.7-fold) and 53.0 + 19.6 nmol/g (40-fold) in the liver and the intestine within 30 min, respectively. Administration of 7,8BH2 caused an even higher rise in BH4 (14.4 ± 2.79 nmol/g) in the liver, while it led to a considerable increase in tissue BH2 in the intestine. When dihydrofolate reductase inhibitor MTX was administered before the pterin feeding, BH4 did not increase in the liver, while it increased 20-fold in the intestine, although the rise was 45% less than that in the absence of MTX. These results suggest that 1) the liver was scarcely able to uptake BH4 in its reduced form; 2) accumulation of BH4 in the liver was achieved through the MTX-sensitive pathway presumably driven by dihydrofolate reductase; 3) a large concentration of BH4 accumulated in the intestine, bypassing the MTX-sensitive pathway, that is, it was taken up directly as the fully reduced form, BH4 ; 4) the other BH4 accumulated in the intestine seemed to have been converted from BH2 through the MTX-sensitive pathway, as in the liver.
Modulation of DNA Methyltransferase 1 Profile by γ-lrradiation Followed by Methyl Donor Starvation
Authors: Batra Vipen , Kesavan Vellappan , Mishra Kaushala P.
Published: August 2013

Role of one-carbon transfer agents methyl donors namely folate, choline and methionine in DNA methylation has been the subject of extensive investigation. The methylation pattern of DNA is established during embryogenesis and is subsequently maintained by maintenance methylation activity of the enzyme DNA methyltransferase 1 (dnmt 1). Ionizing radiation is known to extensively damage the DNA. Folate, a water-soluble vitamin, is known to contribute towards repair of damaged DNA due to its role in synthesis of nucleotide base adenine, guanine and thymidylate. Sufficient dietary availability of methyl donors, therefore, might have ability to modify radiation effects. In the present study, modifications in levels of dnmt 1 by g-irradiation followed by methyl donor starvation were observed. Experiments showed a dose and methyl donors starvation dependent attenuation in dnmt 1 activity. Attenuation of dnmt 1 activity was most significant for diet deprived of all the three methyl donors. Ionizing radiation and methyl donor deficiency were observed to act synergistically towards inhibiting dnmt 1 activity. Present results suggested possibility of interaction among folate, methionine and choline deficiency to potentate symptoms of ionizing radiation stress. These enzymatic modifications might contribute to altered DNA methylation after chronic feeding of methyl donor free diets after gamma irradiation. These results suggest that dietary availability of methyl donors and γ-radiation stress might significantly alter the dnmt 1 profile.
Pteridines, CXVI. (1) Synthesis and Reactivity of 6-Substituted l,3-Dimethyl-7-hydroxylumazines and 7-Substituted l,3-Dimethyl-(5H)-lumazin-6-ones
Authors: Arendt Reinhardt , Pfleiderer Wolfgang
Published: August 2013

6-Substituted 1,3-dimethyl-7-hydroxylumazines (5-7) have been synthesized from 1,3-dimethyluracil-5,6- diamine (1) and a-ketoacid esters (2-4) under weakly acidic conditions. The isomeric 7-substituted 1,3-dimethyllumazin- 6-ones (18-20) resulted from a regioselective Boon synthesis starting from 6-chloro-l,3-dimethyl-5- nitrouracil (8) and α-aminoacid esters (9-11) in a three-step procedure. H202 oxidations led with 6 and 7 to the corresponding 5-N-oxides (21, 22) whereas in the lumazin-6-onc scries only the 7-phenyl derivative (20) reacted also at N-5 position forming a cyclic hydroxamic acid (23). The newly synthesized compounds have been characterized by elemental analyses,1H-NMR and UV spectra based upon pKa-determinations.
Difference of DNA Compaction Performed by Two kinds of Oncopterin-Mimic Pteridine - Polyamine Conjugates
Authors: Murata Shizuaki , Chen Ning
Published: August 2013

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

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

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

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

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

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

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

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

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

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

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

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

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.
Circulating Vascular Endothelial Growth Factor, C-reactive Protein and Urinary Neopterin Concentrations During dose-dense Chemotherapy
Authors: Melichar Bohuslav , Balloková Anna , Malirová Eva , Urbánek Lubor , Krcmová Lenka , Hyspler Radomir , Hornychová Helena , Ryska Ales , Solichová Dagmar
Published: August 2013

Angiogenesis plays a crucial role in tumor progression. Prominent among angiogenic factors is vascular endothelial growth factor (VEGF). VEGF is produced by cancer cells as well as by the cells infiltrating tumor stroma, mainly macrophages. Macrophage activation may be assessed by measuring serum or urinary neopterin. Systemic inflammatory response could be evaluated by measuring serum C-reactive protein concentrations. The aim of the present study was to examine the effect of a regimen combining dose dense combination of doxorubicin and cyclophosphamide with sequential weekly paclitaxel on plasma VEGF, urinary neopterin and serum C-reactive protein concentrations. Thirty-four female patients with histologically verified breast carcinoma treated with dose-dense regimen combining doxorubicin and cyclophosphamide with sequential weekly paclitaxel administration were studied. Plasma VEGF was measured by enzyme-linked immunosorbent assay. Urinary neopterin was determined by high performance liquid chromatography. Compared to baseline plasma VEGF was significantly decreased one week after the start of therapy. VEGF concentrations subsequently increased, but this increase was significant compared to baseline only at week 16. Urinary neopterin was significantly increased compared to baseline at every visit with the exception of visits 12 and 20 at which the significance was borderline. Serum C-reactive protein was increased compared to baseline only at visits 4, 6 and 8. A positive correlation was observed between plasma VEGF and serum C-reactive protein at baseline and at visits 5 and 19. Significant correlations were observed between serum C-reactive protein and urinary neopterin at visits 6, 7, 9, 11, 14, 15 and 17. In conclusion, only minor changes in plasma VEGF and serum C-reactive protein were observed during dose-dense chemotherapy. In contrast, urinary neopterin was increased throughout the course of treatment. Correlations between VEGF and C-reactive protein and between Creactive protein and urinary neopterin were observed only at some time points.
Immunological Markers in Plasma and CSF distinguish Vascular Parkinsonism from Idiopathic Parkinson's Disease
Authors: Vrecko Karoline , Schwingenschuh Petra , Holl Alexander , Saurugg Ronald , Wenzel Karoline , Katschnig Petra , Tafeit Erwin , Ott Erwin
Published: August 2013

Activation of the cellular immune system is discussed to be partly responsible in the neurodegenerative process of Parkinson's disease. We determined concentrations of neopterin, of cytokine interleukin-6, and of soluble cytokine receptors sIL-2Rα, sTNF-R75α in plasma and cerebrospinal fluid in controls and patients with vascular parkinsonism and idiopathic Parkinson's disease diagnosed according to published clinical diagnostic criteria, to examine if the cellular immune system is activated locally or peripherally or both. Our results show no activation in idiopathic Parkinson's disease and controls, but a significant increased activation in vascular parkinsonism, where concomitant signs of cerebrovascular disease are present.
Cerebrospinal Fluid Neopterin in Patients with Tumors and other Disorders
Authors: Rehák Svatopluk , Malirová Eva , Cermanová Melanie , Suba Petr , Cerman Jaroslav , Plisek Stanislav , Melichar Bohuslav
Published: August 2013

Increased urinary or serum concentrations of neopterin have been reported in cancer patients, but less is known about neopterin concentrations in cerebrospinal fluid (CSF). CSF neopterin was determined with radioimmunoassay in 64 patients. CSF neopterin concentrations in patients with tumors were significantly higher compared to patients with predominantly peripheral infections (Lyme borreliosis and herpes simplex infection) and no infectious, inflammatory or neoplastic disorder, and significantly lower compared to patients with meningitis or encephalitis. Among patients with tumors, CSF neopterin was significantly higher in patients with non- Hodgkin lymphoma (NHL) compared to other tumors. The difference between patients with tumors other than NHL and predominantly peripheral infections was of borderline significance, and a significant difference was observed between patients with tumors other than NHL and no disorder. CSF neopterin was significantly higher in patients with NHL compared to patients with predominantly peripheral infections, multiple sclerosis or polyneuropathy and no disorder, and no difference was evident compared to patients with meningitis or encephalitis. In conclusion, among patients with tumors, high CSF neopterin may suggest the diagnosis of NHL.
Serum Neopterin in Patients with Malignant Melanoma
Authors: Beneš Petr , Melichar Bohuslav , Študentová Hana , Kapustová Miloslava , Malírová Eva , Schneiderka Petr , Šrámek Vlastislav , Cwiertka Karel
Published: August 2013

Increased serum or urinary concentrations of neopterin have been described in patients with tumors of different primary locations, but reports on neopterin in patients with melanoma are scanty. We have studied serum neopterin and a melanoma marker, S-100-beta, in 41 patients with melanoma. Serum neopterin and S-100-beta were determined by immunoassay. Neopterin concentrations were significantly increased compared to controls only in patients with active disease, but not in patients without evidence of disease activity. Serum neopterin and S-100-beta in patients with active disease were higher than in patients without evidence of disease activity. In patients a significant correlation existed between neopterin and S-100-beta (rs = 0.33, p <0.05), and, in patients without active disease, there was also a correlation between neopterin and age (rs = 0.51, p <0.01). In conclusion, increased serum neopterin in patients reflects disease activity. A significant correlation was observed between serum neopterin and S-100-beta. Future studies are necessary to demonstrate whether the combined measurement of serum neopterin and S-100-beta could be useful in the detection of recurrence in patients with melanoma.
Accelerated Tryptophan Degradation in Trauma and Sepsis Patients is Related to Pro-inflammatory Response and to the Diminished in vitro Response of Monocytes
Authors: Ploder Martin , Spittler Andreas , Schroecksnadel Katharina , Neurauter Gabriele , Pelinka Linda E. , Roth Erich , Fuchs Dietmar
Published: August 2013

Immune system activation and inflammation accompanies immune dysfunction in trauma and sepsis patients. Tryptophan degradation via the kynurenine pathway by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO) could contribute to the deficient responsiveness of immunocompetent cells. Activated IDO in patients after trauma and with sepsis is indicated by an increased kynurenine to tryptophan ratio (kyn/trp), which was found to be associated with poor outcome of patients. In this study, tryptophan and kynurenine concentrations in 18 patients post trauma or with sepsis during 12-14 days of follow up (up to 84 specimens were available) were compared to concentrations of neopterin and cytokines tumor necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) and the in vitro response of lipopolysaccharide-stimulated monocytes. Compared to healthy controls, average kyn/trp and kynurenine, TNF-α, IL-6 and neopterin concentrations were increased in patients, and tryptophan concentrations were decreased. During follow-up, only kyn/trp, kynurenine and neopterin concentrations (all p <0.001) were increasing, whereas the changes of tryptophan, TNF-α and IL-6 concentrations were not significant. Non-survivors presented not only with higher kyn/trp and with higher kynurenine and neopterin concentrations than survivors, but also TNF-α and IL-6 concentrations were higher. Kyn/trp correlated with neopterin (rs = 0.590; p <0.001) and also with TNF-α (rs = 0.374; p <0.01) and IL-6 concentrations (rs = 0.262; p <0.05) and inversely with the in vitro response of stimulated monocytes. Data imply that increased tryptophan degradation in patients post trauma is due to IDO activation. Increased IDO activity most likely represents a result of host defence response in patients, and data support a possible role of IDO to diminish immunoresponsiveness in such patients.
Exposure to Helicobacter pylori and Serum Kynurenine to Tryptophan Ratio in Patients with Gastric Cancer
Authors: Engin Ayse Basak , Karahalil Bensu , Karakaya Ali Esat , Engin Atilla
Published: August 2013

In Helicobacter pylori seropositive individuals, the subsequent risk of non-cardia gastric cancer development is frequently attributed to the infection agent. Although the link between inflammation and gastric cancer is formally recognized, the molecular basis of evading mechanisms of Helicobacter pylori from host immune system remains unclear.

The aim of this study was to determine the effect of systemic factors in gastric cancer patients such as serum kynurenine to tryptophan ratios, neopterin, nitric oxide and urinary biopterin levels which may sustain the persistence of Helicobacter pylori seropositivity. This prospective randomized study involved 95 adults with gastric cancer and 108 cancer free patients with extradigestive diseases. Each group was assigned into two subgroups according to Helicobacter pylori IgG seropositivity. Exposure to Helicobacter pylori was detected by serum IgG test (ELISA). Serum tryptophan, kynurenine, neopterin and nitrite concentrations were measured. In simultaneous urinary samples, neopterin, biopterin, and creatinine levels were assayed. Significant decreases were found in serum tryptophan levels of both Helicobacter
pylori seronegative and seropositive gastric cancer patients versus controls without malignant disease. However, marked increase in kynurenine/tryptophan was observed only in Helicobacter pylori seropositive cancer patients. Highly significant correlation between the serum neopterin and kynurenine/tryptophan indicated interferon gamma stimulated tryptophan degradation. Decrease in serum nitrite levels, and a parallel increase in urinary biopterin concentrations in Helicobacter pylori seropositive cancer cases might result from the excessive nitric oxide consumption due to reactive oxygen radical overproduction. Significantly higher kynurenine to tryptophan ratio and its correlation with increased neopterin levels suggested a role of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) and that persistence of Helicobacter pylori seropositivity might participate in enhanced immune tolerance of cancer patients.
Urinary Neopterin, Serum Retinol, α-tocopherol and Homocysteine in Breast Cancer Patients During Treatment with Bevacizumab and Chemotherapy
Authors: Melichar Bohuslav , Kalábová Hana , Krčmová Lenka , Kašparová Markéta , Plíšek Jiří , Hyšpler Radomír , Študentová Hana , Zezulová Michaela , Holečková Petra , Pecka Miroslav , Solichová Dagmar
Published: August 2013

Bevacizumab, monoclonal antibody targeting vascular endothelial growth factor, is effective in different tumors, including colorectal carcinoma, non-small cell lung cancer, renal cell carcinoma and breast cancer. Increased serum or urinary concentrations of neopterin, an indicator of systemic immune response, have been described in patients with tumors of different primary locations, and further increase has been observed during anticancer therapy. An increase of urinary neopterin has been described after administration of cytokines, cytotoxic chemotherapy, or external beam radiation, but less is known about the effects of targeted agents on systemic immune response. We have studied serum homocysteine, C-reactive protein, α-tocopherol and retinol, and urinary neopterin in patients with metastatic breast cancer treated with bevacizumab, taxane and carboplatin. Homocysteine and C-reactive protein were determined immunochemically. α-tocopherol, retinol and urinary neopterin were determined by high performance liquid chromatography. Homocysteine, C-reactive protein and urinary neopterin decreased, while retinol and α-tocopherol increased during the therapy. In conclusion, the treatment of patients with metastatic breast cancer with bevacizumab, taxane and carboplatin resulted in the suppression of systemic inflammatory and immune response. The suppression of systemic inflammatory and immune response was associated with an increase in serum vitamin concentrations.
Clinical Usefulness of Determining the Concentration of Neopterin
Authors: Plata-Nazar Katarzyna , Jankowska Agnieszka
Published: August 2013

Neopterin is one of biochemical markers of immune activity, which seems to be useful in monitoring inflammatory diseases. Increased serum concentration of neopterin is observed in conditions with cell-mediated immune response involvement. In clinical practice, neopterin evaluation is applied in medical conditions such as: infectious diseases, oncology, rheumatology, transplantology, transfusiology, cardiology, neurology and many others. Neopterin can be detected in serum, urine, cerebrospinal fluid, synovial fluid, saliva, ascitic fluid, bile, pancreatic juice and gastric juice. In recently published studies, various non-specific indicators of inflammation such as neopterin, C-reactive protein, procalcitonin were compared and proved to be independently useful.
Hepatotoxicity and Langerhans Islets Regenerative Effects of Polar and Neutral Lipids of Nigella sativa L. in Nicotinamide/streptozotocin-Induced Diabetic Rats
Authors: Sobhi Widad , Khettal Bachra , Belmouhoub Messaoud , Atmani Djebbar , Duez Pierre , Benboubetra Mustapha
Published: August 2013

The extracted oil from Nigella sativa seeds is reported to be effective against various diseases and chemicallyinduced hepatotoxicity and nephrotoxicity. The effect of oral administration of Nigella sativa total, polar and neutral oils was investigated on hepatoprotective status in streptozotocin/nicotinamide (STZ-N)-induced diabetic rats. The toxicity was assessed biochemically by monitoring aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptitase (g-GT) and alkaline phosphatase (AP) activities as well as biluribin titre and histologically under light microscope. The study was also undertaken to evaluate the effect of oil fractions on the regeneration of pancreatic Langerhans islets in treated diabetic rats.

Biochemical analysis showed that lipid fractions from total oil of Nigella sativa seeds are not hepatotoxic. However, histological study of the liver demonstrated major and minor tissue damages with the neutral fraction exhibiting the most protective effect. At the end of the experiment period (17 days) of treatment with thymoquinone (25mg/kg bw/day) or neutral lipid fraction (100mg/kg bw/day), a positive effect on the regenerative of Langerhans islets, initially distorted by STZ, was observed. Thus, the hypoglycaemic effect of neutral lipid fraction could be a result of the regeneration of the pancreatic Langerhans islets.
Bruce Lincoln’s “How to Read a Religious Text”
Authors: Chatterjea Ipsita
Published: August 2013

In Gods and Demons, Priests and Scholars: Critical Explorations in the History of Religions, Lincoln’s “How to Read a Religious Text” is anchored in decades of work with mythological texts or canonical texts, the six points deployed have their origins in his prior work, Theorizing Myth (Lincoln 2012, 5-15; Lincoln 1999, 150-155). 1 The sections from the Chandogya Upani?ds that Lincoln uses to illustrate his points thus, fall in line with a number of his selected examples over the course of his career, add to this the analysis of relatively discrete events. The essay will apply Lincoln’s six lines of inquiry to Sara J. Duncan’s Progressive Missions in the South and Addresses: With Illustrations and Sketches of Missionary Workers and Ministers and Bishop’s Wives (1906) to walk through of the utility, limits and necessary adaptations that surface when Lincoln’s categories are applied to other types of religious texts beyond myth and canon.
Ideology, Ideology-Critique, and the Critical Study of Religion in Bruce Lincoln’s Gods and Demons, Priests and Scholars
Authors: Hewitt Marsha
Published: August 2013

This article is a review essay of Lincoln's latest book, contextualizing it within the general field of his previous work. The article situates Lincoln's work with respect to ideology critique mainly in the theoretical tradition of Marx and his critique of religion. It is argued that Lincoln's diagnosis of the current state of the study of religion remains captive to the current regulating practices deriving from some postmodern ideas, political correctness, and the hegemony of theology in 'religious' studies in the academy and its major professional association.
Open Space Technology and the Study of Religion
Authors: Dion Nicholas , King Rebekka , Baker Tyler , Liang Jingjing , McDonough James , Samuels Joshua
Published: August 2013

This paper, co-authored by two instructors and four of their undergraduate students, details an experimental use of 'Open Space Technology' in a Religion course on social constructionism at the University of Toronto. In addition to describing the format and its purpose, four undergraduate evaluations of the course are offered.
Field Notes
Authors: Editors The
Published: August 2013

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