Showing papers on "Neopterin published in 2010"

Distinct cytokine profiles of systemic-onset juvenile idiopathic arthritis-associated macrophage activation syndrome with particular emphasis on the role of interleukin-18 in its pathogenesis

Abstract: OBJECTIVES To compare the pro-inflammatory cytokine profiles and the cytokine kinetics in patients with secondary macrophage activation syndrome (MAS) due to systemic-onset juvenile idiopathic arthritis (s-JIA) and in both active and inactive disease states of s-JIA (but no MAS), with those demonstrated in EBV-induced haemophagocytic lymphohistiocytosis (HLH) and Kawasaki disease (KD), and to investigate the significance of IL-18 in the pathogenesis of s-JIA. METHODS Five patients with MAS complicating s-JIA (MAS/s-JIA), 10 with HLH due to EBV infection (EBV-HLH), 22 with KD and 28 healthy controls were analysed. Cytokine concentrations (IL-18, IL-6, neopterin and TNF-alpha receptor Types I and II) were quantified in serum by ELISA. Results were compared with clinical features of MAS/s-JIA, including ferritin concentrations. RESULTS Serum IL-18 concentrations in MAS/s-JIA patients were significantly higher than those in EBV-HLH or KD patients (P < 0.05). Serum IL-6 concentrations in KD patients were significantly higher than those in EBV-HLH or MAS/s-JIA patients. Serum neopterin concentrations in EBV-HLH patients were significantly higher than those in MAS/s-JIA or KD patients. Serum IL-18 correlated positively with the following measurements of disease activity: CRP, ferritin, lactate dehydrogenase and other cytokines (P < 0.05). Serum concentrations of IL-18 in s-JIA patients remained elevated in the inactive phase of disease, whereas clinical parameters and other cytokines normalized. CONCLUSIONS IL-18 may be an important mediator in s-JIA. Although serum Il-18 concentrations correlated with markers of the disease activity, IL-18 concentrations remained elevated even when other markers of disease activity normalized. Serum IL-18 concentration may be a promising indicator of the disease activity. The cytokine release pattern in MAS/HLH is different among patients with different aetiologies. Monitoring the cytokine profile, including IL-18, may be useful for differentiation of MAS/HLH and evaluation of disease activity in s-JIA.

Cerebrospinal fluid neopterin: an informative biomarker of central nervous system immune activation in HIV-1 infection

Abstract: HIV-1 invades the central nervous system (CNS) in the context of acute infection, persists thereafter in the absence of treatment, and leads to chronic intrathecal immunoactivation that can be measured by the macrophage activation marker, neopterin, in cerebrospinal fluid (CSF). In this review we describe our experience with CSF neopterin measurements in 382 untreated HIV-infected patients across the spectrum of immunosuppression and HIV-related neurological diseases, in 73 untreated AIDS patients with opportunistic CNS infections, and in 233 treated patients. In untreated patients, CSF neopterin concentrations are almost always elevated and increase progressively as immunosuppression worsens and blood CD4 cell counts fall. However, patients with HIV dementia exhibit particularly high CSF neopterin concentrations, above those of patients without neurological disease, though patients with CNS opportunistic infections, including CMV encephalitis and cryptococcal meningitis, also exhibit high levels of CSF neopterin. Combination antiretroviral therapy, with its potent effect on CNS HIV infection and CSF HIV RNA, mitigates both intrathecal immunoactivation and lowers CSF neopterin. However, despite suppression of plasma and CSF HIV RNA to below the detection limits of clinical assays (<50 copies HIV RNA/mL), CSF neopterin often remains mildly elevated, indicating persistent low-level intrathecal immune activation and raising the important questions of whether this elevation is driven by continued CNS infection and whether it causes continued indolent CNS injury. Although nonspecific, CSF neopterin can serve as a useful biomarker in the diagnosis of HIV dementia in the setting of confounding conditions, in monitoring the CNS inflammatory effects of antiretroviral treatment, and give valuable information to the cause of ongoing brain injury.

The association between serum levels of neopterin and number of depressive episodes of major depression

Abstract: Background There is an interaction between the immune system and the central nervous system by means of hormones, peptides, and neurotransmitters. The aims of the present study were to determine whether the serum neopterin levels in patients with major depression (MD) differ from a healthy control group and to investigate the relationship between previous MD episodes and serum neopterin levels. Methods Thirty patients who were admitted to the GATA Psychiatry Outpatient Clinics and were diagnosed with MD according to DSM-IV, and who agreed to participate in the study, were included in the study. Twenty-six healthy volunteers matched for age, gender, and level of education who agreed to participate in the study were served as controls. Peripheral venous blood samples were obtained from the patients and the control group for complete blood count, routine biochemistry, and the detection of serum neopterin levels. The analyses were performed in the laboratory of the GATA Department of Biochemistry. Results There was no significant difference between the MD group and the healthy controls with respect to age, level of education, smoking, and gender. Serum neopterin levels of the MD group who had experienced two or more episodes were higher than the first-episode group and the control group. Age of onset and the number of previous episodes had an independent impact on serum neopterin levels in MD patients, while smoking did not show any effect. Conclusion In the present study, the neopterin levels of patients who had experienced two or more episodes were higher than the first-episode depressive group and healthy control group. It was also found that the number of previous depressive episodes and the ages of the MD cases had an independent effect on serum neopterin levels.

Serum Levels of the Immune Activation Marker Neopterin Change With Age and Gender and Are Modified by Race, BMI, and Percentage of Body Fat

Abstract: CHRONIC immune activation is involved in a number of diverse pathologies, including AIDS (1), atherosclerosis (2), autoimmune disease (3), cancer (4), obesity, and metabolic syndrome (5,6). Importantly, immune system activation has also been implicated in the aging process in normal healthy individuals (7,8). Neopterin, a metabolite of GTP, is produced in macrophages upon stimulation by interferon gamma released by activated T cells (9). In humans, neopterin is a marker of macrophage activation (10). This marker has been used clinically in the assessment of bacterial and viral infections (11,12), autoimmune diseases (13,14), sleep apnea (15), and in malignant conditions (16). Individual reports have been equivocal regarding correlations of serum neopterin levels with age or gender (17–19). However, these studies typically employed comparison groups with discontinuous age (ie, young adult vs old adult) and did not exclude potential confounding conditions (ie, smoking, hypertension, pulmonary disease, and other chronic inflammatory disease). In addition, a number of recent studies with relatively small numbers of participants (n <50) have suggested that neopterin levels can be influenced by body mass index (BMI) values (20,21). The current study was undertaken to carefully assess the relationship of neopterin with age, BMI, and percentage of body fat (%fat) and to see whether gender and race modulate those relationships.

Macrophage activity in semen is significantly correlated with sperm quality in infertile men.

Abstract: The presence of leucocytes within semen has the potential to impair sperm function. Neutrophils and macrophages make up 95% of seminal leucocytes, with both having the ability to damage sperm via the generation of reactive oxygen species, proteases and the induction of apoptosis. Existing cytological techniques for quantifying leucocyte activity within semen (peroxidase, CD45) are less than ideal as they merely count the number of leucocytes, rather than assess their activity. Seminal plasma elastase effectively determines neutrophil activity, yet gives no insight into macrophage activity. Neopterin, a molecule released from activated macrophages, may be a useful marker for macrophage activity in the male reproductive tract. To examine this possibility a total of 63 asymptomatic subjects with male factor infertility and 11 fertile controls provided semen samples for measurement of various inflammatory markers. We were able to confirm for the first time that seminal plasma does indeed contain neopterin and that the levels of this macrophage activity marker are threefold higher in infertile than fertile men. Furthermore, seminal plasma neopterin concentration was significantly correlated with sperm oxidative stress, DNA fragmentation (TUNEL) and apoptosis (Annexin V), making it a useful marker of sperm quality. By contrast, seminal plasma elastase showed no correlation with any marker of sperm quality.

Early expression of pro- and anti-inflammatory cytokines in left ventricular assist device recipients with multiple organ failure syndrome.

Abstract: To assess whether the combined evaluation of total Sequential Organ Failure Assessment (t-SOFA) score and pro- and anti-inflammatory cytokine profiles early after left ventricular assist device (LVAD) implant discriminates patients at high risk for multiple organ failure syndrome (MOFS) in the first month post-LVAD, we analyzed plasma interleukin (IL)-6, IL-8, IL-10, IL-1ra, IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and urine neopterin levels before (day 0) and at 4 hours, 1, 3, 7, 14, and 30 days after LVAD implant in 23 recipients. Eight patients died of MOFS between days 7 and 30 (nonsurvivors). At preimplant, only blood urea nitrogen and age were higher in nonsurvivors than survivors. At 4 hours, IL-8, IL-10, and IL1-ra levels were higher in nonsurvivors than in survivors; t-SOFA was also higher and peaked on day 3 in nonsurvivors. Only IL-8 levels on day 1 were significantly associated with a t-SOFA > or =10 on day 3 (odds ratio 1.10, 95% confidence interval 1.01-1.21, p = 0.04). Neopterin, marker of monocyte activation, increased significantly only in nonsurvivors (p < 0.001). These findings suggest that an activated inflammatory system soon after LVAD implant is implicated in MOFS development. Early monitoring of inflammatory mediators and t-SOFA score may be a valuable tool for outcome prediction in LVAD recipients.

The importance of alpha-1 antitrypsin (alpha1-AT) and neopterin serum levels in the evaluation of non-small cell lung and prostate cancer patients.

Abstract: OBJECTIVE Increased serum levels of alpha-1 antitrypsin (alpha1-AT) and neopterin were observed in many diseases including different types of cancer. The aim of this work is to determine alpha1-AT and neopterin serum levels in newly diagnosed untreated non-small cell lung and prostate cancer patients and to test their relation to cancer staging. METHODS Radial Immunodiffusion and ELISA methods were used to determine alpha1-AT and neopterin serum levels, consequently. RESULTS alpha1-AT and neopterin mean serum levels were found to be elevated in non-small-cell lung and prostate cancer patients. In non-small cell lung cancer patients alpha1-AT was 454.5+/-129.2 mg/dL (p<0.0005) and neopterin was 7.9+/-4.2 ng/mL (p<0.0005). In prostate cancer patients alpha1-AT was 462.7+/-116.9 mg/dL (p<0.0005) and neopterin was 8.1+/-3.1 ng/mL (p<0.0005). These elevated levels were significantly correlated with the stage of cancer. The mean serum level of alpha1-AT in stages I, II, III, and IV among non-small cell lung cancer patients were 305.1, 453.6, 490.3 and 616.0 mg/dL respectively, and the mean serum levels for neopterin were 4.0, 7.0, 8.1 and 14.9 ng/mL, correspondingly. The mean serum level of alpha1-AT in stages A, B, C, and D among prostate cancer patients were 342.9, 418.5, 467.8 and 593.5 mg/dL respectively and the mean serum levels for neopterin were 4.9, 6.6, 8.7 and 11.6 ng/mL, correspondingly. CONCLUSIONS Based on the above mentioned findings alpha1-AT and neopterin serum levels should be considered in the follow up as well as in the prognosis of cancer patients.

Evaluation of procalcitonin and neopterin level in serum of patients with acute bacterial infection

Abstract: BACKGROUND: Fever as a common presenting complaint in pediatric patients can be due to various causes. Differentiating bacterial infection from other causes is important because the prompt use of antibiotics is critical in bacterial infection. Traditional markers of infection such as BT and WBC count may be unspecific and culture may be late or absent. CRP and Procalcitonin (PCT) have been considered to evaluate the evolution of infections and sepsis in patients presenting with SIRS. Neopterin has also been proposed to aid in the diagnosis of bacterial infection. In this study, we compared the value of the serum PCT, neopterin level, and WBC count for predicting bacterial infection and outcome in children with fever. METHODS: 158 pediatric (2-120-month-old) patients suspected to have acute bacterial infection, based on clinical judgment in which other causes of SIRS were ruled out were included in the study. WBC count with differential was determined and PCT and neopterin levels were measured. RESULTS: PCT level was higher in bacterial infection and patients who were complicated or expired. CONCLUSION: Rapid PCT test is superior to neopterin and WBC count for anticipating bacterial infection, especially in ED where prompt decision making is critical. ABBREVIATIONS: BT, body temperature; WBC, white blood cell; PCT, procalcitonin; CRP, C-reactive protein; SIRS, systemic inflammatory response syndrome; ED, emergency department.

New universal definition of myocardial infarction applicable after complex percutaneous coronary interventions

Abstract: Objectives This study aimed to characterize myocardial infarction after percutaneous coronary intervention (PCI) based on cardiac marker elevation as recommended by the new universal definition and on the detection of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR). It is also assessed whether baseline inflammatory biomarkers are higher in patients developing myocardial injury. Background Cardiovascular magnetic resonance accurately assesses infarct size. Baseline C-reactive protein (CRP) and neopterin predict prognosis after stent implantation. Methods Consecutive patients with baseline troponin (Tn) I within normal limits and no LGE in the target vessel underwent baseline and post-PCI CMR. The Tn-I was measured until 24 h after PCI. Serum high-sensitivity CRP and neopterin were assessed before coronary angiography. Results Of 45 patients, 64 (53 to 72) years of age, 33% developed LGE with infarct size of 0.83 g (interquartile range: 0.32 to 1.30 g). A Tn-I elevation >99% upper reference limit (i.e., myocardial necrosis) (median Tn-I: 0.51 μg/l, interquartile range: 0.16 to 1.23) and Tn-I >3× upper reference limit (i.e., type 4a myocardial infarction [MI]) occurred in 58% and 47% patients, respectively. LGE was undetectable in 42% and 43% of patients with periprocedural myocardial necrosis and type 4a MI, respectively. Agreement between LGE and type 4a MI was moderate (kappa = 0.45). The levels of CRP or neopterin did not significantly differ between patients with or without myocardial injury, detected by CMR or according to the new definition (p = NS). Conclusions This study reports the lack of substantial agreement between the new universal definition and CMR for the diagnosis of small-size periprocedural myocardial damage after complex PCI. Baseline levels of CRP or neopterin were not predictive for the development of periprocedural myocardial damage.

Early increase of plasma homocysteine in sepsis patients with poor outcome

Abstract: Moderate hyperhomocysteinemia is a well-established coronary risk factor that develops when dietary supply with folate and/or vitamin B(12) is inadequate. Recently, stimulated peripheral blood mononuclear cells were shown to produce homocysteine. Thus, the stimulated immune system may contribute to moderate hyperhomocysteinemia during certain diseases. Because multiple trauma and sepsis are accompanied by often strong inflammatory responses, we investigated whether hyperhomocysteinemia may develop in patients. Total homocysteine and cysteine concentrations were measured in 83 plasma specimens from 18 patients (14 men, 4 women; 15 posttrauma with sepsis and 3 with sepsis alone) every third day of follow-up. Finally results were compared with concentrations of cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6, the immune activation marker neopterin and the extent of tryptophan degradation as indicated by the kynurenine-to-tryptophan ratio (kyn/trp). Compared with baseline, average total homocysteine (P < 0.05, d 4-d 10) and cysteine (P < 0.05, d 7-d 13) concentrations increased during follow-up of patients. However, only the increase of homocysteine was related to the survival status: total homocysteine was significantly higher in nonsurvivors (P < 0.05, d 4 and d 10) than in survivors, whereas cysteine concentrations increased in both subgroups. Homocysteine correlated with kyn/trp but not with neopterin concentrations. Increase of total homocysteine is common in patients after trauma with unfavorable outcome. Because all patients received standardized enteral nutrition after the end of hypodynamic shock, inconsistent vitamin supply is unlikely to be the reason for hyperhomocysteinemia in some of the patients; rather, it is associated with a stronger proinflammatory response. Certainly, the number of patients in our study is still small and results can only be regarded as preliminary.

Enhanced degradation of tryptophan in patients on hemodialysis.

Abstract: BACKGROUND Hemodialysis patients often present with increased concentrations of tryptophan catabolites perhaps related to an enhanced activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) that is inducible by pro-inflammatory stimuli. The often chronic inflammation and immune activation status in dialysis patients may accelerate tryptophan degradation, which could influence patients' psychological performance. PATIENTS AND METHODS In this study, plasma concentrations of kynurenine and tryptophan were determined by HPLC in 75 dialysis patients, aged 65.3 ± 15.0 years. Forty patients were female, 35 male; 21 (28%) had diabetes mellitus Type 1 or 2 and 32 (43%) suffered from sleep disturbances and/or depression. Their dialysis vintage was 4.26 ± 4.72 years. HPLC results were compared to concentrations obtained from 40 healthy blood donors, to immune activation marker neopterin, and to psychological test results based on INTERMED scores. RESULTS Compared to those in healthy controls, tryptophan concentrations were decreased in patients. Neopterin, kynurenine and the kynurenine to tryptophan ratio (kyn/trp, an index of tryptophan degradation) were increased in patients (all p < 0.01). Kyn/trp correlated with neopterin concentrations (rs = 0.393, p < 0.01). INTERMED scores were 21.0 + 8.4 and slightly higher in females (U = -1.831, p < 0.07); they correlated with tryptophan concentrations (rs = -0.227, p < 0.05) but with no other parameter studied. Data point to a possible relationship between tryptophan metabolic disturbances and psychologic presentation of patients, although only a rather weak relationship was found. CONCLUSION We conclude that tryptophan degradation is increased in dialysis patients. The association with increased neopterin concentrations indicates activated IDO.

Neopterin and atherosclerotic plaque instability in coronary and carotid arteries.

Abstract: Inflammation plays a key role in atherosclerosis and plaque vulnerability, and monocyte/macrophage activation contributes to these processes. Neopterin, a by-product of the guanosine triphosphate pathway, is produced by activated macrophages on stimulation with interferon-γ released from T lymphocytes, and is an activation marker for monocytes/macrophages. Coronary angiographic studies have shown a relationship between increased circulating levels of neopterin and the presence of complex coronary lesions in patients with unstable angina pectoris (UAP). Furthermore, in an immunohistochemical study performed using coronary atherectomy specimens, a significantly higher prevalence of neopterin-positive macrophages was found in culprit lesions in patients with UAP than in those with stable angina pectoris (SAP). We recently clarified that the presence of complex carotid plaques detected by carotid ultrasound was related to increased circulating levels of neopterin, and immunohistochemical localization of neopterin was observed in complex carotid lesions obtained from carotid endarterectomy in patients with SAP. These findings suggest that neopterin is an important biomarker of plaque instability in both coronary and carotid atherosclerotic lesions.

Bone mineral density, bone turnover markers and cytokines in alcohol-induced cirrhosis.

Abstract: Aims: Liver cirrhosis is a risk factor for osteoporosis. However, the pathogenesis of the bone mass loss in patients with alcohol-induced cirrhosis (AC) is not well understood. Serum concentrations of soluble tumour necrosis factor receptor (sTNF-R55), neopterin and soluble interleukin 2 receptor (sIL-2R), activation markers of cellular immunity, correlate with clinical activity and se- verity of the AC. The aim of this study is to evaluate the association of these soluble markers with the development of osteoporosis in patients with AC. Methods: W e studied 33 consecutive patients with AC and 24 healthy volunteers. Bone mineral density (BMD) was measured by X-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN). Neopterin was measured by radioimmunoassay. Serum concentrations of sTNF-R55 and sIL-2R were measured by enzyme immunoassay. We also determined serum levels of osteo- calcin and bone alkaline phosphatase as biochemical markers of bone formation, and deoxypyridinoline urinary excretion (D-Pyr) as marker of bone resorption. Results: Patients with AC had reduced BMD (expressed as z-score) in all sites (LS: P<0.001 and FN: P< 0.05). Serum concentrations of sTNF-R55 were significantly higher in patients with both AC and osteoporosis than in those with only AC (P< 0.001). Serum levels of sTNF-R55 positively correlated with D-Pyr urinary excretion (r=0.354; P=0.01). Serum levels of sIL-2R were significantly higher in patients with both AC and osteoporosis than in those with only AC (P<0.05). Conclusions: There is a relation between activation of the cellular immunity and osteoporosis in AC. Bone mass loss could be related to the increased bone resorption found in these patients.

Increased tryptophan degradation in patients with bronchus carcinoma.

Abstract: Expression of tryptophan-degrading enzyme indoleamine (2,3)-dioxygenase in tumour tissue is proposed to represent an important tumour immunoescape mechanism. To further investigate the potential role of activated indoleamine (2,3)-dioxygenase in bronchus carcinoma, we examined serum tryptophan and kynurenine concentrations in nine patients with small cell lung cancer and in 27 patients with non-small cell lung cancer. Tryptophan metabolic changes were compared with markers of inflammation and immune activation namely C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and neopterin. Compared with controls, patients presented with lower tryptophan concentrations (P < 0.01) and with higher serum kynurenine to tryptophan ratios (P < 0.01), an index of tryptophan degradation. Also ESR and CRP and neopterin concentrations were increased in the patients (all P < 0.001), and there was a weak correlation between kynurenine to tryptophan ratio and ESR, CRP and neopterin concentrations. We conclude that in the majority of patients with non-small cell lung cancer and small cell lung cancer, enhanced tryptophan degradation can be observed. It seems to relate to an inflammatory response and may reflect activation of indoleamine (2,3)-dioxygenase at the tumour site. The capacity of the tumour to escape normal host immune defence may be influenced by tryptophan degradation. Results of this pilot study deserve further confirmation.

Total homocysteine in patients with angiographic coronary artery disease correlates with inflammation markers

Abstract: Moderate hyperhomocysteinaemia is considered as an independent risk marker for cardiovascular disease and stroke. Earlier, increased homocysteine production was detected in stimulated immunocompetent cells in vitro, and several markers of inflammation like neopterin or C-reactive protein (CRP) were demonstrated as significant indicators of cardiovascular risk. The relationship between coronary artery disease (CAD), homocysteine metabolism and markers of immune activation and inflammation was investigated in a population of 1717 patients undergoing coronary angiography, recruited as participants of the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study. 1325 patients (77.2%) suffered from coronary artery disease (CAD), which was was defined as the occurrence of a visible luminal narrowing (>or=20% stenosis) in at least 1 of 15 coronary segments according to the classification of the American Heart Association, the remaining 392 individuals of the study population served as controls. Significant differences regarding systolic blood pressure, homocysteine, neopterin and folic acid concentrations were observed between patients and controls. Older age, decreased creatinine-clearance and higher concentrations of homocysteine and CRP were indicative for CAD. Low B-vitamin availability, therapy and the extent of immune activation strongly influenced homocysteine concentrations. Homocysteine concentrations were correlated with neopterin levels (r(s) =0.325, p<0.001), and hyperhomocysteinaemic patients also presented with significantly higher CRP concentrations. Homocysteine accumulation coincided with impaired renal and heart function (as reflected by ProBNP[Brain natriuretic peptide]-concentrations). We conclude that homocysteine accumulation could result from B-vitamin deficiency which is related to chronic immune activation.

The value of neopterin and procalcitonin in patients with sepsis.

Abstract: Objective: Neopterin (NT) is a compound of low molecule-based pteridine. It is secreted by macrophages as a response to the stimulation of cytokines such as interferon-γ, interferon- 1β, tumor necrosis factor α or bacteria compounds such as lipopolysaccharides. Procalcitonin (PCT) levels may increase in the course of bacterial, parasitic, and fungal infections. Therefore, it can be used for the differential diagnosis of the infection, especially in cases of serious inflammation. In this study, the role of NT, and PCT in sepsis as a prognostic factor, and the relationship between the two parameters are examined. Methods: From November 1, 2005 through December 31, 2005, fifty patients with sepsis admitted to the Department of the Infectious Diseases and Clinical Microbiology and/or Department of Anaesthesiology and Reanimation were enrolled in the study. Patients were divided in two subgroups according to their survival: group I (n = 23) nonsurviving patients and group II (n = 27) surviving patients. Results: Serum NT levels have been found to be increased in group I (median: 15 ng/mL, range: 2-69) when compared to group II (median: 5 ng/mL, range: 2-130). The difference was statistically significant (P = 0.03). Other laboratory parameters and PCT levels (group I median: 0.13; group II median: 0.08; P < 0.05) were not different between the two groups. Conclusions: NT was found to be a prognostic factor in patients with sepsis.

Plasma levels of nitric oxide related amino acids in demented subjects with Down syndrome are related to neopterin concentrations.

Abstract: Subjects with Down syndrome (DS) have abnormalities in virtually all aspects of the immune system and almost all will be affected with Alzheimer’s disease (AD). It is thought that nitric oxide (NO) is involved in the pathophysiology of AD. In the present study, including a total of 401 elderly DS subjects, the spectrum of plasma amino acids and neopterin was investigated and related to development of AD. Concentrations of nearly all amino acids in DS subjects differed significantly from those of healthy controls. Neopterin was increased in DS subjects, especially in dementia. The production of NO as reflected by an increased citrulline/arginine ratio (Cit/Arg ratio) was enhanced during development of clinical dementia. Neopterin concentrations correlated to the Cit/Arg ratio only in the group of prevalent demented subjects (ρ = 0.48, P = 0.006). The results of this study are suggestive for an increase in oxidative processes in DS subjects with AD.

Urinary neopterin and nitric oxide metabolites as markers of interferon beta-1a activity in primary progressive multiple sclerosis.

Abstract: Background: Interferon beta has not been demonstrated to be effective in exploratory phase 2 clinical trials in primary progressive multiple sclerosis. However, using more sensitive indicators of a treatment response, such as biomarkers, might help to identify sub-groups of patients who may benefit from therapy.Objective: To assess the utility of measuring urinary neopterin and nitric oxide metabolite excretion for monitoring interferon beta-1a (IFN beta-1a) treatment in patients with primary progressive multiple sclerosis.Methods: Fifty patients from a phase II trial of IFN beta-1a (Placebo n = 20; Avonex (R) 1 x 30 mu g/week (IFN-30), n = 15; Avonex (R) 1 x 60 mu g/week (IFN-60), n = 15), were enrolled. Patients were assessed using the Expanded Disability Status Scale. Urine samples were collected on each visit, 3 months apart, for a period of 24 months. Nitric oxide metabolites, nitrite/nitrate (NOx), were measured by colorimetric assay and neopterin and creatinine (Cr) were assayed using a high-performance liquid chromatography technique. NOx/creatinine ratio (NOxCR) and urinary neopterin/creatinine ratio (UNCR) quotients were calculated.Results: There was no significant difference between pre-dose, baseline levels of UNCR or NOxCR between the study groups. On the intention-to-treat analysis, there was a significant difference in UNCR levels between the placebo compared with IFN-30 (p = 0.03) or IFN-60 (p = 0.002) groups. The IFN-30 and IFN-60 groups did not differ. Within IFN beta-1a-treated patients with primary progressive multiple sclerosis, median UNCR values were significantly higher in clinically stable (no Expanded Disability Status Scale change) compared with progressive patients (p = 0.002). IFN beta-1a treatment did not significantly influence NOx excretion in patients with primary progressive multiple sclerosis.Conclusions: Urinary neopterin is a potential biomarker to monitor the in vivo effects of IFN beta-1a in primary progressive multiple sclerosis and other multiple sclerosis sub-types.

Immune Activation and Neuropsychiatric Symptoms in HIV Infection

Abstract: This study examined the role of biological processes in the development of specific neuropsychiatric complications in HAART-naive adults with HIV/AIDS. Depressive symptoms were modestly associated with elevated IL-6 mRNA expression (r s =0.40, p 0.05). Mean neopterin levels were higher in the depressed as compared with nondepressed group but only for those taking antidepressants (F=45.66, df=1, 11, p<0.001). Neuropsychological impairment was not associated with the biological markers. These findings suggest that systemic immune markers (like neopterin) may be useful in differentiating treatment-resistant individuals at greater risk of developing chronic depression.

The association between neopterin and acetaminophen-induced nephrotoxicity.

Abstract: Introduction: In large dosages, acetaminophen (APAP) produces acute kidney necrosis in most mammalian species. High neopterin levels have been accepted as strong indicators for the clinical severity of some diseases. In this study, we aimed to evaluate whether neopterin is a biomarker in the identification of APAP-induced nephrotoxicity. Materials and Methods: Thirty adult male Wistar rats were randomly divided into three groups: control, APAP-1, and APAP-2 groups. APAP-1 and APAP-2 group rats were given a single dose of 1 and 2 g/kg body weight of APAP by gastric tube, respectively. Kidney tissues and blood samples were obtained for biochemical and histopathological analyses. Biochemical parameters, serum and kidney neopterin levels, and the grade of tubular injury were compared in the control, APAP-1, and APAP-2 group animals. Results: APAP treatments caused tubular necrosis in the kidney and increase in serum creatinine concentrations accompanied by elevated serum and kidney neopterin levels. In the rats of groups APAP-1 and APAP-2 when compared with that of the control group (109.1 pmol/mg protein), median kidney neopterin concentrations were 162.1 (p = 0.089) and 222.2 (p < 0.001) pmol/mg protein, respectively. The grade of tubular injury of the APAP-1 and APAP-2 groups was higher than the group of control (both p < 0.001). Conclusions: Serum and kidney neopterin levels could be sensible alternative to evaluate the risk to have nephrotoxicity because of APAP overdose. The elevated serum and kidney neopterin in the APAP-induced tubular necrosis might be a marker of acute histological kidney injury.