新喋呤与内毒素对烧伤后多器官功能障碍综合征的诊断价值

目的：探讨循环新喋呤与内毒素对严重烧伤后多器官功能障碍综合征（Ｍｕｌｔｉｐｌｅｏｒｇａｎｄｙｓｆｕｎｃｔｉｏｎｓｙｎｄｒｏｍｅ，ＭＯＤＳ）的诊断价值；方法：对４７例烧伤面积（ＴＢＳＡ）大于３０％（３０％～１００％）患者血清新喋呤、血浆内毒素水平的变化进行动态观察。分别计算新喋呤、内毒素、新喋呤合并内毒素诊断多器官功能障碍综合征（ＭＯＤＳ）的敏感性、特异性及准确性等。结果：根据新喋呤、内毒素对ＭＯＤＳ的预警阈值（３５．０ｎｍｏｌ／Ｌ和５００ＥＵ／Ｌ），新喋呤合并内毒素诊断ＭＯＤＳ的敏感性、特异性及准确性分别为８８．３％、９３．７％、９１．６％，均明显高于单独应用新喋呤或内毒素。结论：动态同步观察循环新喋呤和内毒素水平的变化，对于严重烧伤后ＭＯＤＳ的早期诊断与病程监测具有一定的临床价值。     

Increased serum neopterin concentration as indicator of disease severity and poor survival in multiple myeloma

In this study we investigated serum neopterin levels in 73 multiple myeloma (MM) patients (63 determinations at diagnosis, 58 in remission, and 35 at relapse), in 56 monoclonal gammopathies of undetermined significance (MGUS), and in 70 normal controls. Median neopterin level was 5.3 nmol/l in normal controls, 6.8 nmol/l in MGUS, and 10.7 nmol/l in MM patients. In comparison to healthy subjects, significantly higher levels were observed in MM patients (p less than 0.0001). A statistical difference was observed between MGUS and MM patients at diagnosis (p less than 0.007). Compared to diagnosis, a further increase was noticed during relapse, suggesting a correlation between neopterin and disease activity. The prognostic significance of raised neopterin levels was confirmed by a survival analysis. Median survival for patients with high values was 20 months, whereas it was 63.9 months for those with low values (log-rank test p less than 0.003). Serum neopterin concentrations also correlated to beta 2 microglobulin levels and the percentage of CD38+ circulating lymphocytes, indicating a link between neopterin and other myeloma prognostic factors.     

Elevated urinary neopterin: A clue of activated macrophage and cellular immune response in the pathogenesis of idiopathic nephrotic syndrome

Summary: A study of cell mediated immunity (CMI) activation in patients with idiopathic nephrotic syndrome (INS) in the tropics was undertaken. Cell mediated immunity activation was investigated by measuring urinary neopterin excretion. All 31 patients with idiopathic nephrotic syndrome due to either minimal change nephrotic syndrome (MCNS), and focal and segmental glomerulosclerosis (FSGS) had significant elevation of neopterin excretion (mean values 451, 544 μmol neopterin/mol creatinine) when compared with 222 normal subjects (mean value 130, P < 0.001). However, in 25 patients with non-nephrotic IgA nephropathy and eight nephrotic membranous nephropathy the urinary neopterin was not raised (mean value 131 and 129). A further 10 patients with MCNS were restudied when in complete remission and their urinary neopterin was found to have decreased significantly (mean value 186); however, this level was still above the normal range. Our study suggests that CMI and macrophage activation takes place in the pathogenesis of idiopathic nephrosis.     

Extensive white matter involvement in hemorrhagic shock and encephalopathy syndrome

Reported is a case of hemorrhagic shock and encephalopathy syndrome (HSE) with extensive white matter involvement. A three year old, previously healthy boy was presented with an acute onset of fever, loss of consciousness and convulsions. He had disseminated intravascular coagulation, metabolic acidosis, non-ketotic hypoglycemia and hepatorenal dysfunction. The computed tomography (CT) scan of his head on the second day of illness demonstrated symmetric, extensive low-density areas in the cerebral and cerebellar white matter. The child died on the 13th hospital day. A post-mortem histopathological examination of the liver revealed centrilobular necrosis and infiltration of fatty acid droplets. The concentrations of serum 2′,5′-oligoadenylate synthetase and urinary neopterin were markedly elevated, indicating excessively activated cell-mediated immunity. This overproduction of inflammatory cytokines might play an important role in the pathogenesis of the brain lesion as well as in other clinical and laboratory manifestations. The patient had a decreased serum level of α1-antitrypsin, which may have been associated with the development of uncontrolled inflammation and coagulation disorder.     

Interleukin-6 and neopterin in renal transplant recipients: a longitudinal study

Serum and urine interleukin-6 (IL-6) levels and serum neopterin/creatinine ratios were longitudinally studied in 86 renal transplant recipients until 4 months after transplantation. During acute rejection and acute tubular necrosis (ATN), serum and urine IL-6 levels were elevated compared to during stable transplant function (P<0.001). During acute rejection, serum IL-6 levels increased at least 2 days before plasma creatinine started to rise (P<0.05), indicating its early involvement in the rejection process. During cytomegalovirus (CMV) disease, serum, but not urine, IL-6 levels were higher (P<0.01), and serum neopterin/creatinine values were higher than during stable transplant function, ATN, or acute rejection (P<0.01). No significant differences with stable transplant function occurred during cyclosporin A toxicity. Measurement of serum IL-6 provided a sensitivity of 84% and a specificity of 85% for the diagnosis of acute rejection episodes not coinciding with ATN. All cases of CMV disease could be diagnosed by measurement of serum neopterin/creatinine, which provided a specificity of 73%.     

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.     

Urinary biopterin and neopterin excretion and pituitary-adrenal activity in psychiatric patients

The urinary excretion of biopterin and neopterin, pterin compounds related to tetrahydrobiopterin, the cofactor for the initial steps in monoamine synthesis, was serially measured in a heterogeneous group of psychiatric patients and compared to excretion in control subjects, to state of illness, and to the results of the dexamethasone suppression test. Patients with major depression had increased excretion of biopterin compared to normal subjects. There was no relationship between biopterin or neopterin excretion and postdexamethasone cortisol levels. Pterin excretion did not significantly change with improvement in mood or with conversion from nonsuppressor to suppressor status. The meaning of increased urinary biopterin is presently unclear, although its relation to hormonal state and sympathoadrenal tone deserves further study.     

Pharmacokinetics of Recombinant Human Interferon-βser in Healthy Volunteers and Its Effect on Serum Neopterin

The pharmacokinetics of and biologic response modification by recombinant human interferon-_ser (rIFN-_ser) were evaluated in 12 healthy male volunteers. Subjects received a single intravenous (iv) injection of 90 × 10⁶ IU of rIFN-_ser followed by a single or eight consecutive daily 90 × 10⁶ IU subcutaneous (sc) doses. Blood samples collected after the iv, first sc, and last sc doses and prior to each sc dose were assayed for interferon antiviral activity and the inter-feron-inducible marker neopterin. Following iv administration, serum interferon concentrations generally declined biexponentially, with a mean serum clearance of 0.76 ± 0.28 L/hr-kg, a mean steady-state volume of distribution of 2.88 ± 1.81 L/kg, and a mean terminal half-life of 4.29 ± 2.29 hr as determined by noncompartmental analysis. Following sc administration, absorption of rIFN-_ser was prolonged, with serum concentrations generally below 100 IU/mL. No accumulation of rIFN-_ser in serum was noted after eight daily sc injections. In contrast, serum neopterin levels did not increase above baseline levels until 12 hr after iv dosing and 24 hr after sc dosing. The mean increase in serum neopterin at 24 hr post iv injection was significantly greater than that at 24 hr post sc dosing.     

Aspirin down-regulates tryptophan degradation in stimulated human peripheral blood mononuclear cells in vitro

Acetylsalicylic acid (aspirin) is one of the most widely used drugs worldwide, due mainly to its broad therapeutic spectrum with anti-inflammatory, antipyretic, antithrombotic and analgesic effects. However, the exact mechanisms by which aspirin influences inflammation, pain and immune system activation are only partly understood. Within activation of the cellular immune system, Th1-type cytokine interferon (IFN)-gamma induces enzyme indoleamine-2,3-dioxygenase (IDO) which converts tryptophan to kynurenine. In parallel, IFN-gamma induces enzyme GTP-cyclohydrolase I, which gives rise to neopterin production by activated human macrophages. Similarly, tryptophan degradation and neopterin formation increase during several disease states involving Th1-type immune activation. Using stimulated human peripheral blood mononuclear cells (PBMC), the effect of aspirin on tryptophan degradation and neopterin production was investigated. Stimulation of PBMC with mitogens concanavalin A, phytohaemagglutinin and pokeweed mitogen induced significant tryptophan catabolism as was reflected by a decline in tryptophan levels and a parallel increase in kynurenine concentrations compared with unstimulated cells. In parallel, neopterin production was enhanced. Treatment of stimulated PBMC with increasing doses of 1-5 mM aspirin significantly decreased stimulation-induced tryptophan degradation and neopterin production as well. All the effects of aspirin were dose-dependent. The parallel influence of aspirin on both biochemical pathways implies that there was no direct inhibitory effect of aspirin on IDO; rather, it inhibits production of IFN-gamma in mitogen-treated PBMC. The influence of aspirin on biochemical pathways induced by IFN-gamma may represent an important part of its broad pharmacological effect.     

Neopterin and hsCRP are not correlated in gestational diabetes mellitus

Objective: To determine serum neopterin and high sensitive C-reactive protein (hsCRP) levels in patients with and without gestational diabetes mellitus (GDM).

Methods: Neopterin and hsCRP levels were quantified in 28 women with GDM and 20 pregnant women with normal glucose tolerance (NGT). Postpartum neopterin and hsCRP levels were measured in a follow-up study.

Results: Neopterin levels were significantly higher in women with GDM than in women with NGT (15.89?±?8.19?nmol/L versus 10.4?±?3.8?nmol/L, p?p?p?=?0.9, respectively). In contrast, hsCRP levels decreased after delivery in patients with GDM (5.74?±?3.91 versus 3.78?±?2.78, p?r?=?0.3, p?=?0.02) and fasting glucose (r?=?0.4, p?=?0.004), postprandial glucose (r?=?0.3, p?=?0.01), HbA1c (r?=?0.3, p?=?0.02), whereas hsCRP levels were correlated with pre-pregnancy (r?=?0.3, p?=?0.04) and pregnancy body mass index (r?=?0.4, p?=?0.008). No correlation between serum neopterin and hsCRP levels was found (p?=?0.9).

Conclusion: Neopterin levels increased in patients with GDM; hence, it may be related to inflammation. However, the lack of correlation between neopterin and hsCRP suggests the role of different attitudes of these two parameters in the course of pregnancy and GDM.