Serum Neopterin Concentrations Research Articles

Effect of perioperative autologous versus allogeneic blood transfusion on the immune system in gastric cancer patients

Allogeneic blood transfusion-induced immunomodulation (TRIM) and its adverse effect on the prognosis of patients treated surgically for cancer remain complex and controversial. However, the potential risk associated with allogeneic blood transfusion has heightened interest in the use of autologous blood transfusion. In the present study, the serum concentrations of neopterin, interferon-gamma (IFN-gamma), T lymphocyte subsets (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+)) and a possible association between these variables were investigated. The purpose was to further evaluate the effect of autologous versus allogeneic blood transfusion on immunological status in patients undergoing surgery for gastric cancer. Sixty ASA I-II (American Society of Anesthesiologists) patients undergoing elective radical resection for stomach cancer were randomly allocated to receive either allogeneic blood transfusion (n=30) or autologous blood transfusion (n=30). Serum concentrations of the neopterin, IFN-gamma and T lymphocyte subsets in the recipients were measured before induction of anesthesia, after operation, and on the 5th postoperative day. Both two groups, serum neopterin, IFN-gamma, percentages of T-cell subsets (CD3(+), CD4(+)), and CD4(+)/CD8(+) ratio had significantly decreased after operation, but decreased more significantly in group H (receiving allogeneic blood transfusion) than those in group A (receiving autologous whole blood transfusion) (P<0.05). On the 5th postoperative day, serum neopterin, IFN-gamma, CD3(+), CD4(+) T-cells, and CD4(+)/CD8(+) ratio returned to the baseline values in group A. In contrast, the above remain decreasing in group H, where there were no significant relations between serum neopterin and IFN-gamma. Perioperative surgical trauma and stress have an immunosuppressive impact on gastric cancer patients. Allogeneic blood transfusion exacerbates the impaired immune response. Autologous blood transfusion might be significantly beneficial for immune-compromised patients in the perioperative period, clearly showing its superiority over allogeneic blood transfusion.

Reference Standard of Serum Neopterin Concentration in Healthy Children

Abstract 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 with Diabetes Mellitus and Foot Ulcers

Abstract 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.

Inverse association between serum selenium concentrations and parameters of immune activation in patients with cardiac disorders

As a component of the enzyme glutathione peroxidase, the essential trace element selenium contributes to the reduction of peroxides. Disturbed selenium availability may relate to an activated immune response. In humans, immune activation is reflected by increased neopterin production and accelerated tryptophan degradation, expressed as the kynurenine to tryptophan ratio (kyn/trp). Th1-type cytokine interferon-gamma induces both these immunobiological events in human macrophages and they are often activated in patients with cardiac disorders. The aim of this study was to determine the relationship between serum selenium concentrations and neopterin production and tryptophan degradation in patients with cardiac disorders. In 56 patients (28 females) with cardiac disorders, serum selenium concentrations were determined by graphite-furnace atomic absorption spectrometry. Serum neopterin concentration was measured by ELISA and tryptophan degradation was examined by HPLC. Selenium concentrations were in the range 0.41-1.90 micromol/L (median 1.02) and were well within the local normal range. Approximately two-thirds of patients presented with higher neopterin concentrations (median 16.4 nmol/L) and tryptophan degradation (median 57 micromol/mmol kyn/trp). There was an inverse correlation between serum selenium and kyn/trp (Spearman's rank correlation, r(s)=-0.431; p<0.001) and neopterin concentrations (r(s)=-0.300; p<0.05). Neopterin concentrations correlated strongly with kyn/trp (r(s)=0.712; p<0.0001). A higher degree of tryptophan degradation and of neopterin production in patients with cardiac disorders coincides with lower, albeit still normal, serum selenium concentrations. Data show that in these patients immune activation is associated with lower serum selenium concentrations.

Mid-life stress is associated with both up- and down-regulation of markers of humoral and cellular immunity

Perception of stress with consequent activation of a neuroendocrine cascade causes changes in immune function that may be bi-directional, with alterations in basal levels of biological parameters outside the optimal range. In this cross-sectional study of 302 healthy persons (males 56.3%, females 43.7%) aged 41–46 years, higher stress levels, as assessed by questionnaire measures of recurrent and recent perceived stress, were associated with a 4-fold greater risk of having a high compared to mid-range serum neopterin concentration, indicating activation of cellular immune mechanisms [adjusted odds ratio, OR; (95% confidence intervals, CI): Low stress = 1.00 (reference group); Medium stress = 4.13 (1.51, 11.29); High stress = 4.63, (1.35, 15.83), p for trend = 0.01]. Higher stress levels were associated with a 3-fold greater risk of having signs of humoral immune activation, as indicated by salivary IgA concentration [high compared to mid-range salivary IgA: Low stress = 1.00 (reference group); Medium stress = 1.06 (0.48, 2.34); High stress = 3.62 (1.26, 10.39), p for trend = 0.02], but also a 4-fold greater risk of humoral immune depression [low compared to mid-range IgA: Low stress = 1.00 (reference group); Medium stress = 1.72 (0.74, 3.99); High stress = 4.38 (1.47, 13.00), p for trend = 0.02]. In conclusion, in this cross-sectional study, higher stress levels were associated with higher serum neopterin and both elevated and depressed salivary IgA levels. These findings emphasise the importance of considering that stress may have bi-directional effects on immune mechanisms, and are consistent with an activational effect of chronic, perceived stress on cellular immunity, and a bi-directional effect on IgA levels, one aspect of humoral immunity.

Muscle Trauma and Immune Activation after a Downhill Marathon (Tyrolean Speed Marathon)

Abstract Prolonged physical exercise is associated with multiple changes in the immune status indicating an acute phase response and an activation of the immune system. Eccentric muscle activation (e.g. downhill running) induces micro-trauma of skeletal muscles thus inducing an inflammatory response. At present there are no data to which extent the immune system is activated after a downhill marathon run and if there arc any correlations between immune activation and markers for muscle damage or functional impairment of leg muscles. As model for severe eccentric exercise we selected the Tyrolean Speed Marathon (42 km downhill run, 795 m vertical difference). 13 volunteers (12 male, 1 female; mean running time 224 min [range 193 - 266 min.]) finished the run. Blood from antecubital veins was collected 3-4 days before (T1 ), 3-4 hrs before (T2) and immediately after the marathon (T3) as well as on the morning after the run (T4). We measured serum neopterin concentrations, white blood cell count. C-reactive protein (CRP), creatine kinase (CK), myoglobin (Mb), cardiac troponin I (cTnl) and troponin Τ (cTnT). Moreover, isokinetic muscle tests were performed. Following significant changes were found (before vs. after the run): increase in neopterin, CRP, total leukocyte count, CK. Mb, cTnl, cTnT, whereas isokinetic dynamometry showed a reduction in peak hamstring torque of both thighs after the marathon. There were no significant correlations (Spearman's rank correlation coefficient) between the observed changes in neopterin and CRP, CK, Mb. cTnT, cTnl or between neopterin concentrations and parameters of isokinetic muscle tests. We could demonstrate that a 42 km downhill marathon is associated a) with an activation of the cellular immune system, as evidenced by the increase in serum-neopterin. b) pronounced micro-skeletal muscle damage with high serum creatine kinase and myoglobin, and c) eccentric hamstring fatigue. The absolute changes in neopterin were moderate and similar to other types of exercise (flat course and bicycle marathon, mountain hiking).

Serum neopterin levels in patients with replicative and nonreplicative HBV carriers

BackgroundInfection by hepatitis B virus (HBV) causes complicated biochemical, immunological and histological changes in host immune response against the virus which can be specific or non-specific. Recent attention has focused on neopterin as a marker for the activation of cell mediated immunity. The aim of this study was to define the pattern of neopterin levels in replicative and nonreplicative HBV carriers.MethodsThirty HBV replicative carriers and 25 nonreplicative HBV carriers and 30 healthy adult patients were included this study. Hepatitis markers were determined by commercial kit based on chemilumminesans assay. HBV DNA was quantified by hybrid capture system. Serum neopterin levels were measured by the method of competitive enzyme-linked immunosorbent assay. Results were expressed as mean ± SD and ranges.ResultsIn the nonreplicative group, except for one patient, all the patients' HBeAg were negative and anti-HBe were positive. That particular patient was HBeAg positive and anti-HBe negative. In the replicative group, 23 out of 30 patients have positive HBeAg and negative anti-HBe; 7 out of 30 patients have negative HBeAg and positive anti-HBe. Serum neopterin concentrations were 14.5 ± 10.0 (4.2–41) nmol/L in replicative HBV carriers, 8.9 ± 4.3 (2.1–22) nmol/L in nonreplicative HBV carriers and 7.1 ± 2.2 (4.0–12) nmol/L in the control group. Serum neopterin levels and the rates of abnormal serum neopterin levels in the replicative group were higher than the control group (P < 0.01 and P < 0.05). In the nonreplicative group, serum neopterin levels were not different from those of the control. There was a difference between replicative and nonreplicative groups in the respect of neopterin levels.ConclusionIn the hepatitis B infected carriers, elevated neopterin levels may be an indicator of the presence of replication.

Alterations in serum neopterin correlate with thrombolysis in myocardial infarction risk scores in acute coronary syndromes

Using serum neopterin as a marker of macrophage activation, we sought to examine the relationship between serum neopterin levels, thrombolysis in myocardial infarction (TIMI) risk scores, and how different treatments of acute coronary syndromes affect change in neopterin. We examined serum neopterin concentrations at presentation and 72 h after treatment in 70 patients with acute coronary syndromes (35 with medical therapy, 25 with uncoated coronary stents, and 10 received rapamycin-eluting stents) using a commercially available immunoassay. Serum neopterin levels were determined for 36 patients with stable coronary artery disease. TIMI risk scores were calculated when appropriate (n=58). Serum neopterin had a strong correlation with the TIMI risk score on admission (P<0.0001). The mean baseline neopterin levels in patients with acute coronary syndromes stratified with TIMI scores between 1 and 7 were the following: patients with TIMI 1 scores had a level of 3.3+/-0.4 nmol/l, TIMI 2 patients 4.6+/-0.6 nmol/l, TIMI 3 patients 5.5+/-1.4 nmol/l, TIMI 4 patients 7.5+/-2.4 nmol/l, TIMI 5 patients 10.8+/-3.3 nmol/l, TIMI 6 patients 17.5+/-4.0 nmol/l, and TIMI 7 patients 23.0+/-7.1 nmol/l. Mean changes in serum neopterin were significantly higher for the uncoated stent group than for each of the other three groups (P<0.05). Serum neopterin concentrations have a high correlation with TIMI risk scores and may represent a marker useful in stratifying patients with acute coronary syndromes. Our results also suggest that the use of uncoated coronary stents results in macrophage activation not found with other treatment modalities.

Evaluation of pteridine metabolism in battery workers chronically exposed to lead

Occupationally-exposed lead affects the neuromuscular junction and might cause disturbances in the locomotor activity. This study was undertaken to evaluate pteridine metabolism, in which neurotransmitters are synthesized in battery workers. Urinary neopterin, biopterin and creatinine were measured using high performance liquid chromatography. Serum neopterin concentrations were detected by enzyme-linked immunoassay. Blood dihydropteridine reductase (DHPR) activities and deltaaminolevulinic acid (delta-ALA) were measured spectrophotometrically. Blood and urinary lead were detected by atomic absorption spectroscopy. Significantly increased blood and urinary lead levels, urinary neopterin, biopterin and delta-ALA were found in workers, while DHPR activities were indifferent compared to control group. Urinary creatinine decreased. This is the first study to demonstrate that increased activity of the pteridine pathway results in the accumulation of the neurotransmitters that may be responsible for the neurological disorders.

Cognitive deterioration in Alzheimer’s disease is accompanied by increase of plasma neopterin

The pro-inflammatory reaction of the immune system is a feature of healthy aging and might influence the progression of Alzheimer’s disease (AD). Neopterin is a pteridine derivative, released from macrophages upon stimulation with pro-inflammatory cytokine interferon-γ. Forty-three probable AD patients were investigated at baseline and follow up (14.5 ± 0.5 months; mean ± s.e.m.). We assessed the clinical progression by the Consortium to Establish a Registry for Alzheimer’s disease (CERAD) battery and compared cognitive changes to serum concentrations of neopterin, C-reactive protein (CRP) and antibody to cytomegalovirus (CMV). The mean neopterin concentrations increased significantly from 9.8 ± 1.0 to 13.6 ± 2.1 nM ( p = 0.04). In contrast, mean CRP concentrations at baseline was 0.46 ± 0.1 and non-significantly decreased to 0.28 ± 0.04 mg/dl. Of AD patients 70% were CMV IgG-seropositive at baseline and CMV-antibody concentrations correlated with levels of neopterin (Spearman r = 0.386, p = 0.016). CERAD scores did not correlate with any of immune parameters at baseline. At follow up, the increase of neopterin correlated significantly with the decrease in the total CERAD and MMSE scores, according to the clinical progression ( r = −0.353, p < 0.05 and r = −0.401, p < 0.01, respectively). Subdividing the sample with respect to baseline MMSE scores, neopterin concentrations significantly increased only in the group of MMSE <20. In the multiple testing covariated for age, gender, Apolipoprotein E-ε4 allele, time difference between both measurements, neopterin remained significantly associated with cognitive decline. In summary, neopterin concentrations correlated with cognitive decline in AD patients, which might be due to high CMV seropositivity in that population.

Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies

Malignant tumors may contribute to host response that involves both the adaptive and innate immune systems. Among other biochemical indicators of systemic immune and inflammatory activity, activation of macrophages by interferon-gamma induces a marked increase in the production of neopterin. Neopterin production by activated macrophages is also associated with tryptophan degradation. In addition to tumors of other primary locations, increased urinary and serum neopterin concentrations have been reported in patients with gynecological cancers, including epithelial ovarian carcinoma, cervical carcinoma, endometrial carcinoma, uterine sarcomas, and vulvar carcinoma, but not in women with benign neoplasms or precancerous disorders. Increased neopterin concentrations have been associated with poor prognosis. Elevated levels of neopterin have also been observed in the tumor microenvironment. Systemic (urinary or serum) or local (ascitic fluid) neopterin concentrations increased after therapeutic administration of cytokines. Elevated neopterin concentrations have been associated with anemia of chronic disease and increased urinary zinc loss in patients with gynecological malignancy. Elevated neopterin has also been connected with depressed function of peripheral blood lymphocytes and a decrease in CD4+ T-cell numbers.

Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies

Malignant tumors may contribute to host response that involves both the adaptive and innate immune systems. Among other biochemical indicators of systemic immune and inflammatory activity, activation of macrophages by interferon-γ induces a marked increase in the production of neopterin. Neopterin production by activated macrophages is also associated with tryptophan degradation. In addition to tumors of other primary locations, increased urinary and serum neopterin concentrations have been reported in patients with gynecological cancers, including epithelial ovarian carcinoma, cervical carcinoma, endometrial carcinoma, uterine sarcomas, and vulvar carcinoma, but not in women with benign neoplasms or precancerous disorders. Increased neopterin concentrations have been associated with poor prognosis. Elevated levels of neopterin have also been observed in the tumor microenvironment. Systemic (urinary or serum) or local (ascitic fluid) neopterin concentrations increased after therapeutic administration of cytokines. Elevated neopterin concentrations have been associated with anemia of chronic disease and increased urinary zinc loss in patients with gynecological malignancy. Elevated neopterin has also been connected with depressed function of peripheral blood lymphocytes and a decrease in CD4+T-cell numbers.

Usefulness of neopterin levels and left ventricular function for risk assessment in survivors of acute myocardial infarction

Background Results of previous studies have shown that serum neopterin levels are higher in patients with acute myocardial infarction (AMI). However, little is known regarding the prognostic value of neopterin in survivors of AMI. The present study analyzes the prognostic value of neopterin serum concentration and left ventricular ejection fraction in survivors of AMI. Methods The additional prognostic information provided by neopterin to parameters of left ventricular function in survivors of AMI was investigated through 82 patients with ST-segment elevation. Results Binary logistic regression analysis identified the following predictors of 6-month cardiac death: Killip class > I at presentation (OR = 2.4, 95% CI: 1.2 to 3.8, p = 0.001), a reduced ejection fraction (OR = 1.9, 95% CI: 1.3 to 2.2, p = 0.001), and greater neopterin (OR = 1.4, 95% CI: 1.1 to 1.6, p = 0.01). Conclusions Neopterin is associated with mortality, in addition to parameters of ventricular function (Killip class and ejection fraction) in survivors of AMI.

Gamma Interferon Is Dispensable for Neopterin Production In Vivo

Previous studies have indicated that neopterin is synthesized in vitro by human monocyte-derived macrophages and dendritic cells upon stimulation with gamma interferon (IFN-gamma). Neopterin production under specific conditions in vitro has also been obtained upon stimulation with IFN-alpha and/or IFN-beta. However, it is unknown if any IFN-gamma-independent neopterin synthesis is possible in vivo. In the present study we investigated the serum neopterin concentrations in patients affected by the syndrome of Mendelian susceptibility to mycobacterial disease (MSMD). Indeed, this syndrome is characterized by deeply impaired or absent IFN-gamma production or function due to severe mutations in molecules involved in IFN-gamma/interleukin-12 (IL-12)/IL-23-dependent pathway. Serum neopterin levels were measured by an enzyme-linked immunosorbent assay in 27 patients with MSMD. We found that serum neopterin levels are elevated in the complete absence of IFN-gamma activity due either to a complete deficiency of its receptor or to deleterious mutations of IL-12 or its receptor. These data clearly indicate that, as reported from in vitro studies, other stimuli are able to induce neopterin synthesis in vivo. Consequently, neopterin cannot be used as means of diagnosis of MSMD due to IFN-gamma-, IL-12-, and IL-23-dependent pathway defects.

Neopterin as a Stimulator of Vascular Endothelial Growth Factor and Erythropoietin Gene Expression in an Ovarian Carcinoma Cell Line

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

Inflammation, Homocysteine, Pyridoxal-5-phosphate and Lipids in Patients with Coronary Artery Disease before and Six Months after Coronary Angioplasty Followed by Stent Implantation

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

Homocysteine and serum markers of immune activation in primary dystonia

The cause of primary dystonia remains unknown. Several reports point to immune system disturbances in primary dystonia and a recent study demonstrated hyperhomocysteinemia in cervical dystonia. Homocysteine (HCY) is an amino acid and elevated HCY concentrations were shown to be associated with immune system activation and increased neopterin serum concentrations. We examined HCY serum concentrations together with serum markers of immune activation in patients with different types of primary dystonia. Eighty-three patients with different types of primary dystonia were included and investigated at least 3 months following botulinum toxin treatment. Thirty-six healthy volunteers with similar age and sex distribution served as controls. Total serum HCY, kynurenine, and tryptophan concentrations were determined by high-performance liquid chromatography; neopterin, folate, and vitamin B12 concentrations were measured by immunoassays. Routine blood analysis, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood count (WBC), was performed. Patients with primary dystonia had significantly higher HCY concentrations compared to controls. Among the dystonia subtypes, no significant difference of HCY serum concentrations was observed. CRP and ESR were within the normal range in >90% of the patients and all had normal WBC. Neopterin, kynurenine, and tryptophan serum concentrations were similar in patients and controls and not correlated with HCY serum concentrations. The results provide evidence against enhanced cellular immune activation in patients with primary dystonia. However, hyperhomocysteinemia was present in all dystonia subtypes and unrelated to immune activation in this study. HCY is a neuronal excitotoxic amino acid and hyperhomocysteinemia is considered an independent vascular risk factor. Further studies are required to define the background of hyperhomocysteinemia in primary dystonia.

Procalcitonin, c-reactive protein and neopterin levels in patients with coronary atherosclerosis

Objective — Recent studies demonstrate that the serum inflammatory markers increase in patients with atherosclerosis.We aimed to assess whether a difference exists between patients with acute coronary syndrome and patients with stable angina pectoris in respect to serum neopterin, procalcitonin (PCT) and C-reactive protein (CRP) levels.Methods and results — A total of 52 patientss (42 male, 10 female) who had atherosclerosis confirmed by angiography and were being followed up for an acute coronary syndrome were recruited and for control group, 45 patients with stable angina pectoris (SA) (35 male and 10 female) who underwent coronary angiography, were examined. Serum concentrations of neopterin, CRP and PCT in the study group (acute coronary syndrome) were compared to control group (stable angina pectoris).The mean neopterin level of the study group was 22.47 ± 2.93 nmol/l, the mean CRP level was 30.40 ± 8.05 mg/l and the mean PCT level was 0.40 ± 0.04 ng/ml. In control group these levels were 12.26 ± 0.61 nmol/l (p < 0.05), 5.26 ± 0.64 mg/l (p < 0.001) and 0.19 ± 0.02 ng/ml (p < 0.001), respectively.Conclusion — In the presented study our results showed that these markers can be useful for the assessment of inflammation related to atherosclerosis.

Elevated serum neopterin predicts future adverse cardiac events in patients with chronic stable angina pectoris

Serum levels of neopterin, an immune modulator secreted by activated macrophages, are elevated in patients with acute coronary syndromes compared with stable angina patients and control subjects. In unstable angina, serum neopterin levels correlate with the presence of vulnerable coronary stenosis, multiple complex coronary lesions, and patient outcome. The present study assessed the prognostic significance of raised serum neopterin concentrations in patients with stable angina pectoris. We carried out a 1-year follow-up prospective study in 297 patients with chronic stable chest pain undergoing diagnostic coronary angiography. The primary study endpoint was the composite of non-fatal myocardial infarction, unstable angina, and cardiac death. Fifty-one patients (17.2%) had adverse coronary events during follow-up. Mean serum neopterin levels were significantly higher in patients with events compared with those without (P=0.02). On multiple regression analysis, neopterin levels (P=0.021), severity of coronary artery disease (P=0.009), and a history of previous myocardial infarction (P=0.001) were independent predictors of adverse events. Serum neopterin is an independent predictor of major adverse coronary events in patients with chronic stable angina pectoris. This marker of macrophage activation may be useful for risk stratification in patients with chronic stable angina.

Serum neopterin, tumor necrosis factor-α and soluble tumor necrosis factor receptor II (p75) levels and disease activity in Egyptian female patients with systemic lupus erythematosus

Objective: To determine the clinical value of assaying serum levels of neopterin, tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor receptor II (p75) (sTNFRII) in patients with systemic lupus erythematosus (SLE), manifested clinically with lupus nephritis (LN), neuropsychiatric lupus erythematosus (NPLE), and/or vasculitis compared with established parameters (complements C3 and C4). Patients and methods: Serum concentrations of neopterin, TNF-α and sTNFRII were studied in 40 female patients with SLE at various degrees of disease activity and in 10 healthy controls, matched for age and sex, using an ELISA kit. Disease activity was assessed by the SLE disease activity index (SLEDAI) score. Thirty-five, 30 and 28 of our patients presented with LN, NPLE and/or vasculitis, respectively, as the main clinical manifestation. Results: Serum levels of neopterin, TNF-α and sTNFRII were significantly increased, while the TNF-α/sTNFRII ratio, C3 and C4 levels of SLE patients were significantly lower than those of healthy controls. Neopterin and sTNFRII were the only parameters that showed significantly higher levels in SLE patients with mild activity compared to normal subjects and were the only parameters that showed a significant elevation in membranous nephritis and in mild NPLE compared to patients without nephritis and NPLE. Patients with vasculitis had significant elevation of serum neopterin, TNF-α and sTNFRII levels compared to patients without vasculitis. We found significant correlations between all measured variables and the SLEDAI score. Also, serum neopterin levels showed significant positive correlation with serum TNF-α, sTNFRII and TNF-α/sTNFRII levels. Serum neopterin and sTNFRII could be used to identify SLE patients from normals with a sensitivity and specificity of 100%. Multivariate linear regression analysis showed that serum sTNFRII was the only significant independent variable among parameters for prediction of SLE disease activity. Conclusion: We suggest that serum sTNFRII and neopterin are more sensitive markers of disease activity than TNF-α, C3 or C4. However, sTNFRII may be a clinically useful independent marker for prediction of SLE disease activity and to differentiate normal subjects from those having mild SLE.