[The effect of solar ultraviolet radiation (UVR) on induction of skin cancers]. / Wplyw slonecznego promieniowania ultrafioletowego (UV) na powstawanie raków skóry.

Ultraviolet radiation is a physical mutagenic and cancerogenic factor. About 95% of ultraviolet A (UVA) (320-400 nm) and 5% of UVB (280-320 nm) reach the Earth's surface. Melanin is a natural skin protective factor against UV radiation. Skin cancers associated with long-term exposure to UV radiation are: basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). The high risk of BCC development is related to acute and repeated exposure to UV causing sunburn. Molecular studies of BBC demonstrated disorders in sonic hedgehog (SHH) cell signaling regulation pathway, associated with the suppressor protein patched homolog 1 gene (PTCH1) mutations. The risk of the BCC development is related to the polymorphism of melanokortin-1 receptor gene (MC1R). Tumor P53 gene mutations observed in BCC cells has been classified as secondary genetic changes. In SCC cells UV-induced mutations were mostly related to P53 gene. Increased expression of cyclooxigenase- 2 gene (COX-2) plays a significant role in the development of SCC. Other pathogenetic factors include intensification of the synthesis of pro-inflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin-1 α (IL-1α), IL-1ß and IL-6). Currently, the role of UVB has been recognized in the pathogenesis of CMM. In CMM cells the following gene mutations were noted: cyclindependent kinase inhibitor 2A INK4A (p16INK4A), cyclin-dependent kinase 4 (CDK4), Ras, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and proto-oncogene B-Raf (BRAF). The BRAF gene mutations were observed in ~50% of CMM cases. Mutations of P53 gene are not characteristic of CMM cells. Med Pr 2016;67(2):255-266.

Angiotensinogen gene T174M polymorphism is related to Hashimoto's thyroiditis.

OBJECTIVES: The Hashimoto thyroiditis is found to be Th1-related autoimmunity. Recently, it has been proved that the renin-angiotensin-aldosterone system (RAAS) may be involved in promoting Th1-mediated autoimmune diseases. However, the role of RAAS in HT pathogenesis remains still unknown. The aim of this study was to determine whether the polymorphisms of ACE, AGTR1 and AGT genes are associated with HT. MATERIAL AND METHODS: Polymerase Chain Reaction (PCR) was performed to determine ACE I/D, AGTR1 A1166C and AGT T174M polymorphisms and next chi-square test was used to compare allele frequencies of genes between HT patients (n=53) and the control group (n=31). RESULTS: TM genotype of AGT gene has been more often presented in HT patients (p <0.05). No others statistically significant differences were found in the distribution of I/D ACE and A1166C, AGTR1 genes polymorphisms between studied groups. CONCLUSION: Our study has examined for the first time the association of genes related to RAAS with autoimmune thyroid disease and results suggest that AGT TM genotype individuals might be at higher risk of HT. Although in the present study we have not found any association between increased activation of RAAS and the risk of HT, still this issue seems to be interesting and worthy further research, considering patients with thyroid cancers.

[The metabolic syndrome. Part I: definitions and diagnostic criteria for its identification. Epidemiology and relationship with cardiovascular and type 2 diabetes risk]. / Zespól metaboliczny. Czesc I: definicje i kryteria rozpoznawania zespolu metabolicznego. Epidemiologia oraz zwiazek z ryzykiem chorób sercowo-naczyniowych i cukrzycy typu 2.

The term metabolic syndrome (MS) refers to a clustering of risk factors of metabolic origin that promote the development of cardiovascular disease and type 2 diabetes. Metabolic syndrome includes such pathological factors as insulin resistance, hyperinsulinemia, abdominal obesity, impaired glucose tolerance, type 2 diabetes, microalbuminuria, high level of triglycerides, low level of HDL cholesterol, elevated blood pressure, and proinflammatory and prothrombotic state. Several organizations have recommended clinical criteria for the diagnosis of metabolic syndrome. The most widely accepted were the worked out by the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR), and the National Cholesterol Education Program--Third Adult Treatment Panel (NCEP-ATP III). In 2005, IDF experts proposed a universally accepted diagnostic tool that is easy to use in clinical practice and does not rely on measurements available only in research settings. All groups agreed on the core components of the metabolic syndrome: obesity, insulin resistance, dyslipidemia, and hypertension. Their criteria are similar in many aspects, but they also reveal fundamental differences in their positioning of the predominant causes of the syndrome. This study provides a brief overview of current definitions of metabolic syndrome, with particular reference to the differences between them, and presents critical remarks on the concept of metabolic syndrome and its usefulness. It also presents epidemiological data which consider metabolic syndrome and its association with increased risk of cardiovascular disease and type 2 diabetes.

[The metabolic syndrome. Part II: its mechanisms of development and its complications]. / Zespól metaboliczny. Czesc II: patogeneza zespolu metabolicznego i jego powiklan

The metabolic syndrome is a cluster of interrelated metabolic factors such as insulin resistance, hyperinsulinemia, abdominal obesity, impaired glucose tolerance, dyslipidemia, hypertension, and a proinflammatory and prothrombotic state. It is a common cause of the development of atherosclerotic vascular disease and type 2 diabetes. Genetic predisposition and environmental factors such as physical inactivity and increased caloric intake are responsible for the predisposition to metabolic syndrome. Available studies on the pathogenesis of metabolic syndrome are discrepant. Insulin resistance and abdominal obesity are the dominant causes of metabolic syndrome. Increased visceral adipose tissue mass and its proinflammatory activity are thought to underlie all the changes observed in metabolic syndrome. Adipose tissue is a dynamic endocrine and paracrine organ that produces and secretes inflammatory factors called adipokines, which link obesity, insulin resistance, atherosclerosis, and type 2 diabetes. Recent data suggest that oxidative stress is a primary pathogenic mechanism leading to the development of insulin resistance associated with over-nutrition. In this study the authors analyze the association between abdominal obesity, hyperinsulinemia, and insulin resistance and show some pathogenic mechanisms which may be responsible for the proatherogenic action of insulin resistance, hyperinsulinemia, and impaired glucose tolerance. Here the association among the disorders mentioned in the definitions of metabolic syndrome is discussed in more detail and it is shown that their clustering is not accidental in patients with insulin resistance. The role of adipose tissue in the development of insulin resistance and metabolic syndrome leading to overt cardiovascular disease and type 2 diabetes is also described.

[Metabolic syndrome. Part III: its prevention and therapeutic management]. / Zespól metaboliczny. Czesc III: postepowanie prewencyjne i terapeutyczne w zespole metabolicznym.

Metabolic syndrome (MS), which is composed of such factors as hyperinsulinemia, insulin resistance, glucose intolerance, abdominal obesity, arterial hypertension, and dyslipidemia, contributes to accelerated development of atherosclerosis, coronary artery disease, and type 2 diabetes. It has thus become one of the major public-health challenges worldwide. The primary goal of its clinical management is to reduce the risk for cardiovascular diseases related to atherosclerosis, especially myocardial infarction, stroke, and peripheral vascular disease, and to lower the risk for type 2 diabetes. The fi rst stage in its successful preventive management is identification of the population at high risk of developing metabolic syndrome. The therapeutic approach to metabolic syndrome consists fi rst of all of lifestyle modification, i.e. the introduction of a low calorie diet, weight reduction, and regular physical activity. For people at high risk for cardiovascular diseases and type 2 diabetes as well as those with coronary artery disease and/or type 2 diabetes, pharmacological therapy should be considered. Pharmacological management must address the multipathological process of metabolic syndrome, with each component identified and properly treated. Current therapies for metabolic syndrome treat fi rst of all obesity, insulin resistance, dyslipidemia, and hypertension. The pharmacological agents most often suggested are those which increase insulin resistance (metformin and thiazolidinediones). Among the medications used in metabolic syndrome therapy are also fibrates and statins for atherogenic dyslipidemia and those lowering blood pressure, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. This review presents the most important aspects of the prevention and treatment of patients with metabolic syndrome, including new therapeutic strategies.

Association of angiotensin-converting enzyme and angiotensin II type I receptor gene polymorphisms with extreme obesity in Polish individuals.

There is strong evidence for the presence of a functional renin-angiotensin system in human adipose tissue. The aim of our study was to investigate the association of polymorphic variants of angiotensin-converting enzyme gene (ACE I/D) and angiotensin II type I receptor gene (AGTR1 A1166C) with extreme obesity and obesity-associated type 2 diabetes mellitus (T2DM) and to examine their combined effect on extremely obese patients. Overall, no significant associations were detected between ACE and AGTR1 gene polymorphisms and extreme obesity. However, extremely obese patients with T2DM showed an increased frequency of ACE II genotype compared with controls (p<0.05) and with non-diabetic extremely obese patients (p<0.01). The results suggest that II genotype of ACE was a significant contributor to extreme obesity in AA homozygotes of AGTR1 gene, regardless of the presence of T2DM. Moreover, the analysis of genetic polymorphisms demonstrated that ACE II and AGTR1 AC genotypes were most frequently observed in patients with extreme obesity and T2DM. On the basis of our results, we suggest that ACE II homozygosity may be a significant predictor of extreme obesity and T2DM and that the interaction between ACE and AGTR1 genes may be considered a predisposing factor for extreme obesity and extreme obesity-associated T2DM development.