bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Hormones and Protein Level on Induction of Enzymes Involved in Histidine Degradation and Folate Metabolism
Authors: Nair C.P.P. , Stokstad E. L. Robert 
Published: March 2013

Summary The effects of the hormones thyroxine, glucagon and hydrocortisone, and of protein level on hepatic histidase, urocanase, and certain folate enzymes were studied in rats. Hypothyroidism, induced either by feeding thiouracil or by thyroidectomy, increased histidase, urocanase, and the folate dependent enzyme formiminotransferase, and increased histidine metabolism as measured by oxidation of the 2-ring carbon of histidine to carbon dioxide. Hyperthyroidism, produced by feeding thyroid powder, decreased histidine oxidation and liver levels of this enzyme. Glucagon and hydrocortisone increased histidine oxidation and increased levels of histidase, urocanase and formiminotransferase. Elevated levels of casein and soy protein produced four to eight fold increases in histidase and urocanase, and 50% increases in formiminotransferase. Thus, increases in histidase and urocanase involved in the formation of formiminoglutamic acid (FIGlu) were accompanied by increases in the FIGlu metabolizing enzyme formiminotransferase.
Ab Initio Quantum Chemical Calculations on the Stability of Different Tautomers of 6- and 7-Phenacetyl Pterin
Authors: Reibnegger Gilbert , Denny Brian J. , Wachter Helmut 
Published: March 2013

Summary In order to investigate the stabilities of different tautomeric forms of pteridine derivatives with a phenacetyl side chain in the 6- or 7-position, we have performed ab initio quantum chemical geometry optimizations of both the keto form and the vinylogous amide form of 6- and 7-phenacetyl pterin. The results are in accordance with experimental expectations: the keto form is slightly more stable for the 6-substituted derivative (1 .8 kcal per mol). while the vinylogous amide form is substantially more stable for the 7-substituted compound (8 .7 kcal per mol). The vinylogous amide forms are planar molecules, and this geometry enables the interaction between the hydrogen atom at N-5 (or N-8) and the carbonyl function of the side chain. Inspection of the calculated electron densities (population analysis) underlines the suggestion that the vinylogous amide form of 7-phenacetyl pterin is stabilized by a shift of electron density from the nitrogen bonded to C-2 to the carbonyl oxygen atom of the side chain (resonance stabilization via an additional highly conjugated vinylogous amide structure).
Investigation of Spectra and Ionization Constants of 8-Alkyl Pterins by Fluorimetry
Authors: Jeong Soon-Seog , Wormell Paul , Gready Jill E. 
Published: March 2013

SummarySpectrofluorimetric studies of the properties of 8-alkyl-pterins arc reported, together with preliminary results on the use of fluorimetry in studying the binding of these new mechanism-based substrates to dihydrofolate reductase (DHFR). The compounds fluoresce strongly in the 460-490 nm range with emission maxima for the cations being blue-shifted by ~5-20 nm. Quantum yields for the cations of ~0.14-0.23 have been measured. pKa values for the basic ionization of ~5.3-5.7 have been determined from fits to both the emission and excitation spectra using sample concentrations in the 1-2 µM range. Although the UV /vis spectra between pH 0 and 4 show little change. there were significant sigmoidal changes in fluorescence intensity which could he fitted to apparent ionization constant values of ~1.4-1.0 with fluorescence intensity decaying to almost zero at pH 0. Studies of the fluorescence for the cations and neutral forms in organic acids and polar organic solvents respectively indicate little solvent dependence. Spectral modelling using the CNDO/S-CI method confirms that the spectra are due to π→π* transitions. and that the long wavelength absorption hand of ~400 nm is due to transitions involving mostly the pyrazine ring and N1. Significant differences in emission wavelength and intensity between 6-methyl- and 7 -methyl-8-alkyl-pterins have been characterised with the latter exhibiting fluorescence stronger by a factor of ~2 and blue-shifted by ~20 nm which arc readily detectable visually: aqua-blue and green fluorescence respectively for the 7-methyl and 6-methyl isomers. From this understanding of the fluorescence properties of 8-alkyl-pterins and their dependence on charge state and pyrazine-ring substituents, and taking into account the fluorescence characteristics of DHFR and cofactor NADP. we have assessed the potential of fluorimetric experiments for studying both pterin dissociation constants and the form of enzyme-bound pterin
Mutagenesis at Five Pteridine Pathway Loci In Drosophila melanogaster: Genetic and Biochemical Characterization
Authors: Millán J.M. , Nájera C. 
Published: March 2013

SummaryIn order to carry out a genetic and biochemical analysis of pteridin pathway eye colour loci, sixteen strains of five eye colour mutants of Drosophila melanogaster (2 dke, 7 sf. 3 se, 3 Hnr and 1 bw) from natural populations were used. Four EMS mutagenesis experiments were carried out to produce induced mutants of the same loci. 54 mutants (mosaics and completes) were obtained but only 7 (4 sf, 1 bw, 1 Hnr and I dke) could be isolated. The 40.48% of the mutations were mosaics. The percentage of mutants appeared during the four first days (85.19%) was significatively higher to the percentage of mutants appeared during the four following (14.18%). Viabilities of EMS-induced mutants were similar to that of the natural ones. For the induced mutants viability at 25°C was higher than at 16°C and heterozygotes had a higher Viability than mutant homozygotes. The low mutagenesis frequencies and the lack of some metabolites for Hnr and se mutants suggest an important role of these mutants in the pteridine pathway.
Activated Macrophages in Preeclampsia
Authors: Schröcksnadel H. , Fuchs D. , Herold M. , Wachter H. , Dapunt O. 
Published: March 2013

SummaryNeopterin (serum. urine) and other markers of macrophage activation (lL-1 IL-6, TNF alpha) were compared in preeclamptic patients and healthy pregnant controls. The prepartal urine neopterin median in preeclampsia (337 μmol/mol creat.) was 33% higher than that of healthy pregnant controls (253 μmol/mol creat.). There was no statistically significant difference between the groups (p = 0.08). In plasma there were no statistically significant differences in cytokine concentrations between healthy pregnant and nonpregnant controls with the exception of neopterin. that showed higher values in pregnant women (p = O.OO4). Elevated levels of IL-6. TNF-alpha and neopterin were observed in hypertensive women. Differences to healthy pregnant controls were statistically significant for IL-6 (p = 0.008). TNF-alpha (p = 0.009) and neopterin (p=0.04) and were more pronounced in severe forms of the disease. These three parameters of monocytic origin showed positive significant correlations amongst each other. A participation of macrophages in the pathomechanism of hypertensive disorders of pregnancy can thus be assumed.
Cyclosporin A Treatment in Psoriasis: Monitoring by Neopterin Concentrations In Serum and Urine
Authors: Sepp N. , Benedikter S. , Kofler H. , Fritsch P. , Wachter H. , Fuchs D. 
Published: March 2013

SummaryPsoriasis is a hyperproliferative skin disorder in which immune mechanisms are thought to play a role. Recently, cyclosporin A has been found effective to treat psoriasis. However, mechanisms of action of cyclosporin A in patients are not well understood. We investigated seven patients (6 males. 1 female, aged 29-58 years) with severe psoriasis, three of them associated with arthropathy. The patients were treated with cyclosporin A given twice daily in gelatine capsules. Four patients were given 5 mg/kg, the others received 2.5 mg/kg initially. Two of them were put on 5 mg/kg (after 4 and 12 weeks of treatment). Clinical evaluation before and during therapy was carried out using the Psoriasis Area and Severity Index (PASI). Patients were followed up for 6 and 15 months. Their cyclosporin A blood levels were adjusted by a monoclonal radioimmunoassay. In parallel, serum and urine neopterin levels were quantified by HPLC. Mean neopterin concentrations in patients prior to therapy were found only slightly higher (serum 6.5± 0.8 mmol/l) than in healthy controls. There was no correlation of neopterin values and the degree of PASIscore. Onset of cyclosporin A was paralleled by decreasing neopterin concentrations and improvement of the skin status. Decrease of cyclosporin A doses was accompanied by an increase of PASI and significantly decreasing neopterin levels. In patients with severe relapses of psoriasis after withdrawal of cyclosporin A, neopterin rose higher than pretreatment levels. In 6/7 patients PASI and neopterin levels were closely correlated.
Immune Stimulation of Interferon-Gamma- and Biopterin Synthesis with Endotoxin in Animal-Experimental Peritonitis
Authors: Kullich W. , Weissenhofer W. , Hunsicker A. , Rokos H. 
Published: March 2013

Summary As a result to a microhial stimulus different defence systems are activated. Bacterial lipopolysaccharids (endotoxins) can lead to activation of the immune system in which phagocytic cells like macrophages. secrete cytokines and inflammatory mediators. Owing to a hyperactivation of immune mechanisms and also to generalized inflammatory processes organic lesions or even multiple failure of organs can evolve due to influences by cytokines and anaphylatoxines. On a standardized peritonitis model with wistar-pragrats. release of endotoxin. interferon-gamma synthesis and release of hiopterin into plasma has heen measured 6 hours after intraperi to neal administration of E.-coli-haemoglobin suspension. In the initial phase of the immune response interferon-gamma - being endogenously induced by endotoxin - stimulates synthesis of pteridines. Due to antagonistic effects to the cytokines (which stimulate the inflammatory processes) interferon-gamma regulatorily intervenes with the inflammatory mechanisms. The production of biopterin serves as a measure of activation of the monocyte/macrophage system. In comparison to a control group. treated with sodium chloride. statistically significant different have been found in the measuring parameters endotoxin. biopterin and interferon-gamma. The significant correlation of all parameters confirm the quick activation of immune mechanisms as response of the immune system to endotoxinaemia in diffuse purulent peritonitis.
Association between Urinary Zinc and Neopterin Excretion: A Manifestation of the Acute Phase Response in the Kidney?
Authors: Melichar Bohuslm 
Published: March 2013

Summary An elevation in urinary neopterin excretion is established to be a sensitive index of immune system activation in various disorders. In many of these conditions, a simultaneous increase in urine zinc output is observed, but this phenomenon remains largely unexplained. In previous studies in patients with different diseases, a significant correlation between urine zinc and neopterin was demonstrated. This suggests that the immune system may be involved in inducing an augmentation in urine zinc loss. As both zinc and neopterin are now known to influence oxidative processes, and lipid peroxidation has been demonstrated 10 play an important role in renal pathology, a protective role of the increase in urine zinc and neopterin, which might represent a manifestation of the acute phase reaction in the kidney, is discussed.
Pteridines CI Synthesis and Properties of Lumazine-6- and -7-carboxylic Acids
Authors: Eisele Roland , Aritomo Keiichi , Pfleiderer Wolfgang 
Published: March 2013

Summary Lumazine-6-(8) and 7-carboxylic acid (23) and their N-methyl derivatives (12, 13, 21, 26, 28, 29) have been synthesized and characterized by the determination of their pK values and the UV spectra of the neutral, mono and dianion species. It was noticed that the acidities of the two N-H protons of the pyrimidine moiety are almost the same indicating that the dianions of 8 and 23, respectively, are I: 1 mixtures of the corresponding N-l and N-3 deprotonated forms. The lumazine-7-carboxylic acids (23, 26, 28, 29, 31, 33) are in comparison to their 6-carboxyJic acid counterparts (8, 12, 13, 21, 39) stronger acids by about I pK unit due to the resonance effect of the 4-oxo function on C-7 but not C-6. Alkaline KMn04 oxidation of 6.7-dimethyl-Iumazine (30) forms expectedly 6-methyl-Iumazine-7-carboxylic acid (31) in high yield according to the activation of the 7-methyl group by the electron-attracting 4-carbonyl residue.
Stereoelectronic Effects in the 02-mediated Autoxidation of Reduced Folate Derivatives
Authors: Fitzhugh Anthony L. 
Published: March 2013

Summary For over forty years pteridinologists have studied the O2-mediated autoxidation of reduced folate derivatives. This effort has resulted in the identification of several transient intermediates and many products. Until now. however, no clear explanation has emerged of why certain reduced folate derivatives arc less susceptible to autoxidation than others. Presented below is a detailed theoretical model which readily explains the chemical behavior of reduced folate derivatives towards O2. Of note are the steric and electronic forces at work during the formation of the 4a-hydroperoxy intermediate and the stereoelectronic factors that predominate during its breakdown.
Effect of 5-Fluorouracil Administered at Low Doses on Cytotoxic Properties of Methotrexate in the in vivo Model of Mice L1210 Leukemia; According to the Schedule of Treatment
Authors: Graczyk Julita 
Published: March 2013

Summary The study compared antineoplastic effects of combined methotrexate and 5-fluorouracil therapy on LI210 lymphoid leukemia in mice according to the schedule of treatment. Methotrexate was administered at doses of: LOw.. 0.5 LOw. 5-Fluorouracil was administered at doses of: 0.2 LOIO, 0.1 LOw, 0.02 LOro. The parameters characterizing the efficacy of the therapy were survival time of mice inoculated with LI2l0 leukemic cells .. as well as 1151 excretory capacity of mice inoculated with 1251-iododeoxyuridine-Iabelled leukemic cells. It has been observed that the longest survival time of mice with LI210 leukemia is obtained when methotrexate is administered prior to 5-fluorouracil. Reversing the schedule, or simultaneous administration of the drugs results in shorter survival time. despite the administration of 5-fluorouracil at low doses, ineffective on LI210 leukemia in monotherapy. Cytotoxic effects on LI210 leukemic cells labelled with 1151UDR were present only when methotrexate was administered prior to 5-fluorouracil.
Serum Neopterin and Angiotensin-converting Enzyme In Cancer Patients
Authors: Melichar Bohuslav , Jandik Pavel , Vavrova Jaroslava , Mergancová Jindřiška , Maliřová Eva , Vobořil Zbyněk 
Published: March 2013

Summary An elevation of serum angiotensin-converting enzyme (ACE) has been reported in some disorders associated with immune activation, e.g. sarcoidosis, HIV infection or ulcerative colitis. Both endothelial cells and macrophages are thought to be the possible source of increased ACE levels. We have investigated serum ACE and neopterin, an indicator of macrophage activation, in 23 patients with solid tumors as well as in 8 controls. Similar ACE levels have been observed in the cancer patients and the controls (2.6 ± 2.1 vs 3.4 ± 1.1 μkat/1, while neopterin has been significantly higher in the cancer patients (15.4 ± 12.6 vs 7.2 ± 2.2 nmol/I, P<O.02). No correlation has been observed between serum ACE and neopterin. We conclude that an elevation of ACE is not present in cancer patients. Macrophage activation in cancer is not accompanied by increased ACE release.
Pteridines CV
Authors: Hanaya Tadashi , Torigoe Kiyoshi , Soranaka Kazuyuki , Yamamoto Horoshi , Qizhengt Yao , Pfleiderer Wolfgang 
Published: March 2013

Summary Treatment of L-biopterin (I) with N,N-dimethyformamide dimethyl- (or diethyl)acetal and then with acetic anhydride in pyridine gave 1',2'-di-O-acetyl-N'-(N,N-dimethylaminomethylene)-L-biopterin (4), which was converted by the Mitsunobu reaction into 3-methyl (5) and 3-p-nitrophenetyl derivatives (7). The protective groups on the side chain diols and N2 of these compounds were selectively cleaved to furnish products 6, 8-10, among which 9 is naturally occurring 3-methyl-L-biopterin and 8 is N',N(3)-protected biopterin, a versatile intermediate for various reactions on the side-chain diol. In contrast, the same Mitsunobu reactions of tri-N2:I',2'-0-acetyl-L-biopterin (II) afforded 04-methyl (12) and 04-NPE derivatives (13), both of which yielded 0 4-methyl-L-biopterin (14) and subsequently led to 4-amino-L-biopterin (18).
Neopterin-induced Suppression of Erythropoietin Production In Vitro
Authors: Schobersberger W. , Jelkmann W. , Fandrey J. , Frede S. , Wachter H. , Fuchs D. 
Published: March 2013

Summary The production of neopterin increases in several diseases with activation of the ceIlular immune response. As previously shown serum concentrations of neopterin are inversely correlated with blood hemoglobin concentrations in the anemia of hematological and malignant disorders. Besides the role of chronic immune activation on the disturbed iron metabolism, an inhibitory influence of pteridines on cellular erythropoietin production could not be excluded. To test the possibility that pteridines are able to suppress the hypoxia-induced production of erythropoietin, the effects of neopterin and 7,8-dihydroneopterin on the human ceIl line HepG2 (hepatoceIlular carcinoma) were investigated. 24 h incubation with neopterin induced a dose-dependent reduction of erythropoietin production. The erythropoietin concentration significantly decreased by - 57.6% with 300 11M and by - 34.9% with 100 11M neopterin, respectively. 7,8 dihydroneopterin did not influence erythropoietin production. The inhibitory effect of neopterin on erythropoietin production was a consequence of reduced erythropoietin-mRNA levels. The results of this study show a neopterin-induced suppression of hypoxia-induced erythropoietin formation in HepG2 cultures in a dose dependent manner. We speculate that under in vivo conditions high concentrations of neopterin can aggravate the anemia of chronic disease.
An Improved Synthesis of t-Butyl N-(4-propargylaminobenzoyl)-γ-oligo (L-glutamate )s
Authors: Kempny Michal , Rzeszotarska Barbara , Pawelczak Krzysztof 
Published: March 2013

SummaryA simple synthesis in solution, of the series of six consecutive t-butyl N-(4-propargylaminobenzoyl)-yoligo( L-glutamate)s (8-13) containing from two to seven L-glutamic acid residues (Scheme 1) is described. a-t-Butyl N-(4-propargylaminobenzoyl)-L-glutamate (1), the versatile synthon is coupled with one of the t-butyl y-oligo(L-glutamate)s (2-7) by means of 2-chloro-l-methylpyridinium tosylate to give the title compounds in 91-95% yield subsequent to edulcoration of a post-reaction mixture and crystallization. These compounds were characterized by melting points, elemental analyses and HPLC and are 96.7-100.0% pure according to the last method (Table I).
Expression and Characterization of Recombinant Drosophila 6-pyruvoyl tetrahydropterin Synthase
Authors: Shik Park Young , Kim Nacksung , Kim Hajeong , Park Dongkook , Yim Jeongbin 
Published: March 2013

Summary 6-Pyruvoyl tetrahydropterin synthase is involved in the synthesis of pteridine eye pigments in Drosophila. The purple gene which was known to be one of the target loci of the suppressor mutation su(sj2 has been identified to encode the enzyme, and its cDNA has been cloned recently. The cDNA encoding the 19.3 kDa subunit of the 6-pyruvoyl tetrahydropterin synthase was expressed as fusion proteins in E. coli. The recombinant protein was shown to be active and purified from the E. coli crude extract by metal-chelation chromatography. The fused metal-chelating oilgopeptide was removed by thrombin for further characterization. Apparent Km for the substrate dihydroneopterin triphosphate was determined to be 590 IlM, which was slightly higher than the value of the native enzyme. The isoelectric point of 6.4 was also different from the known value of 4.3 determined by the native enzyme. Heat stability and the stimulatory effect of reducing agents were similar to the native enzyme. The modification of cysteine residues in the recombinant enzyme, one of which is known to be conserved in human and rat enzymes, by iodoacetamide inhibited its activity by up to 80%.
Functional Studies on the Promoter Region of the Human GTP Cyclohydrolase I Gene
Authors: Gütlich Markus , Witter Klaus , Katzenmeier Gerd , Rödl Wolfgang , Wernert Thomas , Ziegler Irmgard , Bacher Adelbert 
Published: March 2013

Summary We have isolated genomic clones that contained the gene for human GTP cyclohydrolase I. One clone containing the 5'-regulatory region of this gene was further analysed. It encompassed the first exon, parts of the first intron and about 2.6kb of the promoter region. The transcription start site was localised by rapid amplification of cDNA ends (5'-RACE). The 2.6 kb region upstream of the transcription start site showed promoter activity when ligated upstream of a reporter gene. 5'-truncations of the promoter region increased its activity as long as the CAAT and TATA boxes remained unchanged. Several putative Spl responsive elements were located within a GC-rich region close to the transcription start site.
Effect of 7,8 -Dihydroneopterin, Biopterin and Isoxanthopterin on Cholesterol and Phospholipid Content and Phospholipid Biosynthesis in Vitro
Authors: Rudzite Vera , Jurika Edite , Baier-Bitterlich Gabriele , Wachterl Helmut , Fuchs Dietmar 
Published: March 2013

Summary
Incorporation of fatty acids into phospholipids has been investigated using samples of rat liver tissue homogenate (Krebs-Ringer-phosphate buffer, pH=7.4, containing 0.3% albumin, fatty acid mixture and glycerol). The addition of 7,8-dihydroneopterin and biopterin (5 and 30 pmol/g wet weight) to incubation medium induced a decrease of palmitic (7,8-dihydroneopterin) and stearic acid (7,8-dihydroneopterin, biopterin) and an increase of linolenic (7,8-dihydroneopterin) and arachidonic acid (7,8 - dihydroneopterin, biopterin) incorporation into phospholipids. Cholesterol content decreased but phospholipid content did not change in samples containing 7,8-dihydroneo-pterin or biopterin. No changes of fatty acid incorporation into phospholipids as well as of the content of cholesterol and phospholipids were observed in samples after addition of isoxanthopterin (5 and 30 pmoljg wet weight) to incubation medium for phospholipid biosynthesis in vitro. Despite the fact that 7,8-dihydroneopterin and biopterin have different oxidation states and some similar effects on phospholipid biosynthesis and cholesterol content have been observed in our study, we suggest that the oxidation state of pteridines is more important than the pterin-( 6 )-side chain in the deviations of fatty acid incorporation into phopholipids as well as in the regulation of cholesterol content in samples
Chronopharmacokinetics of Methotrexate in Mice: Modulation by Administration of 5-Fluorouracil in Combination Chemotherapy
Authors: Graczyk Julita 
Published: March 2013

Summary The basic pharmacokinetic parameters of MTX administered as monotherapy as well as in the combined therapy with simultaneous and prior administation of FU were investigated. The parameters were determined in the two-compartment open system on the basis of measurement of MTX levels in mice after i.p. administration of a single dose 20 mg/ kg of the drug. The FU dose was 20 mg/kg, too. The effect of the circadian rhythm on the kinetics of MTX have been taken into consideration. In one series of experiments the drugs were administered in the morning and in the other during midday hours . The statistical analysis of the obtained results showed the essential effect of the administration time on the pharmacokinetic parameters of MTX in mice. The statistical significal differences could be found: C max, AUC, CL, T0,5 . The differences in T0,5 , parameter resulting from coadministration of FU with the same circadian rhythm of MTX administration have been observed.