Serum neopterin levels in children with primary nephrotic syndrome

AIM: To assess the changes that occurs in serum neopterin levels in children with primary nephrotic syndrome. METHODS: Serum neopterin levels were measured by ELISA in 38 children with active primary nephrotic syndrome (group I) and 17 children with primary nephrotic syndrome in remission (group II) and 20 healthy controls. All patients had normal creatinine clearance. Among group I, 28 patients were steroid-sensitive while 10 patients were steroid-resistant. RESULTS: Serum neopterin levels were significantly elevated in group I patients (median = 30, 7.2-43.2 nmol/l) compared with group II (median = 6, 2-10 nmol/l, P<0.001) and controls (median = 3.2, range: 0.4-1.8 nmol/l, P<0.001). Group II patients had similar neopterin levels compared with controls (P=0.71). There was a significant positive correlation between serum neopterin levels and the degree of proteinuria in group I patients (r = 0.4, P=0.01). No significant differences in serum neopterin levels were noted between steroid-sensitive and steroid-resistant patients (P=0.4). CONCLUSION: Serum neopterin could be used as a marker of the activity of primary nephrotic syndrome but it could not be used to differentiate between steroid-sensitive and steroid-resistant patients.     

The Effects of Medical Ozone Therapy on Renal Ischemia/Reperfusion Injury

Introduction: This study was designed to investigate the possible beneficial effects of medical ozone therapy (OT), known as an immunomodulator and antioxidant, on the renal function, morphology, and biochemical parameters of oxidative stress in kidneys subjected to ischemia/reperfusion injury (IRI). Materials and methods: Thirty male Sprague–Dawley rats were classified into three groups: control, renal IRI, and renal IRI + OT. The IRI group was induced by bilateral renal ischemia for 60 min, followed by reperfusion for 6 h. After reperfusion, the kidneys and blood of rats were obtained for histopathologic and biochemical evaluation. Results: Renal IRI increased the tissue oxidative stress parameters (lipid peroxidation, protein oxidation, and nitrite plus nitrate) and decreased the antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase). The serum neopterin levels showed correlation with oxidative stress parameters. All these parameters were brought to control values in the treatment group. Histopathologically, the kidney injury in the treatment group was significantly lesser than in the renal IRI group. Conclusions: Our results clearly showed that OT has beneficial effect to protect kidney against IRI. The serum neopterin levels might be used as a marker to detect the degree of renal IRI.     

The association between neopterin and acetaminophen-induced nephrotoxicity

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.     

Serum Neopterin as a Prognostic Indicator in Patients with Gastric Carcinoma

ABSTRACT?

Purpose: To evaluate the possible association between serum neopterin level and clinical and laboratory findings and their prognostic value of patients with gastric carcinoma. Methods: Serum samples were collected from patients (n = 38) and normal volunteers (n = 39) and stored at –80°C until analyzed. Neopterin, C-reactive protein (CRP), and IL-6 concentration were measured by ELISA. The clinicopathological parameters were determined by reviewing both medical charts and pathological records. Results: Mean neopterin levels were 15.26 ± 11.46 nmol/L in patients with gastric carcinoma and 9.87 ± 2.90 nmol/L in the control group. Serum neopterin concentrations were significantly higher in patients with gastric carcinoma than in the control group. The number of patients with elevated neopterin level was significantly correlated with stage, gastric wall involvement, the number of metastatic lymph nodes, and the level of serum CRP. The mean neopterin concentrations were significantly elevated in patients older than 60 years, in the presence of venous invasion and increased metastatic lymph node number, and in patients with elevated CRP levels. Neopterin level was also correlated with overall survival as an independent prognostic indoicator. Conclusions: Serum neopterin levels were elevated in patients with advanced gastric cancer and correlated with prognostic parameters and overall survival. Moreover, neopterin measured at the time of diagnosis can be used to predict the survival of gastric carcinoma.     

新蝶呤和白介素-6在不稳定型心绞痛中的变化

目的 :研究不稳定型心绞痛 (UAP)患者血中免疫反应标记物新蝶呤和炎症反应标记物白细胞介素 6 (IL 6 )的变化。方法 :采用酶联免疫法测定 77例经冠状动脉造影证实的冠心病患者血中新蝶呤、IL 6、C 反应蛋白 (CRP)的浓度。 77例中UAP 36例 ,年龄 4 2～ 82 (6 3± 11)岁 ;慢性稳定型心绞痛 (SAP)患者 4 1例 ,年龄 4 0～ 80(6 4± 9)岁。结果 :与SAP患者相比 ,IL 6〔(12 .72± 13.4 2 )∶(7.0 1± 3.0 8)ng/L ,P <0 .0 1〕、CRP〔(2 .0 3± 3.6 8)∶(0 .85± 0 .99)mg/L ,P <0 .0 5〕、新蝶呤〔(7.0± 3.16 )∶(5 .38± 3.2 0 )nmol/L ,P <0 .0 5〕及经血肌酐校正的新蝶呤水平 (× 10 -2 ) (7.5 9± 2 .87∶5 .0 9± 2 .86 ,P <0 .0 1)在UAP患者中显著增高。结论 :新蝶呤和IL 6、CRP在UAP患者中增高 ,均可作为提示斑块不稳定性的指标 ,辅助UAP的诊断。免疫反应和炎症反应均参与了UAP的发生     

Immune activation and the anaemia associated with chronic inflammatory disorders

Chronic inflammatory disorders are associated with an increased risk of patients developing anaemia. There is some evidence that cytokines released during cell-mediated immune responses are capable of inhibiting bone marrow haematopoiesis. In vitro, interferon gamma and tumour-necrosis factor alpha inhibit growth of erythroid precursor cells. The mode of action of these cytokines is probably associated with their antiproliferative capacity. Decrease of serum iron and increase of storage iron in patients appears to be a consequence of the defense strategy of macrophages during long-lasting inflammatory disorders. Decreased serum iron correlates to decreased haemoglobin concentrations. In view of this, the development of anaemia seems likely to result from the altered iron metabolism induced by stimulated macrophages. Low haemoglobin levels and associated hypoxia up-regulate the release of erythropoietin, which can explain why increased circulating erythropoietin is usually found in patients with anaemia.     

Relations between Concentrations of Asymmetric Dimethylarginine and Neopterin as Potential Risk Factors for Cardiovascular Diseases in Haemodialysis-Treated Patients

Objectives. To investigate the correlation between concentrations of asymmetric dimethylarginine (ADMA) and neopterin (NP) as potential risk factors for cardiovascular diseases in chronic renal failure patients. Method. In this study, 33 patients with renal failure before and after haemodialysis were compared with healthy control subjects. Serum ADMA and NP levels were measured using high performance liquid chromatography (HPLC). Results. When ADMA and NP concentrations in renal failure patients were compared before and after dialysis, before dialysis ADMA and NP concentrations were higher than those in the control group. However, ADMA and NP levels showed a falling mean and clear after dialysis. While there is no correlation between ADMA and NP levels before dialysis, there is a mean and positive correlation between ADMA and NP levels after dialysis. Conclusion. Potential risk factors for cardiovascular diseases include high concentrations of both ADMA and NP levels in chronic renal failure patients. A correlation mean between ADMA and NP levels after dialysis was found, but no correlation between ADMA and NP levels before haemodialysis was discovered. These can be evaluated as two different risk factors independent from each other.     

Defining and Evaluating HIV-Related Neurodegenerative Disease and Its Treatment Targets: A Combinatorial Approach to Use of Cerebrospinal Fluid Molecular Biomarkers

There are a number of reasons that the accomplishments of clinical trials related to HIV-related neurodegenerative disease (HRND) and the AIDS dementia complex (ADC) have had such limited impact on clinical practice. These include: rapid evolution and progress in the treatment of systemic HIV infection that has quickly outpaced neurological efforts and has markedly reduced disease incidence; ethical constraints that (rightly) demand neurologically compromised patients receive the best available treatment before experimental therapeutics; complicated backgrounds and comorbidities of patients now most susceptible to HRND; and reluctance of general AIDS clinicians and drug companies to look beyond systemic or pivotal outcomes. However, the field has also been slow to adopt methods that better exploit advances in understanding of the pathogenesis of central nervous system (CNS) infection and brain injury, and that might circumvent some of these constraints. Using a simple model of pathogenesis, we propose an approach to characterizing patients, selecting treatment targets, and evaluating outcomes that emphasize a combination of cerebrospinal fluid (CSF) markers. This model begins by using three markers related to cardinal components of HRND: CNS HIV infection (measurement of CSF HIV RNA), intrathecal immunoactivation (CSF neopterin), and brain injury [CSF light chain neurofilament (NFL)]. Careful analysis of this and other marker combinations promises more rational trial design and more rapid progress in managing CNS HIV infection and HRND using both antiviral and adjuvant treatment approaches. Presented at the HIV Preclinical–Clinical Therapeutics Research Meeting, May 15–16, 2006, by RW Price.     

Comparative pharmacokinetics and pharmacodynamics of recombinant human interferon beta-1a after intramuscular and subcutaneous administration

The pharmacokinetics and pharmacodynamics of recombinant human interferon beta (IFN-β-la) were compared after intramuscular administration of two preparations (Rebif® and Avonex™) and subcutaneous administration of Rebif®. Healthy volunteers ( n = 30) received a single dose (6O μg) of each of the three treatments in a randomised crossover study. Serum concentrations of IFN-β were measured by enzyme-linked immunosorbent assay over 24 h after dosing. Pharmacodynamics were assessed by measurement of intracellular 2',5'-oligoadenylate synthetase activity, and serum neopterin and β₂-microglobulin concentrations, over 144 h after dosing. There was no significant difference between the three treatments in peak serum IFN-β concentrations ( C _max) or area under the concentration-time curve (AUC). No significant differences in pharmacodynamic measures were observed between the three treatments. It is concluded that the bioavailability of IFN-β-1a is equivalent after subcutaneous or intramuscular administration of Rebif®, and intramuscular administration of Avonex™.