[Higher percentages of T regulatory cells in children at risk for developing type 1 diabetes mellitus]. / Podwyzszone odsetki limfocytów T regulatorowych u dzieci z grupy ryzyka zachorowania na cukrzyce typu 1.

INTRODUCTION: The natural history of type 1 diabetes is concerned with the appearance of autoantibodies against antigens of pancreatic beta cells. The last decade revealed some evidence of the participation of T regulatory lymphocytes - cells which suppress immune response - in the pathogenesis of type 1 diabetes and prediabetes. AIM OF THE STUDY: was the assessment of T regulatory cells in the blood of children at risk for developing type 1 the diabetes mellitus. MATERIAL AND METHODS: 85 subjects, siblings of children with type 1 diabetes, were enrolled into the study. The presence of anti-GAD65 antibodies was assessed. With the use of flow cytometry the following cell subpopulations were noted: CD4+, CD4+CD25high and CD4+CD25highCD127low with the coexpression of: CD28, CD45RO, CD54, CD62L and CD134 molecules. RESULTS: We did not observe any differences in white blood cell count, lymphocyte (including CD4+) count and the percentage between the examined and control groups. We noted higher percentages of T regulatory cells: CD4+CD25high, CD4+CD127low and CD4+CD25highCD127low in children with the presence of anti-GAD65 antibodies as compared to the control children. CONCLUSION: Higher percentages of T regulatory cells in the blood of children with the presence of anti-GAD65 antibodies may suggest an intensive regulatory response present in patients at risk for developing type 1 diabetes.

Equal metabolic control but superior caregiver treatment satisfaction with insulin aspart in preschool children.

BACKGROUND: The aim of this study was to compare the metabolic outcomes, safety, and caregiver treatment satisfaction of basal-bolus multiple daily injection (MDI) therapy with mealtime insulin aspart (IAsp) or human insulin (HI) (both with basal NPH insulin), or of continuous subcutaneous infusion (CSII) with IAsp in preschool-age children with type 1 diabetes mellitus. METHODS: After a 3-week HI MDI run-in, 61 children <7 years old were randomized to IAsp MDI or HI MDI or allocated to IAsp CSII for 26 weeks. Efficacy measures were glycated hemoglobin (A1C) and overall metabolic control at study end point. Safety evaluation included hypoglycemia and adverse events. Caregiver treatment satisfaction was evaluated using a World Health Organization questionnaire with 7-point scale answers. RESULTS: A1C level and overall metabolic control remained unchanged in all groups. Minor hypoglycemic episodes were equivalent between groups; few major hypoglycemic events occurred. Caregivers of children receiving IAsp CSII documented a greater increase in treatment satisfaction total scores (P = 0.04 vs. HI MDI and IAsp MDI group) and expressed satisfaction with the frequency of hypoglycemic events. CONCLUSIONS: After 26 weeks of treatment with IAsp CSII, IAsp MDI, or HI MDI, all metabolic control parameters remained unchanged and equivalent. Caregiver treatment satisfaction was higher in parents who chose IAsp CSII pump therapy for their children.

Percentage of LFA-1+ and ICAM-1+ peripheral blood mononuclear cells in children and adolescents with type 1 diabetes does not distinguish patients with vascular complications.

There are only few studies evaluating lymphocytes activation in the diabetic vascular complications. ICAM-1/LFA-1 adhesion molecules not only participate in the lymphocyte T proliferation but also mediate leukocyte migration to the site of inflammation. We assess a relationship between the percentage of ICAM-1 and LFA-1 expressing PBMCs and the evolution of vascular complications in T1D in children and adolescents. The study was carried out on 60 children and adolescents with T1D (aged 9-20): (a) T1D lasting <5 years (n=20), (b) T1D lasting >5 years (n=20), without complications c) T1D lasting >5 years complicated with microalbuminuria, arterial hypertension, diabetic retinopathy (20 n). 20 healthy volunteers, age and sex matched constituted the control group. The expression of adhesion molecules was evaluated by using three-color flow cytometry. In children and adolescents with T1D <5 years, the percentage of ICAM-1+ and LFA-1+ PBMCs was decreased vs. controls (p<0.05 and p<0.001, respectively). Both in patients with T1D>5 years without vascular complications and in T1D with vascular disease the percentage of LFA-1+ T lymphocytes was significantly reduced in the peripheral blood (p<0.001 vs. healthy controls). In conclusion the percentage of LFA-1+ and ICAM-1+ PBMCs does not distinguish patients with vascular complications however decreased percentage of LFA-1+ PMBCs could serve as a nonspecific marker of the development of local inflammatory process in Type 1 diabetes.

Diminished expression of ICOS, GITR and CTLA-4 at the mRNA level in T regulatory cells of children with newly diagnosed type 1 diabetes.

Diabetes mellitus is one of the most common chronic diseases in children. T regulatory cells (Tregs) modulate response to autoantigens and probably play a role in pathogenesis of type 1 diabetes (T1DM). The aim of the present study was the assessment of T regulatory cells including their percentages and expression of critical genes in these cells in children with newly diagnosed type 1 diabetes. The examined group consisted of 50 children with T1DM. A flow cytometric analysis of T-cell subpopulations was performed using the following markers: anti-CD4, anti-CD25 and anti-CD127 (=IL-7R). Additionally, T regulatory cells were isolated for assessment of mRNA levels for chosen genes with the real-time RT-PCR technique. The percentages of CD4(+)CD25(high)CD127(dim/-) were very low and did not differ between T1DM and control children. We did not observe any statistically significant differences between healthy and diabetic children in mRNA expression for FoxP3, IL-7R (CD127), IL-8RA, IL-10RA, IL-12A, IL-2RA (CD25), IL-21, STAT1, STAT3, SOCS2, SOCS3, TGF-beta1-R1, TGF-beta-R2 and TBX-21 genes. Interestingly the mRNA level for CTLA-4, ICOS1, IL-23, IL-27, SMAD3 and GITR were lower in Treg cells of children with diabetes compared to the control patients. No disturbances in the percentages of T regulatory cells in patients with diabetes but diminished expression of some elements important in Treg function could be the result of an immunologic imbalance accompanying the onset of the diabetes. The results of our study should be used in future research in the field of immunotherapy in pediatric diabetes.

[Do the regulatory T cells play a role in the pathogenesis and therapy of type 1 diabetes?]. / Czy limfocyty T regulatorowe odgrywaja role w patogenezie i leczeniu cukrzycy typu 1?

In the paper the current knowledge concerning the role of T regulatory cells in the pathogenesis and modern therapy of diabetes type 1 is discussed. Type 1 diabetes is one of the most well-known autoimmunological diseases. In its pathogenesis the destruction of pancreatic beta cells by autoreactive T lymphocytes plays the main role. It is considered that in the autoimmunologic reaction participate the disturbances in the number/function of T regulatory cells - responsible for the inhibition of hyperreactive immune response. According to the newest data the regulatory cells possess CD4+/ CD25++/CD127 low phenotype. Results concerning the role of T regulatory cells in the pathogenesis of diabetes are diverse, further both the experimental and clinical studies are required including the use of those cells in immunotherapy. Most authors observed the lack of number and/or function of T regulatory cells in type 1 diabetes. Among produced cytokines most valuable is TGF-p. Important disturbances in this field were also observed in the patients' families including the carriers of high-risk group genes. There are also ideas to use T regulatory cells in the prevention and therapy of diabetes. Some reports noted the role of T regulatory cells in the response to novel immunotherapies in diabetes like the use of TNF-a, anti-CD3 antibodies or dendritic cells inducing pancreatic islet tolerance. It is possible that further research will allow to use the immunotherapy including T regulatory cells in type 1 diabetes.

[Analysis of serum levels of ghrelin and obestatin in children and adolescents with autoimmune thyroid diseases]. / Analiza stezenia ghreliny i obestatyny w surowicy krwi u dzieci i mlodziezy w schorzeniach autoimmunologicznych tarczycy.

INTRODUCTION: Thyroid disease is leading to a change of weight - in hyperthyroidism body mass is reduced, but in hypothyroidism it is increased. Recently researches suggest that many new bioactive substances, like ghrelin and obestatin, play a role in regulation of body mass. These closely related hormones have different effects- ghrelin increases, but obestatin decreases the appetite. The aim of the study was to evaluate ghrelin and obestatin levels in young patients with untreated Graves' disease, subclinical Hashimoto' thyroiditis and in children with nodular goiter in the euthyroid clinical state. MATERIAL AND METHODS: The study group formed 78 patients of the Outpatient Endocrinology of the 2nd Department of Children's Disease (Medical University in Bialystok) and Outpatient Endocrinology IHC in Warsaw suffering from Graves' disease (29 girls and 2 boys; aged from 6 to 21 - mean 15,2 yrs) and Hashimoto's thyroiditis (29 girls and 3 boys; aged from 9 to 18 - mean 14,5 yrs). The control group consisted of children with nodular goiter (euthyroid) - 13 girls and 2 boys; aged from 9 to 18 - mean 14,8 yrs. In all patients, ghrelin and obestatin levels were analyzed by RIA's method (Phoenix Pharmaceuticals, USA). RESULTS: In children and adolescents with hyperthyroidism in Graves' disease we found lower levels of ghrelin compared to the group of children with nodular goiter and with subclinical hypothyroidism in Hashimoto's thyroiditis (123+/-23 vs. 151+/-45; vs. 140+/-36 pg/ml, p<0,02, ns). On the other hand obestatin levels were lower in children with untreated subclinical hypothyroidism in Hashimoto's thyroiditis compared to a group with nodular goiter or Hashimoto's thyroiditis in euthyroidism (203,28+/-59 vs. 222.49+/-49; 267.24+/-70 pg/ml, p<0.03, p<0.02). In a group of untreated hyperthyroidism in Graves' disease we found correlations between ghrelin and fT3 (r=-0.36, p<0,4) and fT4 levels (r=- 0.45, p<0.01). CONCLUSIONS: In conclusion, we suggested that disturbances in thyroid hormones in thyroid diseases have an essential effect on changes of hormones controlled appetite: ghrelin (in hyperthyroidism) and obestatin (in hypothyroidism).

Lower percentages of T regulatory cells in children with type 1 diabetes - preliminary report.

INTRODUCTION: Type 1 diabetes (T1D) isa well-known autoimmune disease, however there are still some processes in its pathogenesis to be elucidated. In the last few years the role of T regulatory cells in the pathogenesis of T1D has been investigated. The aim of study was to determine the percentages and numbers of T regulatory cells in the peripheral blood of children with type 1 diabetes. MATERIAL AND METHODS: A total of 25 children with newly diagnosed type 1 diabetes were studied, and compared to the control group consisted of 30 healthy children with no signs of autoimmune, chronic, inflammatory, neoplastic disease, and no evidence of T1D in their families. Flow cytometric analysis ofT-cell subpopulations was performed using the following markers: anti-CD3, anti-CD4, anti-CD25, and anti-CD127 (IL-7R). RESULTS: In the group of children with type 1 diabetes we noted statistically significant lower percentages of T regulatory cells, i.e., CD4+CD25 high and CD4+CD127 low comparing to the control children. There were no differences in other assessed parameters: white blood cell count, lymphocytes, CD4+ and CD4+CD25 high CD127 low cells (percentage and count). We did not find the correlation between patients' age and any of analysed parameters. CONCLUSIONS: Our results suggest the lower percentages of Tregs in children with T1D, however those data need to be confirmed in a larger cohort of patients and complemented with functional studies, e.g. at mRNA level. In our opinion T regulatory cells could be excellent candidates for cell therapy in newly diagnosed type 1 diabetic children.

[Correlation between intima-media thickness in carotid artery and markers of epithelial cell dysfunction in patients with juvenile idiopathic arthritis]. / Ocena zaleznosci pomiedzy gruboscia warstwy wewnetrznej i sródblonka u dzieci z mlodzienczym idiopatycznym zapaleniem stawów (MIZS).

UNLABELLED: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Prolonged immunological inflammatory process leads in these patients to an early onset of atherosclerosis. That is why it seems to be important to find methods of detecting atherosclerosis in its very early stage to start appropriate treatment. AIM: The aim of this study was to determine whether there is any correlation between intima-media thickness (IMT) in carotid artery and concentrations of markers of epithelial cell dysfunction - C-reactive protein and Intercellular Adhesive Molecule -1 (sICAM-1). MATERIALS AND METHODS: 63 children were enrolled in the study (40 with JIA and 23 healthy as control group). C-reactive protein concentration was assayed by immunoturbidimetric method with Hitachi 912 Chemistry Analyzer and sICAM-1 was assayed by ELISA. IMT was measured as defined by Pignoli. RESULTS: Mean CRP concentration in the study group was 1.97 mg/dl and in the control group -0.08 mg//dl. sICAM-1 concentration was 333.4 mg/ml, and mean IMT in carotid artery in children with JIA was 0.43 mm (max=0.58 mm, min=0.36 mm). There was a correlation between IMT and sICAM-1 concentration (r=0.75, p<0.001). CONCLUSIONS: Assessment of IMT in carotid artery and concentrations of sICAM-1 and CRP may be used as a marker of preclinical arthrosclerosis in children with JIA.

[The assessment of T regulatory cells in the peripheral blood of children with metabolic syndrome]. / Ocena limfocytów T regulatorowych we krwi obwodowej dzieci z zespolem metabolicznym.

UNLABELLED: The metabolic syndrome is defined as the co-existence of risk factors for the development of cardio-vascular disease: obesity, hypertension, insulin resistance and dyslipidemia. For a few years there has been a growing interest in immune-inflammatory aspects of obesity and metabolic syndrome. According to many authors the disturbances in the number and(or) function of T regulatory cells are responsible for autoimmune diseases. It is possible that they play a role in a pathogenesis of chronic inflammation accompanying obesity. THE AIM OF THE STUDY was to determine the percentages of T regulatory cells in children with metabolic syndrome. MATERIAL AND METHODS: Fourty seven children with metabolic syndrome were prospectively enrolled into the study according to the IDF criteria (central obesity and two of: hypertension, hypertriglycerydemia, low HDL, hyperglycemia/glucose intolerance/diabetes). With the use of five-colour flow cytometry the following percentages of T cells in the peripheral blood were assessed: CD4(+), CD4(+)CD25(high), CD4(+)CD25(high)FoxP3(+), CD4(+)CD25(high)CD127(low), CD4(+)CD25(high)FoxP3(+)CD127(low). RESULTS: In the group of children with metabolic syndrome we noted lower percentages of CD4(+)CD25(high) cells compared to control children: 1.7 vs. 3.7% (p = 0.01). The differences in CD4(+)CD127(low) cells were not statistically significant: 15.7 vs. 17.6% (p = 0.1). We did not observe the differences between examined and control group in the percentages of CD4(+)CD25(high)CD127(low) and CD4(+)CD25(high)FoxP3(+) cells (respectively: 0.54% vs. 0.58%, 0.49 vs. 0.59%, p > 0.05). CONCLUSIONS: Results of our investigation suggest the lower percentages of CD4(+)CD25(high) but not other Tregs subpopulation cells in children with metabolic syndrome. The further research concerning the role of Tregs in the pathogenesis of immunologic disturbances accompanying metabolic syndrome will continue.

[Genetic syndrome, most likely vascular type of Ehlers-Danlos syndrome, in a 14-years old boy with extrapyramindal symptoms dominating the early childhood and growth failure]. / Zespól genetyczny sugerujacy naczyniowy fenotyp Zespól Ehlersa-Danlosa u 14-letniego chlopca z dominujacymi objawami pozapiramidowymi we wczesnym dziecinstwie i z zaburzeniami wzrastania.

INTRODUCTION: The Ehlers-Danlos Syndrome (EDS) is a heterogeneous group of rare genetic disorders with various clinical features, which result from faulty collagen structure or disturbances in collagen synthesis. THE CASE STUDY: The Ehlers-Danlos Syndrome was diagnosed in patient at the age of 7 as easy bruising and tearing of the skin with scars being left afterwards and spontaneous ruptures of skin's blood vessels were observed. In earlier years extrapyramidal symptoms, which were dominating the clinical picture, perinatal complications and delayed psychomotor development led to a suggestion of the infantile cerebral palsy. Growth failure and low bone mass are also observed in this patient. CONCLUSION: Diverse symptoms can occur in patients with EDS, so all of them must be included into diagnostics and treatment. In the vascular type of EDS the biggest fear is about some rupture of a major blood vessel or an internal organ (bowels etc.), so educating the patient and his/hers family, especially about everyday physical activity, plays a very important role.

[Identification of the CD40 (CD154) ligand expression on the surface of conglomerate platelet-monocyte in children with the metabolic syndrome]. / Identyfikacja ekspresji liganda CD40 (CD154) na powierzchni konglomeratu plytka-monocyt u dzieci z zespolem metabolicznym.

INTRODUCTION: The increased expression of the transmembrane protein CD40 on macrophages, endothelium, smooth muscle cells, platelet-monocyte conglomerate is connected with an enlarged risk of the occurrence of diseases of the cardiovascular system in the metabolic syndrome. THE AIM OF THE STUDY: was to establish whether metabolic syndrome in children can already be a precursor of cardiovascular diseases. MATERIAL AND METHODS: The study was carried out on 35 children aged 10-18 years with the metabolic syndrome recognized according to the National Cholesterol Educational Program Adult Treatment Panel III (ATP III) criteria. The control group consisted of 26 healthy children without risk factors. In the examined children we evaluated BMI, the blood pressure, lipids, hsCRP, and the HOMA index. The analysis of the expression CD 40L (CD154) was performed with a three-color flow cytometer. The identification surrendered 104 cells. Statistical analysis was performed with use of U-Mann-Whitney test, for correlation analysis we used Spearman and Pearson tests. RESULTS: We observed an elevated expression of CD40 ligand on the surface on platelet-monocyte conglomerate in patients with the metabolic syndrome compared to healthy children (12.7 vs. 4.95%, p=0.0036). In addition, we found a statistically significant correlation between the expression of the CD40L and HOMA index (r = -0.33, p<0.028). CONCLUSIONS: Enlarged expression of the transmembrane protein CD40L not only initiates and influences the progression of the atherosclerosis, but modulates the architecture of atherosclerotic plaque as well.

[Evaluation of adiponectin level in children and adolescents with diabetes type 1]. / Ocena stezenia adiponektyny u dzieci i mlodziezy z cukrzyca typu 1.

INTRODUCTION: Adipose tissue is not only an energy storage place, but it also secretes numerous "adipocytokines" - substances that have systemic influence. Adiponectin has an anti-inflammatory, antiatherogenic properties and increases insulin sensitivity. It is emphasized that adiponectin levels are different in type 1 and type 2 diabetes. THE AIM OF THE STUDY: was to evaluate adiponectin levels in young patients with diabetes type 1, and to analyse of the correlation between adiponectin and: BMI, lipid parameters, glomerular filtration rate and microalbuminuria. MATERIAL AND METHODS: The study group was formed by 95 patients from the Outpatient Diabetology Department 2nd Department of Children's Diseases, 45 girls and 50 boys, aged from 7 to 20 years (mean - 14.97 yrs) suffering from diabetes from 1 to 17 years (mean 6.68 yrs). Control group consisted of healthy children, age matched, without family history of cardiovascular diseases. In all patients anthropometric measurements were performed (BMI was calculated), metabolic control was evaluated on the basis of HbA1c level, microalbuminuria was studied in 24 hour urine sample. We assessed glomerular filtration rate (endogenous creatinine clearance), lipid parameters and adiponectin level. RESULTS: In children and adolescents with diabetes type 1 we found significantly higher levels of adiponectin compared to control group: 32.72+/-13.49 vs. 26.53+/-7.63 ug/ml; p=0.024. Adiponectin level was higher in girls than in boys (33.56 vs. 28.75 ug/ml; p=0.036). Adiponectin level did not depend on metabolic control and on diabetes duration. We found a statistically significant negative correlation between adiponectin and creatinine (r=-0.26; p=0.011). In patients with diabetic complications we found insignificantly lower adiponectin level compared to patients without complications (30.99+/-14.29 vs. 33.67+/-11.68 ug/ml; p=0.35). CONCLUSIONS: 1. In patients with diabetes type 1 significantly higher level of adiponectin was found compared to healthy control group. 2. Adiponectin level correlated negatively with creatinine level end microalbuminuria. 3. Elevated level of adiponectin in patients without diabetic complications may help to explain the pathogenesis of diabetic angiopathy.

[Relationship between bone mineral content and growth disorders in children with juvenile idiopathic arthritis]. / Zaleznosc miedzy masa mineralna kosci a zaburzeniami wzrastania u dzieci chorych na mlodziencze idiopatyczne zapalenie stawów.

UNLABELLED: In chronic inflammatory processes in children efforts are made to evaluate bone mineral content (BMC) with the use of densitometric parameters, which at the same time determine equivalent of lean body mass (LBM). This functional analysis of the musculoskeletal system by using DXA method seems to be particularly useful for the examination of bone mass in children suffering from juvenile idiopathic arthritis (JIA). THE AIM OF THE STUDY was to assess body mass content having regard of the BMC/LBM ratio in JIA children, depending on the degree of growth inhibition, disease advancement phase and the therapy applied. MATERIAL AND METHODS: The study comprised 97 children aged 5-18 (mean age 12.7+/-3.8 years), 45 girls and 52 boys with diagnosed JIA according to ILAR criteria of 1997. The average duration of disease was 4.1+/-3.1 years. Antropometric and densitometric measurement was made in every child. Body height was defined by Standard Deviation Height Velocity Score - SDHVS (SDS). Patients were divided into 2 groups: I - 28-group with SDS ratio < -2.0; 11 - 69 children with normal height. For the evaluation of disease development and advancement of anatomic changes in joints criteria of Steinbrocker were applied: I grade - without joint damage, II - insignificant or moderate joints damage, III-IV - established deformation. The densitometric research was conducted with the use of double-energy X-ray absorptiometry (DXA) method. Bone mineral density (BMD) was assessed in the whole skeleton (TB BMD), in the vertebras L2-L4 (SB MD), Z-score index for SBMD and BMC, LBM, TB BMC/LBM defined by the Z-score index and compared to norms for age and growth. RESULTS: Bone mineral density defined as Z-score index for SBMD <-2.0 was reported in 21 children (21.6%). Muscle-skeletal Z-score index for TB BMC/LBM in relation to norms of gender and growth lower than -1.0 was proved in 23 children (23.6%). Considerably lower Z-score index for TB BMC/LBM (p < 0.01) characterized children with growth inhibition and children with significant joints damage (p < 0.02). There was no significant correlation between densitometric parameters and applied treatment with glucocorticoids and without glucocorticoids. CONCLUSIONS: Decrease of bone mineral mass defined as muscle-skeletal Z-score index for TB BMC/LBM was found in almost quarter of patients within the group of JIA children. In the group of children with growth deficiency and with larger joints damage bone mass was significantly lower.

Bone mineral metabolism in children with juvenile idiopathic arthritis--preliminary report.

INTRODUCTION: There are very few reports assessing bone mineral mass and its metabolism in the course of juvenile idiopathic arthritis (JIA). STUDY OBJECTIVE: To assess the levels of selected serum markers of bone formation (OCN) and resorption (CTx) in JIA children. MATERIAL AND METHODS: The study involved 52 children with JIA diagnosed according to the EULAR criteria of 1997, aged 6-18 years. All patients underwent densitometric measurements using dual-energy X-ray absorptiometry (DXA) to assess TBBMD (g/cm2), Spine BMD (g/cm2), Z-score for SBMD, TBBMC (g), and LBM (g). The following parameters were determined in blood serum: the level of osteocalcin (OCN) and C-terminal type I alpha-collagen chain telopeptide (CTx) using the Elecsys 2010 system (N-MID Osteocalcin, Beta-CrossLaps). A gender- and age-matched control group consisted of 16 healthy children. RESULTS: The mean concentrations of both osteocalcin (p<0.001) and CTx (p<0.005) were significantly higher in JIA patients as compared to the healthy controls (OCN 113.2+/-54.9 ng/ml vs. 70.2+/-48.3 ng/ml; CTx 1.4+/-0.5 mug/l vs. 1.2 +/-0.45 microg/l). The concentrations of the bone turnover markers were significantly reduced in children with higher degrees of joint destruction compared to those with anatomically normal joints (p<0.05). The mean concentration of CTx showed a significant negative correlation with the TB BMC/LBM Z-score (p<0.05). Reduced bone mass (Z-score for SBMD< -2.0) was found in 23.6% of the affected children. CONCLUSIONS: The JIA patients had elevated levels of OCN and CTx compared to the healthy controls. Reduced bone turnover was observed in children with higher degrees of joint destruction.

[Precocious puberty due to hypothalamic hamartoma]. / Przedwczesne dojrzewanie plciowe w przebiegu guza hamartoma podwzgórza.

INTRODUCTION: Central precocious puberty is usually idiopathic. Appearance of the precocious puberty symptoms in early childhood or pre-school period indicate that also it could be caused by organic disorder of the central nervous system. The aim of this work is to present the case of the 4-year-old girl, diagnosed with precocious puberty. THE CASE REPORT: The first clinical symptoms of precocious puberty such as increased growth rate and breast enlargement were observed when the girl was 4 years old. The height (above the 97 centile) and weight (90-97 centile) were measured during the physical examination. The advancement of sexual features was determined as follows: thelarche III degrees , pubarche II degrees , axillarche II degrees . The LHRH test used in this differential diagnosis revealed the pubertal level of gonadotropins, when plasma levels of dehydroepiandrosterone, prolactin, thyroid-stimulating hormone and alpha-fetoprotein levels were correct. The advanced bone age was 8 years and 10 months, while the height age was 7 years. The final diagnosis was based on MRI scan. The patient is currently treated with an analog of gonadoliberine (Diphereline). In conclusion, we aspired to notice that the pharmacological treatment of hypothalamic hamartoma may be safe and effective. Suppression of puberty to the normal time of pubescence gives a child the chance to reduce health discomforts as well as further emotional and social problems.

Impairment of microcirculation in juvenile idiopathic arthritis - studies by nailfold videocapillaroscopy and correlation with serum levels of sICAM and VEGF.

Impairment of vascular endothelium plays a key role in the pathogenesis of inflammatory diseases including juvenile idiopathic arthritis (JIA) and atherosclerosis. We hypothesized that structural abnormalities of the smallest blood vessels (capillaries) might exist and reflect endothelial dysfunction in children with JIA. Microcirculation was studied, by means of nailfold videocapillaroscopy with computer-associated image analysis, in 43 patients with JIA and compared with 20 healthy children. Moreover, capillaroscopic findings were correlated with the activity of the disease and the levels of serum biomarkers of endothelial injury, namely soluble intercellular adhesion molecule (sICAM) and vascular endothelial growth factor (VEGF). We found that in JIA patients capillaries were significantly wider and longer than in healthy controls. Moreover, irregular capillaries and dilated subpapillary venous plexus were found significantly more frequently in JIA in comparison with the control group. Serum levels of sICAM and VEGF were significantly higher in JIA patients with capillary abnormalities than in JIA patients with normal capillaroscopy. Our study indicates that there are structural changes in the microcirculation of patients with JIA and that these changes might reflect endothelial injury. Whether capillaroscopy might have a role in early identification of JIA patients being at higher risk of atherosclerosis requires further studies.

[Analysis of Fas, FasL and Caspase-8 expression in thyroid gland in young patients with immune and non-immune thyroid diseases]. / Analiza ekspresji czasteczek Fas, FasL oraz kaspazy 8 w tkance gruczolu tarczowego u mlodych pacjentów z chorobami immunologicznymi i nieimmunologicznymi gruczolu tarczowego.

INTRODUCTION: Apoptosis, programmed cell death is a regulating mechanism enabling the removal of superabundantly produced and unnecessary at the certain moment cells. Disturbances of the apoptosis regulation contribute to the pathogenesis of many diseases, including autoimmune thyroid disorders. The aim of this study was to estimate expression of proapoptotic Fas/FasL and caspase-8 in thyroid tissues in patients with Graves' disease (GD), non-toxic nodular goiter (NTNG) and Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: Inclusion criteria of Graves' patients were: large goiter, ophthalmopathy, TRAb > 5 U/L, positive titre of anti-TPO and anti-TG antibodies and concentration of TSH < 0.45 microIU/mL for more the 2-3 months from an onset of the disease. Isolated thyrocytes were identified by indirect method: in the first stage mouse monoclonal antibodies (mAbs) anti-TPO were bound to rabbit anti-mouse antibodies IgG (Fab')2 labeled FITC. To obtained cellular suspension mAbs directed against apoptotic Fas/FasL molecules labeled with PE (Phycoerythrin) was added. All investigations were performed on Coulter EPICS XL flow cytometer. Detection of apoptotic proteins was confirmed by Western Blot and immunohistochemistry methods using mAbs in DAB chromogene visuality and marked by Mayer's haematoxylin. Evaluation of caspase-8 expression in thyroid follicular cells was performed by Western Blot test. RESULTS: The analysis of Fas and FasL expression on surface of thyroid follicular cells was higher in patients with Hashimoto's thyroiditis (38%, 26%) in comparison with patients with Graves' disease (18%, 14%). In case of patients with Hashimoto's thyroiditis significantly lower percentage of thyroid tissue infiltrating immune Fas+ (13%) and FasL+ (22%) T cells in comparison with Graves' patients (33%, 43% respectively) was observed . Identification of proapoptotic Fas and FasL molecules in the thyroid follicular cells revealed higher expression of both proteins in patients with GD (++,++) and HT (+++; +++, respectively) in comparison with NTNG patients (+/0; +/0). Caspase-8 expression was detected in band 55 kDa using Western Blot test in patients with thyroid autoimmune diseases. CONCLUSIONS: We conclude that alteration in the expression of proapoptotic proteins in thyroid follicular cells may play a role in pathogenesis of thyroid autoimmune disorders. In addition, suppression of apoptosis in Graves' disease led to increased proliferation of thyroid follicular cells which is responsible for goiter formation.

Relationship between endothelial dysfunction, carotid artery intima media thickness and circulating markers of vascular inflammation in obese hypertensive children and adolescents.

BACKGROUND: Adhesion molecules released by dysfunctional endothelium are considered as markers of vascular inflammation in early atherosclerosis. Non-invasive ultrasound methods are now available to detect first preclinical signs of the disease. AIM: To investigate the relationship between selected adhesion molecules and ultrasound indicators of early atherosclerosis: endothelial function measured by flow-mediated dilatation (FMD) and intima media thickness (IMT). PATIENTS: The study group consisted of 85 children, mean age 14.6 years, of whom 22 were obese, 31 were hypertensive, and 32 obese and hypertensive. The control group included 26 healthy children. METHODS: Adhesin concentrations were determined by ELISA. FMD and IMT were evaluated by ultrasound. RESULTS: A positive correlation was found between sICAM-1 (soluble intercellular adhesion molecule 1) and IMT (r = 0.32, p = 0.013, 95% CI: 0.11 to 0.49) and a negative correlation between IMT and FMD (r = -0.26, p = 0.04, 95% CI: -0.43 to -0.04) in the whole study group. In the particular groups, we found significant correlations only in obese hypertensive children. sICAM-1 correlated positively with IMT (r = 0.52, p = 0.001, 95% CI: 0.2 to 0.72) and negatively with FMD (r = -0.31, p = 0.027, 95% CI: -0.6 to -0.2). sE-selectin correlated positively with IMT (r = 0.41, p = 0.012). In regression models, IMT correlated with sICAM-1 (beta = 0.37, p = 0.03) and body mass index (beta = 0.55, p = 0.02), and FMD correlated negatively with sICAM-1 (beta = -0.47, p = 0.04). CONCLUSIONS: The association between inflammatory markers of the endothelium with impaired vasodilatation activity and the first atherosclerotic structural changes in the common carotid arteries were found in obese hypertensive children and adolescents. The coexistence of obesity and hypertension predisposes these young patients to closely related disturbances connected with early atherosclerosis.

Heart rate turbulence in children--age and heart rate relationships.

Heart rate turbulence (HRT) is a chronotropic response of the sinus heart rhythm to ventricular premature beat (VPB). Children show decreasing heart rate together with the maturation of the autonomic nervous system. The aim of the research was to assess the relationship between HRT parameters, age, and heart rate and time domain heart rate variability (HRV) parameters in healthy children. Twenty-four-hour ECG Holter recording was performed on 398 healthy children. The mean RR interval preceding VPB, number of VPBs, and HRT parameters-turbulence onset (TO) and turbulence slope (TS)-were determined. We observed significant correlation among TS and mean RR and age. Children with prepubertal status have lower values of TS compared with those during puberty. According to given quartiles, upper for TO was > or =-0.8%, lower for TS was < or =4.56 ms/RR, 13 patients (3%) obtained abnormal both TO and TS. The correlations between HRT and HRV parameters were observed among the youngest children. Age and heart rate preceding VPB have no effect on HRT onset in children, whereas HRT slope is highly dependent on these variables. Our results support hypothesis that in older children HRT is dependent on autonomic tone and also determined by other intrinsic modulators.

[Analysis of intracellular proapoptotic (Bax, Bak) and antiapoptotic (Bcl-2, Bcl-XL) proteins expression in thyrocytes from young patients with immune and non-immune thyroid disorders]. / Analiza ekspresji wewnatrzkomórkowych proapoptotycznych (Bax, Bak) i antyapoptotycznych (Bcl-2, Bcl-XL) bialek w tyreocytach u mlodocianych pacjentów ze schorzeniami immunologicznymi i nieimmunologicznymi gruczolu tarczowego.

Apoptosis one of the form of programmed cell death is a physiological occurrence, requisite to the correct function of every organism. This is an active process that proceeds with a participation of the cellular metabolism embracing the activation of genes and the synthesis of proteins. The signal to apoptosis can be started practically in every cell of our organism. Disturbances of the apoptosis regulation determine the essential link of the pathogenesis of many diseases, including autoimmune thyroid disorders. The aim of this study was to estimate the expression of proapoptotic (Bax, Bak) and antiapoptotic (Bcl-2, Bcl-XL) proteins in thyroid tissues from 12 patients with Graves' disease (GD), 10 with non-toxic nodular goitre (NTNG) and 10 with toxic nodular goitre (TNG). Criteria for qualification of Graves' patients: large goitre, ophthalmopathy, TRAb > 5 U/L, positive titre of anti-TPO and anti-TG antibodies and concentration of TSH <0.45 microIU/mL more the 2-3 months from onset of the disease. Detection of apoptotic proteins in thyroid follicular cells was performed by Western Blot. These analysis was confirmed by immunohistochemistry using monoclonal antibodies in DAB chromogene visuality and marked by Mayer's haematoxylin. Identification of antiapoptotic Bcl-2 and Bcl-XL molecules in the thyroid follicular cells revealed a higher expression of both proteins in patients with Graves' disease (+++; ++, respectively) in comparison to patients with NTNG (++/+; +) and TNG (++; +). The detection of proapoptotic molecules showed higher expression of Bak (++/+) and Bax (+) in Graves' thyroid tissues while Bax was in trace amount in NTNG (0/+) and TNG (0/+). We conclude that alteration in the expression of antiapoptotic and proapoptotic proteins on surface of thyroid follicular cells may play a role in the pathogenesis of thyroid autoimmune disorders. In addition, suppression of apoptosis in Graves' disease led to predominance for proliferation of thyroid follicular cells which is responsible for goitre formation.