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1.
Biochem Biophys Res Commun ; 458(3): 639-643, 2015 Mar 13.
Article in English | MEDLINE | ID: mdl-25684189

ABSTRACT

OBJECTIVES: The aim of the study was to perform analyses of plasma and urinary glycosaminoglycan isolated from juvenile idiopathic arthritis (JIA). METHODS, RESULTS: Chondroitin/dermatan sulfate (CS/DS), heparan sulfate/heparin (HS/H) and hyaluronic acid (HA) were evaluated in samples obtained from JIA patients before and after treatment. Electrophoretic analysis of GAGs identified the presence of CS, DS and HS/H in plasma of healthy subjects and JIA patients. CS were the predominant plasma GAGs constituent in all investigated subject. The plasma CS level in untreated patients was significantly decreased. Therapy resulted in an increase in this glycan level. However, plasma CS concentration still remained higher than in controls. Increased levels of DS and HA in untreated JIA patients were recorded. Anti-inflammatory treatment led to normalization of these parameters concentrations. Plasma and urinary concentrations of HS/H were similar in all groups of individuals. Urinary CS/DS and HA were decreased only in untreated patients. CONCLUSIONS: The data presented indicate that changes in plasma and urinary glycosaminoglycan occur in the course of JIA. There are probably the expression of both local articular cartilage matrix and systemic changes in connective tissue remodeling.


Subject(s)
Arthritis, Juvenile/blood , Arthritis, Juvenile/urine , Glycosaminoglycans/blood , Glycosaminoglycans/urine , Adolescent , Arthritis, Juvenile/therapy , Child , Child, Preschool , Chondroitin/blood , Chondroitin/urine , Dermatan Sulfate/blood , Dermatan Sulfate/urine , Female , Heparin/blood , Heparin/urine , Heparitin Sulfate/blood , Heparitin Sulfate/urine , Humans , Hyaluronic Acid/blood , Hyaluronic Acid/urine , Male
2.
Clin Res Cardiol ; 102(1): 63-71, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22885951

ABSTRACT

OBJECTIVE: To investigate the presence of possible early atherosclerotic changes in a group of prepubertal children with juvenile idiopathic arthritis (JIA) and to establish the potential beneficial effects of 1-year treatment. MATERIALS AND METHODS: Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate), proinflammatory cytokines (IL-1ß, IL-6, IFN-γ, TNF-α), lipid profile and oxidant-antioxidant status (urinary isoprostanes [PGF-2α]) were assessed in 38 JIA children (12M/26F, mean age 7.05 ± 2.39 years) and compared with 40 controls (18M/22F, mean age 6.34 ± 2.25 years). Carotid intima-media wall thickness (cIMT) was obtained and blood pressure was measured. All parameters were reassessed in JIA children after 1 year of therapy. RESULTS: At baseline JIA children presented compared to controls higher levels of inflammatory markers, proinflammatory cytokines, total cholesterol, LDL cholesterol, and PGF-2α (all p ≤ 0.01). Furthermore, blood pressure and cIMT were significantly increased (both p ≤ 0.01). After a 1-year treatment with non-steroid anti-inflammatory (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs), a significant reduction of all parameters was detected (all p ≤ 0.01). This was associated with a significant reduction in blood pressure and cIMT (both p ≤ 0.01). Within the JIA group, patients requiring etanercept presented worse laboratory values and cIMT measurements at baseline. Nevertheless, the same improvement of all parameters was obtained after a 1-year treatment. In stepwise multiple regression, LDL cholesterol and IL-1ß were mainly related to cIMT. CONCLUSION: Chronic and systemic inflammation seems to lead to early atherosclerotic abnormalities even in pre-pubertal JIA children. Substantial improvement can be obtained with 1-year of appropriate therapy.


Subject(s)
Antioxidants/analysis , Arthritis, Juvenile/complications , Atherosclerosis/etiology , Carotid Arteries/diagnostic imaging , Carotid Intima-Media Thickness , Inflammation Mediators/blood , Ultrasonography, Doppler, Color , Age Factors , Antirheumatic Agents/therapeutic use , Arthritis, Juvenile/blood , Arthritis, Juvenile/immunology , Arthritis, Juvenile/therapy , Arthritis, Juvenile/urine , Atherosclerosis/blood , Atherosclerosis/diagnostic imaging , Atherosclerosis/immunology , Atherosclerosis/therapy , Atherosclerosis/urine , Biomarkers/blood , Biomarkers/urine , Blood Pressure , Case-Control Studies , Child , Child, Preschool , Female , Humans , Linear Models , Lipids/blood , Longitudinal Studies , Male , Plaque, Atherosclerotic , Predictive Value of Tests , Prospective Studies , Risk Assessment , Risk Factors , Sexual Development , Time Factors , Treatment Outcome
3.
Pediatr Res ; 65(5): 530-6, 2009 May.
Article in English | MEDLINE | ID: mdl-19218887

ABSTRACT

Lupus nephritis (LN) is among the main determinants of poor prognosis in systemic lupus erythematosus (SLE). The objective of this study was to 1) isolate and identify proteins contained in the LN urinary protein signature (PS) of children with SLE; 2) assess the usefulness of the PS proteins for detecting activity of LN over time. Using surface-enhanced or matrix-assisted laser desorption/ionization time of flight mass spectrometry, the proteins contained in the LN urinary PS were identified. They were transferrin (Tf), ceruloplasmin (Cp), alpha1-acid-glycoprotein (AGP), lipocalin-type prostaglandin-D synthetase (L-PGDS), albumin, and albumin-related fragments. Serial plasma and urine samples were analyzed using immunonephelometry or ELISA in 98 children with SLE (78% African American) and 30 controls with juvenile idiopathic arthritis. All urinary PS proteins were significantly higher with active vs. inactive LN or in patients without LN (all p < 0.005), and their combined area under the receiver operating characteristic curve was 0.85. As early as 3 mo before a clinical diagnosis of worsening LN, significant increases of urinary Tf, AGP (both p < 0.0001), and L-PGDS (p < 0.01) occurred, indicating that these PS proteins are biomarkers of LN activity and may help anticipate the future course of LN.


Subject(s)
Blood Proteins/urine , Lupus Erythematosus, Systemic/diagnosis , Lupus Nephritis/diagnosis , Proteinuria/diagnosis , Adolescent , Albuminuria/diagnosis , Arthritis, Juvenile/diagnosis , Arthritis, Juvenile/urine , Biomarkers/blood , Biomarkers/urine , Case-Control Studies , Ceruloplasmin/urine , Enzyme-Linked Immunosorbent Assay , Female , Humans , Intramolecular Oxidoreductases/blood , Intramolecular Oxidoreductases/urine , Lipocalins/blood , Lipocalins/urine , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/urine , Lupus Nephritis/etiology , Lupus Nephritis/urine , Male , Nephelometry and Turbidimetry , Orosomucoid/urine , Predictive Value of Tests , Prognosis , Proteinuria/etiology , Proteinuria/urine , ROC Curve , Reproducibility of Results , Serum Albumin/metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Time Factors , Transferrin/urine
4.
Arthritis Rheum ; 58(12): 3932-40, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19035501

ABSTRACT

OBJECTIVE: To determine the effects of calcium supplementation on bone physiology in corticosteroid-free children with juvenile rheumatoid arthritis (JRA) by measuring serum and urinary bone-related hormones, minerals, and markers of bone formation and resorption. METHODS: In this double-blind trial, patients were randomized to receive daily oral supplementation with 1,000 mg of calcium and 400 IU of vitamin D or with placebo and 400 IU of vitamin D for 24 months. The effect of calcium supplementation on bone physiology was determined periodically using markers of bone turnover. RESULTS: One hundred ninety-eight patients met the inclusion criteria and were followed up in the study. At baseline, there were no differences in markers of bone turnover between the groups. Patients with < or = 4 joints with active disease had higher serum levels of calcium and parathyroid hormone (PTH). Calcium-treated patients with < or =4 joints with active disease had lower levels of osteocalcin (OC). At followup, levels of 1,25-dihydroxyvitamin D3, PTH, OC, and urine phosphorus were lower in the group receiving calcium supplementation. Hypercalciuria, as determined by the urinary calcium-to-creatinine ratio, was not noted in 24-hour urine studies. CONCLUSION: Levels of markers of bone physiology were significantly decreased in children with JRA receiving calcium supplementation. The physiologic changes were noted as early as 12 months into calcium supplementation. The hypercalciuria noted on spot testing of the urinary calcium-to-creatinine ratio was not demonstrated on further evaluation, nor did it lead to renal pathology. These findings suggest that the calcium supplementation met physiologic needs and caused an increased calcium loss in urine.


Subject(s)
Arthritis, Juvenile , Biomarkers/blood , Biomarkers/urine , Calcium/administration & dosage , Drug Monitoring/methods , Administration, Oral , Adolescent , Amino Acids/blood , Amino Acids/urine , Arthritis, Juvenile/blood , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/urine , Bone Density/drug effects , Bone and Bones/drug effects , Bone and Bones/metabolism , Calcium/blood , Calcium/urine , Child , Creatinine/blood , Creatinine/urine , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Osteocalcin/blood , Osteocalcin/urine , Parathyroid Hormone/blood , Patient Compliance , Phosphorus/blood , Phosphorus/urine , Placebos , Vitamin D/administration & dosage , Vitamin D/blood , Vitamin D/urine , Vitamins/administration & dosage , Vitamins/blood , Vitamins/urine
6.
Acta Haematol ; 113(2): 124-9, 2005.
Article in English | MEDLINE | ID: mdl-15802891

ABSTRACT

Macrophage activation syndrome (MAS) is a life-threatening complication in children with rheumatic diseases, particularly systemic-onset juvenile chronic arthritis (SOJCA). Because of the potential fatality of this condition, prompt recognition and immediate therapeutic intervention are important. This study assessed the clinical features of nine MAS events in five children with SOJCA. Nonremitting fever and decreased platelet and white blood cell counts led to a diagnosis of MAS. The urinary beta2-microglobulin (beta2MG) level was a sensitive indicator of MAS. Serum levels of beta2MG and soluble interleukin-2 receptor were also elevated. These biologic markers reflecting hyperactivated cellular immunity are useful indicators of MAS. Four children treated with cyclosporin A (CSP) achieved rapid and complete recovery, but one patient without CSP died due to rapidly progressive respiratory failure. All children treated with CSP responded quickly, and fever abated within 36 h of initiation of treatment. CSP should be added to first-line therapy of MAS.


Subject(s)
Arthritis, Juvenile/complications , Macrophage Activation , Receptors, Interleukin-2/blood , beta 2-Microglobulin/blood , beta 2-Microglobulin/urine , Adolescent , Arthritis, Juvenile/blood , Arthritis, Juvenile/urine , Biomarkers/blood , Biomarkers/urine , Child , Child, Preschool , Cyclosporine/administration & dosage , Female , Humans , Immunosuppressive Agents/administration & dosage , Infant , Infusions, Intravenous , Leukocyte Count , Macrophage Activation/drug effects , Male , Platelet Count , Syndrome
7.
Pediatr Nephrol ; 20(2): 154-8, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15599770

ABSTRACT

This study investigates whether renal damage occurs in children with juvenile idiopathic arthritis (JIA) either secondary to the disease per se or due to the side effects of non-steroidal anti-inflammatory drugs (NSAIDs) and slow-acting anti-rheumatic drugs (SAARDs) used in treatment. In this cross-sectional study, albuminuria, N -acetyl glucosaminidase (NAG), beta(2)-microglobulin (beta(2)M), and creatinine (Cr) levels were measured in urine samples of 45 patients (23 female, 22 male, 9.4+/-3.9 years) with JIA and a sex- and age-matched control group of 33 healthy children. The urinary albumin/Cr, NAG/Cr, and beta(2)M/Cr ratios of children with JIA and of the control group did not differ statistically. No difference was noted between patient groups with different types of JIA (12 systemic, 18 polyarticular, and 15 oligoarticular JIA). JIA patients with active disease (n=16) had higher NAG/Cr values than patients with inactive disease (P=0.002). NAG/Cr levels correlated with erythrocyte sedimentation rate (r=0.66, P<0.001) and platelet count (r=0.61, P<0.001) and showed a slight correlation with the number of joints with active arthritis in children with polyarticular JIA (r=0.45, P=0.055). Neither beta(2)M/Cr nor albumin/Cr ratios were associated with disease activity. No difference was noted between patient groups treated with different NSAIDs and SAARDs. In children with JIA tubular enzymuria increases during the active phase of the disease; however, it seems that permanent renal damage does not occur.


Subject(s)
Albuminuria/etiology , Arthritis, Juvenile/complications , Kidney Diseases/urine , Acetylglucosaminidase/urine , Adolescent , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Juvenile/urine , Biomarkers/urine , Child , Child, Preschool , Creatinine/urine , Cross-Sectional Studies , Female , Humans , Kidney Diseases/etiology , Male , beta 2-Microglobulin/urine
8.
Biopharm Drug Dispos ; 25(1): 1-7, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14716747

ABSTRACT

UNLABELLED: The aim of the present study was to compare the effect produced by juvenile rheumatoid arthritis (JRA) or rheumatic fever (RF) on the pharmacokinetics of acetyl salicylic acid (ASA) and its metabolites in children with autoimmune diseases (AD). METHODS: A prospective, open labelled study was performed in 17 children with JRA and 17 with RF who received a single dose of 25 mg ASA/kg orally. The pharmacokinetics of ASA and its metabolites were determined. The blood and urine levels of each salicylate collected during 24 h were measured by HPLC. A group of 15 healthy teenage volunteers was included as a control group. RESULTS: The maximum plasma concentration, half-life time, area under the curve and the amount of salicylates excreted were statistically different between the JRA and the RF groups, as well as between the RF group and the controls, however, there were no significant differences between the JRA group and the controls. CONCLUSIONS: Dosage schemes must be adjusted for JRA patients, since the half life in these patients is longer than in RF patients. However, due to ample variability of pharmacokinetic parameters it is recommended that dose schemes are individualized on the type of autoimmune disease considered.


Subject(s)
Arthritis, Juvenile/drug therapy , Aspirin/metabolism , Aspirin/pharmacokinetics , Autoimmune Diseases/drug therapy , Rheumatic Fever/drug therapy , Administration, Oral , Adolescent , Area Under Curve , Arthritis, Juvenile/blood , Arthritis, Juvenile/urine , Aspirin/administration & dosage , Autoimmune Diseases/metabolism , Biological Availability , Child , Chromatography, High Pressure Liquid , Female , Gentisates/blood , Gentisates/metabolism , Gentisates/urine , Half-Life , Hippurates/blood , Hippurates/metabolism , Hippurates/urine , Humans , Male , Mexico , Prospective Studies , Rheumatic Fever/blood , Rheumatic Fever/urine , Salicylic Acid/blood , Salicylic Acid/metabolism , Salicylic Acid/urine , Tablets
9.
Clin Exp Rheumatol ; 17(2): 251-5, 1999.
Article in English | MEDLINE | ID: mdl-10342056

ABSTRACT

OBJECTIVE: To study the biochemical markers of bone turnover in children with juvenile chronic arthritis (JCA) and to compare these parameters with those in healthy children in order to evaluate the relationships between age, disease activity and biochemical variables. METHODS: Sixty-two children with JCA and 157 healthy children were studied. Serum samples were analyzed for their concentrations of minerals, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP). Urine samples were examined to monitor the excretion of hydroxyproline (HYP) and deoxypyridinoline crosslinks (DPD). RESULTS: OC, BAP, HYP/Cr, DPD/Cr values were decreased in healthy girls more than 12 years of age and in healthy boys more than 14 years of age compared to younger children from the same population. Lower levels of OC and BAP were observed in younger children with JCA (girls < or = 12 yrs.; boys < or = 14 yrs.) compared to healthy children of the same age. Older girls with JCA (> or = 13 yrs.) were found to have increased HYP/Cr and DPD/Cr values compared to older healthy children. CONCLUSION: These results indicate that abnormalities of bone metabolism occur in an age-related fashion in JCA. This was demonstrated by a reduction in the markers of bone formation in younger JCA patients. Moreover, in older girls the markers of bone resorption were found to be elevated. Taken together, these findings suggest that bone formation is reduced from early childhood to mid-puberty, while resorption levels increase in children with JCA after this time.


Subject(s)
Arthritis, Juvenile/blood , Arthritis, Juvenile/urine , Biomarkers/analysis , Bone Remodeling , Absorptiometry, Photon , Adolescent , Alkaline Phosphatase/blood , Amino Acids/urine , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Juvenile/drug therapy , Bone Density/physiology , Child , Child, Preschool , Female , Glucocorticoids/therapeutic use , Humans , Hydroxyproline/urine , Male , Minerals/blood , Osteocalcin/blood
10.
J Rheumatol ; 25(5): 993-6, 1998 May.
Article in English | MEDLINE | ID: mdl-9598905

ABSTRACT

OBJECTIVE: To investigate the frequency of hypercalciuria and the relationship between hypercalciuria and hematuria in patients with juvenile rheumatoid arthritis (JRA). METHODS: Twenty-eight children with JRA were studied, as well as 10 patients with acute arthritis unrelated to JRA and 14 healthy children as control groups. Cases with urinary calcium excretion (UCE) >4 mg/kg/day were considered hypercalciuric. Urinalysis was performed for detecting hematuria in all cases. RESULTS: UCE was 4.19 +/- 2.9 mg/kg/day in patients with JRA, 1.94 +/- 1.57 mg/kg/day in children with acute arthritis, and 2.0 +/- 1.45 mg/kg/day in healthy children. UCE was significantly higher in JRA compared with the other study groups. Of the 28 patients with JRA, 13 (46.4%) had hypercalciuria and 6 (21.4%) had hematuria. UCE was significantly higher in hematuric patients with JRA than in those with no hematuria (p<0.05). UCE in patients with JRA without hematuria was also higher than the UCE values detected in the disease and healthy control groups (p<0.05). CONCLUSION: Hypercalciuria is a frequent finding in patients with JRA [13/28 (46.4%)] and should be considered during the investigation of hematuria in patients with JRA.


Subject(s)
Arthritis, Juvenile/complications , Calcium Metabolism Disorders/complications , Calcium/urine , Hematuria/complications , Adolescent , Arthritis, Juvenile/blood , Arthritis, Juvenile/urine , Calcium/blood , Calcium Metabolism Disorders/blood , Calcium Metabolism Disorders/urine , Child , Child, Preschool , Female , Humans , Infant , Male
11.
Acta Univ Carol Med (Praha) ; 40(1-4): 43-5, 1994.
Article in English | MEDLINE | ID: mdl-9355671

ABSTRACT

Demineralization of bone is a frequent finding in children with juvenile chronic arthritis (JCA). Recently there have been reports about hypercalciuria accompanying JCA. This is believed to be associated with increased bone resorption due to cytokines and immobility of the patients and steroid treatment. In 12 patients with confirmed diagnosis of JCA basic biochemical indices of bone metabolism, were performed (S-Ca, P, ALP, U-Ca/U-creatinine, U-P). Bone mineral density (BMD) was measured using DPXA method and results obtained were compared to the Lunar BMD DPXA standards. In spite of decreased BMD, no significant hypercalciuria was found and other mentioned biochemical indices of bone and mineral metabolism were normal as well.


Subject(s)
Arthritis, Juvenile/urine , Calcium/urine , Adolescent , Adult , Arthritis, Juvenile/complications , Arthritis, Juvenile/metabolism , Bone Density , Bone Resorption/etiology , Bone Resorption/urine , Child , Female , Humans , Male , Prednisone/adverse effects
12.
Arthritis Rheum ; 37(1): 93-7, 1994 Jan.
Article in English | MEDLINE | ID: mdl-8129769

ABSTRACT

OBJECTIVE: Endogenous synthesis of cysteinyl leukotrienes in juvenile rheumatoid arthritis (JRA) was investigated. METHODS: Cysteinyl leukotriene synthesis was assessed by measuring the excretion of leukotriene E4 (LTE4) in urine by radioimmunoassay. The identity of urinary LTE4 was investigated by gas chromatography-mass spectrometry (GC-MS), and 2,3-dinor-thromboxane B2 was measured with GC-MS. RESULTS: Excretion of LTE4 into urine was significantly (P < 0.05) enhanced in children with JRA compared with that in healthy children (n = 10). Aspirin, in a dosage of 2.5 gm/day, had no effect on urinary LTE4 levels, but it reduced urinary 2,3-dinorthromboxane B2 levels by more than 85% in healthy adults. There was a positive correlation between LTE4 excretion and the number of affected joints. CONCLUSION: This study demonstrates a markedly enhanced cysteinyl leukotriene synthesis and a positive correlation between LTE4 excretion and the number of affected joints in children with JRA.


Subject(s)
Arthritis, Juvenile/metabolism , Leukotriene C4/biosynthesis , Leukotriene D4/biosynthesis , Leukotriene E4/biosynthesis , Adolescent , Adult , Arthritis, Juvenile/urine , Aspirin/pharmacology , Child , Gas Chromatography-Mass Spectrometry , Humans , Leukotriene E4/urine , Thromboxane B2/analogs & derivatives , Thromboxane B2/urine
13.
Dev Pharmacol Ther ; 15(2): 57-60, 1990.
Article in English | MEDLINE | ID: mdl-2078973

ABSTRACT

Administration of salicylates during prodromal viral illness has been associated with the development of Reye's syndrome (RS). We studied salicylate biotransformation in RS patients and compared it with those on chronic salicylate therapy for juvenile rheumatoid arthritis (JRA). Urine of RS patients contained significantly more salicylic acid and less gentisic acid than that of JRA patients while the conjugated metabolites were not different between the two groups. These results suggest decreased salicylate microsomal oxidation in RS. The role of altered salicylate metabolism in the pathogenesis of RS is unclear.


Subject(s)
Arthritis, Juvenile/metabolism , Gentisates , Reye Syndrome/metabolism , Salicylates/pharmacokinetics , Arthritis, Juvenile/urine , Biotransformation , Humans , Hydroxybenzoates/urine , Oxidation-Reduction , Reye Syndrome/urine , Salicylates/metabolism , Salicylates/urine , Salicylic Acid
15.
J Rheumatol ; 14(1): 145-6, 1987 Feb.
Article in English | MEDLINE | ID: mdl-3572917

ABSTRACT

We describe a case of persistent microscopic hematuria as initial finding in incomplete Still's disease or Wissler-Fanconi syndrome. Renal biopsy findings were compatible with intravascular coagulation. Wissler-Fanconi syndrome and the associated renal abnormalities are briefly reviewed.


Subject(s)
Arthritis, Juvenile/diagnosis , Hematuria/etiology , Wissler's Syndrome/diagnosis , Adolescent , Arthritis, Juvenile/complications , Arthritis, Juvenile/urine , Humans , Male , Wissler's Syndrome/complications , Wissler's Syndrome/urine
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