The incidence of Alzheimer's disease (AD) increases significantly following chronic stress and brain ischemia which, over the years, cause accumulation of toxic amyloid species and brain damage. The effects of global 15-min ischemia and 120-min reperfusion on the levels of expression of the amyloid precursor protein (APP) and its processing were investigated in the brain cortex (Cx) of male Wistar rats. Additionally, the levels of expression of the amyloid-degrading enzymes neprilysin (NEP), endothelin-converting enzyme-1 (ECE-1), and insulin-degrading enzyme (IDE), as well as of some markers of oxidative damage were assessed. It was shown that the APP mRNA and protein levels in the rat Cx were significantly increased after the ischemic insult. Protein levels of the soluble APP fragments, especially of sAPPβ produced by β-secretase, (BACE-1) and the levels of BACE-1 mRNA and protein expression itself were also increased after ischemia. The protein levels of APP and BACE-1 in the Cx returned to the control values after 120-min reperfusion. The levels of NEP and ECE-1 mRNA also decreased after ischemia, which correlated with the decreased protein levels of these enzymes. However, we have not observed any changes in the protein levels of insulin-degrading enzyme. Contents of the markers of oxidative damage (di-tyrosine and lysine conjugates with lipid peroxidation products) were also increased after ischemia. The obtained data suggest that ischemia shifts APP processing towards the amyloidogenic β-secretase pathway and accumulation of the neurotoxic Aβ peptide as well as triggers oxidative stress in the cells. These results are discussed in the context of the role of stress and ischemia in initiation and progression of AD.

The aim of our study was to correlate the serum concentration of human epididymis protein 4 (HE4) in lung cancer patients with the bone metastases detected by whole-body bone scintigraphy. The serum concentrations of HE4 were determined by electrochemiluminescence immunoassay method in 60 patients with lung cancer and in 10 persons without malignant disease (control group). All participants were examined by whole-body bone scintigraphy with hybrid gamma camera of type BrightView XCT. We found bone metastases in 25.0% of patients by whole-body bone scintigraphy and probable bone metastases in 18.3% of patients. We did not observe bone metastases in 56.7% of patients and in nobody from control group. We observed that 73.33% patients with bone metastases had more than 3 bone metastasis deposits. Patients had significantly increased concentration of HE4 (p < 0.0001). All three subgroups of patients (bone metastases, probable bone metastases, no evidence of bone metastases) had significantly increased concentration of HE4 compared to controls. The highest concentration of HE4 had 9 patients with small-cell lung cancer of whose 4 patients had bone metastases, 4 patients had probable bone metastases and one patient was with no evidence of bone metastases. We found that HE4 has a discriminatory ability to differentiate groups of patients and healthy controls, as well as within scaffold scintigraphy in patients with lung cancer (p = 0.0002). The serum concentration of human epididymis protein 4 was significantly increased in patients with lung cancer in comparison with persons of control group. A quarter of lung cancer patients had identified bone metastases by whole-body bone scintigraphy and approximately 20% of patients had probable bone metastases. The increasing serum concentrations of human epididymis protein 4 can have importance in the diagnosis of bone metastases in patients with lung cancer, in particular in small-cell lung cancer.

Adenoid hypertrophy (AH) represents a common problem in children associated with many complications. It was suggested, that allergic sensitization and immune dysregulation could contribute to AH development. In a group of 97 children undergoing adenoidectomy (AT), we analyzed the contribution of allergic sensitization and passive smoking to the development of AH and to the changes of musocal microbiome. We evaluated the concentration of E-cadherin (measured by standard human ELISA E-cadherin kit), a mediator of immunological functions of airway epithelium, in relationship to the surgery and allergic background (evaluated by skin prick tests). Atopy was confirmed in 83% of children and the most prevalent allergens were house dust mites (HDM) and animal dander. Passive smoking was detected in 37% of children assessed by the questionnaires. In the whole group, no changes in E-cadherin levels before and after the surgery were detected. However, in children exposed to passive smoking, E-cadherin significantly increased after the AT (5393±372 ng/mL vs. 6727±427 ng/mL, p=0.034) and was higher compared to children without exposure to passive smoking (p=0,039). Children sensitized to HDM allergens yielded higher concentration of E-cadherin before and after the surgery compared to non-sensitized (before AT: 7248±599 vs. 5302±387 ng/mL, p =0.028; after AT: 6446±513 vs. 5722±419 ng/mL, p=0.045). Children allergic to Alternaria had higher E-cadherin after AT (7294±906 vs. 5607±336 ng/mL, p=0.049). Passive smoking and sensitization to perennial allergens damage and modify the immunological functions of airways epithelium and could contribute to the development of adenoid hypertrophy.

Background/Aim: Interleukin-6 is an important modulator of inflammation, which is one of the factors involved in prostate cancer. The aim of the study was to evaluate the possible association of the IL-6 -174 polymorphism (rs1800795) with the risk of prostate cancer development and progression. Materials and Methods: The study population consisted of 446 prostate cancer patients, 377 benign prostatic hyperplasia (BHP) patients and 276 healthy men. Genotyping was performed by PCR-RFLP analysis. IL-6 plasma levels were measured by the ELISA method. Results: The GC genotype (OR=0.61, p=0.005) and C allele (OR=0.8, p=0.04) of the IL-6 -174 polymorphism were significantly associated with prostate cancer. No genotype was associated with BHP. IL-6 plasma levels were significantly increased in prostate cancer patients compared to both healthy men (p=0.02) and BHP patients (p=0.008). No significant differences were observed in IL-6 plasma levels in connection with IL-6 -174 genotypes. Conclusion: The IL-6 -174 polymorphism was significantly associated with prostate cancer in Slovak patients.

Transient hypogamaglobulinemia of infancy (THI) is one of the most frequent primary immunodeficiencies in children, however, its genetic background and factors modifying clinical picture are widely unknown. In a group of 71 children with THI (52% boys, aged 3.36±2.64 years) clinical and laboratory characteristics were evaluated and associations with clinical symptoms and complications were assessed. Single nucleotide polymorphism in MBL2 gene (codon 54) was also determined. Average age of the THI diagnosis establishment was 9.37±4.33 months with the correction of IgG levels to the normal values at the age of 31.65±15.73 months. Mean IgG concentration at the beginning of monitoring was 2.60±0.77 g/L. The atopy was confirmed in 64% of children. Boys had higher levels of mannose-binding lectin (MBL), total IgE, peripheral blood eosinophils and total number of CD3+ T-lymphocytes in the peripheral blood compared to girls. More than half of the patients suffered from the recurrent respiratory tract infections, which were associated with lower serum IgG and MBL, lower markers of specific cellular immunity and higher age of IgG normalization. We were not able to find any association of MBL2 gene polymorphism and clinical complication, however, children with genotype GA or AA showed lower MBL concentration. Despite the general opinion that THI is mild immunodeficiency, significant proportion of children is symptomatic and usually suffers from respiratory infections. The clinical presentation of THI is modified by the specific and non-specific cellular immunity and by the gender. Symptomatic THI children require regular follow-up and adequate therapy.

Bronchial asthma is one of the most common chronic inflammatory diseases of the airways. In the pathogenesis of this disease, the interplay among the genes, intrinsic, and extrinsic factors are crucial. Various combinations of the involved factors determine and modify the final clinical phenotype/endotype of asthma. Oxidative stress results from an imbalance between the production of reactive oxygen species and reactive nitrogen species and the capacity of antioxidant defense mechanisms. It was shown that oxidative damage of biomolecules is strongly involved in the asthmatic inflammation. It is evident that asthma is accompanied by oxidative stress in the airways and in the systemic circulation. The oxidative stress is more pronounced during the acute exacerbation or allergen challenge. On the other hand, the genetic variations in the genes for anti-oxidative and pro-oxidative enzymes are variably associated with various asthmatic subtypes. Whether oxidative stress is the consequence of, or the cause for, chronic changes in asthmatic airways is still being discussed. Contribution of oxidative stress to asthma pathology remains at least partially controversial, since antioxidant interventions have proven rather unsuccessful. According to current knowledge, the relationship between oxidative stress and asthmatic inflammation is bidirectional, and genetic predisposition could modify the balance between these two positions-oxidative stress as a cause for or consequence of asthmatic inflammation.

Introduction: The genetic background of bronchial asthma is complex, and it is likely that multiple genes contribute to its development both directly and through gene-gene interactions. Cytokines contribute to different aspects of asthma, as they determine the type, severity and outcomes of asthma pathogenesis. Allergic asthmatics undergoing an asthmatic attack exhibit significantly higher levels of pro-inflammatory cytokines, such as interleukins and chemokines. In recent years, cytokines and their receptors have been shown to be highly polymorphic, and this prompted us to investigate interleukin 6 promoter polymorphisms at position -174G/C(rs1800795) and at -572G/C (rs1800796) in relation to asthma in children.Methods: Interleukin 6 promoter polymorphisms were analyzed in bronchial asthma patients and healthy children using polymerase chain reaction-restriction fragment length polymorphism analysis.Results: We observed a significant association between polymorphism at -174G/C and bronchial asthma (OR= 3.4, 95% CI: 2.045-5.638, P<.001). Higher associations between polymorphism at IL-6 174G/C and bronchial asthma were observed in atopic patients (OR = 4.1, 95% CI: 2.308-7.280, P<8.10-(7)).Conclusions: Interleukin 6 polymorphism is associated with bronchial asthma, particularly its atopic phenotype. Expression and secretion of interleukins in asthmatic patients may be affected by genetic poly-morphisms, and could have a disease-modifying effect in the asthmatic airway and modify the therapeutic response. (C) 2016 SEPAR. Published by Elsevier Espaila, S.L.U. All rights reserved.

Interleukin-18 (IL-18), pro-inflammatory cytokine, plays important role in antitumor immunity.Polymorphisms in the IL-18 gene may lead to its altered production/activity and such modulate susceptibility to prostate cancer.The aim of this study was to evaluate the relationship between the -607 and +105 polymorphisms in the IL-18 gene and the risk of prostate cancer development and progression in Slovak population.The study was performed using 425 patients with prostate cancer, 270 patients with benign prostatic hyperplasia (BHP) and 263 healthy male controls.The statistically significant association of the -607 AC genotype (OR = 2.24; p < 0.001), CC genotype (OR = 1.86; p = 0.006), as well as C allele (OR = 1.27; p = 0.033) with the higher risk of prostate cancer development was observed.No association of the IL-18 -607 polymorphism and BHP was detected.The subset analysis revealed the significant association of the -607 AC genotype (OR = 2.01; p = 0.008) with development of higher-grade carcinomas (Gleason score ≥7) and the strong association of the -607 AC genotype (OR = 3.11; p < 0.001), CC genotype (OR = 2.96; p < 0.001) as well as C allele (OR = 1.51; p = 0.003) with the higher risk of prostate cancer development in the group of patients with PSA < 10 ng/ml.The -607 AC genotype was also connected with significantly higher IL-18 plasma concentrations.No association between the IL-18 +105 polymorphism and prostate cancer was observed.The analysis of the distribution of the -607 and +105 haplotypes showed significant association of the -607 C/ + 105 A and -607 C/ + 105 C haplotypes with the risk of prostate cancer.This study found that the IL-18 -607 promoter polymorphism could contribute to prostate cancer development in Slovak population.Its presence was also associated with development of higher-grade carcinomas and therefore may influences the prognosis and aggressiveness of the disease.

AIM:The complex influence of internal and external environmental factors on the individual and his/her immune system and the lack of suitable markers to assess and reduce the risk of the development of allergies during the lifetime can explain the continuous increase in the number of people affected by some form of allergy. According to the results of some studies, cord blood IgE level could be a useful early marker for assessing the risk of atopic diseases, but the studies showed controversial results. In addition, several authors discuss the origin of these antibodies (synthesis in utero, peripartum contamination from maternal blood or placental transfer). The aim of our pilot study was to investigate the possible influence of modifying factors on cord blood IgE level.MATERIAL AND METHODS:Our group of patients consisted of 184 retrospectively selected neonates (98 boys, 53.3% and 86 girls, 46.7%) from whom cord blood was collected and cord blood IgE level was measured 25 years ago (PRIST method). The impact of selected modifying factors (sex, type of delivery or month of birth) on cord blood IgE level was assessed retrospectively.RESULTS:Higher cord blood IgE levels were found in boys than in girls, in neonates born by Caesarean section than in those born by natural delivery, and in those born in the winter months than in other seasons of the year. Our findings are in agreement with those of other authors.CONCLUSION:Based on our results and those of others, we assume that the selected factors affect the cord blood IgE levels to varying degrees. These facts should be taken into consideration while interpreting the cord blood IgE levels.

Malignant melanoma is a malignancy located predominantly in the skin and the incidence of melanoma increases. We compared the markers of bone metabolism – osteocalcin (OC), beta-carboxyterminal cross-linked telopeptide of type I collagen (β-CrossLaps, β-CTx) and tumour marker – human epididymis protein 4 (HE4) in the serum with finding during the entry examination and the check-up of whole-body bone scintigraphy of the patient with a malignant melanoma. Serum concentrations of OC, β-CTx, HE4 were determined in 1 patient (female, age 64 years) with malignant melanoma and correlated with the presence of equivocal bone metastases detected by whole-body bone scintigraphy (the entry examination and check-up after 6 months). Concentrations of bone metabolism markers decreased during six months and we observed progress in bone metastases. The change of the markers levels during the entry examination and the check-up of the whole-body bone scintigraphy with equivocal finding of bone metastases could be a sign of a possible initiating progression of malignant melanoma despite a clinically negative finding that does not prove the progression of the disease.

During the normal menstrual cycle, endometrial tissue undergoes many biochemical and morphological changes which are under the control of steroid hormone levels. DNA methylation plays a key role in gene expression regulation and influences functional changes in endometrial tissue. Eliminating senescent cells from the functional layer of the endometrium is mediated by apoptotic cell death, which helps maintain cellular homeostasis. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and thus apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients with advanced disease. Despite intensive study of the cancer epigenome, there is missing information about disrupted apoptotic gene regulation in DNA methylation levels. Therefore, it is necessary to spread our knowledge in the field of epigenetics to help us differentiate normal and cancer tissues and detect the early stages of cancer disease.