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Journal Article 2016; 37(3): 217-225 PubMed PMID: 27618601 Citation  Keywords:  Adolescent, Animals, Apoptosis:radiation effects, Capillaries:radiation effects, Cell Proliferation:radiation effects, Child, Collagen:radiation effects, Female, Fibroblasts:radiation effects, Humans, Ligaments:radiation effects, Lung:radiation effects, L.   

OBJECTIVES: In this paper we study effects of irradiation to pulmonary tissue on a micro and ultrastructural level to get insights into the dynamics of morphological changes and associated post-radiative physiological conditions.

METHODS: Animal and human pulmonary tissue with and without radiation damage was subject to light, transmission, scanning and polarization microscopy and morphometric evaluation.

RESULTS: The present investigations on the influence of irradiation on experimental and human lung tissue demonstrate that complex changes are induced in the cells which are essential for mucociliary clearance. These changes are a shortage of alveolar macrophages, cell apoptosis, proliferation of collagen ligament in the barrier of gaseous exchange, retraction of endothelial lining of capillaries and significant broadening of the gaseous exchange barrier, resulting in serious damage for the O2 and CO2 exchange.

CONCLUSIONS: These changes at microscopic, cellular, and ciliary level trigger conditions for various diseases of the respiratory system, which is further assessed by a simultaneous computer aided estimation of ciliary function. With the concurrent world-wide increase of respiratory diseases, these findings are important knowledge for the clinical practice....

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Comparative Study 2016; 37(1): 65-69 PubMed PMID: 26994388 Citation  Keywords:  Adolescent, Adult, Aged, Case-Control Studies, Child, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Membrane Transport Proteins:genetics, Middle Aged, Protein Tyrosine Phosphatase, Non-Receptor Type 22:genetics, Receptors, Immunologic.   

BACKGROUND: Numerous genetic studies revealed several susceptibility genes of autoimmune thyroid diseases (AITD), including CTLA4, PTPN22 and FCRL3. These immune-modulating genes are involved in genetic background of AITD among children and adult patients. However, possible age-related differences in overexpression of these genes remain unclear.

PURPOSE: The goal of this single centre cohort study was evaluation of expression levels of three (3) genes CTLA4, PTPN22 and FCRL3 in adult patients and children with autoimmune thyroiditis.

METHODS: A total of 47 patients--24 adults (mean age--47.7 years) and 23 children (mean age--12.4 years) with autoimmune thyroiditis were assessed for the level of expression of CTLA4, PTPN22 and FCRL3 genes, utilizing ABI PRISM' 7500 Sequence Detection System (Applied Biosystem, Foster City, CA, USA).

RESULTS: The overexpression of PTPN22 (mean RQ = 2.988) and FCRL3 (mean RQ = 2.544) genes were confirmed in adult patients with autoimmune thyroiditis, at the same time the expression level of CTLA4 gene was significantly decreased (mean RQ = 0.899) (p < 0.05). Similar discrepancies were not observed in children with autoimmune thyroiditis in whom overexpression of all three genes--CTLA4, PTPN22 and FCRL3--was observed. Differences in CTLA4 and FCRL3 genes expression levels in patients with autoimmune thyroiditis were found depending on the age, with increased expression levels of CTLA4 (mean RQ = 3.45 1) and FCRL3 (mean RQ = 7.410) in children when compared to adults (p < 0.05) (Mann-Whitney's U-test). There were moderate negative linear correlations between two genes in question (CTLA4 and FCRL3) expression level and patients' age [correlation coefficient (r) = -0.529 (p < 0.0002) and -0.423 (p < 0.0032), respectively; Spearman's rank correlation test].

CONCLUSION: Our results are consistent with the hypothesis that there are few age-dependent genetic differences as regards autoimmune thyroiditis in adults and children. Accordingly, CTLA4 and FCRL3 genes overexpression may play an important role in children suffering from autoimmune thyroiditis....

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Journal Article 2016; 37(1): 29-32 PubMed PMID: 26994382 Citation  Keywords:  Adolescent, Attention Deficit Disorder with Hyperactivity:drug therapy, Basal Ganglia:abnormalities, Brain:abnormalities, Central Nervous System Stimulants:therapeutic use, Child, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging, Male, .   

: We discussed the cross section studies and the meta-analysis of published data in children and adolescents with ADHD (both drug naive and receiving stimulant medications), in comparison with healthy children and adolescents of the same age. In children and adolescents with ADHD the deceleration of the maturation dynamics of discrete CNS structures is found, volume reduction and decreased grey matter in prefrontal and occipital regions, which is accompanied by reverse asymmetry of the basal ganglia volume (putamen, nucleus caudate). The above mentioned developmental characteristics are valid only for the ADHD children, who have not been treated by stimulant medications. The stimulant treatment eliminates the mentioned changes into various extend. These developmental changes of CNS structures volume are missing in girls....

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Journal Article 2015; 36(5): 504-510 PubMed PMID: 26707052 Citation  Keywords:  Adolescent, Birth Weight, Blood Glucose:metabolism, Body Mass Index, C-Peptide:metabolism, Case-Control Studies, Child, Diabetes, Gestational:epidemiology, Female, Glucose Intolerance:epidemiology, Glucose Tolerance Test, Hemoglobin A, Glycosylated:metabo.   

OBJECTIVES: The study was undertaken to assess the selected carbohydrate parameters in children exposed to gestational diabetes in utero.

METHODS: 50 children exposed to gestational diabetes were compared with 46 control subjects. Anthropometric parameters of a newborn were obtained from the medical records. In all participants height, body mass, waist and hip circumferences were measured; BMI, WHR and WHtR were calculated. Values of fasting glucose, insulin, C-peptide and HbA1c were measured and HOMA2-IR, HOMA2-S, HOMA2-B were calculated. In obese children (BMI ≥95th percentile) OGTT was performed.

RESULTS: The prevalence of overweight/obesity in the study group was 38%, in the control group 41% (p=0.19). Higher fasting glucose level (p=0.02) and HbA1c (p=0.00004) were found in the study group comparing to the control. In children exposed to GDM in utero a positive correlation of fasting insulin and WHR (Rs=0.31, p=0.028) as well as significantly lower HOMA2-B (p=0.03) were observed. In the study group higher HOMA2-IR (p=0.0002) and HOMA2-B (p=0.0000039) and also lower HOMA2-S (p=0.0002) were observed among participants with overweight/obesity comparing to children with normal body weight. In the study group a correlation of HOMA2-IR and SD of the birth weight was found (Rs=0.28, p=0.049).

CONCLUSIONS: Children exposed to gestational diabetes in utero, in spite of similar prevalence of overweight/obesity comparing to their non-exposed peers, could have higher risk of glucose intolerance and diabetes mellitus in future. Towards observed decreased insulin sensitivity and compensatory increase in insulin secretion, prevention of overweight and obesity in this group seems to be essential....

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Journal Article 2015; 36(5): 458-464 PubMed PMID: 26707047 Citation  Keywords:  Adolescent, Autoantibodies:immunology, Candida albicans, Candidiasis:immunology, Carrier State:immunology, Child, Child, Preschool, Cross Reactions, Female, Ghrelin:immunology, Growth Disorders:immunology, Helicobacter Infections:immunology, Helicobacter .   

OBJECTIVES: Many of peptides synthesized in gastrointestinal tract (GI) and adipose tissues, regulate growth and food intake. The GI microflora is an antigenic source. Based on the molecular mimicry hypothesis, intestinal microbe-derived antigens may trigger the production of autoantibodies cross-reacting with some neuropeptides.

DESIGN: The aim of the study was to assess whether in idiopathic short stature (ISS) children with Candida albicans (C.albicans) colonisation and/or Helicobacter pylori (H.pylori) infection the autoantibodies (in positive levels) against selected neuropeptides [anti-NP Abs(+)]: ghrelin, leptin, orexin A, αMSH are more prevalent than in Controls.

SETTING: The study group comprised 64 children with ISS and 36 children with normal height (Controls). In each child, IgG antibodies against H.pylori, ghrelin, leptin, orexin A and αMSH were assessed in serum, while presence of C.albicans - in stool samples.

RESULTS: The higher prevalence of anti-NP Abs(+) in ISS children with C.albicans and/or H.pylori than in normal height children with the colonization in question (34.4% vs 21.1%, p<0.01) was found. The prevalence of anti-NP Abs(+) in groups of children without C.albicans and H.pylori were low, anti-NP Abs(+) were detected in 9.4% of ISS children only, while in Controls they were not found.

CONCLUSIONS: In short children with C.albicans and/or H.pylori the incidence of autoantibodies against selected neuropeptides is high. It probably is connected with molecular mimicry between antigens of these microbiota and the mentioned peptides. It is tempting to speculate that presence of cross-reacting autoantibodies against regulatory neuropeptides may results in worse growth velocity. However, further studies are necessary to elucidate this issue....

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Journal Article 2015; 36(5): 452-457 PubMed PMID: 26707046 Citation  Keywords:  Adolescent, Adult, Aged, Anodontia:genetics, Case-Control Studies, Child, Czech Republic, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Mutation, PAX9 Transcription Factor:genetics, Polymorphism.   

OBJECTIVES: Tooth agenesis is one of the most common developmental anomalies in humans. Genetic and environmental factors may be of etiological importance in this condition. Among genes involved in tooth morphogenesis, mutations in PAX9, MSX1, AXIN2, WNT10a, and EDA genes have been associated with tooth agenesis. The aim of our study was to investigate the relationship between the PAX9 gene variants and tooth agenesis in the Czech population.

METHODS: The selected regions of the PAX9 gene were analysed by direct sequencing and compared with the reference sequence from the GenBank online database (NCBI).

RESULTS: We found several novel variants in the PAX9 gene, e.g. insertion g.5100_5101insC (rs11373281) with simultaneous substitution g.5272C>G (rs4904155) in exon 1, and mutation g.10934C>T (Gly203Gly, rs61754301) in exon 3. In subjects with full dentition we observed polymorphisms g.10276A>G (rs12882923) and g.10289A>G (rs12883049) in IVS2 (intervening sequence 2) previously related to tooth agenesis in Polish study.

CONCLUSIONS: In our study we excluded a direct effect of rs12882923 and rs12883049 polymorphisms on the dental agenesis in the Czech population. All described PAX9 genetic variants were present both in patients with tooth agenesis and controls. We expect that tooth agenesis in our cohort of patients is caused by mutations in regions different from PAX9 exons analyzed in our study....

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Journal Article 2015; 36(4): 348-353 PubMed PMID: 26454490 Citation  Keywords:  Adolescent, Body Height:drug effects, Child, Dwarfism:drug therapy, Female, Growth Hormone:administration & dosage, Human Growth Hormone:deficiency, Humans, Male, Neural Networks (Computer), Outcome Assessment (Health Care):methods, Recombinant Proteins,.   

INTRODUCTION: The leading method for prediction of growth hormone (GH) therapy effectiveness are multiple linear regression (MLR) models. Best of our knowledge, we are the first to apply artificial neural networks (ANN) to solve this problem. For ANN there is no necessity to assume the functions linking independent and dependent variables. The aim of study is to compare ANN and MLR models of GH therapy effectiveness.

MATERIAL AND METHODS: Analysis comprised the data of 245 GH-deficient children (170 boys) treated with GH up to final height (FH). Independent variables included: patients' height, pre-treatment height velocity, chronological age, bone age, gender, pubertal status, parental heights, GH peak in 2 stimulation tests, IGF-I concentration. The output variable was FH.

RESULTS: For testing dataset, MLR model predicted FH SDS with average error (RMSE) 0.64 SD, explaining 34.3% of its variability; ANN model derived on the same pre-processed data predicted FH SDS with RMSE 0.60 SD, explaining 42.0% of its variability; ANN model derived on raw data predicted FH with RMSE 3.9 cm (0.63 SD), explaining 78.7% of its variability.

CONCLUSION: ANN seem to be valuable tool in prediction of GH treatment effectiveness, especially since they can be applied to raw clinical data....

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Case Reports 2015; 36(4): 306-310 PubMed PMID: 26454484 Citation  Keywords:  Adolescent, Child, Preschool, Female, Humans, Hyponatremia:drug therapy, Male, Sodium:blood, Tuberculosis, Meningeal:complications,.   

: Cerebral salt wasting syndrome (CSWS) is characterized by severe natriuresis and volume depletion in the presence of cerebral pathology. In literature, there are few reports about tuberculous meningitis and cerebral CSWS. In this article, we report two tuberculous meningitis cases with CSWS and present a review of the literature on this topic. Cerebral salt wasting diagnosis was based on hyponatraemia associated with high urinary sodium excretion and inappropriately high urine output in the presence of dehydration. Treatment was made with sodium-fluid replacement plus fludrocortisone therapy in both cases. In agreement with the literature we argue that cerebral salt wasting syndrome might be more common than the syndromes of inappropriate antidiuretic hormone secretion (SIADH) in cerebral disorders. Differentiating the cerebral salt wasting syndrome from the SIADH is very important because unrecognized cerebral salt wasting syndrome can lead to inadequate management and result in unnecessary hyponatremia-related morbidity. The electrolyte and hydration status of patients should be monitored closely in patients with tuberculous meningitis....

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