Urinary neopterin, a marker of clinical activity in patients with Crohn's disease

Urinary neopterin excretion was measured in 34 patients with Crohn's disease. Neopterin excretion showed a significant correlation with disease activity using a clinical activity score. An interacting effect of previous medical or surgical therapy on neopterin excretion could be ruled out. Disease localization and extent did not exert any influence on neopterin excretion. Neopterin values were significantly correlated with disease duration, body weight and the presence of a palpable abdominal mass. Multiple stepwise regression analyses identified the combination of neopterin, hematocrit, weekly stool frequency, palpable abdominal mass and related symptoms as predicting clinical activity better than Crohn's Disease Activity Index (CDAI). Thus, neopterin determination may be introduced as an additional biochemical parameter in the assessment of disease activity.     

Neopterin as tumour marker serum and urinary neopterin concentrations in malignant diseases

Serum and urinary neopterin concentrations were measured in 142 patients suffering from various malignant diseases. Increased serum and urinary neopterin levels were found in 48% and 55% of patients respectively. Neopterin showed sufficient sensitivity in the detection of haematological disorders and hypernephroma, whereas the sensitivity of neopterin was rather poor in patients with other solid tumours. Comparison of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) concentrations and serum or urinary neopterin levels in testicular cancer patients showed that determination of neopterin provides no further information in the management of these patients. In testicular cancer patients receiving adjuvant chemotherapy, a significant increase in serum (p less than 0.005) and urinary (p less than 0.0005) neopterin concentrations was measured after chemotherapy, reflecting the release of neopterin from macrophages during the damage by cytotoxic drugs. In the adjuvant testicular tumour patients, known to be tumour free, 1 out of 16 patients showed elevated serum and 3 out of 15 patients showed false positive urinary neopterin levels. False positive serum (24%) and urinary (37%) neopterin values were also obtained in 28 patients with various nonmalignant diseases, but no evidence for an inflammatory process. In 23 patients with inflammatory diseases pathological serum and urinary neopterin levels were measured in 55% and 59% respectively. When a RIA was compared with a HPLC method, higher urinary neopterin values were obtained with the RIA, indicating that non-oxidized pterines are also determined by the RIA method. In conclusion, neopterin might be a helpful biological marker in monitoring patients with malignant haematological disorders and renal cell carcinoma, but provides no additional information in other solid tumours studied.     

The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases.

The accumulated knowledge about the organization and function of the human immune system contributes to a better understanding of the pathogenesis of most diverse disorders and is opening new avenues for therapeutic regimens. To gain further insight into the complex interactions within the components of the immune system, it has become increasingly necessary to develop rapid and simple methods to monitor the status of the immune system in patients. The determination of neopterin concentrations in human body fluids allows to investigate sensitively the cell-mediated immune status to be investigated with considerable sensitivity. In recent years it was shown that production and release of neopterin is inducible in human monocytes/macrophages by interferon gamma. Increased neopterin levels indicate endogenous formation of gamma interferon, and monitoring of neopterin levels therefore permits the activation status of the cell-mediated immune system to be examined. Neopterin concentrations in serum and in urine increase in parallel to the clinical course of infections with viruses, intracellular bacteria, and parasites. In patients with human immunodeficiency virus infection neopterin concentration in serum and urine is a significant predictor of disease progression, the statistical power being similar to CD4+ T-cell numbers. In patients with autoimmune disorders, neopterin levels correlate with the extent and the activity of the disease. Neopterin concentrations are also sensitive indicators of immunological complications in allograft recipients. In certain malignant diseases neopterin concentrations correlate with the stage of the disease and bear prognostic information. Results of neopterin measurements agree with the important role that the cellular immune system plays in these disorders.     

Association between plasma thiols and immune activation marker neopterin in stable coronary heart disease

BACKGROUND: Studies have associated elevated plasma levels of the thiols homocysteine and cysteine with an increased risk of atherosclerosis. Their relationship with systemic inflammatory parameters and sclerosis scores was investigated in this study. METHODS: Total homocysteine, total cysteine, neopterin and C-reactive protein (CRP) concentrations were measured in blood samples of 242 patients undergoing elective coronary angiography. A total of 181 patients had coronary artery disease (CAD), as defined by occlusion of > 75% of at least one of the three main coronary arteries, and 61 subjects did not have relevant coronary stenoses. RESULTS: Total cysteine concentrations were higher in patients suffering from coronary artery sclerosis with stepwise increases relative to the extent of coronary artery sclerosis (p < 0.001). In contrast, neither total homocysteine nor the inflammatory markers, CRP and neopterin, differed between patients and controls. However, total homocysteine concentrations correlated with total cysteine (r = 0.468) and neopterin concentrations (r = 0.290), as well as serum creatinine (r = 0.226; all p < 0.001), the latter indicating a dependence of total homocysteine concentrations on kidney function. Total cysteine concentrations were associated with increased neopterin levels (r = 0.231, p < 0.001). CONCLUSIONS: Total cysteine concentrations were well suited to estimate the extent of coronary artery sclerosis, while in our study of stable CAD patients total homocysteine was not increased compared to controls. The association between homocysteine, cysteine and parameters of immune activation and inflammation in our study suggests that these markers of CAD may be interdependent.     

The spectrum and activity of urinary Ig-proteinases as a marker of chronic pyelonephritis

AIM: To study the activity of Ig-splitting proteinases of various classes in the urine in patients with chronic pyelonephritis. MATERIAL AND METHODS: Clinical, device and laboratory examinations were made in 50 patients (age 20-60 years). Admission and dynamic measurements were also made of the activity of serin, metal-dependent and thiol Ig-splitting proteinases in the urine. RESULTS: Total proteolytic activity in the urine of the patients was higher than in healthy subjects. Thiol proteinase activity was detected in 98% cases. This activity was 100 times higher in the patients than in healthy subjects. Significant differences were registered in the activity of serin proteinases. After the treatment the level of serin proteinases approached the normal value while thiol proteinase activity decreased significantly (2-fold, on the average) but remained high. If this activity was high, the patients (70%) had 1-2 exacerbations annually, in low activity exacerbations were absent. CONCLUSION: The activity of Ig-splitting proteinases of different classes is an important diagnostic and prognostic laboratory criterion of chronic pyelonephritis and can serve a criterion of treatment efficacy.     

Prognostic significance of urinary neopterin levels in patients with hepatocellular carcinoma

Urinary neopterin levels were measured by high-performance liquid chromatography in 15 patients with liver cirrhosis, 18 patients with hepatocellular carcinoma and 20 normal subjects. The mean levels of urinary neopterin in patients with hepatocellular carcinoma were significantly elevated (p less than 0.01) compared to those in cirrhotics and normal subjects, but did not significantly differ between cirrhotics and normal subjects. Urinary neopterin levels correlated significantly with tumor size in patients with hepatocellular carcinoma but not with serum alpha-fetoprotein. Hepatocellular carcinoma patients with high urinary neopterin levels appeared to have more serious hepatic dysfunction than those with normal urinary neopterin levels, and moreover, there was a significant difference (p less than 0.05) in survival between the two groups. These findings suggest that urinary neopterin excretion may be a good biochemical marker to assess the progression of tumor and a useful prognostic indicator in patients with hepatocellular carcinoma.     

Altered urinary excretion of pteridines in neoplastic disease. Determination of biopterin,neopterin, xanthopterin,and pterin

Urinary pteridine concentrations in healthy control subjects and patients with cancer and non-malignant diseases were determined by HPLC and TLC after partial purification by ion exchange and Sephadex chromatography. Elevated concentrations of neopterin were found in 70% of the 50 cancer patients investigated. In patients with non-Hodgkin's lymphoma (seven cases) or with liver metastases (12 cases) neopterin concentrations were significantly higher than in control subjects (p < 0.01). Biopterin was less frequently increased (22%). Xanthopterin was generally raised when neopterin and/or biopterin excretion was high. Neopterin/biopterin ratios were higher in some patients with cancer or with severe renal insufficiency than in controls. These findings suggest that alterations in pteridine metabolism are common in malignant disease. The pathogenic, diagnostic and therapeutic significance of these changes remains to be established.     

A study of urinary myo-inositol as a sensitive marker of glucose intolerance

BACKGROUND: We assessed the possibility of using myo-inositol as a marker of glucose intolerance. METHODS: We measured urinary myo-inositol enzymatically before and 2 h after a 75-g oral glucose tolerance test in 564 volunteers, who were divided into four groups [normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM)]. Furthermore, we classified NGT into NGT-A (2-h blood glucose <120 mg/dl and 2-h glucosuria <50 mg/dl) and NGT-B (remaining NGT subjects). We then compared deltamyo-inositol (myo-inositol/creatinine ratio: 2-h after glucose load--before load) of each group to investigate the relationship between glucose intolerance and deltamyo-inositol. RESULTS: The glucose tolerance of NGT-B appeared to have deteriorated compared with NGT-A as determined by blood glucose, insulin, and glucosuria. There was very little effect of gender or age on deltamyo-inositol in NGT-A. deltamyo-inositol was significantly higher than that in NGT-A (0.5+/-7.1 mg/g Cr) not only in IFG (8.7+/-19.5 mg/g Cr, P<0.0001), IGT (14.8+/-22.9 mg/g Cr, P<0.0001) and DM (79.5+/-37.1 mg/g Cr, P<0.0001), but in NGT-B (7.4+/-12.7 mg/g Cr, P<0.0001). With 2 mg/g Cr as a tentative cut-off for deltamyo-inositol to detect NGT-A, sensitivity and specificity were 68% and 72%, respectively. CONCLUSIONS: The deltamyo-inositol can be use of a non-invasive and sensitive marker for glucose intolerance.     

A preliminary study of urinary transferrin as a marker for prostatic cancer

Traditional serum markers used in the diagnosis of prostate cancer lack sensitivity and specificity. Prostatic fluid is in direct contact with the prostate epithelium and, thus, has been investigated as a better source for potentially useful markers. Since prostatic fluid contents can enter the urine directly through the urethra, without prerequisite entry into blood, proteins present in significant quantities in prostatic fluid represent candidate markers for entry into the urine, particularly in diseases affecting the prostate epithelium, such as adenocarcinoma. High concentrations of transferrin in prostatic fluid led us to examine urine transferrin levels, using an immunoturbidimetric technique. Urine transferrin was significantly increased in 18 out of 22 patients with prostate cancer in comparison to age-matched controls. Since there was no evidence of increased transferrin excretion, we suggest that prostatic fluid is the source of transferrinuria.     

尿新蝶呤在112例儿童肺结核耐药性监测中的临床价值

目的探讨尿新蝶呤在儿童肺结核耐药性监测中的临床价值。方法应用纸片扩散法进行结核耐药性检测。根据耐药检测结果,将肺结核活动期患儿112例分为耐药组（n=48）和非耐药组（n=64）,健康儿童50例作为健康对照组。ELISA法检测其尿新蝶呤水平。结果结核耐药组、非耐药组、健康对照组尿新蝶呤水平差异有统计学意义,结核患儿尿新蝶呤水平显著高于健康对照组,耐药组又显著高于非耐药组。结论尿新蝶呤水平测定不仅对儿童肺结核有辅助诊断价值,而且在儿童结核耐药性监测中有重要的预警价值。尿新蝶呤测定作为一种无创、快速、简捷、敏感的结核耐药性初筛方法,值得临床推广应用。     

Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway

The renin-angiotensin system (RAS) is a key regulator of vascular tone and blood pressure. In addition, angiotensin II also has a number of cellular effects that may contribute to disease pathogenesis. Using Agtr1a(-/-) mice, which lack AT(1A) receptors for angiotensin II, we have identified a novel function of the RAS to modulate the immune system. We find that angiotensin II, acting through type 1 (AT(1)) receptors on immune cells, triggers the proliferation of splenic lymphocytes. These actions contribute to the vigor of cellular alloimmune responses. Within lymphoid organs, sufficient components of the RAS are present to activate AT(1) receptors during an immune response, promoting cell growth. These actions require activation of calcineurin phosphatase. In an in vivo model of cardiac transplantation, the absence of AT(1) signaling accentuates the immunosuppressive effects of the calcineurin inhibitor cyclosporine. We conclude that inhibition of AT(1) receptor signaling should be useful as an anti-inflammatory and immunosuppressive therapy. Furthermore, the actions of the RAS to promote lymphocyte activation may contribute to inflammation that characterizes a number of diseases of the heart and the vascular system.     

红细胞免疫、细胞免疫与胃溃疡患者Hp感染的关系

目的分析研究红细胞免疫、细胞免疫与胃溃疡患者Hp感染的关系。方法选取76例胃溃疡患者为观察组,76例同龄健康者为对照组,检测2组的红细胞免疫及细胞免疫指标,并比较观察组中不同Hp感染DOB值患者的红细胞免疫及细胞免疫指标,同时采用Logistic分析红细胞免疫、细胞免疫与胃溃疡Hp感染的关系。结果观察组的红细胞及细胞免疫指标均差于对照组,且观察组中Hp感染者的红细胞及细胞免疫指标均差于未发生感染者,Hp感染DOB值较高者则差于DOB值较低者。经Logistic分析显示,红细胞免疫、细胞免疫均与胃溃疡Hp感染有密切关系(P0.05)。结论胃溃疡患者Hp感染者的红细胞免疫及细胞免疫呈现较差的状态,且Hp感染程度对其免疫指标的表达影响较大,应给予针对性的调节干预。     

Evaluation of urinary bladder cancer antigen as a marker for diagnosis of transitional cell carcinoma of the urinary bladder

The internal carotid arteries were evaluated with Doppler ultrasound technique in patients with acute cerebrovascular disease. The results of the Doppler examination of 325 vessels were compared to presence of carotid bruits on auscultation. In 126 arteries the findings were also compared with those on aortocervical, single carotid or post-mortal angiography.

The Doppler flow reaction was normal in 74% of the vessels, uncertain in 20% and pathologic in 6%. The sensitivity of the Doppler assessment in finding stenosis of more than 75% lumen diameter reduction was 85% with a specificity of 94%. The specificity increased with higher degree of vascular stenosis.

Carotid bruits were heard in 34 arteries. The sensitivity of auscultation in detecting stenosis 75% was 47% with a specificity of 83%. The sensitivity fell with higher degree of stenosis.

The Doppler procedure is a valuable tool in detecting haemodynamically significant stenoses in the internal carotid artery. The method could serve the following purposes in the clinical situation: 1. Screening procedure for further investigations in TIA and minor stroke patients fit enough to be candidates for vascular surgery. 2. Before blood-pressure can be safely reduced in patients with cerebrovascular disease. 3. For evaluation of the arteriosclerotic process in stroke-patients thereby improving prognostication.     

Evaluation of urinary bladder cancer antigen as a marker for diagnosis of transitional cell carcinoma of the urinary bladder

The purpose of the present study was to assess a new quantitative urinary tumor marker for transitional cell carcinoma of the urinary bladder (TCC), measuring fragments of cytokeratin 8 and 18 in the urine (UBC). Urine samples of 355 individuals (77 healthy volunteers, 111 patients with benign urologic disorders, 167 patients with histologically proven bladder cancer) were examined for the presence of UBC antigen. Samples of all patients were obtained prior to therapy. Compared to healthy volunteers or patients with benign urologic disease, patients with TCC had significantly higher median urinary levels of UBC antigen (0 vs. 4.18 vs. 7.46 microg/g creatinine; p<0.001, and p<0.01, respectively). UBC antigen levels were positively correlated with tumor grade and stage. Patients with invasive TCC had significantly higher levels of UBC antigen than patients with superficial TCC (p<0.001). Elevated levels of UBC antigen were also found in patients with benign urologic disorders (median: 4.18 microg/g creatinine vs. 7.46 microg/g creatinine in cancer patients). Using a cutoff of 14.06 microg/g creatinine (corresponding to 95% specificity in the group of healthy individuals), sensitivity of UBC antigen ranged between 21.6% (pTa) and 75% (pT4). Overall specificity was 76.6%. Based on our data we conclude that the UBC antigen test in its current format is not clinically useful for detection of bladder cancer.     

Humoral and cellular immune responses of atopic individuals in a tropical environment

In this study we compared immediate, intermediate and delayed skin test reactivity, total and specific serum IgE, IgG, A, M antibody and lymphocyte proliferative responses, between atopic and normal individuals in the tropical environment of Caracas, Venezuela (Lat. 10 degrees N). The allergenic extracts tested were prepared from house dust, mixed moulds and Aspergillus fumigatus. In lymphocyte stimulation the mitogen Concanavalin A was also employed, the cultures being supplemented with either autologous plasma, or a gamma globulin-depleted pool. The results revealed the association of immediate skin reactions with IgE antibody against house dust, and intermediate reactions with IgG, A, M antibody against moulds. No relation was, however, detected between delayed skin reactivity and in vitro lymphocyte transformation; skin reactions occurred at the highest frequency with moulds, while house dust provoked the strongest in vitro stimulation. Also, although the areas of positive delayed reactions were greatest in the atopic individuals, the lymphocyte proliferative responses were clearly highest in the normal subjects. The significance of the positivity of lymphocyte transformation tests in all of the study group, but lower reactivity in the atopics, is considered.     

Determination of urinary enzymes as a marker of early renal damage in diabetic patients

Diagnosis of diabetic nephropathy in the early stages is very important since there are no clinical signs or symptoms. Urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion has been recommended as a tubular dysfunction marker that elevates before other markers, such as microalbuminuria and a decrease in creatinine clearance. In this study, we compared excretion of urinary enzymes with other markers that are used routinely in diabetic nephropathy assessment. Urinary NAG, lactate dehydrogenase (LDH), alkaline phosphatase (AP) activities, urea, creatinine, and albumin, with levels of serum glucose and creatinine and whole blood glycosylated hemoglobin (HbA1c) were measured in 32 diabetes mellitus patients and 25 healthy subjects (controls). Notably, urinary NAG, AP, LDH excretion, and microalbuminuria in the diabetic patients group were significantly increased compared to those in the control groups (P<0.001, P<0.05, P<0.01, and P<0.01, respectively). Meanwhile, our results showed that the urinary NAG excretion had the highest sensitivity and specificity (100% and 87.5%, respectively) compared to other markers. We showed that measuring urinary NAG excretion could be useful for the assessment of renal failure in diabetes mellitus patients and confirmed the use of NAG as a routine screening test.     

Effect of tinidazole on the cellular immune response

A single 500 mg dose of tinidazole was given to fourteen healthy volunteers. Cellular immune functions were studied, before and 2 and 24 h after drug ingestion. Blast transformation of lymphocytes to Con-A was significantly lower (P less than 0.01) in samples obtained 2 h after ingestion. No significant changes were found in the other immunological parameters studied. We conclude that these findings could be caused by reversible blockage of lectin binding receptors on the lymphocyte surface.     

温度和时间对过氧乙酸稳定性的影响

过氧乙酸系浓过氧化氢和乙酸酐的混合溶液，为广谱高效灭菌剂，今年非典型肺炎爆发时，作为最有效的消毒灭菌剂，全国用量最大。它对细胞繁殖体，芽孢，真菌，病毒均有一定的杀菌作用，经常使用的浓度为0．2％，但此浓度的溶液极不稳定。因此，本文考察了温度和贮存时间对过氧乙酸的稳定性的影响，现介绍如下，以期在以后使用过氧乙酸时有所帮助。