bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary Neopterin in Patients with Diabetes Mellitus and Foot Ulcers
Authors: Melicharova Karolina , Kusalova Marie , Smahelova Alena , Hyspler Radomir , Solichova Dagmar , Melichar Bohuslav
Published: August 2013

Increased urinary or serum concentrations of neopterin have been reported in disorders associated with systemic immune activation, e.g. viral infections, cancer, or autoimmune diseases, but the data on neopterin concentrations in patients with diabetes mellitus are limited. The aim of the present study was to investigate urinary neopterin concentrations in patients with diabetes mellitus and with or without diabetic foot. Urinary neopterin was determined by high-performance liquid chromatography in 51 patients with diabetes mellitus, including 19 patients with diabetic foot, and 18 healthy controls. Neopterin concentrations were significantly increased in patients with diabetes mellitus compared to controls (mean ± standard deviation; 221 ± 149 vs. 139 ± 66 μmol/mol creatinine; Mann-Whitney U test, p = 0.003). Urinary neopterin concentrations in patients with or without diabetic foot were identical (224 ± 113 vs. 219 ± 169 μmol/mol creatinine). No significant difference was also observed between patients with type 1 and type 2 diabetes mellitus, between patients treated with insulin compared to patients not treated with insulin, patients with or without diabetic retinopathy, with or without diabetic neuropathy, with or without diabetic nephropathy, with or without ischemic heart disease, with or without ischemic disease of lower extremities, and with or without ischemic cerebrovascular disease. Atrend of higher neopterin concentrations was observed in patients with any complication of diabetes compared to no complications (234 ± 164 vs. 176 ± 73 μmol/mol creatinine), and compared to controls, urinary neopterin was significantly increased only in patients with complications. No significant correlation was observed between urinary neopterin and glycosylated hemoglobin (rs = - 0.14, p = 0.39) or the duration of diabetes (rs = 0.25, p = 0.09). In conclusion, present results demonstrate that urinary neopterin is increased in patients with diabetes mellitus. No differences were observed in urinary neopterin concentrations based on type of diabetes, therapy or presence of diabetic foot, and urinary neopterin did not correlate with the glycosylated hemoglobin levels or duration of diabetes. Increased urinary neopterin concentrations in patients with diabetes mellitus is associated with the presence of complications and may reflect systemic immune activation associated with atherosclerosis.
Neopterin, Catalase and Superoxide Dismutase in Females with Benign and Malignant Breast Tumors
Authors: Yuksel Osman , Sahin Tevfik Tolga , Girgin Gozde , Sipahi Hande , Dikmen Kursat , Samur Ozlem , Barak Anil , Tekin Ercument , Baydar Terken
Published: August 2013

The aim of the present study was to evaluate the relationship between the levels of neopterin among patients with benign and malignant breast disease and the relation with the stage of the malignant process. In this study, neopterin concentrations and enzyme activities of superoxide dismutase (SOD) and catalase (CAT) were determined in malign (n=30) and benign breast tumor patients (n=30) by high performance liquid chromatographic and spectrophotometric methods, respectively. Results were compared with a healthy control group (n=20). The correlations between neopterin, CAT and SOD were also evaluated in controls and patients. Urinary neopterin level of the control group was (mean value ± S.D.) 128.6 ± 64.6 μmol/mol creatinine. Neopterin concentrations in patients with breast malignancy were 153.6 ± 71.2 μmol/mol creatinine and 107.8 ± 32.1 μmol/mol creatinine in benign disorders patients. The mean neopterin level in the benign group was found to be statistically different from the malign tumor group (p = 0.039). SOD and CAT activities in controls were found as 3.57 ± 0.84 U/mg protein and 2.19 ± 0.20 U/mg protein, respectively. In patients with malignancy, the SOD activity was 3.84 ± 0.73 U/mg protein while CAT activity was 1.03 ± 0.13 U/mg protein. Patients with benign breast disorders, SOD activity was 4.09 ± 1.00 U/mg protein and CAT activity was 1.02 ± 0.18 U/mg protein. Whereas SOD activity did not differ between the groups of patients and controls, the mean catalase level in the control group was higher than in the benign and malign tumor groups (both p <0.001). Urinary neopterin concentration seems to be an important and useful biomarker in diagnosis of breast tumors in clinical practice.
Reference Standard of Serum Neopterin Concentration in Healthy Children
Authors: Plata-Nazar Katarzyna , Luczak Grazyna , Borkowska Anna , Delinska-Galinska Anna , Kozielska Ewa , Marek Krzysztof , Korzon Maria
Published: August 2013

Introduction: Increased neopterin concentrations are observed in many diseases in which cell immunity is stimulated. A quick and sensitive method for monitoring the changes in immune system can be useful for understanding etiopathogenesis of the disease and choosing the appropriate treatment. There are only few known data concerning normal serum neopterin value in children, therefore the wide clinical use of this parameter is limited.

Aim: to evaluate the referential neopterin concentration in serum in healthy children according to age and gender.

Patients and methods: 105 healthy children, 47 girls and 58 boys, aged 1 month - 17.9 years were examined. Clinical examinations and laboratory test including whole blood count, serum C-reactive protein, urea, and creatinine level, were conducted. The serum neopterin level was analyzed by ELISA (BRAHMS, Hennigsdorf/Berlin, Germany). The results were used for reference standard evaluation of serum neopterin level in healthy children. Results: The serum neopterin concentrations in children were 2.87 - 14.78, mean 5.47 ± 2.58 nmol/L. No significant correlation was found between children's age and serum neopterin level. There were also no differences among serum neopterin level in different age groups: under 5, 5 to 10, and over 10 years, and between girls and boys. The estimated cut-off value 11 nmol/L of serum neopterin level for whole group of children made the 94.3% test sensitivity.

Conclusion: Serum neopterin concentration is lower than 11 nmol/L in healthy children after neonatal period, and is independent of childrens' age or gender.
Urinary Neopterin in Patients Treated with Gefitinib
Authors: Kalabova Hana , Dvorak Josef , Hyspler Radomír , Ticha Alena , Krcmova Lenka , Urbanek Lubor , Solichova Dagmar , Melichar Bohuslav
Published: August 2013

Inhibitors of epidermal growth factor receptor (EGFR), including low molecular weight inhibitor erlotinib and gefitinib, have been demonstrated to be active antitumor agents in patients with non-small cell lung carcinoma and head and neck carcinomas. Increased concentrations of urinary neopterin, an indicator of systemic immune activation, have also been reported in patients with lung carcinoma and head and neck carcinomas. EGFR blockade has been reported to induce immune activation. We have measured, using high performance liquid chromatography, urinary neopterin in patients with non-small cell lung carcinoma and head and neck carcinomas treated with gefitinib. Intestinal permeability was also investigated at baseline by measuring, using capillary gas chromatography, urinary xylose, mannitol and lactulose after oral challenge. Compared to controls, urinary neopterin was significantly increased in patients with non-small cell lung carcinoma. No significant change in urinary neopterin was observed during the therapy with gefitinib. A significant correlation was observed between urinary neopterin and xylose absorption (rs = -0.58, p <0.05), lactulose/mannitol (rs = 0.75, p <0.01), and lactulose/ xylose (rs = 0.62, p <0.05) ratios. In conclusion, EGFR blockade had no effect on systemic immune activation, evaluated with urinary neopterin. A significant correlation has been observed between urinary neopterin and parameters of intestinal permeability and absorption.
In vitro Effects of Nigella sativa Seeds Extracts on Stimulated Peripheral Blood Mononuclear Cells
Authors: Winkler Christiana , Schroecksnadel Katharina , Ledochowski Maximilian , Schennach Harald , Houcher Bakhouche , Fuchs Dietmar
Published: August 2013

Nigella sativa, commonly known as black cumin seed, belongs to the botanical family of Ranunculaceae. The active antioxidant components of Nigella sativa display a remarkable array of biochemical, immunological and pharmacological actions, including bronchodilatory, anti-inflammatory, antibacterial, hypoglycaemic, antitumoural and immunopotentiating effects. Effects of Nigella sativa seeds extracts were investigated in freshly isolated human peripheral blood mononuclear cells stimulated with the mitogens phytohaemagglutinin and concanavalin A in vitro. Tryptophan degradation and neopterin production were monitored in culture supernatants, both these immunobiochemical pathways are induced by pro-inflammatory cytokine interferon-γ. Compared to unstimulated cells, the mitogens enhanced degradation of tryptophan and production of neopterin. Nigella sativa seeds extracts significantly suppressed both pathways in a dose-dependent way. Suppression of tryptophan degradation and neopterin formation by Nigella sativa seeds extracts demonstrates an inhibitory influence on activated T-cells and macrophages. Data are in line with an anti-inflammatory activity of the extracts.
Pteridine Pathway in Patients with Degenerative Diseases During Short Time Treatment with Low Dose of Meloxicam, as a Non-steroidal Anti-inflammatory Drug
Authors: Baydar Terken , Girgin Gozde , Fuchs Dietmar , Inanici Fatma , Sipahi Hande , Erol Ozlem , Sahin Gonul
Published: August 2013

The profiles of unconjugated pteridines such as neopterin and biopterin and of tryptophan metabolism change in many pathologic conditions such as rheumatoid arthritis, malignancies and autoimmune diseases and are related to the release of pro-inflammatory cytokines. However, studies on potential effects of drugs are very limited. This study investigates whether meloxicam, a non-steroidal anti-inflammatory drug, may cause any alteration of the pteridine pathway and tryptophan metabolism in 22 patients who admitted to the Physical and Rehabilitation Medicine outpatient clinic in the Hacettepe University Hospital and suffering from various musculoskeletal pain conditions without systemic inflammation. Urine concentrations of neopterin, biopterin and xanthopterin, and serum concentrations of neopterin, tryptophan, and kynurenine, and the activity of dihydropteridine reductase were measured at the beginning of the therapy and after a 15 days treatment with meloxicam. Average urine concentrations (± S.E.M.) of pterins before therapy (neopterin: 263 ± 15.6 μmol/mol creatinine, biopterin: 72.4 ± 13.4 μmol/mol creatinine, and xanthopterin: 675 ± 93.0 μmol/mol creatinine) were not changed during meloxicam therapy (neopterin: 230 ± 30.7 μmol/mol creatinine = 88% of baseline, biopterin 115 ± 26.5 μmol /mol creatinine = 159% of baseline, and xanthopterin 684 ± 88.0 μmol/mol creatinine = 101% of baseline; all differences not significant). The activity of dihydropteridine reductase was 6.02 ± 0.21 nmol/cytochrome C reduced/min/5 mm disc before and 6.28 ± 0.18 nmol/cytochrome C reduced/min/5 mm after treatment (= 104% of baseline; p = 0.088). Serum concentrations of neopterin 6.04 ± 0.33 nmol/L before treatment increased to 6.89 ± 0.48 nmol/L after treatment (= 114% of baseline; p <0.05, paired rank test). Likewise serum kynurenine concentrations increased from 1.52 ± 0.13 μmol/L to 1.87 ± 0.14 μmol/L after treatment (= 123% of baseline; p <0.01). There was a significant correlation between neopterin and kynurenine concentrations which corresponds with their common background of production, namely immune activation. However, also the mean tryptophan concentration in pretreatment samples 51.4 ± 3.34 increased to 59.3 ± 3.34 μmol/L post-treatment (= 115% of baseline; p <0.05). The change of kyn/trp was minor (at baseline: 30.4 ± 2.01, post-treatment: 32.2 ± 2.47 μmol/mmol; = 106% of baseline, not significant). Our findings show an influence of meloxicam treatment on neopterin and tryptophan metabolism in patients. However, significant differences were only found in serum but not in urine of patients. In serum, all marker concentrations increased including tryptophan and kynurenine.
Influence of Neopterin on Ciliary Beat Frequency of Human Nasal Epithelial Cells in vitro
Authors: Neher Andreas , Schobersberger Wolfgang , Augustijns Patrick , Fuchs Dietmar , Wolf-Magele Astrid , Hoffmann Georg
Published: August 2013

Acute infectious diseases of the respiratory tract are regularly associated with increased concentrations of neopterin in serum and/or urine. Most likely, the pteridine compound is not only a marker of an activated cellular immune system but may exert distinct biochemical functions in the process of infections as well. In response to viral contact, macrophages located in the nasal mucosa may represent a source for neopterin in the nasal cavity with potential hazardous effects on ciliary beat frequency (CBF), thus promoting chronic infectious processes. The aim of the present study was to investigate the effects of neopterin at different concentrations (10 nM, 100 nM, and 100 μM) on CBF in human nasal epithelial cells in vitro. Samples were taken from the inferior nasal turbinate and incubated with neopterin dissolved in either aqua destillata or in sodium chloride (0.9%) at the given amounts for 2, 5, 10, and 20 min. In a preliminary set of experiments, neopterin inhibited CBF following the 5 and 10 min. incubation protocol, respectively. However, analyses of pooled data from 28 experiments using sodium chloride (0.9%) as solvent could not confirm these findings: in no setting a significant reduction of CBF was detected at the end of the 20 min. experimental procedure. Therefore, we conclude that neopterin most likely does not affect the mucociliary clearance defense mechanisms in the course of infections of the nasal respiratory tract.
In Vitro Effect of Neopterin on Erythropoiesis in Mice
Authors: Tsuboi Isao , Hokari Takeo , Harada Tomonori , Yuda Miyuki , Aizawa Shin
Published: August 2013

Neopterin is produced by monocytes and a useful biomarker of inflammatory responses. We found recently in mice that neopterin suppressed erythropoiesis but enhanced myelopoiesis possibly by activating stromal cells, the same phenomenon observed in inflammation. In this study, we investigated whether neopterin affects the proliferation and differentiation of immature erythroid progenitor cells (BFU-E) by stimulating bone-marrow stromal cells in culture. Neopterin decreased the number of colonies of BFU-E formed by unfractionated bone-marrow cells in a semisolid culture system, but increased the number of granulocyte-macrophage progenitor cells (CFUGM). In contrast, it did not affect numbers of BFU-E or CFU-GM among a lineage-negative (fractionated) bonemarrow- cell population cultured without stromal cells. These results suggest that neopterin decreased the number of colonies of BFU-E by activating bone-marrow stromal-cell function.
Neopterin Concentration in Serum and Chosen Markers of Inflammatory Process in Children with Acute Diarrhea Caused by Rotavirus or Salmonella
Authors: Kozlowska-Murawska Jolanta , Obuchowicz Anna
Published: August 2013

Neopterin concentrations reflect the activation of the cellular immune system. Neopterin is released by macrophages stimulated by interferon-γ (IFN-γ), which is produced by activated T lymphocytes. Raised neopterin concentrations in body fluids are found in various disorders, e.g. viral infections (AIDS, cytomegalovirus, hepatitis), intracellular bacteria infections (Mycobacteruim tuberculosis, Mycobacterium leprae), autoimmune disorders and malignancy. Neopterin concentrations are low or not significantly increased in bacterial infections, with exception of infections with intracellular bacteria. The aim of this study was to evaluate the usefulness of neopterin in the differential diagnosis of viral (Rotavirus) and bacterial (Salmonella) origin of diarrhoea.

129 children, aged 1 month -14 years, who were hospitalized for rotavirus gastroenteritis or salmonellosis were included into the study. Rotavirus was identified by latex test and Salmonella by stool cultures and the children were divided into 2 groups: with rotavirus infection (group I (R) - 71 children) and with salmonellosis (group II (S) - 58 children). In this study it was analyzed: disease duration before hospitalization, the general condition of a child on admission, body temperature, the number of loose and bloody stools and the number of vomits. On their admission to hospital, erythrocyte sedimentation rate (ESR), leukocyte count, and in the sera of all children C-reactive protein (CRP) and neopterin concentrations were determined. The serum neopterin concentrations were analyzed by ELISA.

Mean neopterin concentration was 35.0 nmol/L in patients with salmonellosis, and it was significantly higher than in patients with rotavirus infection (22.0 nmol/L; p <0,001). The neopterin level that reliably discriminated between rotavirus diarrhoea and salmonellosis was 22 nmol/L: neopterin concentration higher than 22 nmol/L suggested diarrhoea caused by Salmonella, and neopterin concentrations equal or lower than 22 nmol/L suggested a rotavirus diarrhoea The combination of the results of two (neopterin >10 nmol/L and CRP >10mg/L) or three (neopterin >10nmol/L, ESR >10mm/h, CRP >10mg/L) serum markers helps to achieve better results. The best specificity (100%) was obtained for CRP concentration >15mg/L and neopterin concentration >37 nmol/L.

We conclude that serum neopterin concentrations in children with acute diarrhea are not a laboratory indicator diversifying salmonellosis and rotavirus infection, because it increases in both infections. However higher concentrations indicate salmonellosis.
Theoretical Study on the Relative Energies of Anionic Pterin Tautomers
Authors: Soniat Michael , Martin Christopher B.
Published: August 2013

Pterins exist as several tautomeric forms and behave as weak acids in aqueous solutions. Therefore, several acidbase equilibria may be present. For several pterin derivatives, the range of the experimental pKa lies in the range 6-8. The anionic form of the lactam structure is the only structure considered in the literature to represent the chemistry of pterins in alkaline solution. In the present study, density functional theory calculations were used to determine the relative energies of various anionic tautomers of pterin present in aqueous solution which may play a role in chemical and biological systems.
Temporal Association Between Daily Alcohol Consumption, Emotional States and Urinary Neopterin Levels in a Patient with Systemic Lupus Erythematosus
Authors: Schubert Christian , Lampe Astrid , Geser Willi , Merk Mathias , Jenny Marcel , Fuchs Dietmar
Published: August 2013

In recent years, interest has been growing regarding the role of alcohol intake on systemic lupus erythematosus (SLE) disease activity. This integrative single-case study investigated the dynamic interdependencies between alcohol consumption, various emotional states and cellular immune activity in SLE using time series analysis (i.e., ARIMA modeling, cross-correlational analysis). We determined neopterin concentrations (HPLC) in a 52-year-old woman suffering from SLE, who collected her entire urine on a twice-daily basis for a period of 56 days (total: 112 time-points). Aside from the central interest of our studies, i.e., the impact of everyday incidents on cellular immune system dynamics, the patient also provided daily information on intake of alcoholic beverages (type and quantity) and various emotional state variables (mental activity, irritation, mood). Cross-correlational analyses revealed that moderate alcohol consumption had different effects on urinary neopterin levels depending on whether time series data were analyzed before or after the occurrence of an inflammatory event (acute paranasal sinusitis) that had taken place halfway through the study period (time-points 45-54). Before sinusitis (1-44), increases in alcohol consumption were parallelized by decreases in urinary neopterin levels (lag0: r = -0.371; p< 0.05) whereas after sinusitis (55-112), increases in alcohol intake preceded increases in urinary neopterin levels with a temporal delay of 12 hours (lag1: r = +0.308; p< 0.05). The emotional states under study did not interfere with the associations between alcohol intake and neopterin levels. These findings show that even within the same patient with SLE the relationship between alcohol intake and neopterin levels might not always be stable suggesting a possible reason for inconsistent evidence from cross-correlational studies.
Effect of Neopterin on Splenic Erythropoiesis in Mice
Authors: Tsuboi Isao , Harada Tomonori , Oshima Hideki , Aizawa Shin
Published: August 2013

Neopterin is produced by monocytes and is a biomarker for inflammation. We recently found that neopterin induces stromal cells to produce cytokines that suppress erythropoiesis in the bone marrow of mice. Despite this suppression, the peripheral hematocrit values are not decreased. The goal of the present study was to determine whether the maintenance of hematocrit values is caused by a neopterin-induced acceleration of extramedullary erythropoiesis. We examined the effects of intravenously injected neopterin on splenic erythropoiesis in C57BL/6J mice and found a marked increase (259% of the pretreatment level) in the number of splenic erythroid progenitor cells (BFU-E and CFU-E) after a slight temporal decrease in the number of erythroid progenitor cells. These results suggest that neopterin increases splenic erythropoiesis to compensate for the suppression of erythropoiesis in the bone marrow, resulting in the maintenance of hematocrit levels in peripheral blood.
First Synthesis of a Natural Neopterin Glycoside: 3'-O-(β-D-Glucopyranosyluronic acid)neopterin
Authors: Hanaya Tadashi , Hattori Takafumi , Takayama Daisuke , Yamamoto Hiroshi
Published: August 2013

1',2'-Di-O-acetyl-N2-(N,N-dimethylaminomethylene)-3-[2-(4-nitrophenyl)ethyl]neopterin (1) was prepared from neopterin in 5 steps. Glycosylation of 1 with methyl 2,3,4-tri-O-benzoyl-α-D-glucopyranosyluronate bromide in the presence of silver triflate and tetramethylurea afforded the corresponding 3'-O-(methyl β-D-glucopyranosyluronate) neopterin derivative (2) in 64% yield. The first synthesis of 3'-O-(β-D-glucopyranosyluronic acid)neopterin was achieved by successive removal (4 steps) of the protecting groups of 2.
Immune Modulation by cross-linked Bovine Colostrum in vitro and in vivo
Authors: Pedersen Ninfa R. , Hidayat Budi J.
Published: August 2013

Bovine colostrum (BC) is the early thick yellow fluid produced by cows during the first several days after birth of the calf. BC is different from "mature" milk as it contains nutrients and immune factors, which strengthen the immune system of the newborn calf in its first week of life. BC has a long history of use in traditional medicine throughout the world and is currently also used in a topical cream for the treatment of immuno-related skin problems such as atopic dermatitis or psoriasis. However, despite a large amount of literature concerning the properties of human or bovine colostrum, there are only few reports on the effects of colostrum on the human immune system. In this study, the effects of cross-linked BC containing hyaluronic acid on the T-cell/macrophage interplay were investigated in human peripheral blood mononuclear cells (PBMC) and the results were compared with the effects of euxyl 9010, which was used to preserve the BC ingredients. The cross-linked BC preparations showed significant immunomodulatory effects on unstimulated and phytohaemagglutinin (PHA)-stimulated human PBMC by modulating tryptophan degradation and formation of neopterin in a biphasic manner. These results could be relevant for some of the beneficial effects of BC observed in the treatment of skin lesions of patients with atopic dermatitis or psoriasis. However, additional studies are needed to confirm the first positive results obtained in patients.
Folate Measurement in Mammalian Tissues by Fluorescence Polarization
Authors: Harry Martin , Comeskey Daniel
Published: August 2013

Measurement of folate in animal tissues is expensive and time-consuming. A fluorescence polarization assay has been developed that allows the rapid and inexpensive quantification of folate in various animal tissues. The concentration of tissue folate is determined by its ability to compete with the binding of Alexa-660-folate to bovine milk folate binding protein. The technique uses a few milligrams of material and is amenable to automated screening in 384-well microplates. Using this approach, the folate concentration in mouse liver, kidney & brain was found to be 21.4, 4.22 and 0.73 nanomoles/g fresh tissue, respectively. Packed human erythrocytes were found to contain 1.31 mM folate. These estimates are similar to published folate values for these tissues. Ascorbate was not included in the assay buffer because of its pro-oxidant effects in iron rich tissues such as erythrocytes and liver. The assay is homogeneous, completed within a few hours of the availability of the samples, and will enable the high throughput analyses of folate in human and animal samples.
Electron Transfer Initiated Reactions Photoinduced by Pterins
Authors: Lorente Carolina , Petroselli Gabriela , Dántola M. Laura , Oliveros Esther , Thomas Andrés H.
Published: August 2013

Interest in the photochemistry and photophysics of pterins has increased since the participation of this family of compounds in different photobiological processes has been suggested or demonstrated in recent decades. Pterins participate in relevant biological processes, such as metabolic redox reactions, and can photoinduce the oxidation of biomolecules through both electron transfer mechanisms (Type I) and singlet oxygen production (Type II). This article describes recent findings on electron transfer-initiated reactions photoinduced by the triplet excited state of pterins and connects them in the context of photosensitized processes of biological relevance.
Chronic Immune Stimulation May Cause Moderate Impairment of Phenylalanine 4-hydroxylase
Authors: Scholl-Bürgi S , Schroecksnadel S , Jenny M , Karall D , Fuchs D
Published: August 2013

Phenylalanine (4)-hydroxylase (PAH, E.C. 1.14.16.1) is located mainly in liver and converts amino acid phenylalanine (Phe) to tyrosine (Tyr). In 'classical' phenylketonuria (PKU), PAH activity is reduced, whereas in 'atypical' PKU biosynthesis of the cofactor 5,6,7,8-tetrahydrobiopterin (BH4) is disturbed. Aside from these inherited conditions, elevated plasma Phe concentrations and increased Phe to Tyr ratios (Phe/Tyr) were observed in patients with cancer, burns, sepsis and HIV-1 infection. Results indicate that immune activation and inflammation are associated with moderate impairment of PAH activity. This review discusses findings of increased Phe/Tyr in patients suffering from chronic inflammatory diseases, their clinical relevance and consequences.
Evaluation of Changes in Immune System of Operating Room Personnel by Measurement of Urinary Neopterin Concentrations
Authors: Baydar Mustafa , Capan Zeynep , Girgin Gozde , Baydar Terken , Sahin Gonul
Published: August 2013

Today it is known that neopterin is mainly produced by activated macrophages and a marker of immune activation and macrophage activity. Increased neopterin concentrations are observed in diseases related to cellular immunity including occupational pathologies.

The major goal of the present study was to evaluate the possible alteration of neopterin levels in operating room personnel, and also to show whether screening of neopterin may be useful to monitor the effect of occupational anesthetic exposure on the cellular immune system.

Therefore, urinary neopterin to creatinine levels in both, exposed workers (n = 40) and healthy volunteers (n = 30), were measured by using high-performance liquid chromatography. At the same time, the correlation among urinary neopterin levels and working years, age, and smoking status were evaluated.

Compared to controls, urinary neopterin levels in the exposed group were increased (controls: 85 ± 16 μmol/mol creatinine, workers: 151 ± 39 μmol/mol creatinine; p <0.05).

The findings suggest that the follow up of neopterin levels may have diagnostic value in possible occupational exposure-related immune system disorders. Moreover, its biological monitoring should be performed in workplaces for clinical diagnosis and prognosis.
Effects of Inhalation Anesthetics on the Profile of Urinary Neopterin as an Immune Marker in Patients who Underwent Laparoscopic Cholecystectomy
Authors: Capan Zeynep , Baydar Terken , Girgin Gozde , Dolgun Anil , Dikmen Beyazit , Sahin Gonul
Published: August 2013

It has been claimed that inhalational anesthetics affect many phases of immune response. Although, there are a lot of studies on the effects of widely used anaesthetic agents and methods on the immune system, there are only a few studies to show the effects by evaluation of neopterin concentrations as an important marker of cellular immunity. This study was done to evaluate possible effects of inhalation anesthetics, such as desflurane, isoflurane, and sevoflurane on the immune system by measuring urinary neopterin concentrations in patients who underwent laparoscopic cholecystectomy. The study is randomized, prospective and double blind. Urinary neopterin was measured in patients submitted to general anesthesia with either desflurane (n = 20) or isoflurane (n = 11), or sevoflurane (n = 13) in laparoscopic cholecystectomy. Urine samples were collected preoperatively, at 2nd and 24th hours post-operatively and the neopterin per creatinine concentrations were measured by using high-performance liquid chromatography.

The preoperative neopterin levels were similar across the study groups. Variance analysis of repeated measures showed an effect of time (p <0.05): Neopterin concentrations increased over time, but the effect of different anesthetics on neopterin was similar. The mean increases in neopterin concentrations were similar among all the applied anesthetics. In conclusion, this report shows changes of immune response by investigation of neopterin in urine samples during 24 hours in patients exposed to three different inhalational anesthetic agents sevoflurane, desflurane and isoflurane in laparoscopic cholecystectomy.
Urinary Neopterin in Patients with Metastatic Colon Cancer Treated with Patupilone
Authors: Melichar Bohuslav , Kalábová Hana , Krčmová Lenka , Kašparová Markéta , Plíšek Jiří , Jaroslav Cerman Jr. , Holečková Petra , Solichová Dagmar
Published: August 2013

Despite increased efficacy of regimens combining cytotoxic drugs and targeted agents, most patients with metastatic colorectal cancer will ultimately die of the disease. Only a limited number of drugs have reproducible activity in therapy of this tumor, and new active agents are urgently needed. Promising results in the therapy of metastatic colorectal cancer have been reported for patupilone, an epothilone analogue. Similarly to taxanes, the cytotoxic mechanism of epothilones involves the stabilization of microtubules. Increased serum or urinary concentrations of neopterin have been described in patients with tumors of different primary locations, including colorectal cancer. Neopterin concentrations were reported to increase during the administration of cytotoxic agents, including taxane-based chemotherapy. We have studied serum neopterin in patients with colorectal cancer before and during the therapy with patupilone. Urinary neopterin/creatinine concentrations were determined with highperformance liquid chromatography. Increased urinary neopterin concentrations were observed at baseline in the majority of the patients. In most patients, neopterin concentrations further increased during the therapy, and a significant increase of urinary neopterin was observed in patients with normal baseline neopterin concentrations. A trend of decreased survival was observed for patients with high initial neopterin concentration. In conclusion, urinary neopterin is increased in colorectal cancer patients presenting for second or higher line of treatment. An increase of urinary neopterin during patupilone therapy suggests an activation of immune response by this agent.
Expression of Neopterin and Chemokines in Rheumatoid Arthritis and Cardiovascular Disease
Authors: Fagerer Nicola , Arnold Markus , Günther Bernatzky , Werner Kullich
Published: August 2013

In chronic inflammatory processes like rheumatoid arthritis (RA) and cardiovascular diseases (CVD) the role of pteridines and chemokines in the immune response is of great interest. The objectives of the study were to obtain information about an involvement of specific chemokines on the inflammatory process in patients with RA and CVD with activated production of the pteridine neopterin. 113 patients with RA according to American College of Rheumatology criteria including 24.8% suffering from CVD were included in the study (23% male, 77% female). For the assessment of monocyte activation and chemotaxis as well as the proinflammatory influence of chemokines on B-cells and angiogenesis in RA, neopterin and the chemokines CCL2, CXCL13 and CX3CL1 were measured by radio- and enzyme-immunoassays in serum.

Neopterin and chemokines were all found in high concentrations. Neopterin significantly correlated with all chemokines: CXCL13 (rs = 0.368; p <0.0001), CX3CL1 (rs = 0.241; p <0.02), CCL2 (rs = 231; p <0.02), demonstrating high neopterin levels in RA patients to have a strong association to the chemokine induced chemotaxis of B-cells (CXCL13) and mononuclear cells (CX3CL1, CCL2). Significantly elevated concentrations of neopterin and CXCL13 were seen in patients with RA plus CVD compared to RA without CVD (p <0.03). The high incidence of cardiovascular diseases in rheumatoid arthritis seems to be associated with enhanced mononuclear (neopterin, CCL2) and B-cell activation (CXCL13), and as a consequence increased immune system activity.
Mechanistic Study of ROS-photogeneration by Pterin
Authors: Ji Hong-Fang , Shen Liang
Published: August 2013

Pterins are widespread in biological systems and possess photosensitizing activities. In the present study, the photosensitization mechanism of acid form of pterin (PTA) and basic form of pterin (PTB) is investigated by means of density functional theory calculations. The reactive oxygen species-photogenerating pathways of the lowest triplet excited (T1) state PTA and PTB are proposed as follows. Through direct energy transfer, both T1 state PTA and PTB can photogenerate 1O2. Two possible O2 .−-generating pathways are proposed according to the electronic parameters of PTA and PTB: i) direct electron transfer from T1 state PTA and PTB to 3O2 and the electron transfer reaction is more favorable energetically for PTB in comparison with PTA; and ii) electron transfer from anion radical of PTA and PTB to 3O2.
Giving Consent without Getting Informed: A Cross-Cultural Issue in Research Ethics
Authors: Ghandour Lilian , Yasmine Rola , El-Kak Faysal
Published: August 2013

Informed consent forms (ICFS) maintain the integrity of research ethics and preserve participants' rights. Using cross-sectional online survey data on sexuality and sexual practices of private university students from Lebanon, this paper questions whether participants thoroughly read ICFs, and whether time taken to read ICFs is associated with data completeness. A total of 2,534 surveys were completed; a median time of 18.66 seconds was taken to read the 815-word ICF; 65% of participants consented within the first 30 seconds and 90% in less than the minimum predicted time (2.7 minutes). Our data indicates potential participant neglect of ICFs, raising the question of whether participants who endorse an informed consent form are truly informed of the study objectives and their rights.
Protocols for Protection of Human Participants: A Comparison of Five Countries
Authors: Clough Bonnie A. , Campbell Megan M. , Aliyeva Turana A. , Mateo Niño Jose , Zarean Mostafa , O'Donovan Analise
Published: August 2013

Research ethics protocols relating to human participants were compared across five countries, namely, Australia, Azerbaijan, Iran, the Philippines, and South Africa. These countries were considered to be geographically and culturally diverse, as well as representing both developed and developing countries. The extent to which the research participant is protected across cultures and countries was investigated, with particular focus on the use of informed consent procedures. It was argued that current ethical guidelines and practices fail to ensure the protection of the most vulnerable participants within these cultures. Informed consent mechanisms also often fail to consider cultural differences in self-concept, understanding of research methods, and power differences between researchers and participants. Discussion of these ethical challenges and recommendations for research ethics development within these cultures and countries are discussed.
A Comparative Analysis of the Governance and Use of Residual Dried Blood Spots from State Newborn Screening Programs and Neonatal Biobanks
Authors: Preslan Elicia D. , Mathews Debra J. H.
Published: August 2013

In contrast to prior research, which has focused mainly on legislative content, this study aimed to characterize the current governance structures and procedures used by state newborn screening programs in the United States regarding the research use of residual dried blood spots. Content analysis was performed on newborn screening laws, program policies, survey responses, and online material, and was compared to information from two neonatal biobanks. Important differences between newborn screening programs and neonatal biobanks included the types of permissible research with blood spots, the evaluation criteria used for research requests, and characteristics of the research proposal reviewers. These findings can inform ongoing policy conversations with respect to the governance and use of residual dried blood spots.
Patients' Rights: A Hospital Survey in South Egypt
Authors: Zeina Hanaa A. Abou , El Nouman Azza A. , Zayed Moushera A. , Hifnawy Tamer , El Shabrawy Ekram M. , El Tahlawy Eman
Published: August 2013

We examined the awareness of and practices regarding patients' rights in one of the general hospitals in South Egypt. This cross-sectional study incorporated a convenience sample of the hospitalized patients and their companions (N = 292), as well as the actively working medical care providers (MCPs) at the time of data collection, 72 physicians and 48 nurses. Pretested structured questionnaires inquired about the way in which patients' rights are perceived by and exercised through the lived experiences of the sample group. An in-depth interview about patient rights' practices was conducted with the study hospital's highest-level manager. Three quarters of the patients and companions did not know about the list of patients' rights, compared to about half of the physicians and nurses—77%, 44%, and 48% respectively. Among those patients and companions who were knowledgeable about the list of patients' rights, mass media was their main source of knowledge, about eight times greater than their next source, placards on the hospital wall. The proportion of the physicians who stated undergraduate curriculum as a source of their knowledge was almost half that of the nurses. Strategies to promote awareness among MCPs, and to ensure effective supervision from both the Ministry of Health and local managers, should precede mass community patients' rights awareness efforts.
Perceived Discomfort Levels in Healthy Children Participating in Vaccine Research
Authors: Westra Anna E. , Van Gils Elske J. M. , Aarts Fenne , Rodenburg Gerwin D. , Veenhoven Reinier H. , Hak Eelko , Scharloo Margreet , Sukhai Ram N. , Wit Jan M. , De Beaufort Inez , Sanders Elisabeth (Lieke) A. M.
Published: August 2013

When assessing the risks of a research protocol, review boards need to consider not only the possible harms but also the expected discomfort levels caused by the various study procedures. However, data on how children experience various study procedures are scarce. This study assessed perceived discomfort levels in 671 healthy children aged 0–2 years undergoing vaccinations, venipunctures, and nasopharyngeal swab taking. In half of the study participants, venipunctures caused a moderate or high level of discomfort (49%). Corresponding figures for nasopharyngeal swabbing and vaccinations were 28% and 12%, respectively. Within the reported age group, increasing age was related with higher discomfort levels. In a majority of cases for all study procedures, the perceived levels of discomfort met the parents' expectations.
Risk of thyroid cancer in relatives of patients with medullary thyroid carcinoma by age at diagnosis
Authors: Fallah Mahdi , Sundquist Kristina , Hemminki Kari
Published: August 2013

The familial risk of medullary thyroid carcinoma (MTC alone or as part of multiple endocrine neoplasms, MEN2A/MEN2B) is high, so we aimed to answer open questions about the lifetime cumulative risk of thyroid cancer (LCRTC at 0–79 years) among relatives of MTC patients by age and sex. For this nationwide study, a cohort of 3217 first-/second-degree relatives (FDRs/SDRs) of 389 MTC patients diagnosed in 1958–2010 in the Swedish Family-Cancer Database was followed for the incidence of thyroid cancer. The LCRTC in female relatives of patients with early-onset MEN2B (diagnosis age <25 years) was 44–57%, representing 140–520 times increase over the risk in their peers without a family history of endocrine tumors (men: LCRTC=22–52%, 320–750 times) depending on the number of affected FDRs/SDRs. The LCRTC in female relatives of patients with late-onset MEN2B (diagnosis age ≥25 years) was about 15–43% (men=24%). The LCRTC among relatives of early-onset MTC-alone patients was 3–20%. The LCRTC among relatives of late-onset MTC-alone patients was 5–26%. The LCRTC in female relatives of MEN2A patients was 16–63% (men=52%). The relatives of patients with early-onset MTC exhibited a high tendency to develop early-onset thyroid cancer. Simply available data on the number of FDRs and even SDRs affected with MTC and their age at diagnosis were quite informative for the estimation of the risk of thyroid cancer in probands. In settings where genetic testing is not available or affordable for all, evidence-based cumulative risks reported in this nationwide study may help physicians to identify very high-risk individuals.
The dynamics of the primordial follicle reserve
Authors: Kerr Jeffrey B , Myers Michelle , Anderson Richard A
Published: August 2013

The female germline comprises a reserve population of primordial (non-growing) follicles containing diplotene oocytes arrested in the first meiotic prophase. By convention, the reserve is established when all individual oocytes are enclosed by granulosa cells. This commonly occurs prior to or around birth, according to species. Histologically, the ‘reserve’ is the number of primordial follicles in the ovary at any given age and is ultimately depleted by degeneration and progression through folliculogenesis until exhausted. How and when the reserve reaches its peak number of follicles is determined by ovarian morphogenesis and germ cell dynamics involving i) oogonial proliferation and entry into meiosis producing an oversupply of oocytes and ii) large-scale germ cell death resulting in markedly reduced numbers surviving as the primordial follicle reserve. Our understanding of the processes maintaining the reserve comes primarily from genetically engineered mouse models, experimental activation or destruction of oocytes, and quantitative histological analysis. As the source of ovulated oocytes in postnatal life, the primordial follicle reserve requires regulation of i) its survival or maintenance, ii) suppression of development (dormancy), and iii) activation for growth and entry into folliculogenesis. The mechanisms influencing these alternate and complex inter-related phenomena remain to be fully elucidated. Drawing upon direct and indirect evidence, we discuss the controversial concept of postnatal oogenesis. This posits a rare population of oogonial stem cells that contribute new oocytes to partially compensate for the age-related decline in the primordial follicle reserve.
Regulatory T cells and the immune pathogenesis of prenatal infection
Authors: Rowe Jared H , Ertelt James M , Xin Lijun , Way Sing Sing
Published: August 2013

Pregnancy in placental mammals offers exceptional comprehensive benefits ofin uteroprotection, nutrition, and metabolic waste elimination for the developing fetus. However, these benefits also require durable strategies to mitigate maternal rejection of fetal tissues expressing foreign paternal antigens. Since the initial postulate of expanded maternal immune tolerance by Sir Peter Medawar 60 years ago, an amazingly elaborate assortment of molecular and cellular modifications acting both locally at the maternal–placental interface and systemically have been shown to silence potentially detrimental maternal immune responses. In turn, simultaneously maintaining host defense against the infinite array of potential pathogens during pregnancy is equally important. Fortunately, resistance against most infections is preserved seamlessly throughout gestation. On the other hand, recent studies on pathogens with unique predisposition for prenatal infections have uncovered distinctive holes in host defense associated with the reproductive process. Using these infections to probe the response during pregnancy, the immune suppressive regulatory subset of maternal CD4 T cells has been increasingly shown to dictate the inter-workings between prenatal infection susceptibility and pathogenesis of ensuing pregnancy complications. Herein, the recent literature suggesting a necessity for maternal regulatory T cells (Tregs) in pregnancy-induced immunological shifts that sustain fetal tolerance is reviewed. Additional discussion is focused on how expansion of maternal Treg suppression may become exploited by pathogens that cause prenatal infections and the perilous potential of infection-induced immune activation that may mitigate fetal tolerance and inadvertently inject hostility into the protectivein uteroenvironment.
Scary Scholarship
Authors: Simmons K. Merinda
Published: August 2013

Bruce Lincoln's recent book, Gods and Demons, Priests and Scholars: Critical Explorations in the History of Religions, is a text whose critical offerings threaten analytical engagements that suggest that we answer to those subjects we study. Lincoln, instead, appeals to an uncompromising critical self-reflexiveness that, while potentially uncomfortable--and even scary--forces a vital conversation in the academic study of religion.
Is the Buddhist Doctrine of Non-Self Conceptually Coherent?
Authors: Bernier Paul
Published: August 2013

Virtually all schools of Buddhism do not accept a permanent, substantial self, and see everything as non-self (anatta). In the first part of this article I recall some arguments traditionally given in support of this perspective. Descartes’ cogito argument contradicts this, by suggesting that we know infallibly that the self, understood as a substantial enduring entity, does exist. The German aphorist Lichtenberg has suggested that all Descartes could claim to have established was the impersonal ‘There is thinking’ (Es denkt), which would support the perspective of non-self. Bernard Williams has argued that Lichtenberg’s impersonal version of the cogito is conceptually incoherent, which would entail that the Buddhist perspective of non-self is also incoherent. I propose to defend the coherence of the Buddhist perspective of non-self against Williams’s argument.