bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usefulness of Neopterin, C-reactive Protein, Homocysteine, Pyridoxal-5-phosphate, and Phospholipid Determination in Coronary Artery Disease
Authors: Rudzite Vera , Jurika Edite , Schroecksnade Katharina , Kalnins Uldis , Erglis Andrejs , Trusinskis Karlis , Fuchs Dietmar 
Published: August 2013

Abstract
Blood serum neopterin, high sensitivity C-reactive protein (hsCRP), total homocysteine, pyridoxal-5-phosphatc ( P-5-P) and total phospholipid concentrations have been examined in 30 healthy individuals as well as in patients with coronary artery disease (CAD) verified by coronary angiography (43 patients with 1-artery disease, 24 patients with 2- or 3-artery disease, 17 patients with restenosis) before percutaneous transluminal coronary angioplasty. We have observed increased mean concentrations of neopterin, hsCRP and homocysteine as well as decreased mean concentration of P-5-P and phospholipids in all groups of CAD patients. The positive correlation between neopterin and hsCRP in all CAD patients (r = 0.536; Ρ <0.01 ) as well as an increased frequency of these indices above the upper limit of normal during the course of CAD (30.1 % in eases with 1-artery disease, 54.2% of cases in 2- or 3-artery disease, 76.5% of cases in restenosis) allow to conclude that inflammation has a pivotal role in the progression of CAD. In restenosis the determination ot neopterin was of more significance than the determination of hsCRP. The combination of a mild increase of neopterin and homocysteine concentrations points to the worst prognosis of CAD, both after percutaneous transluminal coronary angioplasty and coronary bypass, restenosis was most liekly to appear. Mild increase of homocysteine concentration in patients with CAD docts not only indicate possible thickening of arterial wall and narrowing of lumen but also to impaired trans-sulfuration and remethylation pathways of homocysteine metabolism as well as to delayed methylation processes in the organism. A decrease of serum P-5-P concentration, which in all groups of CAD patiens reached about 50% as compared with healthy individuals, points to impairment of all metabolic processes, which require the biologically active form of vitamin B6 for their action. The decrease of mean serum phospholipid concentration in all groups of CAD patients may indicate both, impaired phospholipid biosynthesis due to delayed processes of methylation in the organism and increased loss of phosphatidylcholine necessary for transportation of oxidised low density lipoproteins into macrophages. Therefore the determination of serum phospholipid concentration and phosphatidylcholine concentration, especially, has the same significance in the course of CAD as the determination of total cholesterol, high and low density lipoprotein cholesterol widely used at present.
Influence of Meal on Plasma Folate and Vitamin Β12, by Three Methods - and on Vitamin B6, Homocysteine and Red Blood Cell Folate
Authors: Candito Mirande , Houcher Bakhouche , Roux François , Potier de Courcy Genevieve , Caramella Anne , Berthier Frederick , Aberkane Abdelhamid , Van Obberghen E Emmanuel 
Published: August 2013

Abstract
Vitamins are brought by meals. Some of them are cofactors in homocysteine metabolism, and, if plasma homocysteine values are not known to have a circadian rhythm, little is known about meal influence on blood folate, and vitamins Β12 and B6. The aim of this study is to analyze the effect of breakfast and lunch on plasma folate, vitamins B12 and B6. homocysteine and red cell folate (RCF) in 13 subjects; and, in 6 of them, to compare plasma folate and vitamin Β12 values with three analytical methods. In the 13 subjects, folate, vitamins B12 and B6 and RCF were analyzed by RIA, homocysteine by fluorescence polarization immunoassay and vitamin B6 by HPLC. In 6 of the subjects, additionally, plasma folate and vitamin Β12 were analyzed by microbiology and by enzymoimmunoassay (EIA). Mean plasma folate levels at 11AM. 2PM, and 4PM were not significantly different, compared with 9AM mean values, independent of the method, while, when analyzed by microbiology, mean vitamin B12 concentrations decreased significantly (-12%), but not by RIA or by microbiology. Plasma folate concentrations, obtained by the different methods, and RCF concentrations were correlated, as for vitamin B12 concentrations. But, when analyzed by EIA. vitamin B12 v alues were higher than by the two other methods. We conclude that plasma folate levels were constant at the different sampling hours, while vitamin B12 levels were decreased at 11AM, 2PM and 4PM, when compared with the fasting concentrations, and when assayed by microbiology. No difference was seen by RIA or by EIA. The evaluation of clinical data is not easy, due to the lack of a standardized analytical method, and international standards are needed.
The Reaction Mechanism of Phenylalanine Hydroxylase. – A Question of Coordination
Authors: Teigen Knut , Jensen Vidar R. , Martinez Aurora 
Published: August 2013

Abstract
Phenylalanine hydroxylase (PAH) is a non-heme iron and tetrahydrobiopterin-dependent enzyme that catalyzes the hydroxylation of L-phenylalanine to L-tyrosine using dioxygen as additional substrate. The cofactor tetrahydrobiopterin accepts one of the oxygen atoms of dioxygen during catalysis and also seems to be involved in prereduction of the active site iron from the ferric to the activated ferrous form. Structures of the truncated form of PAH in complex with substrate and cofactor are available, but the oxygen binding site and the actual mechanism of electron transfer are uncertain. It is believed that dioxygen binds directly to the metal, where it is activated, and several reaction mechanisms involving end-on binding of 0 2 have been proposed based on both experimental studies and quantum mechanical calculations. However, in this work we aimed to investigate the possibility of side-on binding of dioxygen to the iron. Furthermore, NMR and recent high-resolution crystallographic studies also place the cofactor in closer proximity to the iron, challenging the mechanistic conclusions from earlier crystallographic and computational studies. In this paper we report preliminary results from a density functional theory (DFT) study of the coordination of dioxygen to a structural model of PAH based on a recent crystallographic structure. These results are compared with existing computational and experimental data and their implications for the mechanism of the PAH-reaction are discussed. Particular attention is paid to the binding-mode of dioxygen and the iron-cofactor distance.
Neopterin as a Stimulator of Vascular Endothelial Growth Factor and Erythropoietin Gene Expression in an Ovarian Carcinoma Cell Line
Authors: Rieder Josef , Marth Christian , Schobersberger Wolfgang , Hoffmann Georg 
Published: August 2013

Abstract
Increases in serum neopterin concentrations are a regular finding in patients with ovarian cancer. The strong correlation between neopterin and tumor progression might be explained by a direct influence of the pteridine compound on tumor cell growth. In the present study we investigated whether neopterin affects the production of the angiogenic promotors vascular endothelial growth factor (VEGF) and erythropoietin (EPO) in the human ovarian carcinoma cell line OVCAR-3. VEGF and EPO gene expression were detected via RT-PCR. and a possible involvement of hypoxiainducible factor-1 was assessed by electrophoretic mobility shift assays. Neopterin amplified the hypoxia-induced VEGF and EPO gene expression as well as protein synthesis in a concentration-dependent manner. In addition, generation of both VEGF and EPO could be detected following incubation of cells with neopterin under normoxic conditions, too. Neopterin-induced synthesis of VEGF and EPO was preceeded by a stimulation of hypoxiainducible factor-1 uptake into the nucleus of OVCAR-3 cells. From these data we conclude that neopterin acts as a mediator of angiogenesis. Stimulation of VEGF and EPO generation in ovarian carcinoma cells may promote vascularization of the malignant tissue and thus tumor growth and development.
Urinary Neopterin and Microalbuminuria in Patients Treated by Low-density Lipoprotein Apheresis
Authors: Cermanová Melanie , Melichar Bohuslav , Solichová Dagmar , Bláha Milan , Bláha Vladimir , Blazek Martin , Mašín Vladimir , Cerman Jaroslav , Zadák Zdenek 
Published: August 2013

Abstract
Low-density lipoprotein (LDL)-apheresis is a method of extracorporeal elimination of LDL-cholesterol in patients with severe primary lipoprotein disorders. LDL-cholesterol activates macrophages, which play an important role in atheromatous plaque formation. In the present study, we have investigated urinary neopterin, a specific marker of macrophage activation and microalbuminuria, an indicator of generalized vascular dysfunction, after a single LDL-apheresis procedure in 10 patients with severe primary lipoprotein disorder. The urinary neopterin/creatinine ratio was increased in patients compared to controls. No significant changes of the neopterin/creatinine and albumin/creatinine ratios were observed after LDL-apheresis, except a significant (p < 0.006) decrease of urinary neopterin/creatinine ratio in the evening after the apheresis. This decrease showed significant negative correlation with the pre-apheretic levels of atherogenic cholesterol fractions (p < 0.05) and with cholesterol decrease during the apheresis (p < 0.05). Urinary albumin/creatinine ratio correlated positively with total and LDL-cholesterol levels before the apheresis and with the evening urinary neopterin/creatinine ratio after the apheresis, but did not correlate with glycemia and triacylglycerides. Elevated urinary neopterin in the patients with severe primary lipoprotein disorders reflects the presence of atherosclerosis. A single LDL-apheresis procedure did not significantly affect microalbuminuria. The decrease of urinary neopterin in the evening after the apheresis corresponds with the diurnal rhythm of neopterin excretion and was less pronounced in patients with more severe hypercholesterolemia. The correlations between microalbuminuria, neopterin and pre-apheretic cholesterol concentrations indicate a possible connection between microvascular dysfunction, macrophage activity and severity of hyperlipidemia, but these results should be interpreted with caution because of small number of subjects evaluated.
Inflammation, Homocysteine, Pyridoxal-5-phosphate and Lipids in Patients with Coronary Artery Disease before and Six Months after Coronary Angioplasty Followed by Stent Implantation
Authors: Rudzite Vera , Jurika Edite , Fuchs Dietmar , Kalnins Uldis , Erglis Andrejs , Trusinskis Karlis 
Published: August 2013

Abstract
Thirty healthy individuals as well as 42 patients with coronary artery disease (CAD) verified by coronary angiography were examined before and 6 month after percutaneus transluminal coronary angioplasty followed by stent implantation and statins treatment. Such therapy positively influenced high sensitivity C-reactive protein, total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentration in blood scrum as well as cholesterol to phospholipid ratio. By contrast, scrum concentration of neopterin, total homocysteine, pyridoxal-5-phosphate, triglycerol and phospholipids as well as fatty acid content of phospholipids remained unchanged or became worse. These changes were followed by restenosis or new coronary events in half of observed CAD patients. Findings suggest that cholesterol concentration has no pivotal role, neither in restenosis nor in the development of coronary events after stent implantation. Elevated serum concentration of neopterin and homocysteine before and 6 months after stent implantation appear more significant indicator of new coronary events in CAD patients. Further investigations arc necessary to substantiate these observations.
Tetrahydrobiopterin and Endothelial Dysfunction in Cardiovascular Diseases
Authors: Shinozaki Kazuya , Kashiwagi Atsunori , Masada Masahiro , Okamura Tomio 
Published: August 2013

Abstract
Endothelial vasodilator dysfunction is a characteristic feature of patients at risk for coronary atheroscierosis. We have reported that insulin resistance may be a pathogenic factor for endothehal dysfunction through impaired endothelial nitric oxide synthase (eNOS) activity and increased oxidative breakdown of nitric oxide (NO) due to an enhanced fonnation of Superoxide anion, which arc caused by relative deficiency of tetrahydrobiopterin (BH4) in vascular endothelial cclls. Guanosine-triphosphate cyclohydrolase I, the rate-limiting cnzyme in the production of BH4, is decreased in the aorta of insulin-resistant rats and supplementation of BH4 restored the endothelial function and relieved oxidative tissue damage. The BH4 treatment may evoke these benefits not only by providing eNOS with cofactor to enhance NO synthesis, but also by acting as an indirect and/or direct antioxidant to decrease Superoxide anion derived from the endothelium. A further understanding of the physiological and pathological roles and their regulation may lead to new therapeutic avenues.
Tetrahydrobiopterin Regulates L-tyrosine-induced Elevation of Cytosolic Calcium Concentration in Insulin-secreting Cells
Authors: Ishii Masakazu , Shimizu Shunichi , Watabe Tatsuya , Kiuchi Yuji 
Published: August 2013

Abstract
We examined the role of endogenous tetrahydrobiopterin (BH4) on L-tyrosine-induced increase in cytosolic Ca: concentration ([Ca2+],) in the ß-cell line, HIT-T15. Addition of L-tyrosine to the cells increased [Ca2+], in a conccntration- depcndent manner. Moreover, the L-tyrosine-induced [Ca2+], elevation was blocked by L-3,4-dihydroxyphenylalanine (L-DOPA). Under low levels of BH4 by treatment with 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of BH4 biosynthesis, elevation of [Ca2+], by L-tyrosine was stimulated. Moreover, co-prctreatment with sepiapterin, a precursor of BH4 biosynthesis, reduced the decrease of BH4 content by DAHP, and suppressed L-tyrosine-induccd [Ca2+ ]¡ elevation in DAHP-pretreated cells. These findings suggest that BH4 negatively regulates L-tyrosine-induced [Ca2+] elevation via the production of L-DOPA in ß-cells.
Intravascular Ultrasound Data and Results of Serum Biochemical Indices at the Time of Stenting and after Six Months in Patients with Coronary Artery Disease
Authors: Rudzite Vera , Jurika Edite , Erglis Andrejs 
Published: August 2013

Abstract
Thirty healthy individuals and 23 patients with coronary artery disease (CAD) verfied by coronary angiography were examined at the time of stenting and 6 months after percutaneous transluminal coronary angioplasty (PTCA) followed by intravascular ultrasound ( IVUS)-guided stenting and treatment with statins. Analysis of IVUS volumetric measurement for all stented segments after 6 months showed a small but significant decrease of mean minimal square area (18.39%), mean minimal lumen diameter ( 12.77%), and mean minimal lumen volume (12.66%), if compared with values obtained at the time of stenting. Before stenting we observed an increase of serum triglycerides, total cholesterol, low density lipoprotein cholesterol (LDL-cholesterol) concentrations, cholesterol to phospholipid ratio and the percentage of saturated fatty acids in phospholipids, while serum high density lipoprotein cholesterol (HDL-cholesterol) and phospholipids concentrations as well as the percentage of unsaturated fatty acid in phospholipids were lowered. Six months after stenting and treatment with statins a significant increase of HDL-cholesterol was found, while other indices of lipids mentioned above remained unchanged. Before stenting we have also observed increased scrum concentration of C'-reactive protein (CRP), neopterin, total homocysteine, and kynurenine concentrations, while pyridoxal-5-phosphate (P-5-P) concentration was lowered. Six months after stenting and treatment with statins, CRP, neopterin, homocysteine, and P-5-P serum concentrations remained unchanged, while kynurenine concentration increased (P <0.02).
The results of this study as well as data of our previous investigations suggest that improvement of blood circulation of the heart muscle due to stenting does not normalise intercellular metabolism in patient with CAD. Some improvement observed in lipid metabolism can be the result of treatment with statins, although these changes in lipid metabolism were not followed by improvement of other biochemical indices examined in CAD patients of this study. At present the role of kynurenine in the course of CAD is obscure. Therefore further investigations are necessary.
Effect of Neopterin Derivatives on Mitochondrial Dehydrogenase Activity in Ovarian Carcinoma Cell Lines in Vitro
Authors: Rieder Josef , Marth Christian , Hoffmann' Georg 
Published: August 2013

Abstract
In a recent study we could show that neopterin inhibits nitric oxide-induced apoptosis in ovarian carcinoma cells. This may provide an explanation for the correlation between increased levels of neopterin derivatives and the unfavorable prognosis in patients with ovarian cancer that has been described in the literature. To obtain additional information on the mode of action of neopterin derivatives within the tumor environment, we studied the effects of neopterin (100 and 1000 μΜ) and 7,8-dihydroneopterin (100, 500, and 1000 μΜ) on mitochondrial dehydrogenase activity in three different ovarian carcinoma cell lines (2774, HOC-1, and OVCAR-3). 7,8-dihydroneopterin was an effective stimulus of mitochondrial enzyme turnover rate in any cell culture model under investigation. This suggests that the pteridine compound stabilizes tumor cell viability and therefore acts as a promotor of tumor growth. In contrast to 7.8-dihydroneopterin, neopterin did not affect mitochondrial dehydrogenases in 2774, HOC-7, or OVCAR-3 cells. However, in HOC-7 and OCVAR-3, neopterin was found to antagonize the stimulating effects of 7,8-dihydroneopterin. This might be due to the different impact of both pteridine compounds on the redox status in these cells. Our new data provide further evidence of distinct biochemical effects of neopterin derivatives in ovarian carcinoma cells. Neopterin and 7,8-dihydroneopterin may be involved in separate stages of cellular changes that lead to malignancy or promote tumor progression.
Urinary Neopterin in Patients with Ovarian Cancer
Authors: Melichar Bohuslav , Krcmová Lenka , Kalabova Hana , Svobodova Iveta , Dragounova Emanuela , Vesely Pavel , Hyspler Radomír , Solichova Dagmar , Urbanek Lubor 
Published: August 2013

Abstract
Urinary neopterin, an indicator of systemic immune activation, is increased in most patients with epithelial ovarian carcinoma (EOC) and is an independent prognostic indicator. The data on prognostic significance of neopterin in EOC have been collected before the advent of paclitaxel that has changed the management and natural history of the disease. In the present study, we have evaluated the prognostic significance of urinary neopterin in 49 patients with primary and secondary ovarian neoplasms treated in the late 1990s and in 2000s. Urinary neopterin was measured by high-performance liquid chromatography. Compared to controls, urinary neopterin was significantly increased in patients with both primary ovarian cancer and ovarian metastases of other tumors (341 ± 343, and 328 ± 277 vs. 133 ± 40 μmol/mol creatinine; p <0.001 ). Serious toxicity of chemotherapy was observed in 8 out of 12 (67%) patients with urinary neopterin equal or above 338 μmol/mol creatinine (mean of all patients) compared to 2 of 19 ( 11%) of patients with urinary neopterin below 338 μmol/mol creatinine (Fisher exact test, p - 0.001). No significant changes were observed in urinary neopterin concentrations during the treatment with paclitaxel/platinum. A significant correlation was observed between urinary neopterin and percentage of xylose absorbed (rs = -0.58, p = 0.03), and positive correlations were observed between urinary neopterin and lactulose/ mannitol (rs = 0.63, p = 0.02), lactulose/xylose (rs = 0.79, p = 0.0007) and sucrose/xylose (rs = 0.60, p = 0.02) ratios. Survival was significantly longer in patients with urinary neopterin below 338 μιηοΐ/ιτιοί creatinine in the whole group of 49 patients with ovarian cancer, in 36 patients with primary ovarian cancer as well as in 13 patients in ovarian metastases of other primary tumors. A significant difference in survival was also observed when 37 pretreated patients or 24 pretreated EOC patients were evaluated (p = 0.05). In conclusion, neopterin remains a significant prognostic indicator in patients with recurrent ovarian cancer in the era of newer chemotherapeutic agents. Increased urinary neopterin was associated with chemotherapy toxicity.
Serial Urinary Neopterin Measurements Reflect the Disease Course in Patients with Epithelial Ovarian Carcinoma Treated with Paclitaxel/Platinum Chemotherapy
Authors: Melichar Bohuslav , Kalabova Hana , Urbanek Lubor , Malirova Eva , Solichova Dagmar 
Published: August 2013

Abstract
Increased concentrations of urinary neopterin, an indicator of systemic immune activation, have been reported in patients with cancer, including epithelial ovarian carcinoma (EOC). We have assessed urinary neopterin before the treatment and then daily during the therapy with paclitaxel/platinum combination in 5 EOC patients. A correlation was observed between the clinical course and serial urinary neopterin concentrations. We conclude that the determination of serial urinary neopterin concentrations may be useful for monitoring of EOC patients during chemotherapy.
Tetrahydrobiopterin Slows the Progression of Atherosclerosis
Authors: Kunihiro Suzuki , Hattori Yoshiyuki , Jojima Teruo , Tomizawa Atsuko , Okayasu Toshie , Kase Hiroyuki , Kawagoe Yoshiaki , Banba Nobuyuki , Monden Tsuyoshi , Nakanishi Nobuo , Kasai Kikuo 
Published: August 2013

Abstract
We investigated whether oral tetrahydrobiopterin (BH4) treatment might slow the progression of atherosclerosis using hypercholesterolemic ApoE-knockout (KO) mice. We report that ingesting BH4 in drinking water is effective to inhibit atherogenesis in mice. Furthermore, we report that BH4 treatment improves endothelial dysfunction and attenuates increased mRNA expression of NADPH oxidase components, as well as a number of inflammatory factors, such as LOX-1 and MCP-1, in the aortas of ApoE-KO mice. Strategies such as oral administration of BH4 to ensure continuous BH4 availability may be effective in restoring NO-mediated endothelial function and limiting vascular disease and the progression of atherosclerosis.