Bogdan Marek

Purpose: The aim of the study was to verify hypotheses: Are transforming growth factors TGFβ1-3, their receptors TGFβI-III, and intracellular messenger proteins Smad1-7 involved in the pathogenesis of kidney cancer? What is the expression of genes of the TGFβ/Smads pathway in renal cell carcinoma (RCC) tissues, peritumoral tissues (TME; tumor microenvironment), and in normal kidney (NK) tissue?. Methods: Twenty patients with RCC who underwent total nephrectomy were included into the molecular analysis. The mRNA expression of the genes was quantified by RT-qPCR. Results: The study showed that the expression of the genes of TGFβ/Smads pathway is dysregulated in both RCC and the TME: TGFβ1, TGFβ3 expression is increased in the TME in comparison to the NK tissues; TGFβ2, TGFβ3, TGFβRI, TGFβRIII, Smad1, Smad2, Smad3, and Smad6 are underexpressed in RCC comparing to the TME tissues; TGFβRI, TGFβRIII, and Smad2 are underexpressed in RCC in comparison to the NK tissues. Conclusion: On the one hand, the underexpression of the TGFβ signaling pathway genes within the malignant tumor may result in the loss of the antiproliferative and pro-apoptotic activity of this cytokine. On the other hand, the overexpression of the TGFβ/Smads pathway genes in the TME than in tumor or NK tissues most probably results in an immunosuppressive effect in the space surrounding the tumor and may have an antiproliferative and pro-apoptotic effect on non-neoplastic cells present in the TME. The functional and morphological consistency of this area may determine the aggressiveness of the tumor and the time in which the neoplastic process will spread.

The effects of specific cytokines produced by T cell subsets (such as Th1, Th2, and newly discovered Th17, Treg, Tfh, or Th22) are diverse, depending on interactions with other cytokines, distinct signaling pathways, phase of the disease, or etiological factor. The immunity equilibrium of the immune cells, such as the Th1/Th2, the Th17/Treg, and the Th17/Th1 balance is necessary for the maintenance of the immune homeostasis. If the balance of the T cells subsets is damaged, the autoimmune response becomes enhanced which leads to autoimmune diseases. Indeed, both the Th1/Th2 and the Th17/Treg dichotomies are involved in the pathomechanism of autoimmune diseases. The aim of the study was to determine the cytokines of Th17 lymphocytes as well as the factors modulating their activity in patients with pernicious anemia. The magnetic bead-based immunoassays used (Bio-Plex) allow simultaneous detection of multiple immune mediators from one serum sample. In our study, we showed that patients suffering from pernicious anemia develop the Th1/Th2 imbalance with a quantitative advantage of cytokines participating in Th1-related immune response, the Th17/Treg imbalance with a quantitative advantage of cytokines participating in Treg-related response, as well as the Th17/Th1 imbalance with a quantitative predominance of cytokines participating in Th1-related immune response. Our study results indicate that T lymphocytes and their specific cytokines play an role in the course of pernicious anemia. The observed changes may indicate the immune response to pernicious anemia or be an element of the pernicious anemia pathomechanism.

Introduction: Osteoporosis is the most common metabolic bone disease. Vitamin D deficiency, often associated with osteoporosis and other bone tissue disorders, is spread worldwide. Among other factors, obesity seems to be a major cause of the growing hypovitaminosis D. Aim: The aim of the study was to assess the correlation between body mass index (BMI) and vitamin D concentrations in postmenopausal women diagnosed with osteoporosis. Materials and methods: Sixty nine women with postmenopausal osteoporosis were included in study. Dual- energy X-ray absorptiometry and vitamin D measures were performed in all patients. Three groups, BMI- dependent, were distinguished: normal weight, overweight and obesity group. Results: The vitamin D deficiency was found in all women with postmenopausal osteoporosis. There was no correlation between BMI and vitamin D level. Conclusions: Vitamin D deficiency is frequent in population of patients diagnosed with postmenopausal osteoporosis, regardless of their BMI.

Introduction: Osteoporosis and obesity are considered civilisation diseases. Menopause is a time of increased bone resorption and increased mass of adipose tissue. Adipocytokines secreted by the adipose tissue are believed to be a potential factor in the pathogenesis of osteoporosis. Material and methods: The aim of this research was to assess leptin, adiponectin, and resistin secretion in obese postmenopausal women with osteoporosis and determine whether obesity might be a factor mitigating the risk of osteoporosis. The study involved 80 postmenopausal women with osteoporosis divided into groups: I with BMI of 30.0 34.9, obese; and II with BMI of 18–24.9, normoweight. Leptin, adiponectin and resistin concentrations were assessed, and bone mineral density (BMD) was measured in the L1-L4 section of the spine using the DXA densitometric method. Results: The results of the comparison of the two groups indicate a statistically significant dependence in groups regarding leptin secretion; the group of obese women demonstrated significantly higher concentrations. No differences between the groups were demonstrated for adiponectin or resistin secretion. Conclusions: Higher leptin concentration and a positive correlation with BMI was confirmed in obese postmenopausal women with osteoporosis. It was also demonstrated that BMD increases with growing BMI. No effect of obesity on the secretion of adiponectin or resistin in women with postmenopausal osteoporosis was found. From among the investigated adipocytokines, only leptin can be considered a bone tissue protective factor in postmenopausal women. Introduction: Osteoporosis and obesity are considered civilisation diseases. Menopause is a time of increased bone resorption and increased mass of adipose tissue. Adipocytokines secreted by the adipose tissue are believed to be a potential factor in the pathogenesis of osteoporosis. Material and methods: The aim of this research was to assess leptin, adiponectin, and resistin secretion in obese postmenopausal women with osteoporosis and determine whether obesity might be a factor mitigating the risk of osteoporosis. The study involved 80 postmenopausal women with osteoporosis divided into groups: I with BMI of 30.0 34.9, obese; and II with BMI of 18–24.9, normoweight. Leptin, adiponectin and resistin concentrations were assessed, and bone mineral density (BMD) was measured in the L1-L4 section of the spine using the DXA densitometric method. Results: The results of the comparison of the two groups indicate a statistically significant dependence in groups regarding leptin secretion; the group of obese women demonstrated significantly higher concentrations. No differences between the groups were demonstrated for adiponectin or resistin secretion. Conclusions: Higher leptin concentration and a positive correlation with BMI was confirmed in obese postmenopausal women with osteoporosis. It was also demonstrated that BMD increases with growing BMI. No effect of obesity on the secretion of adiponectin or resistin in women with postmenopausal osteoporosis was found. From among the investigated adipocytokines, only leptin can be considered a bone tissue protective factor in postmenopausal women.

Background: No previous study has investigated cardiometabolic risk factors in untreated patients with congenital adrenal hyperplasia (CAH). Methods: The study population consisted of 14 premenopausal women with previously untreated non-classic congenital adrenal hyperplasia (NC-CAH) and 20 matched healthy women. Apart from 17-hydroxyprogesterone and androgen levels, the outcomes of interest were glucose homeostasis markers, plasma lipids, plasma levels of uric acid, C-reactive protein, fibrinogen, homocysteine and 25-hydroxyvitamin D, as well as urinary albumin-to-creatinine ratio (UACR). Results: As expected, women with NC-CAH were characterised by higher levels of 17-hydroxyprogesterone and were more insulin-resistant than control women. The mean values of C-reactive protein, fibrinogen, homocysteine and UACR were higher while 25-hydroxyvitamin D levels were lower in subjects with NC-CAH. The investigated cardiometabolic risk factors correlated with androgen levels and insulin sensitivity. Conclusions: The obtained results suggest that the occurrence of NC-CAH in premenopausal women may increase cardiometabolic risk.

Introduction: The predominance of high-molecular-weight forms of prolactin in plasma is referred to as macroprolactinaemia. Unlike monomeric hyperprolactinaemia, no previous study has investigated cardiometabolic risk factors in subjects with elevated macroprolactin content. Material and methods: We studied two age-, weight-, and blood pressure-matched groups of premenopausal women: 11 women with macroprolactinaemia and 11 women with prolactin levels within the reference range. The outcomes of interest included: glucose homeostasis markers, plasma lipids, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D. Results: Circulating levels of hsCRP and 2-h postchallenge plasma glucose, as well as the homeostatic model assessment 1 of insulin resistance ratio, were higher, while levels of HDL cholesterol and 25-hydroxyvitamin D were lower in women with macroprolactinaemia than in women without elevated levels of prolactin. In women with elevated levels of big-big prolactin, values of hsCRP and 25-hydroxyvitamin D correlated with the degree of insulin resistance and, similarly to HDL cholesterol and 2-h postchallenge plasma glucose, with macroprolactin content. There were no differences between the study groups in concentrations of fasting glucose, total cholesterol, LDL cholesterol, triglycerides, uric acid, fibrinogen, and homocysteine. Conclusions: The obtained results indicate that young women with macroprolactinaemia seem to be characterised by slightly increased cardiometabolic risk. Introduction: The predominance of high-molecular-weight forms of prolactin in plasma is referred to as macroprolactinaemia. Unlike monomeric hyperprolactinaemia, no previous study has investigated cardiometabolic risk factors in subjects with elevated macroprolactin content. Material and methods: We studied two age-, weight-, and blood pressure-matched groups of premenopausal women: 11 women with macroprolactinaemia and 11 women with prolactin levels within the reference range. The outcomes of interest included: glucose homeostasis markers, plasma lipids, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D. Results: Circulating levels of hsCRP and 2-h postchallenge plasma glucose, as well as the homeostatic model assessment 1 of insulin resistance ratio, were higher, while levels of HDL cholesterol and 25-hydroxyvitamin D were lower in women with macroprolactinaemia than in women without elevated levels of prolactin. In women with elevated levels of big-big prolactin, values of hsCRP and 25-hydroxyvitamin D correlated with the degree of insulin resistance and, similarly to HDL cholesterol and 2-h postchallenge plasma glucose, with macroprolactin content. There were no differences between the study groups in concentrations of fasting glucose, total cholesterol, LDL cholesterol, triglycerides, uric acid, fibrinogen, and homocysteine. Conclusions: The obtained results indicate that young women with macroprolactinaemia seem to be characterised by slightly increased cardiometabolic risk.

Hypoglycaemia is a decrease in blood glucose concentration below the physiological level. It occurs in healthy people and in people with various diseases with inadequate secretion of insulin by beta cells, or deficiency of counterregulatory hormones secreted at the moment of hypoglycaemia. Hypoglycaemia is also associated with diabetes therapy, regardless of whether behavioural therapy, oral hypoglycaemic agents, or insulin are used. Distinguishing the causes of hypoglycaemia is the basis for taking appropriate therapeutic actions that protect patients against subsequent episodes of lowering blood glucose and complications caused by hypoglycaemia.

Introduction: The aim of the study was to determine the frequency of occurrence of antibodies participating in the development of endocrine diseases in patients with autoimmune haematopoietic disease, thus documenting the potential suitability of specific diagnostic and screening tests. Material and methods: The study group consisted of 124 persons (men and women) with newly diagnosed pernicious anaemia (PA) and a control group (C) of 41 healthy people. Antibodies against: intrinsic factor (IFAb), gastric parietal cells (APCA), thyroid peroxidase (TPOAb), thyroglobulin (TgAb), adrenal cortex (AdrenalAb), and pituitary anterior lobe (PituitaryAb) were determined in the blood. Results: 1. The risk of the presence of antibodies against endocrine glands in patients with PA can be classified in order: TPOAb and/or TgAb — 41.1%, TPOAb — 36.3%, TgAb — 25.0%, TPOAb and TgAb — 20.2%, AdrenalAb — 1.6%, PituitaryAb — 0.8%. 2. TPOAb and/or TgAb (mainly TPOAb) are more frequently present in patients with PA, who have IFAb and/or APCA. This correlation is most evident in patients with simultaneous occurrence of IFAb and APCA. 3. Among patients with PA, the simultaneous presence of antibodies IFAb and/or APCA with TPOAb and/or TgAb antibodies is most likely in women over 45 years of age. 4. In group C, 12% had at least one of two antithyroid antibodies (TgAb twice as often as TPOAb), and 2.4% had both. AdrenalAb and PituitaryAb are not found in healthy persons. Conclusions: In patients with PA, a screening for autoimmune thyroid disease is justified, which should first involve the determination of TPOAb (further TgAb) in the blood. The assessment of antithyroid antibodies should be recommended primarily to patients with PA, who have IFAb and/or APCA, and in particular those with concurrent IFAb and APCA. Introduction: The aim of the study was to determine the frequency of occurrence of antibodies participating in the development of endocrine diseases in patients with autoimmune haematopoietic disease, thus documenting the potential suitability of specific diagnostic and screening tests. Material and methods: The study group consisted of 124 persons (men and women) with newly diagnosed pernicious anaemia (PA) and a control group (C) of 41 healthy people. Antibodies against: intrinsic factor (IFAb), gastric parietal cells (APCA), thyroid peroxidase (TPOAb), thyroglobulin (TgAb), adrenal cortex (AdrenalAb), and pituitary anterior lobe (PituitaryAb) were determined in the blood. Results: 1. The risk of the presence of antibodies against endocrine glands in patients with PA can be classified in order: TPOAb and/or TgAb — 41.1%, TPOAb — 36.3%, TgAb — 25.0%, TPOAb and TgAb — 20.2%, AdrenalAb — 1.6%, PituitaryAb — 0.8%. 2. TPOAb and/or TgAb (mainly TPOAb) are more frequently present in patients with PA, who have IFAb and/or APCA. This correlation is most evident in patients with simultaneous occurrence of IFAb and APCA. 3. Among patients with PA, the simultaneous presence of antibodies IFAb and/or APCA with TPOAb and/or TgAb antibodies is most likely in women over 45 years of age. 4. In group C, 12% had at least one of two antithyroid antibodies (TgAb twice as often as TPOAb), and 2.4% had both. AdrenalAb and PituitaryAb are not found in healthy persons. Conclusions: In patients with PA, a screening for autoimmune thyroid disease is justified, which should first involve the determination of TPOAb (further TgAb) in the blood. The assessment of antithyroid antibodies should be recommended primarily to patients with PA, who have IFAb and/or APCA, and in particular those with concurrent IFAb and APCA.

Introduction: Although hyperthyroidism is characterised by female predominance, its presence may lead to the development of numerous complications in both sexes. This study was aimed at investigating sexual function and depressive symptoms in men with overt hyperthyroidism of autoimmune and non-autoimmune origin. Material and methods: The study population consisted of three age-matched groups: men with overt hyperthyroidism and Graves’ disease (group A; n = 20), men with overt hyperthyroidism and toxic multinodular goitre or toxic adenoma (group B; n = 21), and men with normal thyroid function (group C; n = 23). As well as measuring serum hormone levels and antibody titres, and determining calculated parameters of thyroid homeostasis, all included patients filled in questionnaires evaluating sexual function (International Index of Erectile Function-15: IIEF-15) and assessing the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition – BDI-II). Results: Compared with control subjects, men with overt hyperthyroidism obtained lower scores for erectile function, intercourse satisfaction, orgasmic function and overall satisfaction. Scores for erectile function, orgasmic function, and sexual desire differed between both groups of men with thyroid hyperfunction and inversely correlated with thyrotropin receptor antibody titres. The BDI-II score was higher in patients with Graves’ disease than in men with normal thyroid function. Conclusions: The obtained results indicate that overt hyperthyroidism in men causes multidimensional impairment of sexual function, which is particularly pronounced if excessive hormone production results from Graves’ disease. Introduction: Although hyperthyroidism is characterised by female predominance, its presence may lead to the development of numerous complications in both sexes. This study was aimed at investigating sexual function and depressive symptoms in men with overt hyperthyroidism of autoimmune and non-autoimmune origin. Material and methods: The study population consisted of three age-matched groups: men with overt hyperthyroidism and Graves’ disease (group A; n = 20), men with overt hyperthyroidism and toxic multinodular goitre or toxic adenoma (group B; n = 21), and men with normal thyroid function (group C; n = 23). As well as measuring serum hormone levels and antibody titres, and determining calculated parameters of thyroid homeostasis, all included patients filled in questionnaires evaluating sexual function (International Index of Erectile Function-15: IIEF-15) and assessing the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition – BDI-II). Results: Compared with control subjects, men with overt hyperthyroidism obtained lower scores for erectile function, intercourse satisfaction, orgasmic function and overall satisfaction. Scores for erectile function, orgasmic function, and sexual desire differed between both groups of men with thyroid hyperfunction and inversely correlated with thyrotropin receptor antibody titres. The BDI-II score was higher in patients with Graves’ disease than in men with normal thyroid function. Conclusions: The obtained results indicate that overt hyperthyroidism in men causes multidimensional impairment of sexual function, which is particularly pronounced if excessive hormone production results from Graves’ disease.