Persistence of protein oxidation products and plasma antioxidants in juvenile idiopathic arthritis. A one-year follow-up study.

OBJECTIVE: Plasma protein oxidation products and blood antioxidants, like superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidant status (TAS) were investigated in children with juvenile idiopathic arthritis (JIA) in a year follow-up study. METHODS: Carbonyl group content within plasma proteins, activity of red blood cell SOD and GPx, as well as the blood TAS level were determined in 14 children with JIA twice, namely at the admission to the hospital (Time 0 = T0) and then after a year of treatment (Time 1 = T1). RESULTS: An increased level of plasma protein carbonyls was observed in both assessments (T0 and T1) as compared to control. However there was no significant difference in plasma carbonyls level between the initial (T0) and final (T1) examination of the patients. Similarly, SOD activity was higher in children with JIA as compared to control subjects and did not change significantly after a year of follow-up. Red blood cell GPx activity remained within the normal range throughout the study. Interestingly, the blood TAS level was initially comparable to control and rose significantly after the year of treatment. CONCLUSION: A level of plasma protein oxidation products remains significantly higher in children with JIA as compared to healthy subjects. The lack of accumulation of plasma protein carbonyls may result from efficient proteolysis in childhood and/or adaptive increase of the blood TAS level in the course of effective anti-inflammatory therapy. Analysis of plasma oxidative stress markers and antioxidant potential of the blood might be helpful in monitoring the clinical treatment of children suffering from JIA.

Preferential immunoglobulin oxidation in children with juvenile idiopathic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a rare chronic inflammatory disorder of the joints. There is strong evidence that oxidative damage occurs in rheumatoid diseases, including JIA. The increased level of protein oxidation products in total plasma proteins has recently been reported in children with diagnosed JIA. The objective of this study was to find out which fraction of plasma proteins is mostly damaged by oxidative stress and whether the damaging effect correlates with certain clinical or laboratory parameters. METHODS: A new approach to estimate the carbonyl content of plasma protein fractions was developed, based on two-stage electrophoresis and immunochemical detection of the carbonyl derivatives of the proteins. This method allowed us to detect and quantitate carbonyl groups in the albumin, alpha-2, beta and gamma-globulin fractions. Sera of 25 children with JIA and 13 healthy controls were tested. RESULTS: Albumin and gamma-globulins were found to be most modified by oxidation. In a group of children with systemic JIA, both albumin and gamma-globulins were oxidized while plasma gamma-globulin fraction damage was prevalent in pauciarticular JIA. CONCLUSIONS: Among plasma proteins of children with JIA, gamma-globulins were preferentially oxidized, whereas most of the other proteins did not seem to be affected. Oxidative modification of plasma proteins was correlated with the type of JIA. These findings may allow the use of carbonyls as clinical markers of inflammatory process activity in patients with different types of JIA. It is also a potential tool for monitoring oxidative protein damage in other diseases and therapies.

Multicenter retrospective analysis of various primary pediatric malignant hepatic tumors--management in a series of 47 Polish patients (1985-1995).

Forty-seven children treated in various Polish centers between 1985 and 1995 for primary malignant liver tumors were retrospectively analyzed. Hepatoblastoma (HB) prevailed--it was found in 39 cases. There were 6 hepatocarcinoma (HCC) cases and 2 cases of undifferentiated sarcoma (UDS). In 44% of HB patients the tumor involved both liver lobes. 18% of children with HB presented with pulmonary metastases at diagnosis. Chemotherapy was applied in 92% of cases (preoperatively in 67%). Tumor resection was performed in 56% of HB patients. Overall survival of patients with hepatoblastoma was 43.6%, while it was 50% for hepatocarcinoma and 100% for undifferentiated sarcoma (2 cases only). Mean observation time was 58 months. The hepatoblastoma subgroup, being the largest (83% of all cases), was analyzed separately for prognostic factors. Completeness of tumor excision strongly influenced survival. Involvement of both lobes of the liver and multifocality of the tumor were other adverse prognostic factors.

Protein carbonyl groups' content as a useful clinical marker of antioxidant barrier impairment in plasma of children with juvenile chronic arthritis.

The purpose of our study was to find out the intensity of free radical reactions in pediatric patients with different forms of juvenile chronic arthritis (JCA) on the basis of carbonyl groups' content in plasma proteins, evaluated with the use of Levine's method. We examined a population of 52 children with diagnosed JCA of different types and activities in the study. The carbonyl groups' content in plasma proteins of ill children was significantly higher than in healthy group (1.36 +/- 0.68 vs. 0.807 +/- 0.16 nmol/mg of protein). The carbonyls increased parallell with the activity of the disease; their content was significantly higher in children with high-disease activity than in children with medium- or low-disease activity. Moreover, children with oligoarthritis had carbonyls level 1.09 +/- 0.59 nmol/mg of protein, vs. 1.62 +/- 0.82 in children with systemic type of JCA. The values of carbonyls in children with polyarthritis were and 1.36 +/- 0.50 nmol/mg of protein. Correlation between the carbonyl groups content and the activity or the type of JCA may allow use of carbonyls as a clinical marker of antioxidant barrier impairment in this group of patients. This aspect of the disease may undergo pharmacologic modification in future.

[Carbonyl groups content on the basis of protein peroxidation analysis with total antioxidant status in blood of children with cancers]. / Ocena aktywnosci reakcji wolnorodnikowych na podstawie analizy peroksydacji bialek w powiazaniu z calkowita obrona przeciwutleniaczowa krwi u dzieci z choroba nowotworowa.

Toxic oxygen free radicals have been implicated as important pathologic mediators in carcinogenesis. Several reports have found antioxidants and enzymes related to the antioxidants function at increased or decreased levels in blood of patients with cancers. In previous publications we observed that antioxidant barrier can be different in healthy children and children with cancers. This time we were looking for a stable marker of damaging effect of free radicals reactions in association with antioxidant barrier in blood. Carbonyl group level in proteins has been introduced as a good marker of oxidative stress damage. For this study we selected 60 children at the age of 3 to 16, who had been diagnosed as suffering from cancers: malignant (m) bone tumors (t) (n = 25), m. brain t. (n = 20), lymphoma malignum (n = 5), m. liver t. (n = 5) and m. germ cell t. (n = 5). The control group consisted of 40 age-matched healthy children (22 boys and 18 girls). We investigated the concentration of carbonyl groups (CG) in serum spectrofotometrically, according to the method of Levine. Plasma total antioxidant status (TAS) was estimated colorometrically with radical cation ABTS (2,2'-Azino di-[3-ethylbenzthiazoline sulphonatel]), erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were assessed according to the method of Paglia & Valentine and Minami & Yoshikawa respectively (Kits of Randox Laboratories Ltd.). In this study the content of CG in plasma proteins has shown a significant increase (1.60 +/- 0.77 vs 0.78 +/- 0.15 nmol/mg protein, p < 0.001) and erythrocyte GSH-Px activity has shown a significant decrease (16.3 +/- 7.9 vs 25.1 +/- 15.8 U/gHb, p < 0.02) in children with malignant tumors. No differences were observed in SOD activity and TAS between sick and healthy children. A possible interpretation of this data suggests an inadequate antioxidants' protection in children with cancers. The relationship between the oxidative damage and carcinogenesis requires further investigations.

[Ethyol (amifostine): application trial in pediatric oncology]. / Ethyol (Amifostyna)--próba zastosowania w onkologii pediatrycznej.

UNLABELLED: Myelotoxicity is one of the major chemotherapeutic side effects. In some adult and paediatric studies it has been shown that amifostine protects bone marrow from toxic effects of alkylating agents and platinum compounds without reduction in overall cytotoxic action. AIM OF THE STUDY: To test an efficacy of amifostine as a myeloprotectant in multiagent chemotherapy containing alkylating agents or platinum analogues. Amifostine was used in 8 children from 3 to 15 yrs of age treated with chemotherapy (CHT) for cancers. It made total number of 28 courses. Amifostine was administered every other CHT course in a dose of 750 mg/m2. The degree of myelotoxicity measured at nadir was compared between with- and without amifostine CHT courses. Anaemia, leucopenia and thrombocytopenia of WHO grades I and II were qualified as mild toxicity while grades III and IV were recognized as severe. RESULTS: Severe anaemia, leucopenia and thrombocytopenia were found after 3/14 (21%), 8/14 (57%) and 6/14 (43%) courses with amifostine. Proportion of these side effects in identical CHT courses without amifostine in the same pts. was as followed: 1/14 (7%), 7/14 (50%) and 9/14 (64%). Differences among both groups were statistically significant (p = 0.025). Mild side effects (nausea, vomiting, transient hypotension) accompanied amifostine administration in 29% of courses (4/14). CONCLUSION: Preliminary results suggest that amifostine decreased the number of severe thrombocytopenias after CHT. The drug was well tolerated by children.

[Atypical picture of osteosarcoma situated in fibula of a 14-year-old boy]. / Nietypowy obraz miesaka kosciopochodnego kosci strzalkowej u 14-letniego chlopca.

This paper presents the case of osteogenic sarcoma, situated in fibula of 14-year-old boy. The X-ray picture of this tumor was typical of unicameral cyst, but histopathological examination showed traits of osteosarcoma. Only magnetic resonance suggested the presence of malignant neoplasm.

[Results of conservative treatment for regressive vesicoureteral reflux in childhood]. / Wyniki postepowania zachowawczego we wstecznych odplywach pecherzowo-moczowodowych u dzieci.

The study involved 112 children with 169 confirmed vesicoureteric reflux grades I, II, III. During anti-bacterial treatment which lasted at last two years, spontaneous regression occurred in 82% of the vesicoureteral reflux. Renal scars were observed in 8% of the cases. Initially urinary tract infection was diagnosed in 84% of the children. This figure was reduced to 8% after anti-bacterial treatment. 54% of the observed children had associated diseases (anaemia, chronic enteropathy, bronchitis and pneumonia). The results confirmed the efficiency of anti-bacterial treatment in children with vesicoureteral reflux grades I, II, III.

[Selenium, glutathione peroxidase and TBARS in plasma of children with malignant diseases of the hematopoietic system]. / Selen, peroksydaza glutationowa i zwiazki TBA-reaktywne w osoczu dzieci z chorobami rozrostowymi ukladu krwiotwórczego.

The selenium and TBARS concentrations and glutathione peroxidase activity were measured in the plasma of children with leukemia, lymphoma and histiocytosis X. A group of fifty-four children aged 1 to 16 years was divided into the following age groups: 1-3, 3-7, 7-16 years. In the patients aged 3-7 and 7-16 years, plasma selenium concentration and glutathione peroxidase activity were significantly lower than in age-matched healthy children.

Selenium concentration and glutathione peroxidase activity in blood of children with cancer.

In this work we studied 205 children with cancer, aged 6 months to 7 years, who had been diagnosed as suffering from various types of neoplasm. In blood of these children we determined the selenium concentration and glutathione peroxidase activity by fluorometric and spectrophometric methods, respectively. The control group consisted of 128 healthy children. In all groups of children with cancer we observed a significantly lower selenium concentration and lowered glutathione peroxidase activity. We found statistical differences in selenium concentration between first or second and third, and between first and fourth or fifth stages of the disease, only in 3-7 year-old patients. Glutathione peroxidase activity was statistically depressed in the same age group between the first or second and third stages of the disease. Generally, there were no differences in the concentration of the microelement or in the glutathione peroxidase activity between children before and during treatment with cytostatics.

Concentration of zinc and zinc-copper superoxide dismutase activity in red blood cells in normals and children with cancer.

Zinc concentrations and Cu, Zn superoxide dismutase activity in erythrocytes were investigated in 138 healthy children and in 35 children with cancer. The mean zinc concentration in the erythrocytes of healthy children was found to be age-dependent. In the youngest group (children up to 1 year of age) the zinc concentration in erythrocytes is 18.8 +/- 3.4 micrograms/g Hb (5.89 +/- 1.23 mg/l packed cells), which is significantly lower than in other age groups. A strong logarithmic correlation (r = 0.327, p less than 0.0001 and r = 0.436, p less than 0.00001) was found between age and zinc concentration in erythrocytes, expressed as microgram/g Hb and as mg/l packed red cells, respectively. Cancer children were divided into two groups (neuro- and nephroblastoma). In the group of children with neuroblastoma no statistical differences in zinc concentration or enzyme activity were observed. In the patients with nephroblastoma, significantly higher zinc concentrations (p less than 0.05) were observed in erythrocytes. The changes of zinc concentration are accompanied by significant (p less than 0.02) decreases of enzyme activity. In this group of cancer children, statistically significant differences were observed in the zinc concentrations in erythrocytes (microgram/g Hb) between the second and the third stages of the disease. No correlation was observed between the concentration of zinc and enzyme activity in healthy children or in cancer children.

Glutathione peroxidase activity, selenium and lipid peroxides levels in blood of cancer children.

The concentrations of whole blood and plasma selenium, plasma lipid peroxides and the glutathione peroxidase activity in plasma and erythrocytes were measured in untreated and treated children with neuro- (n = 23) and nephroblastoma (n = 32) aged 6 months to 15 years. The patients were divided into the following groups: 0.5-1, 1-3, 3.5-6 and 8-15 years old. In all the groups of cancer patients investigated selenium concentration in whole blood and plasma and glutathione peroxidase activity in erythrocytes and plasma were significantly lower than in the age-matched healthy children. The concentrations of lipid peroxides in plasma of children with cancer was higher than in the age-matched control group. No differences were observed between the levels of the determined parameters in children with neuro- and nephroblastoma. Nor were there any differences in the determined parameters between children before and during treatment with cytostatics and between children at different stages of the disease. A significant linear correlation was found between plasma selenium concentration and glutathione peroxidase activity in the erythrocytes and plasma of children with cancer.