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At least 19 recordsLinked to original sources
PubMed1989

Urinary neopterin concentrations vs total neopterins for clinical utility.

Neopterin measurements are especially useful as an early marker in (e.g.) allograft rejections and in patients infected with human immunodeficiency virus type 1 (HIV-1). An increased concentration of total neopterins (neopterin + dihydroneopterin) is also a significant marker in patients with HIV-1 infection. In this study we compared concentrations of neopterin and total neopterins in urine samples from 77 homosexual men with and 73 without established HIV-1 infection. HIV-1-seropositive homosexual men had higher concentrations of neopterin and total neopterins (and 7,8-dihydroneopterin) in their urine than did those who were HIV-1-seronegative, and there was a close correlation between neopterin and total neopterins. Both neopterin variables correlated inversely with CD4+ T-cell counts and CD4+/CD8+ T-cell ratios but not with CD8+ T-cell counts in the HIV-1-seropositive men. Our data indicate that measurements of neopterin and total neopterins are of almost equal potential for clinical diagnosis. However, when measuring total neopterins, which includes oxidation of 7,8-dihydroneopterin to neopterin, more strict requirements of sample collection and handling are necessary to avoid degradation of the 7,8-dihydro derivative.

Acquired Immunodeficiency Syndrome↗
PubMed1986

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.

Adolescent↗
PubMed2006

Association between neopterin in cord blood, urinary neopterin in early childhood and the development of atopic dermatitis, asthma and hay fever.

It is generally accepted that the increased prevalence of atopic disease is due to a disturbed balance of T-helper (Th)1/Th2-type immunity. Upon stimulation by the Th1-type cytokine interferon (IFN)-gamma, human monocytes/macrophages release large amounts of neopterin. Thus, the determination of neopterin concentrations is an indirect measure of the levels of IFN-gamma and allows us to monitor Th1-type immune response. We evaluated whether neopterin concentrations in the neonatal cord blood could be a valuable marker predicting atopic disease in early childhood and whether there is a difference in actually determined urinary neopterin concentrations in children with and without atopic disease. Five hundred and five children born during 1997-1999 were enrolled, with cord blood neopterin data available at birth. The International study of asthma and allergies in childhood (ISAAC) questionnaire was used to assess the prevalence of wheezy bronchitis (asthma), atopic dermatitis and allergic rhinitis. Morning urinary samples were collected and urinary neopterin concentration was measured by high-pressure liquid chromatography. By the average age of 6 yr, the prevalence of atopic disease in the last 12 months was 31%. There was no significant correlation between cord blood and urinary neopterin concentrations at age 6 yr, and between cord blood neopterin and later atopic disease. Urinary neopterin concentrations were significant lower in children with a family history of atopic disease (p = 0.02). In this study, cord blood neopterin concentration was not a predictor for atopic disease in early childhood. Family history of atopic disease was associated with lower urinary neopterin levels at age 6 yr, which might mirror a Th1/Th2 imbalance.

Asthma↗
PubMedDate not supplied

Neopterin in renal cell carcinoma: inhalational administration of interleukin-2 is not accompanied by a rise of urinary neopterin.

Inhalational administration of interleukin-2 (IL-2) is effective in controlling renal cell carcinoma (RCC) lung metastases with minimal toxicity. Neopterin is an indicator of systemic immune activation in metastatic cancer and is increased after systemic IL-2 administration. Urinary neopterin was investigated in 13 patients with metastatic RCC and 18 controls. In seven patients, urinary neopterin was followed before and after treatment with inhalational IL-2. Neopterin was measured by high-performance liquid chromatography and creatinine was determined by Jaffé reaction. Urinary neopterin was significantly increased in patients with metastatic RCC compared to controls (257 +/- 263 micromol/mol creatinine vs. 110 +/- 41 micromol/mol creatinine; Mann-Whitney U-test, p < 0.05). Median survival was significantly longer in patients with urinary neopterin <173 micromol/mol creatinine compared to patients with neopterin > or = 173 micromol/mol creatinine (698 vs. 245 days; log-rank test, p < 0.05). No significant increase was observed after inhalational IL-2 therapy (147 +/- 101 vs. 153 +/- 54 micromol/mol creatinine). We conclude that urinary neopterin is increased in patients with metastatic RCC, and higher neopterin concentrations are indicative of poor prognosis. The absence of an increase in urinary neopterin after inhalational IL-2 therapy is in accord with the lack of significant systemic toxicity.

Administration, Inhalation↗
PubMed1990

Interleukin-2 and neopterin-induced neopterin release from peripheral blood mononuclear cells.

Stimulation of peripheral blood mononuclear cells (PBMC) by the mitogenic lectins, phytohaemagglutinin (PHA) and concanavalin A (conA), the lymphokine gamma-interferon (gamma-IFN) and interleukin-2 (IL-2) and the pterin neopterin, caused an increased release of neopterin from those cells, with peak levels after 7 days of stimulation. In contrast to gamma-IFN, IL-2 and neopterin failed to induce neopterin release from purified macrophages. IL-2- and neopterin-induced release of neopterin from PBMC is not dependent on proliferation and is partially inhibited by the addition of anti gamma-IFN or anti IL-2 receptor. Neopterin autoinductive production can explain the amplificated neopterin release during activation of the cellular-mediated immune response (CMI), in spite of the decrease in the T helper cell subsets, which are the main gamma-IFN producers.

Biopterins↗
PubMed2005

The value of increased neopterin levels in reducing transfusion-transmitted virus infections: detection of a donation from a HBsAg positive chronic carrier by screening of neopterin in Turkish blood donors.

Neopterin is an early, sensitive and non-specific marker of cellular immunity. In the present study, serum levels of neopterin were measured by ELISA in 2760 volunteer blood donors, all negative by routine screening tests. Neopterin concentrations ranged from 0.001 to 62.1 nmol/l. 141 donors (5.1%) were found to have high (> or =11 nmol/l) neopterin levels, and 57 of them accepted further investigations within about 3 weeks after their donation. Six had clinical symptoms, and 7 were positive for viral markers. Retesting of neopterin revealed that 2 of 57 donors still showed elevated results, who were adenovirus IgM and HBsAg positive donors, respectively. The present detection of a HBsAg positive donor who yielded negative result initially and a patient with adenovirus infection indicates that routine screening of neopterin levels in blood banks may reduce the risk for viral transmission.

Adult↗
PubMed1988

Comparison of serum neopterin levels and urinary neopterin excretion in renal allograft recipients.

Determination of serum and urinary neopterin levels was performed daily in 30 patients undergoing kidney transplantation for treatment of end-stage renal failure. Neopterin serum levels were determined by RIA and urinary excretion by HPLC. In parallel, the same samples were tested for creatinine content. Results indicated a strong correlation between the clearance of neopterin and creatinine. This correlation was independent of the extent of functional impairment as well as of the different causes of renal insufficiency. As a consequence, a strong relationship between serum and urinary neopterin levels was only obtained when values were corrected for different renal function by dividing them by the creatinine levels. It thus appears that major attention has to be paid to the functional state of the kidney when studying neopterin serum and/or urine values. It also appears that under these prerequisites both methods of detection as well as both sample sources yield comparable results.

Adult↗
PubMed1982

Urinary neopterine in the assessment of lymphoid and myeloid neoplasia, and neopterine levels in haemolytic anaemia and benign monoclonal gammopathy.

The urinary neopterine levels were measured by HPLC in 417 normal subjects and in 216 patients with haematological diseases. All patients with active malignancies (multiple myeloma, polycythaemia vera. Hodgkin's lymphoma, non-Hodgkin's lymphoma, chronic myelocytic and chronic lymphocytic leukaemia) showed highly elevated mean and median values compared to the control groups. Those of patients with multiple myeloma stage I were only raised to near the upper limit of healthy subjects. Of 123 patients with active disease 105 (85%) were above the upper limit. In contrast, the mean and median values of 56 patients with neoplasias in remission (Hodgkin's and non-Hodgkin's lymphoma, acute leukemia and multiple myeloma) were not different from those of healthy subjects, and only 7 (12.5%) of these patients had levels above the upper limit. In patients with non-malignant diseases (haemolytic anaemia and benign monoclonal paraproteinaemia) the mean and median values were not raised. In patients with non-Hodgkin's lymphoma and with chronic lymphocytic leukemia, the neopterine levels corresponded with the tumor stage. The present data suggest tht neopterine assay may supplement laboratory measurements in haematological diseases, providing helpful information.

Adolescent↗
PubMed1989

[Monitoring of renal grafts. Value of the determination of serum neopterin and neopterin versus creatinine ratio].

In a longitudinal study, 53 renal allograft recipients were investigated for changes in serum creatinine and neopterin levels and in the neopterin/creatinine (N/C) ratio which makes it possible to disregard the glomerular filtration level. The patients were divided into 5 groups according to their clinical situation: stability, acute renal failure due to acute tubular necrosis, acute graft rejection, bacterial or viral infection and cyclosporin overdosage. Only N/C discriminated between these situations, being normal (less than 200.10(-6) in groups 1 and 2, significantly elevated in groups 3 and 4 and low in group 5. The highest N/C value was observed in patients with primary cytomegalovirus infection. It is concluded that the N/C ratio is a good biochemical parameter to be used in the follow-up of renal allograft recipients.

Adult↗
PubMed2000

[Serum neopterin levels in oncology patients in intensive care].

BACKGROUND: Elevated neopterin serum levels are associated with diseases that stimulate the cellular immune response. This includes viral infections, autoimmune diseases, transplant rejection and dissemination of certain types of cancer. T-helper lymphocytes and macrophages play a key role in neopterin synthesis. The degree of activation of Th1-lymphocytes is responsible for the production of interferon-gamma and interleukin-2, which stimulate neopterin production in human macrophages. DESIGN AND METHODS: We have designed a prospective observational study to assess the dynamics of serum neopterin levels in 75 oncological patients during post-surgery period. We measured serum neopterin by means of RIA method (radioimmunoassay) in 50 uncomplicated surgery patients (group A), in 15 complicated surgery patients (group B--abdominal sepsis, peritonitis, ileus) and 10 medical ICU patients (group C). Serum levels of neopterin were measured in 5 consecutive periods: before surgery, after surgery, and on the 1st, 2nd, 3rd postoperative days. RESULTS: In all groups, we observed gradual elevation of serum neopterin. The lowest values of neopterin were measured in group A in patients with uncomplicated course following surgery: 6.75 nmol/l, 7.67 nmol/l, 8.9 nmol/l, 10.82 nmol/l and 13.66 nmol/l. A significant increase in serum neopterin levels was measured in group B in patients with septic complications during perioperative period: 18.9; 23.2; 26.82; 29.53 and 27.32 nmol/l. High values of neopterin were also measured in medical ICU patients with disseminated cancer and sepsis during ICU stay: 26.1; 58.1; 28.7 and 22.5 nmol/l. We concluded that serum neopterin levels were increased during the post-surgery period. We observed a significant increase in serum neopterin in patients with severe systemic infection or sepsis or in patients with cancer progression or dissemination (more than 15-20 nmol/l). Neopterin is a simple, reliable and sensitive parameter of cell-mediated immunity, suitable for early diagnosis of viral, autoimmune and transplantant rejection diseases. Neopterin can be used also for non-specific laboratory monitoring of cancer progression and/or dissemination. (Tab. 3, Fig. 4, Ref. 7.)

Abdomen↗
PubMed1984

Radioimmunoassay for neopterin in body fluids and tissues.

Specific antibodies against D-erythroneopterin have been prepared in rabbits using a conjugate of D-erythroneopterin to bovine serum albumin (D-erythroneopterinylcaproyl-bovine serum albumin). The antiserum distinguished D-erythroneopterin from other pteridines, i.e., three stereoisomers of neopterin, L-erythrobiopterin, folic acid, xanthopterin, and four other synthetic pteridines. Using this specific antiserum, a radioimmunoassay for D-erythroneopterin has been developed to measure the neopterin concentrations in urine and tissues. The conjugate of D-erythroneopterin with tyramine (NP-Tyra) was synthesized and labeled with 125I as the labeled ligand NP-[125I]tyra for the radioimmunoassay. The minimal detectable amount of neopterin was about 0.1 pmol. The concentration of total neopterin (neopterin, 7,8-dihydroneopterin, quinonoid dihydroneopterin, and tetrahydroneopterin) in the biological samples was obtained by iodine oxidation under acidic conditions prior to the radioimmunoassay, and that of neopterin plus 7,8-dihydroneopterin by oxidation under alkaline conditions. Total neopterin values in human urine obtained by this new radioimmunoassay showed a good agreement with those obtained by high-performance liquid chromatography with fluorescence detection. With rat tissue samples which contained very low concentrations of neopterin as compared to biopterin, biopterin was simultaneously determined by our previously reported radioimmunoassay, and neopterin values were corrected for the cross-reactivity (0.1%). The neopterin concentrations obtained by this method agreed with the values obtained by the radioimmunoassays for neopterin and biopterin after their separation by high-performance liquid chromatography. This very small amount of neopterin, as compared with biopterin, in rat tissues could not be determined by high-performance liquid chromatography-fluorometry alone due to the masking of the neopterin peak by a large biopterin peak.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

BAL neopterin : a novel marker for cell-mediated immunity in patients with pulmonary tuberculosis and lung cancer.

BACKGROUND: Neopterin is derived from guanosine triphosphate and is produced by stimulated macrophages under the influence of gamma-interferon of lymphocyte origin. It has been suggested that it is an excellent marker for the activation of the monocyte/macrophage axis in some clinical situations. However, to our knowledge, the relationship of BAL neopterin levels to disease states has not been studied. AIM: To assess the usefulness of BAL neopterin levels as an index of disease activity in patients with pulmonary tuberculosis and lung cancer. METHODS: BAL and serum neopterin levels were evaluated in 20 patients with pulmonary tuberculosis, 20 patients with bronchogenic carcinoma, and 10 healthy individuals. The concentration of neopterin was evaluated by radioimmunoassay technique. The BAL level of neopterin was standardized using the BAL urea level. RESULTS: The neopterin levels (mean +/- SD) in the BAL and serum of tuberculous patients (88.6 +/- 27.4 nmol/L epithelial lining fluid [ELF], 61.3 +/- 29.4 nmol/L, respectively) were significantly higher when compared with those in lung cancer patients (40.7 +/- 16.6 nmol/L ELF, 26.8 +/- 6.58 nmol/L, respectively, p < 0.001) and when compared with those in control subjects (26.3 +/- 11.3 nmol/L ELF, 6.8 +/- 2.7 nmol/L, respectively, p < 0.001). In the tuberculous group, BAL and serum neopterin levels in patients with far-advanced disease were significantly higher when compared with those in patients with moderately and minimally advanced diseases (p < 0.001). BAL and serum neopterin levels were significantly higher in patients with small cell carcinoma than in those with adenocarcinoma (p < 0.05). BAL neopterin levels were significantly (p < 0.001) higher than serum levels in all patients and control groups. In addition, there were significant positive correlations between BAL and serum neopterin levels in tuberculous (r = 0.92, p < 0.001), lung cancer (r = 0.62, p < 0.001), and control groups (r = 0.93, p < 0.001). CONCLUSIONS: The levels of neopterin in BAL fluid may reflect the degree of disease activity in pulmonary tuberculous patients. In addition, BAL neopterin levels are elevated in patients with lung cancer, especially the small-cell carcinoma type.

Adult↗
PubMed1998

Neopterin concentrations in cerebrospinal fluid and serum as an aid in differentiating central nervous system and peripheral infections in children.

Neopterin is a sensitive indicator for cellular immune activation. Its concentrations were determined in cerebrospinal fluid (CSF) and serum specimens from 91 children with no evidence of central nervous system (CNS) or peripheral inflammations, 43 with definite neuroborreliosis, 51 with other CNS infections, and 33 with peripheral infections. The aim of our study was (a) to establish a range of normal CSF neopterin concentrations in control children, and (b) to inquire into the diagnostic potential of neopterin measurements in both body compartments for aiding in differential diagnosis of inflammatory vs noninflammatory diseases, and CNS vs peripheral inflammations. CSF neopterin concentrations in controls were invariably low (up to 9.3 nmol/L), but in children with neuroborreliosis and, even more so, with other CNS infections neopterin concentrations were significantly (P <0.0001) increased. Children with peripheral infections, however, rarely showed raised CSF neopterin concentrations. Serum concentrations of neopterin, on the other hand, were not significantly different between controls and children with neuroborreliosis. Although serum concentrations were significantly different between controls and children with other CNS infections, diagnostic efficiency was poor for this comparison. Peripheral infections, in contrast, were associated with significantly higher (P <0.0001) serum neopterin concentrations when compared with controls. A classification tree was constructed on the basis of CSF and serum neopterin concentrations, allowing with high accuracy the discrimination between controls, children with CNS infections, and children with peripheral infections. Thus, on the basis of a comparatively large control group, our data underline the diagnostic validity of neopterin as an aid in differential diagnosis of inflammatory vs noninflammatory diseases, and confirm that CSF neopterin concentrations are not correlated with serum neopterin concentrations, and, therefore, CSF neopterin appears to be produced intrathecally.

Adolescent↗
PubMed1992

Neopterin as parameter of cell-mediated immunity response in thermally injured patients.

Serum neopterin levels have been determined retrospectively in 22 patients with burn injuries. Neopterin, which is produced by monocytes/macrophages following stimulation by interferons, is regarded as a marker for the activation of the cellular immune response. In most patients neopterin levels were initially in the normal range. All patients had their first operation and skin transplantation during the first week; mean neopterin levels increased significantly thereafter. Further skin transplantations or infections did not significantly influence the elevated neopterin level. This result may be due to continuous stimulation of the cellular immune system, as indicated by the elevated neopterin levels during most of the follow-up. In four low risk patients, neopterin levels always remained in the normal range. Two patients with inhalation trauma showed highly elevated neopterin levels (30-70 nmol/l) already upon admission and for 3 days thereafter. No correlation of neopterin levels with the burned body surface area was observed. However, mean serum neopterin levels were higher in the group of non-survivors (five patients) compared to survivors during the first 2 weeks after the trauma; rising neopterin levels were observed during the last 5 days before death. Although elevated neopterin levels could not be attributed either to the burn itself or to later events, the cellular immune system of burned patients was shown to be highly activated.

Adult↗
PubMed1985

The value of urinary neopterin as an immunological parameter in patients with malignant tumors of the genitourinary tract.

In 153 patients with verified neoplasias of the genitourinary tract, urinary neopterin excretion was monitored under different conditions. As control, urinary neopterin values were taken from 208 male and 209 female volunteers. Neopterin excretion was measured by high performance liquid chromatography. Patients with early tumor stages, both with bladder tumor and carcinoma of the prostate, presented almost normal urinary neopterin levels. The difference of urinary neopterin excretion between low and high stages in bladder tumor (T0-1 versus T2-4) as well in carcinoma of the prostate (stage A-B versus stage C-D) is highly significant (p less than 0.001). In the group of patients with renal cell carcinoma we could not find any correlation between tumor stage and neopterin excretion. The basal urinary neopterin values in patients with testicle tumors were as follows: 1 of 6 patients stage-I seminomatous tumors and 2 of 4 patients with stage-I non-seminomatous tumors demonstrated elevated neopterin levels. In the higher stages all patients, in both groups, exhibited pathologically increased neopterin excretion. During therapy and follow-up: all 24 stage-I (seminomatous and non-seminomatous tumors) patients showed normal neopterin levels: 1 of 3 stage-II (non-seminomatous tumors) patients and all 5 stage-IV (seminomatous and non-seminomatous tumors) patients had elevated urinary neopterin excretion. Our experience suggests that neopterin measurements may supplement laboratory examinations in patients with malignant tumor diseases of the genitourinary tract, providing meaningful information in regard to early detection of tumor progression, tumor recurrence and follow-up.

Adolescent↗