bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Characteristics and Feelings About Pregnancy Among Black and Puerto Rican Young Adults
Authors: Carter Marion , Kraft Joan M. , Hock‐Long Linda , Hatfield‐Timajchy Kendra
Published: August 2013

Context

Unintended pregnancy is common among black and Hispanic young adults in the United States. How pregnancy intentions form and change is poorly understood, although research indicates that intentions and attitudes are dependent on partners’ views and other relationship factors, and are different by gender.

Methods

A sample of black and Puerto Rican men and women aged 18–25 from low‐income neighborhoods in two cities were surveyed in 2007–2008. Using data on 520 serious and casual sexual relationships reported by 460 respondents, generalized ordered logistic regression analysis was conducted to identify individual‐ and relationship‐level correlates of how respondents would feel if they became involved in a pregnancy with a particular partner.

Results

About one‐quarter of respondents reported each of four possibilities of how they would feel about a pregnancy with a particular partner—very upset, a little upset, a little pleased and very pleased. In 45% of relationships, respondents believed that their partners would be very pleased about a pregnancy, whereas they themselves would be very pleased in only one‐quarter of cases. Overall, women were less likely to feel positive about a pregnancy than were men (odds ratio, 0.3). Respondents’ positive feelings about their relationships were associated with a strong tendency toward more positive feelings about a pregnancy (2.1), as was a measure of how positive respondents thought their partners would feel (1.5–2.6). The latter association was particularly strong among women (1.7).

Conclusions

Relationship characteristics were associated with feelings about pregnancy for both genders. Future research should utilize a more comprehensive framework for conceptualizing and examining sexual relationships.
Analytical and Numerical Deflection Study on the Structure of 10 kW Low Speed Permanent Magnet Generator
Authors: Alam Hilman Syaeful , Irasari Pudji , Dewi Dyah Kusuma
Published: August 2013

Analytical and numerical studies of the deflection in the structure of 10 kW low speed permanent magnet generator (PMG) have been discussed in this paper. This study is intended to prevent failure of the structure when the prototype is made. Numerical analysis was performed with the finite-element method (FEM). Flux density, weight and temperature of the components are the required input parameters. Deflection observed were the movements of the two main rotor components, namely the rim and shaft, where the maximum deflection allowed at the air gap between rotor and stator should be between 10% to 20% of the air gap clearance or 0.1000 mm to 0.2000 mm. Base on the analysis, total deflection of the analytic calculation was 0.0553 mm, and numerical simulation was 0.0314 mm. Both values were in the acceptable level because it was still below the maximum allowed deflection. These results indicate that the structure of a permanent magnet generator (rim and shaft) can be used safely.
Keeping score on congress: explaining variations in interest group ratings of US senators
Authors: Chand Daniel E. , Schreckhise William D.
Published: August 2013

We adopt a novel use for an old type of data – interest group scorecards – to explore the impact business organizations have on the political process. By aggregating congressional scorecards, we can develop a sense of how satisfied groups are with the US Congress as a whole. To do this, we generate interest group-level ratings of the US Senate derived from individual-level ratings of each senator. We find business groups tend to give higher aggregated scores relative to other types of groups, suggesting business organizations more often get what they want form Congress, which in turn, illuminates the importance of these groups in the political process. We also find that well-funded “niche” organizations tend to show higher levels of satisfaction with senators than larger groups with broad public missions.
SAA1 genetic polymorphisms are associated with plasma glucose concentration in non-diabetic subjects
Authors: Xie Xiang , Ma Yi-Tong , Yang Yi-Ning , Li Xiao-Mei , Zheng Ying-Ying , Fu Zhen-Yan , Ma Xiang , Liu Fen , Huang Ying , Chen Bang-Dang
Published: August 2013

Background: Serum amyloid A (SAA) was reported to be associated with insulin resistance and type-2 diabetes. The present study aimed to investigate the association of SAA genetic polymorphisms with plasma glucose levels in non-diabetic subjects.

Methods: All participants (n=1220) were selected from subjects participating in the Cardiovascular Risk Survey (CRS) study. Five single-nucleotide polymorphisms (SNPs) (rs2229338, rs12218, rs4638289, rs7131332 and rs11603089) of SAA gene were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis.

Results: In the present study, we found rs2229338, rs4638289 and rs12218 were significantly associated with plasma glucose levels in a dominate model, recessive model or additive model before and after multivariate adjustment (all p<0.05). These associations were not found in rs7131332 and rs11603089 before and after adjustment of key co-variants.

Conclusions: The genetic polymorphisms of SAA1 were associated with plasma glucose levels in non-diabetic subjects.
Double heterozygosity in the BRCA1 and BRCA2 genes in Italian family
Authors: Vietri Maria Teresa , Molinari Anna Maria , Caliendo Gemma , De Paola Maria Laura , Giovanna D’Elia , Gambardella Anna Laura , Petronella Pasquale , Cioffi Michele
Published: August 2013

Background: Double heterozygosity (DH) is an extremely rare event in which both BRCA1 and BRCA2 are mutated simultaneously in a family. To date, few cases of DH have been reported, especially in Ashkenazi populations. In Italy some cases of DH have been reported. In this study, we have described an Italian family with double heterozygosity in the BRCA genes.

Methods: The proband is a 43-year-old woman with bilateral breast cancer. She presented two pathogenic mutations in both BRCA genes, IVS8+2T>A (c.547+2T>A;p.Gln148Aspfsx51) in BRCA1, K944X (c.2830A>T;p.Lys944X) in BRCA2 and a novel variant IVS4–57A>G (c.426–57A>G) in BRCA2, not previously described. Both mutations were inherited from the paternal lineage in the proband’s family. We investigated all available members of this family and we identified other two family members with DH.

Results and conclusions: Our observations support the hypothesis of a non-specific severe phenotype in DH carriers in terms of age of disease onset, cumulative lifetime risk and multiple primary tumours. Furthermore, our findings confirm that in order to identify all cases of DH, it is important not to limit the identification of mutations in a single gene, but extend the analysis to BRCA1 and BRCA2 and other breast cancer susceptibility genes.
Measured temperature and moisture profiles during thermal modification of beech (Fagus sylvatica L.) and spruce (Picea abies L. Karst.) wood
Authors: Čermák Petr , Horáček Petr , Rademacher Peter
Published: August 2013

The temperature and moisture profiles during thermal modification of beech (Fagus sylvatica L.) and spruce (Picea abies L. Karst.) wood have been investigated. Specimens with dimensions of 80×80×200 mm3 were heat treated based on ThermoWood technology. Heat transfer was continuously measured by several thermocouples placed into various positions of the samples. In the course of the treatment, samples were removed from the chamber at different times, and their moisture content (MC) was measured by the so-called slicing technique. The complete data of heat and moisture movement during the heat treatment process are presented. Significant temperature gradients occur in the initial and modification stages of the process. In the latter, the chamber temperature was 200°C for 3 h, but exothermic reaction increased the sample temperatures to 240°C (beech) and 215°C (spruce). Thermodiffusion (Soret effect) at the beginning of the process was observed. Therefore, the MC under surfaces (in transverse and in longitudinal direction) was increasing ∼0.5%–3% for 5 h. The results provide a better insight into details of thermal modification of wood.
Pregnancy, obesity and insulin resistance: maternal overnutrition and the target windows of fetal development
Authors: Muhlhausler Beverly S. , Gugusheff Jessica R. , Ong Zhi Yi , Vithayathil Mini A.
Published: August 2013

A substantial body of literature has demonstrated that the nutritional environment an individual experiences before birth or in early infancy is a key determinant of their health outcomes across the life course. This concept, the developmental origins of health and disease (DOHaD) hypothesis, was initially focused on the adverse consequences of exposure to a suboptimal nutrient supply and provided evidence that maternal undernutrition, fetal growth restriction, and low birth weight were associated with heightened risk of central adiposity, insulin resistance, and cardiovascular disease. More recently, the epidemic rise in the incidence of maternal obesity has seen the attention of the DOHaD field turn toward identifying the impact on the offspring of exposure to an excess nutrient supply in early life. The association between maternal obesity and increased risk of obesity in the offspring has been documented in human populations worldwide, and animal models have provided critical insights into the biological mechanisms that drive this relationship. This review will discuss the important roles that programming of the adipocyte and programming of the central neural networks which control appetite and reward play in the early life programming of metabolic disease by maternal overnutrition. It will also highlight the important research gaps and challenges that remain to be addressed and provide a personal perspective on where the field should be heading in the coming 5–10 years.
Morphological study of PVDF/PMMA/TiO2 blend films prepared by melt casting process
Authors: Hosoda Tomonori , Yamada Toshiro
Published: August 2013

The influence of chill roll temperature and thermal annealing on the morphology and dynamic mechanical behavior of poly(vinylidene fluoride) (PVDF)/poly(methyl methacrylate) (PMMA)/titanium dioxide blend films prepared by a melt casting process was studied. The β phase of PVDF was formed at the chill roll temperature of 30°C. Furthermore, with the increase in this chill roll temperature, its structural conversion to the α phase was observed. No change in the crystal structure of either the β or α phase occurred on account of thermal annealing at 115°C for 24 h. The decrement in the storage modulus above the glass transition temperature ascribed to the mixed amorphous phase became smaller, as the chill roll temperature increased. Based on morphological observations, we deduced that the reason for this decrement is not that the film cast at 115°C was more crystalline than that cast at 30°C but that the actual weight fraction of PMMA in the mixed amorphous phase of the film cast at 115°C was lower than that of the one cast at 30°C.
Neopterin, soluble adhesion molecules and soluble cytokine receptors correlate with disease activity in rheumatoid arthritis
Authors: Nassonov El , Samsonov My , Tilz Gp , Chichasova Ny , Widner B , Demel U , Nikiphorova El , Fuchs D
Published: August 2013

Serum concentrations of soluble intercellular adhesion molecules, sICAM-I , sICAM-3 and sP-selectin, of serum soluble cytokine receptors, sIL-2R, and sTNF-R55 and of neopterin were measured by commercially available immunoassays in 35 patients with rheumatoid arthritis (RA). Serum sICAM-I, sICAM-3 and sPselectin were significantly elevated in patients with RA compared with healthy controls. Concentrations of sPselectin and sICAM-3 correlated with disease activity and severity indices. sICAM-3 levels significantly correlated with sTNF-R55 and neopterin. There were significant correlations between neopterin and sIL-2R and between sTNF-R55 and sIL-2R. The measurement of sP-selectin and sICAM-3 levels in patients with RA might become useful for monitoring disease activity.
Hydrogen Peroxide Stimulates the LPS-induced Tetrahydrobiopterin Synthesis in Mouse Brain Microvascular Endothelial Cells
Authors: Shiota Kazuhiro , Shimizu Shumchi , Ishii Masakazu , Yamamoto Shinichiro , Iwasaki Michiko , Yamamoto Toshinori , Kiuchi Yuji
Published: August 2013

Tetrahydrobiopterin (BH4) is one of the cofactors for nitric oxide synthase (NOS), and also has a protective effect against reactive oxygen species (ROS)- and/or nitric oxide (NO)-induced cytotoxicities. Lipopolysaccharide (LPS) induces NO production and BH4 synthesis, and also ROS release. This study examined whether hydrogen peroxide, one of the ROS, has a regulatory role in BH4 synthesis in vascular endothelial cells. Addition of LPS to the endothelial cells increased the BH4 content. Although the LPS-induced increase in BH4 content was not affected by the treatment with superoxide dismutase and catalase, co-treatment with hydrogen peroxide further stimulated the LPS-induced increase in BH4 content. Moreover, the hydrogen peroxide-induced increase in BH4 content in the presence of LPS was completely inhibited by the treatment with 2,4-diamino-6-hydroxypyrimidine, an inhibitor of GTP-cyclohydrolase I (GTPCH). These findings suggest that hydrogen peroxide may stimulate LPS-induced BH4 synthesis through the induction and/or activation of GTPCH. Under inflammation, hydrogen peroxide seems to stimulate BH4 synthesis.
3-Hydroxy-3-methylglutaryl-CoA Reductase Inhibitors Enhance Cytokine-mediated Induction of Nitric Oxide Synthesis in Vascular Smooth Muscle Cells
Authors: Hattori Yoshiyuki , Nakanishi Nobuo , Suzuki Manabu , Yoshida Mika , Kasai Kikuo
Published: August 2013

We investigated the effects of by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, cerivastatin and fluvastatin, on the induction of nitric oxide (NO) production in vascular smooth muscle cells ( VSMC) stimulated by interleukin-1β (1L-1) or in combination with interferon-γ (IFN). IL-1 activated VSMC to synthesize and release NO, which was significantly potentiated by IFN. NO production induced by IL-1 or IL-1/lFN was dosedependently enhanced by both HMG-CoA reductase inhibitors. Incubating VSMC with IL-1/IFN stimulated inducible NO synthase (iNOS) mRNA expression. Both HMG-CoA reductase inhibitors significantly upreguiated IL/IFN-stimulated iNOS mRNA expression, and enhanced iNOS gene transcription as shown by nuclear run-on assays. Both IIMG-CoA reductase inhibitors slightly modulated IL-1/IFN-induced NF-kB activation, which was not associated with their effect on NO production. Cytokines induce the de novo synthesis of tetrahydrobiopterin (BH4) in VSMC. This event is essential for the induction of NO synthesis, which requires transcriptional induction of the genes that encode not only iNOS but also guanosine triphosphate cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in de novo BH4 synthesis. The synthesis of BH4 and GFPCH mRNA induced by IL-1/IFΝ were enhanced by both HMG-CoA reductase inhibitors. Exogenous mevalonate significantly prevented and geranylgeranylpyrophosphate reversed the stimulatory effect of HMG-CoA reductase inhibitors. Thus, the effect of HMG-CoA reductase inhibitors on NO production is due at least partly through blocking the biosynthesis of mevalonate, which prevents isoprenoid biosynthesis. Our data demonstrated that HMG-CoA reductase inhibitors enhance immunostimulants-induced NO production by increasing iNOS gene expression at the transcriptional level via an NF-kB-independent pathway. In addition to augmenting iNOS expression, HMG-CoA reductase inhibitors potentiate GTPCH gene expression and BH4 synthesis, thereby prevents a relative shortage of BH4 which may shift in the balance between NOS-catalyzed generation of protective NO and deletorious reactive oxygen species.
Association Between Neopterin Production and other Parameters in a Population of Blood Donors
Authors: Schennach Harald , Murr Christian , Gächter Elmar , Mayersbach Peter , Schönitzer Diether , Fuchs Dietmar
Published: August 2013

Neopterin is released from human monocyte-derived macrophages preferentially upon stimulation with the Thlcell cytokine interferon-γ. In humans, increased concentrations of neopterin in serum and urine have been found in viral infections including human immunodeficiency virus type 1, various malignant disorders, autoimmune diseases and during allograft rejection episodes. In order to find additional parameters which might influence neopterin production, serum neopterin concentrations of 1156 blood donors were compared with other parameters routinely determined in blood transfusion. There existed correlations between serum neopterin concentration and blood donors' age (Spearman's rank correlation: rs = 0.259, ρ <0.0001), arterial diastolic blood pressure (rs 0.132, ρ <0.0001) and body mass index (rs = 0.084, ρ <0.01). Serum neopterin concentrations were lower in smokers compared to nonsmokers (Mann-Whitney test, ρ <0.0001). The data demonstrate that higher neopterin concentrations are associated with older age, higher diastolic blood pressure and higher body mass index, whereas lower neopterin concentrations are found in smokers compared to nonsmokers. It is assumed that immunopathogenetic pathways underlie these relationships, but the exact background of these associations still needs to be resolved.
Stimulation of Tetrahydrobiopterin Synthesis by Basic Fibroblast Growth Factor in Vascular Endothelial Cells
Authors: Shimizu Shunichi , Miyasaka Yoshiyuki , Yamamoto Shinichiro , Ishii Masakazu , Kiuchi Yuji
Published: August 2013

The purpose of this study was to examine whether basic fibroblast growth factor (bFGF) stimulates tetrahydrobiopterin (BH4) synthesis in mouse brain microvascular endothelial cells. BH4 content was determined by oxidation under acidic conditions as biopterin and analysed with reversed-phase high Performance liquid chromatography. Measurement of the mRNA level of QTP-cyclohydrolase I (GTPCH), which is the rate-limiting enzyme of the de novo pathway of BH4 synthesis. The addition of bFGF to endothelial cells increased the BH4 content and GTPCH mRNA levels in an incubation period- and a concentration-dependent manner. 2,4-Diamino-6- hydroxypyrimidine, an inhibitor of GTPCH, strongly reduced the bFGF-induced increase in BH4 content. These findings suggest that bFGF stimulates BH4 synthesis via a de novo pathway with the induction of GTPCH.
Homocysteine, Β Vitamins and Immune Activation in Coronary Heart Disease
Authors: Frick Barbara , Rudzite Vera , Schröcksnadel Katharina , Kalnins Uldis , Erglis Andrejs , Trusinskis Karlis , Fuchs Dietmar
Published: August 2013

Moderate hyperhomocysteinemia is associated with an increased risk of coronary heart disease (CHD). An inverse relationship usually exists between homocysteine and folate concentrations, and folate supplementation is often able to lower homocysteine concentrations. Thus, insufficient dietary intake of folate and/or vitamin B12 is considered to be responsible for the development of hyperhomocysteinemia. Inflammation and immune activation appear also to be important in the pathogenesis of CHD and may influence availability of folate. Blood concentrations of homocysteine, Β vitamins and neopterin were examined in 35 patients with CHD verified by coronary angiography, (2 1 patients with one-artery disease, 9 with two- or three-artery disease, 5 with restenosis). Compared to 30 healthy controls, a significant proportion of patients presented with increased homocysteine concentrations. Hyperhomocysteinemia coincided with lower folate and also with higher neopterin concentrations indicating immune system activation. In addition, correlations existed between neopterin and homocysteine (r = 0.472, ρ < 0.01) and folate (r = -0.370, ρ = 0.01). We conclude that higher homocysteine is not only associated with lower circulating folate but also with higher neopterin. Immune activation could be involved to cause an increased demand for folate resulting in hyperhomocysteinemia even when dietary folate intake is within the recommended range.
Concentrations of Neopterin and Interleukin-10 in Peritoneal Fluid and in Serum of Women with Endometriosis
Authors: Kondera-Anasz Zdzislawa , Sikora Justyna , Mertas Anna , Miciñski Piotr , Bednarz Bartlomiej
Published: August 2013

Endometriosis is a gynaecological disorder characterized by increased number and activation of peritoneal macrophages and release of macrophage-derived cytokines and growth factors. The aim of our work was t(5 study the level of neopterin and interleukin (TL)-10 in peritoneal fluid and serum of women with endometriosis in relation to stage of disease. Concentrations of neopterin and IL-10 were measured by enzyme linked immunosorbent assay in PF and serum of 58 women; 43 with endometriosis and 15 without endometriosis. In our study present of neopterin in PF of women with endometriosis whereas neopterin could not be detected in the control group. Neopterin serum concentrations were significantly higher in affected women compared with control. Significantly increased neopterin concentrations were observed in peritoneal fluid and serum of women with advanced endometriosis. The mean peritoneal fluid and serum IL-10 concentrations were significantly higher ainong studied women than control. In women with early endometriosis, significantly increased concentration of IL-10 in peritoneal fluid and serum was observed. In conclusions, both increased concentrations of neopterin and IL-10 in the peritoneal fluid and serum suggest an important role of these Compounds in pathogenesis of endometriosis and indicate an enhanced macrophage activity in this disease.
Elevated Post-transplant Levels of Neopterin are Associated with Poorer long-term Graft Outcome
Authors: Grebe S. O. , Kuhlmann U. , Müller T. F.
Published: August 2013

Chronic allograft nephropathy (CAN) and death with functioning graft due to cardiovascular disease (CVD) are the key determinants for long-term renal allograft survival. Chronic allograft nephropathy and cardiovascular disease are seen as manifestations of a single disease entity with a common pathogenesis including inflammation and accelerated atherogenesis. Therefore we investigated the relation between early post-transplant inflammatory burden and long-term graft survival.

In 64 consecutive renal transplant patients the acute phase reactants serum amyloid A (SAA) and serum C-reactive protein (S-CRP) as well as the macrophage product neopterin in urine (U-NEOP) and serum (S-NEOP) were determined daily during the immediate postoperative period (mean p.o.obs. χ = 29.2 ± 8.7 days, total of Σ = 1869 days). SAA and CRP were measured with high-sensitive assays (in mg/1; immune nephelometry, Dade Behring Co., Marburg, Germany), NEOP was measured with ELISA-technique (Brahms, Berlin, Germany) and related to serum and urine creatinine levels, resp. (in μπιοΐ/mol creatinine). The association between the mean values of these parameters and the survival distribution function of the 64 patients was tested using the log rank test and the Wilcoxon-test. In this analysis graft loss was defined as either resumption of dialysis treatment or patient death with functioning graft.

The 1- and 5- year graft survival rates in our patients were 93% and 76%, resp. The markers showed the following mean post-transplant levels: S-CRP χ = 21.3 ± 16.1 mg/1, SAA χ = 10.1 ± 6.5 mg/1, U-NEOP χ = 602 ± 427 mmol/mol creatinine and S-NEOP χ = 81 ± 60 μπιοΐ/mol creatinine. Both log rank test and Wilcoxon-test provided evidence that the graft survival is negatively related to the post-transplant levels of U-NEOP (p = 0.009 and ρ = 0.027, resp.). The markers S-NEOP (p = 0.074 and ρ = 0.116, resp.), SAA (p = 0.599 and ρ = 0.294, resp.), and S-CRP (p = 0.059 and ρ = 0.358, resp.) did not reach statistical significance. These findings support the impact of the inflammatory burden on graft survival. In particular, elevated post-transplant neopterin values, reflecting activated innate and adaptive responses, are predictive for long-term graft outcome.
Neopterin to Monitor Clinical Pathologies Involving Interferon-γ Production
Authors: Schroecksnadel Katharina , Murr Christian , Winkler Christiana , Wirleitner Barbara , Fuith Lothar C. , Fuchs Dietmar
Published: August 2013

Upon stimulation with the cytokine interferon-γ human monocytes/macrophages produce neopterin. Accordingly, measurement of neopterin concentrations in body fluids like blood, urine or cerebrospinal fluid provides information about activation of immune response involving type 1 Τ helper cells. Increased neopterin production is found in infections by viruses including human immunodeficiency virus (HIV), infections by intracellular living bacteria and parasites, autoimmune diseases, malignant tumor diseases and in allograft rejection episodes, but also in some neurodegenerative and in cardiovascular diseases. Major diagnostic applications of neopterin measurements are monitoring of the immune status of allograft recipients, detection of infectious diseases in blood donations and monitoring of therapy in HIV-infected individuals. Neopterin concentrations also provide prognostic information in HIV-infected individuals and in several malignant tumor diseases, high neopterin production at the moment of diagnosis is associated with poorer survival expectations. As high neopterin production is associated with increased production of reactive oxygen species and with low serum concentrations of antioxidants like α-tocopherol, neopterin can be regarded as a marker of oxidative stress caused by an activated immune system. Therefore, by neopterin measurements not only the extent of cellular immune activation, but also the extent of tissue damage caused by reactive oxygen specics may be estimated.
Serum Neopterin as a Marker for Screening of Hepatocellular Carcinoma
Authors: Tsuda Yasuhiro , Fukuda Akira , Kobayashi Hiroyuki , Itou Dai , Yoshimoto Satomine , Iwata Kazunari , Hanafusa Toshiaki
Published: August 2013

As Screening markers for hepatocellular Carcinoma (HCC), alpha-fetoprotein (AFP) and protein induced by an absence of vitamin K or antagonist-II (PIVKA-II) are widely used, but the sensitivity and specificity are not satisfactory enough. Neopterin is a biological marker for increased cell-mediated immunity, but has not been fully studied on HCC. To assess the clinical significance of serum neopterin as a screening marker for HCC, fifty-six HCC patients with liver cirrhosis (LC) and thirty-two LC patients without HCC as controls were studied. Serum neopterin level (n mol/L) was determined by immunoenzymatic assay. The sensitivity and specificity were analyzed by using ROC analysis. The mean level oi neopterin in HCC was significantly higher than that in LC (20.4 YS. 7.7 nmol/L, P<0.001). There was no significant relationship among serum AFP, PIVKA-II, and neopterin in HCC patients. When the cut-off value was set at 12 n mol/L, the sensitivity and specificity of neopterin was 88% and 73%, respectively. In patients with early HCC (<3cm), the detection rate of AFP, PIVKA-II, and neopterin was 35%, 35%, and 70 %, respectively. When all three markers were used, 95% of all HCC patients and 90% of early HCC patients could be detected. The detection rate of neopterin was not affected by ALT level, PLT count, liver function, angiographic pattern, histology, TNM stage, and type of tumor. These findings suggests that serum neopterin can be useful as a Screening marker for HCC and makes it possible to detect HCC at its earlier stage when used in combination with AFP or PIVKA-II.
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

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

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

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

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

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

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

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

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

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

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

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.