Blood concentration of aminothiols in children with relapse of nephrotic syndrome.

BACKGROUND: The role of idiopathic nephrotic syndrome (INS) in the pathogenesis of atherosclerosis in childhood has not been clearly elucidated. However, antioxidative defense in INS is thought to be imbalanced. This study aimed to assess the changes of plasma concentration of selected aminothiols in the blood of children with INS at various stages of the disease. METHODS: This cross-sectional study was conducted in 125 children aged 2-18 years. The children were divided into 4 groups: group A, early relapse (n=37); group B, early remission for 4-6 weeks from the onset (n=37); group C, late steroid-free remission (n=31); and group D, long-term remission for 2-5 years (n=20). Control group (E) consisted of 30 age- and gender-matched healthy children. The study protocol comprised an analysis of plasma concentrations of glutathione, homocysteine, cysteine and cysteinylglycine by high-performance liquid chromatography. Fractions of protein-bound and free aminothiols were measured. Endothelial injury was assessed by thrombomodulin, PAI-1 concentration, and von Willebrand factor activity. RESULTS: The children with INS had unbalanced aminothiol metabolism only in relapse and early remission, that shifted towards increased oxidative processes. Administration of cyclosporine A caused a significant increase in homocysteine and cysteine concentration. Changes in aminothiol metabolism were significantly related to endothelial injury. CONCLUSIONS: The findings of this study may be helpful in elucidating the pathogenesis of premature atherosclerosis in patients with INS refractory to the treatment or in the case of frequent relapse.

Serum concentration of interleukin-6 is increased both in active and remission stages of pemphigus vulgaris.

As most studies on pemphigus vulgaris (PV) pathogenesis concern its active stage, we aimed to evaluate the serum concentration of TNF-alpha, IL-1, and IL-6 in PV patients in clinical remission. The study group consisted of sera from 19 PV patients in active stage and from 24 patients in clinical remission. 19 sera taken from healthy subjects served as the controls. Serum IL-6 concentrations in PV active and PV remission group were significantly higher when compared to the controls (P < .05). In patients in active stage of PV, a significant correlation between serum IL-1 and IL-6 concentrations was found (r(P) = 0.46; P < .05). We also found a negative correlation between TNF-alpha level and pemphigus antibodies titer in the patients from the remission group (r(S) = -0.47303; P < .02). Our data suggest that IL-6 and TNF-alpha may be involved in maintaining immunological disturbances in remission stage of PV.

Association of Trp64Arg polymorphism of beta3-adrenergic receptor with insulin resistance in Polish children with obesity.

AIM: To establish the influence of the Trp64Arg variant of the beta3-adrenergic receptor (Trp64Arg- beta3AR) on body mass index (BMI) and insulin resistance (IR) in obese children. METHODS: BMI, presence of the Trp64Arg mutation, plasma glucose and insulin concentrations during an oral glucose tolerance test (OGTT) and IR were determined in 60 obese and 33 normal weight children. RESULTS: The frequency of Trp64Arg was similar in normal weight and obese children. BMI, glucose and insulin concentrations during an OGTT in children with Trp64Argbeta3AR were not different from those with Trp64Trpbeta3AR. IR was confirmed in 42.8% of children with Trp64Argbeta3AR and in 45.6% of children with Trp64Trpbeta3AR (NS). CONCLUSIONS: 1. The similar frequency of the Trp64Argbeta3AR variant in normal weight and obese children suggests that it is not a susceptibility gene for obesity in Polish children. 2. The presence of the Trp64Argbeta3AR variant does not have an unfavourable influence on BMI, glucose or insulin concentrations during OGTT or on IR frequency in Polish obese children.

[Concentration of selected cytokines in serum of patients with acne rosacea]. / Stezenie wybranych cytokin prozapalnych w surowicy chorych na tradzik rózowaty.

INTRODUCTION: Rosacea is a common chronic disorder, mainly affects women in their thirties or fourties. As etiology, inflammation is taken into consideration. AIM OF THE STUDY: To assess the concentrations of proinflammatory cytokines: IL-6, IL-18, TNF-alpha and CRP protein. MATERIAL AND METHODS: the study was performed in 60 patients (45 women and 15 men) with rosacea, median age 51 years (range 28-82 years). Twenty five healthy volunteers, sex and age matched, served as a control group. LEVELS OF SELECTED PARAMETERS OF INFLAMMATION: IL-6, IL-18 were detected by ELISA (Bender MedSystems GmbH, Vienna Austria), level of TNF alpha was detected by an immunoenzymatic, chemiluminescent, sequential test IMMULITE TNF-alpha, while detection of CRP was made using an immunonephelometric method using N High Sensitivity CRP (Dade Behring, Inc.). RESULTS: The concentration of IL-6 in the group of patients was statistically significantly lower than in the control group, 0.9 pg/ml and 1.8 pg/ ml respectively, p < 0.001. In the group of the patients with PPR, obtained result (0.9 pg/ml) did not differ from the group with ETR (1.15 pg/ml), p > 0.05. The concentration of IL-18 in the patients was 163.5 pg/ml and it was statistically significantly lower than median level of this protein in the control group (16.2 pg/ml), p < 0.01. The concentration of TNF alpha in the group of patients was 5.79 pg/ml and was higher than the level in the control group -4.73 pg/ml; nevertheless there was no statistically significant correlations, p > 0.05. Median concentration of TNF alpha in the patients with PPR was 4.975 pg/ml and in the patients with ETR 6.73 pg/ml, p > 0.05. Median concentration of CRP in the group with PPR was 0.085 mg/dl and with ETR 0.14 mg/dl. CONCLUSION: Disturbed levels of IL-6 and IL-18, independent of clinical type of rosacea, confirm their role in the development of an inflammatory state in the course of the disease. This kind of correlation was not present for TNF alpha and CRP protein.

Markers of endothelial dysfunction in children with idiopathic nephrotic syndrome.

Endothelial function impairment may constitute a link between nephrotic syndrome and atherosclerosis. We assessed changes in plasma thrombomodulin, von Willebrand factor and plasminogen activator inhibitor-1 at different stages of idiopathic nephrotic syndrome in children and correlated them with clinical and biochemical parameters. The study group included 132 nephrotic children (aged 2-18 years) divided into four groups, i.e. in acute phase of the disease with proteinuria, during steroid-induced remission, steroid-free remission, and in long-term, steroid-free remission. Forty-one healthy children served as controls. Plasma thrombomodulin, plasminogen activator inhibitor-1 and von Willebrand factor activity were increased in children with early nephrotic relapse. They systematically decreased in later stages of the disease but the increase in von Willebrand factor persisted in drug-free remission. These disturbances were dependent on the degree of proteinuria and serum albumin concentration. The study revealed that nephrotic children show markers of endothelial dysfunction that are dependent on the disease activity. This leads to the hypothesis that children with severe clinical course of nephrotic syndrome may be at high risk of accelerated atherogenesis.

[Soluble transferrin receptor's value in diagnosis infants and small children iron deficiency]. / Znaczenie rozpuszczalnego receptora transferyny w diagnostyce niedoboru zelaza u niemowlat i malych dzieci.

UNLABELLED: Iron deficiency is the most frequent deficiency in people, especially in infants and small children. To obtain a correct diagnosis there is need to perform complex hematological and biochemical tests. In recent years studies on soluble transferrin receptor (sTfR) as an index of iron deficiency have been carried out, but mainly in adults. THE AIM OF THESE STUDIES: To estimate usefulness of signification sTfR level for iron deficiency anaemia diagnosis in children up to three years. MATERIAL AND METHODS: The study group comprised 98 children aged 6 to 36 month. Depending on haematological and biochemical results 5 groups of examined children were separated: (1) with iron deficiency anaemia, (2) with latent iron deficiency, (3) with iron deficiency and chronic diseases anaemia, (4) with periinfections anaemia and (5) control. In all examined children the level of sTfR were estimated and its specificity, sensitivity and soundness was evaluated. RESULTS: Average levels of sTfR in children with iron deficiency were significantly higher compared to results in groups without iron deficiency. Specificity, sensitivity and soundness of sTfR were higher than 90% in all examined groups. CONCLUSION: An analysis of results showed that sTfR level seems to be a test which results correlate with iron status in infants and small children well.

Disturbances of the expression of metalloproteinases and their tissue inhibitors cause destruction of the basement membrane in pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease which pathogenesis is associated with destruction of the basement membrane components and the anchoring fibers. The binding of autoantibodies to antigens localized in the basement membrane of the epidermis activates a series of immunological and enzymatic phenomena that lead to blister formation. There are some data that MMPs are involved in the development of skin lesions in BP, however their exact role in this process is not fully understood. We aimed to investigate whether MMPs and their inhibitors (TIMPs), assessed by their tissue expression, are involved in the pathogenesis of BP. The localization and expression of collagenase (MMP1), gelatinase (MMP2), 92 kD gelatinase (MMP9) and stromelysin 2 (MMP10) and TIMP1, 2, 3 were examined by immunohistochemistry in skin biopsies as well as in normal human skin specimens. The study included 21 patients with BP at an active stage of the disease. The MMPs and TIMPs serum levels were measured by ELISA method. Expression of MMP1, MMP2, MMP9 and MMP10 was observed either in the whole epidermis or in the basal keratinocytes. Most of the enzymes examined, apart from TIMP3, were detected in dermal part of the blister. Expression of the majority of the enzymes examined was observed in blister fluid however, the most intense signal was noted for MMP10. In cellular infiltrate we found expression of all the MMPs and TIMPs, the most distinct for MMP1, MMP2, MMP10 and for TIMP2. In all biopsies obtained from healthy volunteers only single basal keratinocytes gave positive, weak signal for the examined proteins. The MMPs and TIMPs serum levels in the control group were normal while in some cases of BP patients they were increased. Based on the results we conclude that imbalance between these enzymes really occurs in BP and it is likely to take important part in the pathogenesis of the disease.

[Insulinsensitivity and beta-cell function in children with idiopathic nephrotic syndrome]. / Insulinowrazliwosc i czynnosc komórki beta trzustki u dzieci z idiopatycznym zespolem nerczycowym.

Glucose intolerance which is frequently found in patients with the idiopathic nephrotic syndrome (INS) may be linked to an increased cardiovascular risk in these patients. Recently it has been suggested that proteinuria and steroid treatment may independently affect insulin sensitivity. The aim of the study was to assess insulin resistance (IR) and beta-cell function in children with INS at various stages of the disease. The study group comprised 66 children (32 male, 34 female; age 8.1 +/- 5.0 years). 20 healthy, sex- and age-matched subjects served as controls. The study group was divided into 3 subgroups: A (n=24) children in relapse of INS (steroids 60 mg/m2/48h; proteinuria 1.02 +/- 1.04 g/dl); B (n=20) in remission treated with steroids (30 mg/ m2/48h); C (n=22) in remission but without steroids. Fasting glucose and insulin levels were measured to calculate insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta) using Homeostatic Model Assessment. Fasting glucose was within normal range in all subjects. HOMA-IR was significantly higher in group A (3.2 +/- 3.3) and group B (2.4 +/- 1.7) than in group C (1.45 +/- 1.6 and controls (1.12 +/- 0.6) (p<0.05). HOMA-beta was significantly higher in group A and B than in C and controls (p<0.05). In multivariate analysis HOMA-IR correlated with proteinuria (beta=0.45, p<0.001), steroid dose (beta=0.32) and BMI (beta=0.42). In conclusion, an increase in insulin resistance with compensatory enhanced beta-cell secretion is a typical finding in children with INS treated with steroids. Proteinuria seems to be an independent risk factor for decreased insulin sensitivity.

[Glucose and insulin concentrations during oral glucose tolerance test in healthy children--application of insulin resistance index according to Belfiore in the developmental age]. / Stezenie glukozy i insuliny podczas doustnego testu obciazenia glukoza u zdrowych dzieci--zastosowanie wskaznika insulinoopornosci wedlug Belfiore w wieku rozwojowym.

INTRODUCTION: Sensitivity to insulin changes during puberty. It is necessary to distinguish physiological insulin resistance (IR) from pathological one. In children the IR index proposed by Belfiore (IRI(Belfiore)) could be used. Application of this formula is possible, when the reference values of the area under curve of glucose (GLU(AUC)) and insulin (INS(AUC)) concentration during oral glucose tolerance test (OGTT) are available for the studied population. Derivation of such reference values was the goal of this study. MATERIAL AND METHODS: Forty healthy children, aged 8-18.2 years, were enrolled in the study. Regarding the stages of puberty, the children were divided into 3 groups: A--stage I, B--stage II or III and C--stage IV or V. Serum glucose and insulin concentrations were measured for each child during OGTT and GLU(AUC) and INS(AUC) were calculated. The obtained mean values of GLU(AUC) and INS(AUC) for each group were used to calculate IRIBelfiore. To determine the cut-off point between physiological and pathological IR, receiver operating characteristic (ROC) analysis was performed for 40 studied children and 50 obese and insulin resistant children (according to QUICKY and/or elevated insulin concentration during OGTT), matched for age, sex and stages of puberty with the study group. RESULTS: The following mean values of GLU(AUC) and INS(AUC) were obtained in particular groups: A--189.3 mg/dL and 37.1 ulU/mL; B--207.4 mg/dL and 54.5 ulU/mL; C--188.8 mg/dL and 59.4 ulU/mL, respectively. The cut-off point value between physiological and pathological IR at the level 1.27 for IRI Belfiore was calculated. CONCLUSIONS: 1. The mean values of GLU(AUC) and INS(AUC) obtained during OGTT could be used to calculate IRI Belfiore in children. 2. IRI(Belfiore) values above 1.27 indicate pathological IR in developmental age.

[Proinflammatory cytokines in inactive lupus erythematosus patients]. / Stezenia cytokin prozapalnych u chorych na toczen rumieniowaty ukladowy bedacych w fazie remisji klinicznej.

Systemic lupus erythematosus (SLE) is an autoimmune connective tisssue disease. Disregulation of proinflammatory cytokines' secrection plays a pivotal role in its etiopatogenesis. Most studies concerning serum levels of those cytokines were conducted in active SLE patients. To date, there are scarce date on proinflammatory cytokines' serum concentration in inactive SLE patients. The aim of the study was to evaluate serum level of IL-1beta, IL-6, IL-18 and TNF-alpha in inactive SLE patients. The study involved 25 SLE patients aged between 24-65 years (mean age 40.6 years) and 25 age- and sex-matched healthy volunteers. The activity of the disease was assesed by SLAM scale. Serum concentrations of IL-6 and IL18 were determined by ELISA while serum levels of TNF-alpha and IL-1beta were measured using chemiluminescensce assay. In all healthy volunteers and in 23 out of 25 SLE patients, serum level of IL-1beta was undetectable (< 5 pg/ml). Serum concentrations of IL-6, IL-18 and TNF-alpha were detectable in all SLE patients. In 9 out of 27 healthy subjects level of IL-18 was under detection limit. Serum levels of IL-6, IL-18 and TNF-alpha were significanly higher (p < 0.001) in SLE patients when compared to their concentrations in subjects from control group (3.45 pg/ml vs. 2.59 pg/ml for IL-6; 344.87 pg/ml vs. 50.31 pg/ml for IL-18; 7.72 pg/ml vs. 5.21 pg/ml for TNF-alpha, respectively). The evaluation of serum levels of proinflammatory cytokines may be a sensitive marker of disease activity which may be helpful in maintaining or withdrawing chronic therapy in SLE patients.

Increased cystatin C concentration in urine of nephrotic children.

The aim of this study was to evaluate changes in urine and plasma concentrations of cystatin C in children with a relapse of the idiopathic nephrotic syndrome(INS). The study group comprised 12 children with INS with proteinuria and 12 children in an 8-week remission,both treated with steroids. Twelve healthy children served as controls. Cystatin C was detectable in the urine of children with proteinuria. The study suggests that massive proteinuria may influence renal cystatin C handling.

Detection of pemphigus autoantibodies by IIF and ELISA tests in patients with pemphigus vulgaris and foliaceus and in healthy relatives.

BACKGROUND: Pemphigus is a life-threatening, autoimmune blistering disease, mediated by IgG autoantibodies. The aim of our study was to assess the usefulness of a new enzyme-linked immunosorbent assay (ELISA) in detecting circulating pemphigus autoantibodies, and to compare its sensitivity and specificity with the indirect immunofluorescence (IIF) test. We also established the frequency of occurrence of pemphigus autoantibodies in relatives of our patients. MATERIAL/METHODS: IIF and ELISA tests were performed in 24 patients with pemphigus vulgaris, 13 with pemphigus foliaceus, 56 healthy relatives, and 50 controls, selected according to sex and age. RESULTS: The obtained results revealed high specificity and sensitivity of ELISA, comparable to the IIF test, especially in patients who were in the active stage of the disease. We also showed that the profile of anti-Dsg 1 and/or anti-Dsg 3 autoantibodies is associated with the clinical variant of pemphigus. The frequency of occurrence of pemphigus autoantibodies in the relatives (24/55) performed by IIF was significantly higher (p<0.001) than in the controls (0/50). The same antibodies detected by ELISA (11/56) were less frequent. CONCLUSIONS: In clinically doubtful cases, in which autoantibodies titres by IIF are equal on both substrates (monkey and guinea pig esophagus), the assessment of the exact antibody profile (anti-Dsg 1 and/or anti-Dsg 3) is important to establish the subtype of pemphigus. The frequency of pemphigus antibody occurrence in healthy relatives seems not to be incidental, but further studies should be performed to explain this phenomenon.

[Chemiluminescence of peripheral blood neutrophils in infants and small children with food allergy]. / Chemiluminescencja neutrofilów krwi obwodowej u niemowlat i malych dzieci z alergia pokarmowa.

In this study the activity of neutrophils, measured using the chemiluminescence tests, was estimated in 91 children with food allergy. It was shown that the average chemiluminescence values without as well as after stimulation by FMLP, PMA and NZ were considerably higher in children with allergy in comparison to children from the control group.