[Serum levels of matrix metaloproteinase 2 (MMP-2), matrix metaloproteinase 9 (MMP-9) and tissue inhibitor of metaloproteinase 2 (TIMP-2) in children and adolescents with growth hormone deficiency]. / Ocena stezenia metaloproteinazy macierzy pozakomorkowej 2 (MMP-2), metaloproteinazy macierzy pozakomorkowej 9 (MMP-9) i tkankowego inhibitora metaloproteinazy 2 (TIMP-2) u dzieci i mlodziezy z niedoborem hormonu wzrostu.

INTRODUCTION: Matrix metaloproteinases (MMPs) have been implicated in various pathological processes including inflammatory response, atherosclerosis and cardiovascular disease. Growth hormone deficiency (GHD) is associated with prematury atherosclerosis and cardiovascular disease. Circulating levels of matrix metaloproteinases and their tissue inhibitors (TIMPs) so far have not been assessed in children and adolescents with GHD. MATERIAL AND METHODS: Serum levels of matrix metaloproteinase 2 (MMP-2), matrix metaloproteinase 9 (MMP-9) and tissue inhibitor of metaloproteinase 2 (TIMP-2) were measured in 44 (11 girls and 33 boys) children and adolescents with newly diagnosed GHD [age (mean+/-SD) 12.5+/-2.7 years, height 1.3+/-0.1 m, body surface area (BSA) 1.1+/-0.2 m(2) and body mass index (BMI) 17.4+/-2.2 kg/m(2)] and in 32 (11 girls and 21 boys) healthy children and adolescents (age 12.4+/-2.9 years, height 1.6+/-0.2 m, BSA 1.4+/-0.3 m(2) and BMI 18.7+/-2.6 kg/m(2)). Human MMP-2, MMP-9 and TIMP-2 measurements were carried out with the use of ELISA kits. RESULTS: Patients with GHD had significantly higher concentrations of MMP-2 (287.2+/-60.5 vs. 235.8+/-41.3 ng/ml, p<0.0001) and TIMP-2 (81.4+/-14.9 vs. 62.7+/-15.9 ng/ml, p<0.0001) levels than the control healthy group. There was no difference in MMP-9 levels (338.5+/-197.9 vs. 276.3+/-121.7 ng/ml, p=0.12) between patients with GHD and controls. CONCLUSIONS: Children and adolescents with GHD have elevated serum concentrations of MMPs-2 and TIMP-2.

[Ultrasonographic evaluation of atherosclerotic changes in carotid and brachial arteries in children with growth hormone deficiency before GH replacement therapy]. / Ocena zaawansowania procesu miazdzycowego za pomoca badania ultrasonograficznego tetnic szyjnych wspólnych i ramiennych u dzieci z niedoborem hormonu wzrostu przed wdrozeniem leczenia substytucyjnego.

BACKGROUND: According to very well documented onset of atherosclerosis in early childhood, scientists are looking for good diagnostic methods for evaluating first changes in arterial blood vessels non-invasively. We want to know more about pathogenetic mechanisms and about changes in vessels especially in the group of young people with risk factors of premature atherosclerosis. The role of endothelial dysfunction in the very early phase of this process is known very well so far. High resolution echocardiography seems to be a good method which allows to examine arteries in children and adolescents. Because of localization, brachial and carotid arteries are a very good field for this kind of examinations. OBJECTIVES: Evaluation with high resolution echocardiography, selected parameters of endothelial function in children with growth hormone deficiency before replacement therapy. We measured the intimal plus medial thickness in carotid communis arteries (IMT) also. MATERIAL AND METHODS: We examined a group of 24 children (19 boys and 5 girls) aged 8-16 yr (mean 12 yr) suffered from growth hormone (GH) deficiency. The control group consisted of 24 children in similar age and sex relation. Using high resolution echocardiography, B-mode images, we measured in end diastole, distance "m-m" in brachial arteries (distance between two "m" lines which are borders among media and adventitia of near and far wall of the artery) at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilatation FMD), again at rest and after sublingual glyceryl trinitrate (causing endothelium-independent dilatation NTGMD). Using Doppler technique we evaluated baseline flow and calculated degree of reactive hyperemia. We also measured intimal plus medial thickness in every carotid artery three times and calculated mean value. In our analysis we estimated concentrations of cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides. RESULTS: In children with growth hormone deficiency the vessel size was smaller then in the control group and FMD was significantly impaired (10.05% v. 14.62%; p=0.058). NTGMD was similar to the control group (p=0.,371). We noticed higher IMT values in the whole examined group compared to the control group (0.52 mm v. 0.41 mm; p=0.0000). We noticed an important correlation between FMD and IMT in whole patients (examined plus control group) (p=0.004). The level of total cholesterol was higher in the examined group (p=0.039). CONCLUSIONS: 1. FMD evaluated in brachial artery, seems to be an useful sign of impaired endothelial function in children suffering from the risk factors of atherosclerosis. 2. The evaluation of IMT in carotid arteries in patients with growth hormone deficiency showed a more advanced degree of atherosclerotic changes in this group compared to healthy controls. 3. Ultrasonographic evaluation of premature atherosclerosis in children with growth hormone deficiency is a basis for the future estimation of positive effects of the replacement therapy.

[Left ventricular mass and function in growth hormone deficient children and adolescents before and after one year of recombinant human growth hormone (GH) replacement therapy]. / Masa i funkcja lewej komory serca u dzieci i mlodziezy z niedoborem hormonu wzrostu przed leczeniem i po 12 miesiacach leczenia substytucyjnego hormonem wzrostu (rhGH).

UNLABELLED: A total of 25 patients (10 girls and 15 boys) aged 8.1-16.9 years (mean 13.3+/-1.8 years), height 1.15-1.61 m (mean 1.4+/-0.1 m), body area 0.84-1.47 m2 (mean 1.14+/-0.18 m2) were examined in our study. After 12-month--rhGH therapy, 23 children (9 girls and 14 boys) were re-evaluated. Twenty two healthy and slim children (11 girls and 11 boys) aged 6.6-16 years (mean 12,6+/-2.7 years), height 1.33-1.8 m (mean 1.58+/-0.16), body area 0.93-1.8 m2 (mean 1.38+/-0.3 m2) with a family history without atherosclerosis and cardiovascular diseases constituted controls. Mass and function of LV were evaluated by means of M-mode and 2D echocardiography and the Doppler method with simultaneous 2D picture recording. Systolic function parameters (SF and EF) were normal in each patient before therapy. LV systolic fraction (SF) equaled on average 35.4+/-4.5 % in the examined group and 36.7+/-3.9 % in controls. LV ejection fraction (EF) was on average 65.1+/-5.9 % in the examined group and 67.9+/-6.4 % in controls. The differences noted were not statistically significant. After a year-rhGH therapy, SF and EF were within a normal range in each patient. SF was on average 35.9+/-3.6% in the examined group and 36.7+/-3.9% in controls. EF was on average 65.7+/-4.6% in the examined group and 67.9+/-6.4% in controls. The differences were not statistically significant. SF and EF did not differ before and after rhGH therapy. LV mass indexed by body superficial area (LVA/BSA) equaled 68.3+/-18.6 g/m2 before therapy and did not differ significantly in comparison with controls (68.2+/-15.5 g/m2). After a year-GH therapy, LV/BSA was significantly higher when compared to LV/BSA mass before therapy (78.2+/-14.9 g/m2 vs 68.3+/-18 6 g/m2, p<0.05). After a year-GH therapy LV/BSA mass was significantly higher in comparison with LV/BSA mass before therapy (78.2+/-14.9 g/m2 vs 68.3+/-18.6 g/m2, p< 0.05). Before therapy, IVRT parameter was found significantly extended in comparison with controls (70.8+/-14.2 vs 64.1+/-8.5 ms, p<0.05). Other parameters characterising LV diastolic function were not significantly different between the groups. After a year-GH therapy, IVRT parameter was still extended in comparison with controls (72.3+/-9.2 vs 64.1+/-8.5 ms, p<0.05). No significant differences were observed with regard to IVRT before and after therapy. CONCLUSION: 1. A significant extension of isovolumetric relaxation time (IVRT) was proved in children with GH deficiency, which may suggest an impaired diastolic function of the heart left ventricle. 2. 12-month-rhGH replacement therapy causes an increase in the left ventricle mass when compared to the values before therapy, whereas isovolumetric relaxation time remains still longer. 3. Children with GH deficiency should have their circulatory system monitored to observe the dynamics of the left ventricle functional disorders.

[Selected adhesion molecules: sICAM-1 and sVCAM-1 as markers of endothelial dysfunction in diabetic children and adolescence]. / Wybrane czasteczki adhezyjne: slCAM-1 oraz sVCAM-1 jako markery dysfunkcji sródblonka u dzieci i mlodziezy chorych na cukrzyce typu 1.

UNLABELLED: Atherosclerotic process is accelerated in children with atherosclerosis risk factors, such as type 1 diabetes. Infiltration of the vessel wall by monocytes and lymphocytes, which starts atherosclerotic process, takes place under influence of adhesion molecules. Adhesion molecules play an important role in the first stage of atherosclerosis, and it is suggested that expression of adhesion molecules in children can be greater than in adults. The aim of the study was to evaluate the concentration of soluble forms of adhesion molecules slCAM-1 and sVCAM-1 in children and adolescents with type 1 diabetes. The concentration of adhesion molecules was additionally assessed depending on metabolic compensation, complications, diabetes duration and family history of cardiovascular disease. MATERIAL AND METHODS: The study was carried out in 28 children and adolescents with type 1 diabetes, aged 10.5-18 years (mean 15.3), with diabetes duration 5-15 years (8.1); mean HbA1c level during last six months was 6-11.4% (8.2%). Control group included 16 healthy, slim children aged 11-18 years (15.5). slCAM-1 and sVCAM-1 levels were assessed by means of immunoenzymatic methods (Parameter Human soluble lCAM-1 Immunoassay, Parameter Human soluble VCAM-1 Immunoassay, R&D Systems). RESULTS: slCAM-1 concentration in diabetic children was 305 +/- 71 ng/dl and was significantly higher than in controls--262.1 +/- 59 ng/dl (p = 0.04). sVCAM-1 concentration in diabetic children was 499.5 +/- 162 ng/dl and did not differ from the controls--446.3 +/- 95 (ns). In 5 children with positive family history of cardiovascular disease we found significantly higher slCAM-1 level: 323 +/- 72 ng/dl vs 244 +/- 30 ng/dl in children with negative family history (p < 0.05). The level of slCAM was slightly higher in ill children with worse metabolic compensation (314 +/- 90 ng/dl in group with HbA1c > 8%, 322 +/- 84 ng/dl in group with HbA1c < 8% but > 7%, and 285 +/- 68 ng/dl in group with HbA1c < 7%). We found a significant correlation between HbA1c and slCAM-1 (r = 0.39, p = 0.014) as well as between BMI and sVCAM-1 (r = 0.39, p = 0.044). CONCLUSIONS: 1. Elevated level of slCAM-1 in young diabetic patients correlates with metabolic compensation and positive family history of cardiovascular diseases. 2. sVCAM-1 level in diabetic children correlates significantly positively with body mass index (BMI). 3. Evaluation of adhesion molecules levels can be useful tool in the observation of the dynamic development of early phases of atherosclerotic process in young patients with type 1 diabetes.