Artur Bossowski

Publications of Artur Bossowski

• [Polymorphism rs9939609 of FTO gene is related to the body mass index in children from podlaskie voievodship.]

  Authors: Magdalena Tercjak-Rećko, Włodzimierz Luczyński, Paweł Bernatowicz, Grzegorz Zalewski, Małgorzata Rembińska, Urszula Lachowska, Przemysław Rećko, Paweł Suchoń, Marcin Czaban, Justyna Sokal, Anna Kopalińska, Zuzanna Pajer, Karolina Bogdanowicz, Jacek Nikliński, Artur Bossowski

  Medycyna wieku rozwojowego. 01/2012; 16(1):53-60.

  Introduction: The presence of obesity and the features of metabolic syndrome plays a predictive role in cardiovascular diseases (CVD) in adults. It seems reasonable to seek new risk factors in theIntroduction: The presence of obesity and the features of metabolic syndrome plays a predictive role in cardiovascular diseases (CVD) in adults. It seems reasonable to seek new risk factors in the development of CVD. Defining the genetic background of obesity could help to select patients from a high risk group and help to introduce prevention and treatment, which, in consequence, lead to the lowering of morbidity and mortality. One of the genes probably related to the body weight is the Fat Mass and Obesity Associated Gene (FTO). The aim: of the study was an attempt to assess the relationship between the FTO polymorphism rs9939609 and body mass index in children from Podlaskie voievodship. Material and methods: 405 children aged 4-18 were selected for the study. The examination included body mass index, waist circumference, blood pressure and lipid profile analysis. FTO rs9939609 polymorphism was assessed using a discrimination allele method with the application of ABI 7900HT Fast Real-Time PCR System. Results: FTO rs9939609 polymorphism was related to the standarized body mass index and the AA genotype carriers had a higher risk of obesity. This polymorphism was also associated with waist circumference, systolic blood pressure and triglycerides concentration. It was not correlated with diastolic blood pressure and total HDL- and LDL-cholesterol concentrations. Conclusions: Our results demonstrate that rs9939609 FTO gene polymorphism is related to the body mass index in children. Our results should be confirmed in studies on a large cohort of healthy Polish children.

• Cytometric evaluation of intracellular IFN-γ and IL-4 levels in thyroid follicular cells from patients with autoimmune thyroid diseases.

  Authors: Artur Bossowski, Jerzy Harasymczuk, Anna Moniuszko, Anna Bossowska, Maciej Hilczer, Karol Ratomski

  Thyroid research. 09/2011; 4:13.

  ABSTRACT: In recent few years is underlined that altered balance of pro- and anti-inflammatory cytokines play an important role in the pathogenesis of AITD.The aim of this study was to estimateABSTRACT: In recent few years is underlined that altered balance of pro- and anti-inflammatory cytokines play an important role in the pathogenesis of AITD.The aim of this study was to estimate intracellular INF-γ and IL-4 levels in thyroid-infiltrating lymphocytes and thyrocytes isolated from thyroid tissues in 54 adolescent patients aged 8-21 years, with Graves' disease (GD; n = 18), Hashimoto's thyroiditis (HT; n = 18) and non-toxic multinodular goiter (NTMG; n = 18). Fresh thyroid tissues were taken on culture medium RPMI -1640, it was mechanically prepared. In next step were added cell activators -12- myristate 13- the acetate (PMA) and Ionomycin as well as the inhibitor of transportation of proteins - Breferdin A. They were cultured 24 hours in 50 ml flasks at 37°C in a 5-95% CO2-air water-saturated atmosphere. After that, thyrocytes were identified by mouse mAb directed against human TPO epitope 64 conjugated with rabbit anti-mouse antibodies IgG (Fab')2 labeled by FITC. After incubation at room temperature to each of samples added reagent A fixative the cellular membrane. In next step into the cell suspensions were added reagent B to permeabilization of cellular membrane and specific anti-IL-4-PE or anti-IFN-γ-PE mAbs. Identification of intracellular cytokines in T lymphocytes was performed in the same procedure with application of anti-CD4-PerCP and anti-CD8-PerCP mAbs specific for T lymphocytes. The cells were analyzed in a flow cytometry (Coulter EPICS XL). In examined group of patients with GD we observed statistically significant higher mean percentage of cells with phenotype CD4+IL-4 (p < 0.05; p < 0.025), CD8+IL-4 (p < 0.033; p < 0.01) and TFCs-IL-4+ (p < 0.05; p < 0.01) in comparison to patients with HT and NTMG. The analysis of mean percentages of positive TILs and TFCs with intracellular INF-g levels in patients with HT revealed statistically significant increase percentage of CD4+INF-γ (p < 0.04; p < 0.001), CD8+ INF-γ (NS; p < 0.025), TFCs+INF-γ (p < 0.03; p < 0.001) cells in comparison to the percentage of positive cells from patients with GD and NTMG. We conclude that human thyrocytes in autoimmune thyroid disorders could be a source of cytokine production and that their activation influences local interaction with T lymphocytes inflowing to the thyroid gland.

• [Changes in the cardiovascular system in selected endocrinopathies in children].

  Authors: Kornel Semeran, Artur Bossowski

  Pediatric endocrinology, diabetes, and metabolism. 01/2011; 17(1):42-7.

  Hormones have influence on many tissues and organs including the cardiovascular system. This article analyzes fluctuations that happen in a child's cardiovascular system in selected endocrinopathies.Hormones have influence on many tissues and organs including the cardiovascular system. This article analyzes fluctuations that happen in a child's cardiovascular system in selected endocrinopathies. We are pointing out the higher risk, in the course of diabetes, of development of arterial hypertension and atherosclerosis including participating mechanisms in their pathogenesis - disorders of the lipid metabolism, hiperinsulinaemia, insulin resistance or/and autonomic neuropathy. We are describing how the increased and reduced action of thyroid hormones on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangement. In the article, we are signaling also that the cardiovascular consequences of cortisol excess are elevation of blood pressure, obesity, hyperinsulinemia and/or dyslipidemia. This review analyzes the relationship of cortisol excess to these cardiovascular risk factors and to putative mechanisms for hypertension. In reference to clinical studies we are describing how the deficiency of the growth hormone is connected with a development of risk factors of cardiovascular diseases. In conclusion we underlined that early diagnosis and proper treatment of illnesses of the endocrine system can protect our pediatric patients from serious cardiac complications in later years.

• [Endothelial progenitor cells as a new marker of endothelial function with respect to risk of cardiovascular disorders].

  Authors: Barbara Głowińska-Olszewska, Włodzimierz Luczyński, Artur Bossowski

  Postȩpy higieny i medycyny doświadczalnej (Online). 01/2011; 65:8-15.

  The discovery of endothelial progenitor cells (EPC), over a decade ago, has refuted the previous belief that vasculogenesis only occurs during embryogenesis. The results of several studies revealedThe discovery of endothelial progenitor cells (EPC), over a decade ago, has refuted the previous belief that vasculogenesis only occurs during embryogenesis. The results of several studies revealed altered number and impaired function of EPC in hyperlipidemia, hypertension, diabetes, obesity as well as in rheumatoid arthritis. The population of developmental age is characterized by higher counts of EPC compared to adults. However, among young patients with chronic disorders that affect the vascular system, the number of EPC decreases. The reduced circulating concentration of EPC has become a surrogate marker of endothelial function and has been implicated in the pathogenesis of many vascular diseases. This article aims to review the biology and pathophysiology of EPC in the conditions of cardiovascular risk factors. The potential possibilities of increasing EPC number and function as well as the use of EPC in the treatment of vascular pathology will also be discussed.

• Transformation of conventional T cells into regulatory T cells in children with metabolic syndrome.

  Authors: Włodzimierz Luczyński, Natalia Wawrusiewicz-Kurylonek, Artur Bossowski, Elżbieta Iłendo, Marek Hryszko, Adam Krętowski, Anna Stasiak-Barmuta

  Kardiologia polska. 01/2011; 69(12):1221-6.

  Much research has been done in the recent years to establish an association between obesity, metabolic syndrome and the immune system. Numerous data suggest that the decreased number and/or functionMuch research has been done in the recent years to establish an association between obesity, metabolic syndrome and the immune system. Numerous data suggest that the decreased number and/or function of regulatory T cells (Treg cells) can lead to chronic minimal inflammation present in patients with obesity and trigger formation of atherosclerotic plaque. To generate Treg cells from the peripheral blood in children meeting the diagnostic criteria of metabolic syndrome. A total of 25 children with metabolic syndrome and 25 controls were enrolled in the study. Peripheral blood was collected, CD4(+)/CD25(-) cells were separated and cultured for 4 weeks in the presence of a Treg expander (CD3/CD28) and interleukin-2. The expression of the transcription factor FoxP3 as a Treg marker was assessed before and after culture using reverse transcriptase polymerase chain reaction (RT-PCR) and flow cytometry. Before the culture we observed a slightly lower percentage of Treg cells in children with metabolic syndrome vs controls. After the culture we noted a significant increase in mRNA expression and in the percentage of FoxP3-positive cells. We observed no differences in the results between the children with metabolic syndrome and the controls. Our study shows that it is possible to generate Treg cells from peripheral blood of children with metabolic syndrome. In future, these findings could be used to develop a model of immunotherapeutic intervention for patients at risk of cardiovascular disease.

• [Generation of T regulatory cells in children with type 1 diabetes mellitus].

  Authors: Włodzimierz Luczyński, Natalia Wawrusiewicz-Kurylonek, Agnieszka Szypowska, Elżbieta Iłendo, Artur Bossowski, Adam Krętowski, Barbara Głowińska-Olszewska, Marek Hryszko, Maria Górska, Anna Stasiak-Barmuta

  Pediatric endocrinology, diabetes, and metabolism. 01/2011; 17(2):64-70.

  In spite of intensive research the pathogenesis of type 1 diabetes mellitus is not thoroughly understood. One of the ideas which currently has a great number of supporters is the theory of theIn spite of intensive research the pathogenesis of type 1 diabetes mellitus is not thoroughly understood. One of the ideas which currently has a great number of supporters is the theory of the participation of T regulatory cells in the mechanism of insufficient suppression of the immune response against pancreatic self -antigens. According to some authors, the infusion of T regulatory cells in autoimmune diseases could lead to long -term remission or even a complete cure. Aim of the study: The aim of our present study was to achieve T regulatory cells from conventional T lymphocytes isolated from a small amount of peripheral blood in children with type 1 diabetes mellitus and their comparison to the Tregs generated from the blood of control children. Additionally, we assessed the changes in the expression of selected genes essential for the function of these cells during Tregs generation. The examined group consisted of 20 children with type 1 diabetes mellitus, the control group consisted of 20 non -diabetic children. From the peripheral blood CD4+CD25 - cells were separated and cultured with T -reg expander and interleukin (IL) 2. Before and after the culture the cells were analysed according to the expression of transcription factor FoxP3 and other molecules/cytokines: OX40, 4 -1BB, GITR, ICOS -1, CTLA -4 and IFN -γ, IL -10 and TGF -β. We observed a significantly higher percentage of T regulatory cells after the culture (with no difference between diabetic and control children). Moreover, we observed a lower expression of mRNA for GITR molecule and a higher IL -10 expression in the cultures of diabetic children compared to the control ones. The cells cultured from the blood of control children were characterised by a higher increase in the expression of mRNA for ICOS -1 and a lower expression of mRNA for TGF -β in comparison to the cultures from diabetic children. The results of our investigations confirm the possibility of generating T regulatory cells from conventional T lymphocytes from peripheral blood of children with newly recognised type 1 diabetes mellitus.

• Overweight, obesity and features of metabolic syndrome in children with diabetes treated with insulin pump therapy.

  Authors: Włodzimierz Łuczyński, Agnieszka Szypowska, Barbara Głowińska-Olszewska, Artur Bossowski

  European journal of pediatrics. 12/2010; 170(7):891-8.

  There has been no specific evaluation of atherogenic risk factors in children with type 1 diabetes mellitus (T1DM) treated with continuous subcutaneous insulin infusion (CSII). We, therefore, studiedThere has been no specific evaluation of atherogenic risk factors in children with type 1 diabetes mellitus (T1DM) treated with continuous subcutaneous insulin infusion (CSII). We, therefore, studied the prevalence of overweight/obesity and metabolic syndrome among these patients. Five hundred children with T1DM treated with CSII and multiple daily insulin (MDI) regimen were included in the study. Anthropometric data/physical examination, data concerning diabetes, and a lipid profile were assessed in this group, and compared with respect to treatment method (CSII vs. MDI). Almost one-third (30.2%) of the children were overweight/obese. The body mass index (BMI) values at the time of the present evaluation were significantly higher in comparison with the BMI values 3-6 months after the diagnosis. Dyslipidemia was recognized in 51.6%, hypertension in 4.8%, and the metabolic syndrome in 3.2%. of the subjects. The overweight/obese children differed from their normal-weight counterparts with respect to metabolic control, the incidence of hypertension, dyslipidemia, and metabolic syndrome. The girls showed higher prevalence of overweight/obesity and higher BMI values compared to the boys. The children treated with CSII had the same prevalence of overweight/obesity, but a lower incidence of dyslipidemia, and a better metabolic control compared to the children treated with MDI regimen. Our study shows a high prevalence of overweight/obesity and dyslipidemia in children with T1DM including those treated with an insulin pump.

• Analysis of serum adiponectin, resistin and leptin levels in children and adolescents with autoimmune thyroid disorders.

  Authors: Artur Bossowski, Beata Sawicka, Mieczysław Szalecki, Alicja Koput, Jolanta Wysocka, Beata Zelazowska-Rutkowska

  Journal of pediatric endocrinology & metabolism : JPEM. 04/2010; 23(4):369-77.

  Leptin, adiponectin and resistin, mainly produced by adipocytes, play a major role in body weight regulation. Disturbances in the maintenance of normal body weight are found to occur also in thyroidLeptin, adiponectin and resistin, mainly produced by adipocytes, play a major role in body weight regulation. Disturbances in the maintenance of normal body weight are found to occur also in thyroid diseases. There is a close relationship of the changes in thyroid hormones with the contents of adipose tissue and adipocyte-secreted proteins regulating energetic metabolism in the body. The study objective was to analyze the levels of leptin, adiponectin and resistin in children with untreated Graves' disease, subclinical hypothyroidism in Hashimoto's thyroiditis and in children with simple goiter. The study involved 78 patients with Graves' disease (29 girls and 2 boys, aged 6-21 years, mean 15.2) and with Hashimoto's thyroiditis (30 girls and 2 boys, aged 9-18 years, mean 14.5). The control group consisted of adolescents with simple goiter (13 girls and 2 boys, aged 9-18 years, mean 14.8). The levels of leptin, adiponectin and resistin were determined using the ELISA method (R&D System, USA). Patients with untreated Graves' disease showed higher adiponectin level than the patients with hypothyroidism in Hashimoto's thyroiditis and in simple goiter (14.24 +/- 0.89 vs. 9.18 +/- 2.65, 10.15 +/- 2.5, p < 0.007, p < 0.01), but lower resistin level as compared to simple goiter and Hashimoto's thyroiditis (10.24 +/- 5.2 vs. 13.29 +/- 3.8, 12.2 +/- 2.8, p < 0.01, NS). The analysis of leptin levels revealed no significant differences between children with subclinical hypothyroidism and untreated Graves' disease (4.42 +/- 0.87 vs. 3.1 +/- 0.45 NS). In conclusion, we suggest that disturbances in thyroid hormones in thyroid diseases have an essential effect on the levels of adiponectin and resistin released by adipose tissue.

• The mRNA expression of pro- and anti-inflammatory cytokines in T regulatory cells in children with type 1 diabetes.

  Authors: Włodzimierz Łuczyński, Anna Stasiak-Barmuta, Agnieszka Juchniewicz, Natalia Wawrusiewicz-Kurylonek, Elzbieta Iłendo, Justyna Kos, Adam Kretowski, Maria Górska, Lech Chyczewski, Artur Bossowski

  Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society. 01/2010; 48(1):93-100.

  Type 1 diabetes mellitus (T1DM) is caused by the autoimmune-mediated destruction of insulin-producing beta cells in the pancreas. T regulatory cells (Tregs) represent an active mechanism ofType 1 diabetes mellitus (T1DM) is caused by the autoimmune-mediated destruction of insulin-producing beta cells in the pancreas. T regulatory cells (Tregs) represent an active mechanism of suppressing autoreactive T cells that escape central tolerance. The aim of our study was to test the hypothesis that T regulatory cells express pro- and anti-inflammatory cytokines, elements of cytotoxicity and OX40/4-1BB molecules. The examined group consisted of 50 children with T1DM. Fifty two healthy individuals (control group) were enrolled into the study. A flow cytometric analysis of T-cell subpopulations was performed using the following markers: anti-CD3, anti-CD4, anti-CD25, anti-CD127, anti-CD134 and anti-CD137. Concurrently with the flow cytometric assessment of Tregs we separated CD4+CD25+CD127dim/- cells for further mRNA analysis. mRNA levels for transcription factor FoxP3, pro- and anti-inflammatory cytokines (interferon gamma, interleukin-2, interleukin-4, interleukin-10, transforming growth factor beta1 and tumor necrosis factor alpha), activatory molecules (OX40, 4-1BB) and elements of cytotoxicity (granzyme B, perforin 1) were determined by real-time PCR technique. We found no alterations in the frequency of CD4+CD25highCD127low cells between diabetic and control children. Treg cells expressed mRNA for pro- and anti-inflammatory cytokines. Lower OX40 and higher 4-1BB mRNA but not protein levels in Treg cells in diabetic patients compared to the healthy children were noted. Our observations confirm the presence of mRNA for pro- and anti-inflammatory cytokines in CD4+CD25+CD127dim/- cells in the peripheral blood of children with T1DM. Further studies with the goal of developing new strategies to potentiate Treg function in autoimmune diseases are warranted.

• [The role of FTO gene polymorphism in the pathogenesis of obesity].

  Authors: Magdalena Tercjak, Włodzimierz Luczyński, Natalia Wawrusiewicz-Kurylonek, Artur Bossowski

  Pediatric endocrinology, diabetes, and metabolism. 01/2010; 16(2):109-13.

  Both environmental and genetic factors play a role in the pathogenesis of obesity. At present, researchers are examining the genetic background of overweight. Over 100 genes are suspected toBoth environmental and genetic factors play a role in the pathogenesis of obesity. At present, researchers are examining the genetic background of overweight. Over 100 genes are suspected to influence the obesity. One of those genes is FTO (fat mass and obesity-associated gene). In the manuscript, the relationship between FTO gene polymorphism (AA allele) and overweight, obesity and their consequences are discussed. It was proved, in studies on large number of people, that FTO gene polymorphism is related to higher body mass index, weight and abdominal circumference. Some authors showed that FTO gene polymorphism influences the food intake, energy expanditure and insulin resistance. The expression of FTO gene product was noticed in both, the peripheral as well as central nervous system (hypothalamus). It is possible that FTO gene product is involved in the DNA and RNA reparation and other metabolic processes, however, its function is not yet clear. The assessment of FTO gene polymorphism can allow us to separate patients with the tendency for higher weight. The elucidation of the role of FTO in the pathogenesis of obesity can result in the development of new therapeutic options for this epidemic of XXI century.

• [Asymmetric dimethylarginine (ADMA) in children with diabetes type 1].

  Authors: Barbara Głowińska-Olszewska, Włodzimierz Luczyński, Jolanta Jabłońska, Agnieszka Otocka, Bożena Florys, Artur Bossowski

  Pediatric endocrinology, diabetes, and metabolism. 01/2010; 16(3):137-41.

  Asymmetric dimethylarginine (ADMA), a naturally occurring product of asymmetric methylation of proteins, is an endogenous inhibitor of endothelial nitric oxide synthase. ADMA is now recognized as anAsymmetric dimethylarginine (ADMA), a naturally occurring product of asymmetric methylation of proteins, is an endogenous inhibitor of endothelial nitric oxide synthase. ADMA is now recognized as an independent marker of endothelial dysfunction and atherosclerosis. Data concerning ADMA level in type 1 diabetes (DM1) are controversial. The aim of the study was to evaluate ADMA level in children with DM1, without clinical evidence of vascular complications, with particular attention to additional cardiovascular risk factors (hypertension, obesity, hyperlipidemia). The study group included 72 children with DM1, aged mean 15±3 yrs (8-20 yrs), 33 boys and 39 girls, with diabetes duration time mean 6.6±3.5 yrs (1-14 yrs), HBA1c mean level 8.2±2.3% (5.6-15%). The control group consisted of 41 (19 boys and 22 girls) healthy children, aged mean--14.8±2.6 yrs, from 8 to 18 yrs, gender matched, with no family history of cardiovascular disease. ADMA level was determined in plasma using ELISA kit (DLD Diagnostica, Hamburg, Germany) ADMA level was similar in children with diabetes and in the control group: 0.69±0.33 vs. 0.7±0.27 μmol/L, ns. We did not find differences in ADMA level in diabetic children with the presence of additional diseases being cardiovascular risk factors. In the group of 13 children with hypertension ADMA level was the highest: 0.79±0.25 μmol/L, but the difference was statistically insignificant in comparison to children with diabetes without hypertension and in comparison to healthy controls. Children with DM1, without clinically evident vascular complications, have ADMA levels similar to healthy children. A possible relationship between ADMA and hypertension in these patients requires further investigation.

• [The role of T-regulatory cells in the pathogenesis of immunological disturbances accompanying obesity and atherosclerosis].

  Authors: Włodzimierz Luczyński, Artur Bossowski, Barbara Głowińska-Olszewska, Justyna Kos, Anna Stasiak-Barmuta

  Postȩpy higieny i medycyny doświadczalnej (Online). 01/2010; 64:156-60.

  Obesity and atherosclerosis, and their consequences, including cardiovascular disease, are plagues of the 21st century. Chronic inflammation, whose mechanism is not well understood, underlies theObesity and atherosclerosis, and their consequences, including cardiovascular disease, are plagues of the 21st century. Chronic inflammation, whose mechanism is not well understood, underlies the pathophysiological bases of both processes. T lymphocytes, macrophages, and the proinflammatory cytokines produced by these cells play key roles in the immunological disturbances accompanying obesity and atherosclerosis. It was recently shown that T-regulatory cells can play a role in these processes. T-regulatory cells are a small subpopulation of T cells which are responsible for inhibition of the immune response. In this review, experiments conducted in mice and human models on the role of diminished number and/or function of T-regulatory lymphocytes in the pathogenesis of immune disturbances accompanying obesity and atherosclerosis are discussed. The results of studies using T-regulatory cells to stabilize and decrease atherosclerotic lesions in blood vessel walls are also summarized. The results of experiments performed so far are encouraging and give some hope for the future use of T-regulatory cells in the therapy of obesity and atherosclerosis.

• [Overweight, obesity and metabolic syndrome in children with type 1 diabetes melllitus].

  Authors: Włodzimierz Luczyński, Agnieszka Szypowska, Artur Bossowski, Anna Ramotowska, Przemysław Rećko, Małgorzata Rembińska, Magdalena Tercjak, Bernadetta Blecharczyk, Urszula Lachowska, Paweł Suchoń, Karolina Wiśniewska, Paweł Bernatowicz, Barbara Głowińska-Olszewska

  Pediatric endocrinology, diabetes, and metabolism. 01/2010; 16(2):83-8.

  Obesity can be an additional risk factor for developing cardiovascular diseases in patients with diabetes. Aim of the study was the assessment of overweight, obesity and other elements of theObesity can be an additional risk factor for developing cardiovascular diseases in patients with diabetes. Aim of the study was the assessment of overweight, obesity and other elements of the metabolic syndrome in children with type 1 diabetes mellitus. 300 children treated with insulin at least one year were enrolled in the study. In the examined group anthropometric data, data concerned with diabetes and additional laboratory tests including risk factors for cardiovascular diseases were assessed. The median age of the examined group was 13.7 years. The body mass deficiency was noted in 0.66%, normal body mass in 71.6%, overweight in 15.3% and obesity in 12.3%. The abdominal obesity was noted in 16.0% of children. The rise in the body weight between 3-6 months from the beginning of the insulin therapy and the present assessment was statistically significant. Children with normal weight had a better metabolic control in comparison to children with overweight/obesity. Girls had a higher rise in body mass index values between the time of diagnosis and the present investigation compared to boys. Higher values of blood pressure or hypertension were noted in 16.6% of children. Altogether in 25.3% of children some dyslipidemia was observed. The metabolic syndrome criteria were noted in: 28.0% - one criterion, 13.0% - two criteria, and 0.3% - three criteria. The population of children with type 1 diabetes is characterized by high frequency of overweight/obesity, abdominal obesity, dyslipidemia and hypertension. The features of metabolic syndrome are less frequent. It is worthwhile to monitor the risk for development of cardiovascular diseases in this group of children.

• [Analysis of serum levels of ghrelin and obestatin in children and adolescents with autoimmune thyroid diseases.]

  Authors: Beata Sawicka, Artur Bossowski, Mirosława Urban, Mieczysław Szalecki, Jolanta Wysocka, Alicja Koput, Beata Zelazowska-Rutkowska, Jolanta Tobolczyk, Marcin Skrzydło, Franciszek Rogowski, Magdalena Luba

  Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologów Dziecięcych. 02/2009; 15(1):20-7.

  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 bioactiveIntroduction: 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, wesuggested thatdisturbances in thyroid hormones in thyroid diseases havean essential effecton changesofhormones controlled appetite: ghrelin (in hyperthyroidism) and obestatin (in hypothyroidism).

• [The role of lymphocytes and secrete cytokines in autoimmune thyroid diseases]

  Authors: Ewa Polkowska, Artur Bossowski

  Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologów Dziecięcych. 01/2009; 15(2):114-7.

  Grave's disease and autoimmune hypothyroidism represent the two main autoimmune thyroid diseases, where an immune response is directed against the thyroid gland. The essence of these diseases is lossGrave's disease and autoimmune hypothyroidism represent the two main autoimmune thyroid diseases, where an immune response is directed against the thyroid gland. The essence of these diseases is loss of tolerance of own tissues caused by malfunction of the T lymphocytes, which effect the production of antibodies reacting with particular cell structures and tissues. Cytokines participate in the induction and effector phase of the immune and inflammatory response and therefore play a critical role in the development of autoimmune thyroid diseases. Regulatory T cells take part in regulation of immune response and play a leading role in developing immune tolerance through active suppression.

• The activity of gastric ghrelin positive cells in obese patients treated surgically.

  Authors: Jacek Dadan, Hady Razak Hady, Robert Lukasz Zbucki, Paweł Iwacewicz, Artur Bossowski, Irena Kasacka

  Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society. 01/2009; 47(2):307-13.

  Ghrelin is a 28 amino acid peptide hormone regulating food intake and stimulating releasement of growth hormone. It is produced in a distinct endocrine call known as X/A - like cells. The mostGhrelin is a 28 amino acid peptide hormone regulating food intake and stimulating releasement of growth hormone. It is produced in a distinct endocrine call known as X/A - like cells. The most abundant source of this very important factor in energy homeostasis is gastric fundus. Regulatory mechanisms of ghrelin synthesis and secretion in physiological and pathological states are not discovered completely. The aim of our study was evaluation of the activity of gastric X/A-like cells in obese patients before and after the most popular surgical bariatric procedures - Roux - Y Gastric Bypass (RYGB) and Laparoscopic Adjustable Gastric Banding (LAGB). Obese patients in number 18 took part in the study. LAGB was performed in 7 patients and RYGB in 11 patients. Peripheral blood was taken from each patient before operation and first day, seventh day, one month and three months after surgery. Ghrelin level was determined by RIA technique. The specimen of stomach was taken from circular stapler after gastrojejunostomy during RYGB and immunohistochemical study of gastric mucosa, using the EnVision method and specific monoclonal antybodies against ghrelin was performed. The intensity of ghrelin-immunoreactivity in X/A-like cells was analyzed using Olympus Cell D image analysis system. Efficiency of bariatric procedures was estimated by EWL- excess weight loss. We observed very strong immunohistochemical reactions of gastric X/A-like cells, accompanied by lower ghrelin plasma concentration, in comparison to the control group. LAGB procedure induced increase of ghrelin plasma level while RYGB procedure induced decrease of this hormone. The main finding of the present study is the hypoactivity of gastric X/A-like cells in obese patients in comparison to the control group.

• [Precocious puberty due to hypothalamic hamartoma.]

  Authors: Magdalena Luba, Artur Bossowski, Justyna Kulikowska, Mirosława Urban, Maria Szarras-Czapnik, Robert Rutkowski, Tomasz Parol, Tomasz Gasiorek, Beata Sawicka, Marcin Skrzydło

  Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologów Dziecięcych. 02/2008; 14(4):257-61.

  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 organicIntroduction: 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.

• [Identification of the CD40 (CD154) ligand expression on the surface of conglomerate platelet-monocyte in children with the metabolic syndrome.]

  Authors: Mirosława Urban, Remigiusz Urban, Irena Krasowska, Barbara Głowińska-Olszewska, Anna Stasiak-Barmuta, Artur Bossowski, Alicja Koput

  Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologów Dziecięcych. 01/2008; 14(2):71-5.

  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 theIntroduction: 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.

• Analysis of apoptotic markers Fas/FasL (CD95/CD95L) expression on the lymphocytes in patients with acute coronary syndrome.

  Authors: Anna Bossowska, Artur Bossowski, Bogdan Galar

  Kardiologia polska. 08/2007; 65(8):883-9; discussion 890-2.

  BACKGROUND: Acute coronary syndromes are caused by the rupture or erosion of an atherosclerotic plaque which by secreting a variety of proteases is capable of degrading pericellular matrix componentsBACKGROUND: Acute coronary syndromes are caused by the rupture or erosion of an atherosclerotic plaque which by secreting a variety of proteases is capable of degrading pericellular matrix components induces death of endothelial cells. This mechanism plays the main role in apoptosis. AIM: To estimate expression of apoptotic Fas/FasL (CD95/CD95L) on lymphocytes in the peripheral blood. METHODS: We examined patients with acute myocardial infarction (n=18, mean age 62+/-8 years), in unstable angina pectoris (n=31, mean age 62+/-10 years) and in a control group (n=20, mean age 62+/-9 years) without coronary risk factors and inflammatory condition. All investigations of Fas/FasL were performed by flow cytometry. Inflammatory parameters and standard risk factors were investigated by standard methods (ELISA). RESULTS: The analysis revealed a higher expression of Fas and FasL molecules on the lymphocytes from patients with acute myocardial infarction (p<0.001, p<0.002) and unstable angina (p<0.01, p<0.02) compared to the control group. Moreover we found a statistically significant positive correlation between the level of LDL cholesterol and hypertension and prevalence of CD95 (p<0.001, p<0.01) and CD95L (p<0.02, p<0.03) in patients with acute myocardial infarction. CONCLUSIONS: A higher expression of apoptotic molecules (Fas and FasL) on lymphocytes occurs before the onset of acute ischaemia and contributes to the plaque rupture and acute coronary syndrome. Furthermore, antiapoptotic therapy leads to plaque stabilisation.

• [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]

  Authors: Artur Bossowski, Barbara Czarnocka, Krzysztof Bardadin, Mirosława Urban, Marek Niedziela, Jacek Dadan

  Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologów Dziecięcych. 01/2007; 13(2):63-70.

  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 ofApoptosis 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.