Increased urinary excretion of nitric oxide metabolites in longitudinally monitored migraine patients

This study evaluated a relationship between nitric oxide (NO) and migraine attacks in order to gain insight into migraine pathomechanism. The study groups consisted of 12 migraineurs and eight controls. All subjects collected morning urine samples for 40 consecutive days. Urinary NO metabolites, nitrite/nitrate (NO _x ) levels were measured with the vanadium-based assay, whilst creatinine (Cr) and neopterin were determined with high-performance liquid chromatography. The mean urinary NO _x /Cr ratio and number of NO _x peaks was significantly greater in the migraine group compared with controls ( P  = 0.01 and P  = 0.007, respectively). In the second approach, high NO _x values were re-assessed in relation to raised neopterin, a marker of systemic infection or inflammation, and were excluded. The excretion of NO _x persisted being pulsatile, and migraineurs had more peaks compared with controls ( P  = 0.01). In seven patients, NO _x peaks coincided with headache days. This was more frequent than expected by random association in four patients (Monte-Carlo simulation; odds ratios: 2.16–7.77; no overlap of 95% CI). In four patients, NO _x peaks preceded or followed headache days. Although there is a difference in the pattern of urinary NO _x excretion between control and migraine populations, the variable temporal association of NO _x peaks and headaches suggests a complex role of NO in this condition.     

Tryptophan metabolism and oxidative stress in patients with chronic brain injury

The kynurenine pathway generates the excitotoxic N-methyl-d-aspartate receptor agonist, quinolinic acid and the glutamate antagonist, kynurenic acid, as well as free-radical generators. We investigated the status of the pathway following severe brain injury sustained at least 1 year previously in 15 patients compared with controls. At baseline, patients with brain injury showed increased levels of neopterin, erythrocyte sedimentation rate, C-reactive protein and peroxidation products in the blood compared with controls, indicating persistent inflammation and oxidative stress. At baseline and following tryptophan depletion, more tryptophan was converted to kynurenine in patients than controls, but less kynurenine was converted into the neuroprotectant, kynurenic acid. This suggests that neuroprotection by kynurenic acid may be inadequate in brain-damaged patients even many years after injury. On tryptophan loading, patients metabolized more kynurenine into kynurenic acid than controls, a process which may be neuroprotective. In addition, lower levels of 3-hydroxykynurenine and 3-hydroxyanthranilic acid in patients after tryptophan loading should be protective since these compounds generate free radicals. The results suggest that for brain-damaged patients, increased activation of the kynurenine pathway, oxidative stress and raised levels of inflammation continue many years after the original insult, possibly contributing to the continuing cerebral dysfunction in these patients.     

CD44 splice variant expression in normal and malignant uterine cervical epithelium

Uhl-Steidl M, Huy VQ, Müller-Holzner E, Ruth N, Zeimet AG, Stauder R, Daxenbichler G, Marth C. CD44 splice variant in normal and malignant uterine cervical epithelium. Int J Gynecol Cancer 1998; 8 : 460–466.
CD44 expression was investigated immunohistochemically on paraffin sections obtained from 88 uterine cervical cancers and 31 normal cervices, using monoclonal antibodies against CD44 variant epitopes v4, v5, v6, v7/8, v9 and the standard form of the CD44 protein. Normal epithelium showed expression of all CD44 splice variants, at least in traces, and it was located predominantly in basal and parabasal cells. In cervical carcinomas CD44 expression was widely heterogeneous. CD44 variant v9 staining was moderate or strong in 86% of the tumors, and it was significantly correlated with CD44 v6 staining. Also a significant correlation between expression of CD44 v4 and v6 occurred. Highly significant correlations between CD44 expression of variants v4 and v6 and tumor stage as well as patients age were found. In addition, these variants were more frequently expressed in squamous cell carcinomas than in adenocarcinomas. However, in contrast to the recently reported data, we were not able to confirm the hypothesis that CD44 v6 represents a prognostic indicator in cervical cancer. In FIGO stages III and IV, patients with CD44 variant v4 positive tumors had a significantly longer disease-free and overall survival than patients with CD44 variant v4 negative tumors. In conclusion, our data indicate that CD44 v6 tissue expression cannot be considered as a prognostic factor in cervical cancer. Regarding the unexpected outcome of patients with CD44 v4 positive tumors, further investigations are needed to elucidate the exact clinical value of this variant isoform.     

Frailty Status in Older Adults Is Related to Alterations in Indoleamine 2,3-Dioxygenase 1 and Guanosine Triphosphate Cyclohydrolase I Enzymatic Pathways

Background

Frailty is a multidimensional syndrome correlated to the loss of homeostasis and increased vulnerability to stressors, which is associated with increase in the risk of disability, comorbidity, hospitalization, and death in the elderly. It is based on the interplay of physiological, psychological, social, and environmental factors.

Investigation of pregnancy associated plasma protein‐A and neopterin levels in Behçet's patients

Behçet's disease (BD) is an autoimmune disease that affects many organs. We aimed to investigate the relationship between BD and these pregnancy‐associated plasma protein A (PAPP‐A), neopterin, and high sensitive C‐reactive protein (hsCRP) parameters. The study included 57 BD patients and 54 healthy controls. After evaluating the active and inactive disease status of the patients, analyzes were performed. When comparing the patient and control groups, neopterin (111.27 ± 37.49; 76.77 ± 38.27 [nmol/L]; P < .001) and hsCRP (11.81 ± 16.8; 3.62 ± 5.06 [mg/L]; P = .001) parameters were significantly higher in patients. Neopterin (117.68 ± 41.67; 94.85 ± 14.75 [nmol/L]; P = .038) and hsCRP (14.68 ± 18.7; 4.47 ± 7.27 [mg/L]; P = .002) found different in active and inactive patients. The sensitivities of neopterin and hsCRP were also found to be high in BD (respectively 93%, 67%). PAPP‐A was especially elevated in skin pathologies (P = .02) and neopterin in joint involvement (P = .03). We think that the use of neopterin and hsCRP can help in diagnosis and follow‐up of BD.     

Elevated urine neopterin levels in nonalcoholic steatohepatitis

OBJECTIVES: The aim of this study was to relate urine levels of neopterin, a marker of activation of the cellular immune system, with grading and staging of NASH. DESIGN AND METHODS: Urine concentrations of neopterin, routine tests, insulin and C-peptide levels were assessed in 50 patients with NASH, 25 patients with chronic viral hepatitis (CVH), and in 26 healthy controls. RESULTS: Urine neopterin levels were found elevated in the NASH and CVH groups compared with controls. There was no significant correlation between urine neopterin levels and inflammation grade in the liver. CONCLUSIONS: Urine neopterin levels are a marker of cellular immunity and are higher in patients with NASH. However, neopterin levels were not significantly associated with histopathological grade and stage of disease.     

血清新蝶呤及hs-CRP与冠状动脉粥样硬化病变程度的关系

目的探讨血清新蝶呤及hs-CRP与冠状动脉粥样硬化病变程度的关系。方法选取2013年8月至2013年11月郑州大学第一附属医院心内科88例冠状动脉粥样硬化患者,均接受冠状动脉造影检查,根据Gensini积分<20、20~40、≥40分为A、B、C组。测定所有患者血清新蝶呤及hs-CRP水平,分析血浆新蝶呤及hs CRP与冠脉病变程度的关系。结果 B、C组血清新蝶呤、hs-CRP水平较A组高,差异有统计学意义(P<0.05)。C组血清新蝶呤、hs-CRP水平较B组高(P<0.05)。结论血清新蝶呤与hs-CRP水平可以反映冠状动脉粥样硬化病变程度。     

Increased inflammatory markers in children with familial hypercholesterolaemia

BACKGROUND: While data are abundant on increased levels of inflammatory markers in adult patients with hypercholesterolaemia, such data in children are limited. Therefore, we sought to investigate the degree and character of inflammation in children with heterozygous familial hypercholesterolaemia (FH) by measuring levels of neopterin, high-sensitivity C-reactive protein (hsCRP), and soluble CD40 ligand (sCD40L). MATERIALS AND METHODS: In the present study, we compared the concentration of inflammatory markers in children suffering from heterozygous FH (n = 207) with those in unaffected siblings (n = 84). Furthermore, we investigated the effect of 2-year treatment with pravastatin (20-40 mg qd) or placebo on plasma levels of those markers. RESULTS: Our main finding was that serum levels of neopterin and hsCRP were significantly higher in FH children compared with healthy siblings, whereas sCD40L was not. Body mass index and high-density lipoprotein cholesterol levels were significant independent predictors of hsCRP and neopterin. Furthermore, pravastatin therapy decreased neopterin, but not hsCRP and sCD40L, in the FH children, but these changes were not different from the placebo group. CONCLUSION: These findings indicate low-grade monocyte/macrophage hyperactivity in the early stages of atherogenesis, but our findings also suggest that inflammation as well as anti-inflammatory effects of statins are less prominent features of atherosclerosis in FH children than in FH adults.     

Homocysteine but not neopterin declines in demented patients on B vitamins

Summary. Inflammation and immune system activation seem to play an important role in the development and progression of dementia. Hyperhomocysteinemia is common in various forms of dementia, and a significant relationship was found between concentrations of homocysteine and immune activation marker neopterin. B vitamin supplementation is able to slow-down homocysteine formation in patients. In an open-label study, effects of B vitamin supplementation (Beneuran compositum ^?) on concentrations of homocysteine and neopterin were investigated in 58 patients with Alzheimer’s disease (n = 30), vascular dementia (n = 12) and mild cognitive impairment (n = 16). In all groups of patients, a significant percentage of patients presented with homocysteine concentrations >15 μmol/L and with elevated concentrations of immune activation marker neopterin. Decline of homocysteine concentrations was observed after one month of B vitamin supplementation (all p < 0.01; paired Kruskal-Wallisn-test). By contrast, neopterin concentrations remained unchanged (all p > 0.05). B vitamin supplementation in patients with various forms of dementia did not influence neopterin concentrations, which indicates that the degree of immune activation and inflammation remained unchanged. The question remains, if lowering of homocysteine by folate supplementation alone could have any beneficial effect to modulate the course of dementia development and if longer period of supplementation would also ameliorate immune system activation status.     

Plasma amino acids and neopterin in healthy persons with Down’s syndrome

Summary In persons with Down’s syndrome (DS) immunological abnormalities as well as hypothyroidism and Alzheimer type dementia are frequently observed. In addition, the activity of the enzyme cystathionine beta-synthase (CBS) is over-expressed which results in an altered homocysteine metabolism. In the present study, 48 older healthy DS persons without signs of dementia, psychiatric or somatic comorbidity and free of medication were analyzed for plasma levels of amino acids, neopterin and monoaminergic metabolites. Data were compared with those obtained from age and sex matched healthy controls. It was found that the spectrum of amino acids showed widespread differences in that levels of nearly all essential amino acids were lower in DS patients as compared to healthy controls. In addition, a significantly lower methionine and higher taurine concentration were observed which is in accordance with a disturbed homocysteine metabolism. With respect to the monoamine metabolites, the concentration of 5-hydroxyindoleacetic acid was not altered whereas that of homovanillic acid was significantly increased. Finally, the concentration of the immune activation marker neopterin was increased in persons with DS. It is concluded that healthy DS persons of older age show extensive biochemical abnormalities suggesting a compromised homocysteine metabolism, an activated cell-mediated immune response and an enhanced turnover of dopamine.