Detection of immunodeficiencies and persistent infections by urinary neopterin measurement

We evaluated the clinical significance of measurement of urinary neopterin levels in primary immunodeficiencies and persistent infections exclusively at afebrile or asymptomatic periods. Despite the examinations at afebrile or asymptomatic periods, urinary neopterin levels were elevated in some patients with primary immunodeficiencies and in patients with persistent infections of human immunodeficiency virus (HIV) or Epstein-Barr virus (EBV). Therefore, urinary neopterin measurement at afebrile periods will be useful as one of the screening tests in the detection of such disorders among children with occasional episodes of infections.     

Neutrophil and macrophage activation and anaphylatoxin formation in orthotopic liver transplantation without the use of veno-venous bypass

Background. Activation of neutrophils and activation of complement may be an aetiologic factor behind circulatory insufficiency in association with reperfusion of the grafted liver.
Methods. Neutrophil and macrophage activation (determined as PMN elastase and neopterin release) and complement activation were evaluated in 15 consecutive patients undergoing orthotopic liver transplantation without the use of veno-venous bypass.
Results. The PMN elastase concentrations were increased at the end ot the anhepatic phase, 2, 5 and 30 min after start of reperfusion and 6 and 24 h postoperatively. There were significantly higher PMN elastase concentrations in patients with circulatory instability (postreperfusion syndrome) compared with those without postreperfusion syndrome. The neopterin concentration was increased 2 min after the start of reperfusion and remained elevated until 6 h postoperatively. The plasma complement C3a concentrations were increased at the end of the anhepatic phase and 2, 5 and 30 min after the start of reperfusion. The plasma C3a levels were higher in patients with postreperfusion syndrome compared to those without.
Conclusions. Activation of neutrophils and macrophages and of the complement cascade with the formation of biologically active substances may be one explanation for the circulatory instability often seen in patients undergoing orthotopic liver transplantation.     

Neopterin production in posttraumatic stress disorder before and after pharmacotherapy

Post-traumatic stress disorder (PTSD) has been associated with decreased neopterin levels. In the present study, we evaluated whether this low neopterin levels would normalize following pharmacotherapy with sertraline in PTSD. Fourteen patients with PTSD and 14 controls were enrolled in the study. A clinical evaluation and measurements of neopterin levels before and after sertraline treatment were performed. In addition, all patients were assessed with the Clinician Administered PTSD Scale (CAPS). The mean neopterin levels were significantly lower in the patient group than control group at baseline and were negatively correlated with the duration of illness, or severity of illness. Sertraline treatment decreased the symptoms of PTSD; however this was not accompanied by a significant increase in neopterin production. In conclusion, our results reveal that the failure for neopterin to normalize through symptom alleviation suggests that either neopterin may be a trait marker of the illness, or that more sustained treatment is necessary to elevate the neopterin production. Received: 30 September 2002 / Accepted: 12 December 2002 Correspondence to Dr. Murad Atmaca     

Low serial serum neopterin does not predict low risk for chronic renal graft rejection

Research has provided new and potent immunosuppressants which can potentially stop ongoing rejection. Subclinical rejection is a particular problem in the pediatric age group and early identification of children at risk is of the utmost importance. Neopterin has been previously shown to be a non-specific but sensitive marker for immunologic activity. In this study we hypothesized that low serum neopterin in the 1st year after transplantation predicts a low risk of chronic rejection. We retrospectively analyzed serial neopterin data obtained beyond the early postoperative period in 21 children and correlated the peak and average with glomerular filtration rate (GFR) loss during the subsequent years (P=0.63, NS, r=0.10). Our results show that serum neopterin did not differ between the majority of children who developed chronic transplant dysfunction and children with stable transplant function beyond the early post-transplant period. Thus serum neopterin failed to delineate a low-risk population who might be spared more invasive diagnostic procedures such as protocol biopsy. Received: 22 November 1999 / Revised: 3 August 2000 / Accepted: 11 August 2000     

CSF neopterin as marker of disease activity in multiple sclerosis

Levels of neopterin, a factor known to be released from macrophages and monocytes at increased rates in cellular immune reactions, were higher in cerebrospinal fluid (CSF) in 10 of 12 patients with multiple sclerosis (MS) during exacerbations in comparison with remissions. This significant elevation in CSF during exacerbations was not reflected in serum. These results indicate that determination of neopterin in CSF may be a useful marker of disease activity in MS.     

Effects of etanercept on urine neopterin levels in patients with psoriasis in a controlled, open-label study

Neopterin is an immunological marker of cellular immune activation. Etanercept is a tumor necrosis factor-α (TNF-α) antagonist that decreases excessive levels of TNF-α associated with inflammatory disease down to physiological levels. The objective of this study was to investigate urine neopterin levels in psoriatic patients treated with etanercept, to study the effect of etanercept as a TNF-α blocker on urine neopterin levels. Urine neopterin levels and urine neopterin/creatinine ratios were measured by high-performance liquid chromatography in 22 patients with psoriasis before and after treatment with etanercept. Results were compared with a group of 20 healthy volunteers, and 20 patients with inflammatory skin diseases as control groups. Urine neopterin levels, neopterin/creatinine ratios and Psoriasis Area and Severity Index (PASI) scores were evaluated at baseline, and the 12th and 24th week after treatment. Urine neopterin levels were significantly elevated in the psoriatic group compared with control and inflammatory skin diseases groups ( P  < 0.05). Urine neopterin levels were significantly reduced after etanercept treatment. Statistically we did not find any correlation between neopterin levels and PASI scores. Our findings indicate that urine neopterin concentrations may reflect the disease activity in psoriasis, and may be used as a marker for monitoring disease activity and response to treatment with etanercept in psoriatic patients.     

Utility of measuring serum levels of anti-PGL-I antibody, neopterin and C-reactive protein in monitoring leprosy patients during multi-drug treatment and reactions

Objective To verify the validity of measuring the levels of Mycobacterium leprae‐specific anti‐phenolic glycolipid (PGL)‐I antibody, neopterin, a product of activated macrophages, and C‐reactive protein (CRP), an acute phase protein, in serial serum samples from patients for monitoring the leprosy spectrum and reactions during the course of multi‐drug treatment (MDT). Methods Twenty‐five untreated leprosy patients, 15 multi‐bacillary (MB) and 10 paucibacillary (PB), participated. Eight patients developed reversal reaction and five developed erythema nodosum leprosum (ENL) during follow‐up. The bacterial index (BI) in slit‐skin smears was determined at diagnosis and blood samples collected by venipuncture at diagnosis and after 2, 4, 6 and 12 months of MDT. PGL‐I antibody and neopterin were measured by enzyme‐linked immunosorbent assay, whereas the CRP levels were measured by the latex agglutination method. Results The levels of PGL‐I antibodies and neopterin were higher in the sera of MB than PB patients, which correlated with the patients’ BI. The serum levels of CRP did not differ significantly between the MB and PB patients. The serum levels of PGL‐I and neopterin were no higher in reactional patients than non‐reactional patients prone to such reactions. However, ENL patients had higher serum CRP levels than non‐reactional MB patients. The serum PGL‐I antibody levels declined significantly during MDT, in contrast to neopterin and CRP levels. Conclusion Measuring the serum levels of PGL‐I antibodies and neopterin appeared to be useful in distinguishing MB from PB patients, whereas monitoring the levels of PGL‐I antibodies appeared to be useful in monitoring MB patients on MDT. Measuring serum CRP, although not useful in monitoring the patients, has limited significance in detecting ENL reactional patients.     

The Effect of Aggressive Versus Conventional Lipid-lowering Therapy on Markers of Inflammatory and Oxidative Stress

Purpose Recent trial results are in favor of aggressive lipid lowering using high dose statins in patients needing secondary prevention. It is unclear whether these effects are solely due to more extensive lipid lowering or the result of the potentially anti-inflammatory properties of statins. We aimed to determine whether aggressive compared with conventional statin therapy is more effective in reducing systemic markers of inflammation and oxidative stress. Materials and methods This was a multi-centre, double-blind, placebo-controlled trial. Patients with previous cardiovascular disease, who did not achieve low density lipoprotein (LDL) cholesterol levels <2.6 mmol/l on conventional statin therapy (simvastatin 40 mg) were randomized to continue with simvastatin 40 mg or to receive atorvastatin 40 mg for 8 weeks and thereafter atorvastatin 80 mg for the final 8 weeks (aggressive treatment). Lipids, C-reactive protein, soluble cellular adhesion molecules, neopterin, von Willebrand Factor, and antibodies against oxidized LDL were measured at baseline and after 16 weeks. Results Lipid levels decreased significantly in the aggressive treatment group (LDL-C reduction 20.8%; P < 0.001), whereas a slight increase was observed in the conventional group (LDL-C increase 3.7%; P = 0.037). A significant reduction in antibodies against oxidized LDL was seen in the aggressive (13.4%; P < 0.001) and the conventional (26.8%; P < 0.001) group, but there was no difference between groups (P = 0.25). Furthermore, no significant differences in change in other biomarkers was observed between both groups. Conclusions This study does not support the hypothesis that a more profound reduction in inflammatory and oxidative stress contributes to the benefits of aggressive statin therapy.     

大承气颗粒对腹部手术后内毒素及细胞因子的影响

目的 :探讨大承气颗粒对腹部手术后血中内毒素、细胞因子等的影响。 方法 :根据手术类型及大小分层随机将2 1例患者分为 2组 :对照组采用西医综合治疗并用安慰剂 ,观察组在西医综合治疗基础上加用大承气颗粒。于术前 1d开始口服大承气颗粒 ,术后次日开始予大承气颗粒灌肠 (除外部分结肠切除者 )至可口服时 ,改用口服大承气颗粒。术前及术后 0、3、7、14d取患者外周静脉血测定内毒素、IL - 6、新喋呤。 结果 :观察组疗效优于对照组 (P <0 0 1) ;观察组在术前大便次数有增多趋势 (P =0 0 5 ) ,手术结束至术后第 3d、第 4～ 7d、第 8～ 14d大便次数显著增多 (P <0 0 1) ;术后首次出现肠鸣音、排气及大便所需时间均缩短 (P <0 0 5 ) ;术毕内毒素低于对照组 (P <0 0 5 ) ,IL - 6有降低趋势 (P =0 0 5 6 ) ;术后第 3d新喋呤亦呈降低趋势 (P =0 0 6 9)。术毕IL - 6水平与术后开始大便所需时间呈正相关 (r=0 .5 78,P <0 0 5 )。 结论 :手术前后口服和 /或灌肠使用大承气颗粒可促进中等以上腹部手术后肠功能恢复 ,降低循环内毒素水平 ,并有一定的减低术后IL - 6和新喋呤升高的作用 ,对改善术后状态有一定价值。     

Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment.

BACKGROUND: Tryptophan (TRP) degradation into kynurenine (KYN) by the enzyme, indoleamine-2,3-dioxygenase, during immune activation may contribute to development of depressive symptoms during interferon (IFN)-alpha therapy. METHODS: Twenty-six patients with malignant melanoma were randomly assigned in double-blind fashion to receive either placebo or paroxetine, beginning 2 weeks before IFN-alpha treatment and continuing for the first 12 weeks of IFN-alpha therapy. At treatment initiation and at 2, 4, and 12 weeks of IFN-alpha treatment, measurements of TRP, KYN, and neopterin (a marker of immune activation), were obtained, along with structured assessments of depression, anxiety, and neurotoxicity. RESULTS: Regardless of antidepressant treatment status, all patients exhibited significant increases in KYN, neopterin, and the KYN/TRP ratio during IFN-alpha therapy. Among antidepressant-free patients, patients who developed major depression exhibited significantly greater increases in KYN and neopterin concentrations and more prolonged decreases in TRP concentrations than did nondepressed, antidepressant-free patients. Moreover, in antidepressant-free patients, decreases in TRP correlated with depressive, anxious, and cognitive symptoms, but not neurovegetative or somatic symptoms. No correlations were found between clinical and biological variables in antidepressant-treated patients. CONCLUSIONS: The results suggest that reduced TRP availability plays a role in IFN-alpha-induced depressive symptoms, and paroxetine, although not altering the KYN or neopterin response to IFN-alpha, attenuates the behavioral consequences of IFN-alpha-mediated TRP depletion.