Multicolor flow cytometry immunophenotyping and characterization of aneuploidy in pediatric B-cell precursor acute lymphoblastic leukemia.

The aim of this study was to assess the incidence of DNA aneuploidy in Polish children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and the relationship between aneuploidy and immunological phenotype, age, leukocyte count, S-phase fraction (SPF) and early response to induction chemotherapy assessed by the percentage of residual blast cells in bone marrow aspirates. The study group consisted of 267 patients. DNA content and immunophenotype were assessed in the bone marrow before treatment using multicolor flow cytometry (FC). DNA aneuploidy was detected in 50/267 (19%) patients. High hyperdiploidy was found to be associated with lower leukocyte count (p = 0.006) and common ALL immunophenotype. Flow cytometry analysis revealed that high hyperdiploid BCP-ALL patients showed significantly higher expression of CD9, CD20, CD22, CD58, CD66c, CD86 and CD123 antigens as compared to other groups of ploidy. In contrast, CD45 showed decreased expression. The percentage of leukemic blasts at diagnosis was lower in high hyperdiploid BCP-ALL cases than in diploid (79% vs. 85.7%, p = 0.001). The difference in minimal residual disease (MRD) levels on day 15 and 33 of induction therapy between analyzed groups was not significant. This study showed that high hyperdiploidy is associated with lower WBC count and specific immunological phenotype. Flow cytometric evaluation of expression of selected antigens can be used for fast identification of markers of aneuploidy in pediatric BCP-ALL, before genetic tests results are available. Understanding the biological significance of aneuploidy in leukemia can potentially be exploited therapeutically using targeted therapies against specific blast cell subclones.

ATP4A autoimmunity in pediatric patients with type 1 diabetes and its relationship to blood count, iron metabolism, and vitamin B12.

OBJECTIVE: We aimed to assess the prevalence of autoantibodies against the 4A subunit of the gastric proton pump (ATP4A) in pediatric type 1 diabetes (T1D) patients and explore the relationship between ATP4A positivity and blood cell count, iron turnover, and vitamin B12 concentration. SUBJECTS: The study included 94 (59% female) T1D children (aged 12.5 ± 4.1 years, T1D duration 4.2 ± 3.6 years, HbA1c 7.3 ± 1.5% (57 ± 12.6 mmol/mol) with no other autoimmune diseases. METHODS: ATP4A antibodies were measured in T1D patients using a radioimmunoprecipitation assay. Blood cell count, iron concentration, total iron binding capacity, ferritin, transferrin, hepcidin, and vitamin B12 concentration were measured in all the study participants. RESULTS: A total of 16 (17%) children were ATP4A positive. Serum concentrations of ferritin were significantly lower in ATP4A positive than in antibody negative subjects (P = .034). Overall the levels of ATP4A antibodies (ATP4A Index) correlated positively with the age at T1D diagnosis (r = 0.228, P = .026) and negatively with ferritin levels (r = -0.215, P = .037). In ATP4A positive patients, the ATP4A Index correlated positively with age at diagnosis (r = 0.544, P = .032) and negatively with vitamin B12 levels (r = -0.685, P = .004). CONCLUSIONS: ATP4A antibodies were present in a significant proportion of children with T1D. Higher ATP4A levels in T1D children are associated with lower, yet still fitting within the normal range, levels of vitamin B12, and ferritin. Routine screening of T1D children for gastric autoimmunity (ATP4A) should be considered with follow-up of those positive for vitamin B12 and iron deficiency.

The role of alert pathogens in bacterial diseases in patients hospitalized at the Department of Pulmonary Diseases and Tuberculosis Public Clinical Hospital No 3 in Zabrze in 2008-2012

BACKGROUND: The current public health problem is the increasing bacterial resistance to antibiotics. Microorganisms isolated from infections are more often non-susceptible to most available drugs. The microorganisms producing resistance mechanisms have been classified as so called alert pathogens. METHODS: We performed a total number of 3810 tests of bronchoalveolar lavage and sputum of patients hospitalized for respiratory diseases at the Department of Pulmonary Diseases and Tuberculosis at Public Clinical Hospital No 3 in Zabrze (Poland). The research was performed in the microbiological laboratory of the Department of Microbiology and Immunology in Zabrze, Medical University of Silesia in Katowice, Poland. The analysis included Gram-positive and Gram-negative alert species strains. RESULTS: In the period of five years, 144 strains of alert microorganisms have been isolated. The percentage of Gramnegative alert pathogens producing ESBL and KPC increased. MRSA, Steptococcus pneumoniae and Streptococcus pyogenes have been found to be the most often present among Gram-positive alert microorganisms. The lowest value of cultured alert pathogens (3.9%) was noted in 2008, whereas the highest (16.5%) in 2011. Gram-positive alert microorganisms showed resistance to macrolides and lincosamides, however, Gram-negative alert microorganisms showed the highest percentage of resistance to penicillins, penicillins with inhibitors and cephalosporins. CONCLUSIONS: Our work has shown that over the period 2008­2012 an increased percentage of Gramnegative and Gram-positive alert microorganisms was observed.

Interleukin 1-ß, interleukin-1 receptor antagonist and vitamin D levels in children with atopic dermatitis.

INTRODUCTION: Among the broad spectrum of cytokines, interleukin 1-ß (IL-1ß) has been implicated in induction and subsequent aggravation of skin lesions in atopic dermatitis (AD). A considerable body of evidence suggests that vitamin D status also influences the risk and/or severity of AD. MATERIAL AND METHODS: Fifty-seven children suffering from mild to severe AD were enrolled in the study. The control group consisted of 33 matched healthy children. In all the children serum concentrations of IL-1ß/IL-1F2 and the interleukin-1 receptor antagonist IL-Ra/1F3 were measured. Serum 25(OH)D concentration was obtained for 49 patients with AD and all healthy children. RESULTS: In children with AD 59.2% of children had insufficiency, 24.5% had deficiency and 16.3% had a sufficient serum 25(OH)D level. In the control group 26.5%, 52.9% and 20% of participants had insufficiency/deficiency/sufficiency of 25(OH)D, respectively. The severity of AD was positively correlated with total IgE level, percentage and absolute count of eosinophils and IL-1Ra. IL-1ß correlated with IL-1Ra. CONCLUSIONS: In children with AD the serum vitamin D level was lower than in healthy children. The correlation between severity of AD and IL-1Ra may prove that inflammasome-dependent IL-1ß is involved in immunopathogenesis of the disease. Further studies are needed on a larger population of children to confirm the role of this cytokine in development of AD.

Serum adiponectin levels in adolescents and young adults with growth hormone deficiency.

INTRODUCTION: Adiponectin (APN) is adipose tissue-derived hormone influencing energy metabolism. Growth hormone deficiency (GHD) may contribute to the development of disturbances in the hormonal function of adipose tissue (AT), and many disorders observed in untreated patients with GHD coincides with these contributed to low serum APN levels. OBJECTIVES: The assessment of serum adiponectin levels in adolescents and young adults with severe or partial GHD and analysis of relationships between serum APN and GH/IGF-1 axis function impairment as well as cardiometabolic risk factors. DESIGN AND SETTING: Based on the results of insulin tolerance test (ITT) patients were qualified for one of the following groups: 1) severe GHD - SGHD (26 patients; 8 women and 18 men); 2) partial GHD - PGHD (22 patients, 7 women and 15 men); 3) normal GH status - NGHS (28 patients, 9 women and 19 men). The fourth examined group consisted of healthy individuals - H (46 participants; 15 women, 31 men). Anthropometric measurements (height, weight, BMI), analysis of body composition and serum glucose, lipids, insulin, IGF-1 and APN assays were performed in all participants. RESULTS: There were no significant differences in the concentrations of APN between groups. After calculation of the total APN content in extracellular fluids per unit of fat tissue mass (TAPN/FM), these values were significantly lower in the SGHD (p<0.001) and correlated with the degree of impairment of the GH/IGF-1 axis functioning. In patients with GHD positive correlations between APN and serum HDL cholesterol (r=0.39, p<0.05) have been demonstrated. In the subjects with normal GH secretion serum APN correlated positively with serum HDL cholesterol (r=0.28; p<0.05), and negatively with fasting blood glucose (r=-0.31; p<0.05). CONCLUSIONS: Severe, but not partial growth hormone deficiency impairs adiponectin production in the adipose tissue that is compensated by the increase of fat mass. The degree of GH/IGF-1 axis disruption is related to the TAPN/FM. This parameter may be potentially useful in diagnosing severe growth hormone deficiency in the adults.

Changes in Serum Ceruloplasmin Levels Based on Immunomodulatory Treatments and Melatonin Supplementation in Multiple Sclerosis Patients.

BACKGROUND The cause of multiple sclerosis (MS) is currently unknown, but it is thought that oxidative damage and iron metabolism mechanisms are involved. The aim of this study was to examine ceruloplasmin concentration in MS patients based on various immunomodifying therapies and to test the effect of antioxidative melatonin on ceruloplasmin levels. MATERIAL AND METHODS This prospective study included 102 MS patients and 15 healthy controls. Patients were divided into groups according to different immunomodifying therapies: interferons beta 1a, interferons beta 1b, glatiramer acetate, mitoxantrone, and immunomodifying pre-treatment (A, B, G, Mx, and P groups, respectively), and the relapse R group. MS patients were supplemented with melatonin for 3 months. Serum ceruloplasmin concentrations, EDSS, brain MRI, serum C-reactive protein level, and white blood cell count were examined. RESULTS The results indicated significantly increased levels of ceruloplasmin in MS patients. No differences in ceruloplasmin concentrations between the relapse group and controls were observed. In A and G groups, ceruloplasmin levels before and after melatonin were similar to levels in controls. In group B, ceruloplasmin concentration was significantly higher vs. control and relapse groups. After melatonin administration in group B, ceruloplasmin levels decreased. Ceruloplasmin concentrations in the Mx group were significantly higher compared to controls. CONCLUSIONS We found for the first time that ceruloplasmin concentration in MS patients varies depending on different immunomodulatory treatment and decrease after 3 months of melatonin administration. Ceruloplasmin could be a valuable serum marker for the chronic demyelinating process participating in oxidative stress mechanisms, as well as a neurodegenerative marker, but not a marker of acute-phase MS.

The inhibitory effect of flavonoids on interleukin-8 release by human gastric adenocarcinoma (AGS) cells infected with cag PAI (+) Helicobacter pylori.

INTRODUCTION: It is well known that the presence of Helicobacter pylori in the stomach induces gastritis and causes an immune response. Exposure of gastric epithelial cell lines to this germ induces the secretion of interleukin-8 (IL-8), which is a potent PMN-activating chemotactic cytokine. Interleukin-8 is usually elevated in gastric biopsy samples of patients with H. pylori-associated gastritis and significantly increases in the supernatant of in vitro cultivated biopsy samples of gastric mucosa with active H. pylori gastritis. Interleukin-8 is an activating factor for leucocytes and other pro-inflammatory factors, free radicals, and proteolytic enzymes. That is why natural compounds potentially useful in therapy are still investigated - among them flavonoids. They reveal anti-oxidative and anti-inflammatory activities and significantly inhibit the gastric mucosa damage. THE AIM OF THE STUDY: Was the estimation of the anti-inflammatory effects of flavonoids on H. pylori-induced activation of human gastric adenocarcinoma cells (AGS). After infection of AGS cells by cag PAI (+) H. pylori in vitro, secretion of IL-8, effects of flavonoids on viability of AGS cells, and effects of flavonoids on increase of H. pylori were determined. Such flavones as chrysin, quercetin, kaemferide, flavanone, galangin, and kaempferol were examined. RESULTS: This study has shown an inhibitory effect of flavonoids on the release of IL-8 through infected AGS cells (except chrysin), and no toxic effects to AGS cells were observed. Galangin revealed antibacterial effects against H. pylori. Flavonoids limit the inflammatory process through the inhibition of IL-8 release in infected AGS cells with H. pylori. The strongest inhibitor of IL-8 was galangin.

Selected CC and CXC chemokines in children with atopic asthma.

INTRODUCTION: There are only limited data on CC and CXC chemokines regulation in children with asthma. AIM: We compared the serum profile of selected CC and CXC chemokines in patients with atopic asthma and healthy children. MATERIAL AND METHODS: Serum concentration of CC chemokines RANTES, MCP-1, and CXC chemokines IP-10, MIG, IL-8, RANTES was measured using cytometric bead array in 44 children with atopic asthma and 17 healthy subjects. RESULTS: The concentration of RANTES was significantly higher and the MIG level was lower in all children with asthma as compared to their control counterparts. We observed increased RANTES and decreased MIG levels also in patients with stable asthma when compared with children in the control group. The IP-10 concentration was similar between the whole asthma group and healthy controls, while significantly increased levels of this chemokine in acute asthma have been observed when compared to stable asthma. For MCP-1 and IL-8, the serum concentration was similar in all compared groups. The MIG concentration correlated positively with IP-10, IL-8, and CRP levels and negatively with the eosinophil count. A negative correlation between the IP-10 and eosinophil count and a negative correlation between FEV1 and IP-10 were found. CONCLUSIONS: An increased serum RANTES level in children with asthma may result in enhancement of Th2 lymphocyte recruitment into the airway. A decreased expression of Th1 chemokine MIG in children with stable asthma may contribute to a diminished antagonizing effect on Th2 cytokine production and hence intensify Th2 predominance. An increased IP-10 level in children during an asthma attack suggest that this chemokine is a serological marker of disease exacerbation.

Expression of chemokine receptors on peripheral blood T cells in children with chronic kidney disease.

Chemokine receptors play a role in leukocyte recruitment, activation, and maintaining effector functions and regulate adaptive immune response and angiogenesis. The study aimed at flow cytometric analysis of T cell subsets with selected surface chemokine receptors (CCR4, CCR5, CCR7, CXCR3, and CXCR4) or receptor combination in peripheral blood of children with chronic kidney disease (CKD) on hemodialysis (HD). The percentage of T lymphocytes with CD8 and combined CD28,CCR7 expression was higher in HD children. The percentage of T lymphocytes expressing CCR7, CD28,CCR7, and CXCR4,CD8 was increased in children on conservative treatment. Total number (tn) of CXCR4+ cells was reduced in children on hemodialysis. The tn of T CXCR3+ cells was lower in children on conservative treatment. During HD the percentage of T CD4+ cells was higher and of T CXCR3+ lymphocytes was lower after HD session as compared to 15 min of session duration. During HD tn of T cells with expression of CCR4, CCR5, CCR7, CXCR3, and CXCR4 was constant. The alteration of chemokine receptors expression in children with CKD occurs early in the development. Diminished expression of CXCR3, CXCR4 on T cells in patients with CKD on HD might result in impaired inflammatory response. Increased CCR7+ T cell percentage could be responsible for the alteration of migration of cells into secondary lymphatic organs.

[The aging of the immune system].

The age-related deterioration of health condition associated with progressive impairment of innate and adaptive immunity was defined as the aging of the immune system (also known as immunosenescence). Many changes occur within the immune system with age, including in particular quantitative changes in populations and subpopulations of cells resulting in dysfunction of the immune system. Elderly patients often have chronic systemic low grade inflammation process which is an effect of the inflammatory mediators secretion. Changes in the levels of mediators have a negative impact on coexisting disease and body's ability to fight infections. The purpose of the paper is to characterize the changes in proportions and functions of immune cells during the aging.

Association of NK Cells with the Severity of Fibrosis in Patients with Chronic Hepatitis C.

Some NK cell subpopulations may be involved in the modulation of fibrogenesis in the liver. The aim of the study was to evaluate the relationship between the number and phenotype of NK cell subsets in peripheral blood (PB) and total NK cell percentage, population density and the degree of liver fibrosis of patients infected with hepatitis C virus (HCV+). The study group consisted of 56 HCV+ patients, divided into two subgroups: patients with mild or moderate fibrosis and patients with advanced liver fibrosis or cirrhosis (F ≥ 3 in METAVIR classification). The preparations were stained with H-E and AZAN staining. NK cells were targeted with anti-CD56 antibody and identified automatically in situ using the DakoVision system. Assessment of different NK cell subsets in PB was performed with the flow cytometry technique. In the PB of HCV+ patients with advanced liver fibrosis, there was a lower proportion of CD62L+; CD62L+/CD94++; CD27+; CD127+/CD27+ and CXCR3+/CD27+ NK subsets, as compared to patients with mild/moderate liver fibrosis. The results also showed no association between total PB NK cell level and total intrahepatic NK cell population density between patients with mild/moderate fibrosis and with advanced liver fibrosis. However, positive correlations between the PB levels of CD94+ and CD62L+ NK cell subsets and the intrahepatic total NK cell percentage and population density in the liver, irrespectively to the extent of fibrosis, were observed. Additionally, positive correlation was found between the PB CXCR3+/CD94+ NK cell percentages and intrahepatic NK cell percentages in patients with advanced hepatic fibrosis. Lower blood availability of specific NK subsets in patients with chronic type C hepatitis might be a cause of progression of liver fibrosis via insufficient control over hepatic stellate cells.

Clinical features and immunological markers of atopic dermatitis in elderly patients.

BACKGROUND: Atopic dermatitis (AD) is increasing among the elderly. Staphylococcus aureus colonization is one of the most important aggravating factors in AD. OBJECTIVE: This study analyses the clinical features of AD in elderly patients and determines the pathogenic roles of staphylococcal superantigens in AD with low and high total IgE levels. METHODS: S. aureus enterotoxin genes were evaluated using PCR. Additionally, S. aureus-specific IgE levels and peripheral blood lymphocyte profiles were assessed. RESULTS: A total of 44 women and 77 men diagnosed with AD with a mean age of 68.92 ± 6.51 years were evaluated. In 17 (68%) patients with AD and low levels of total IgE, there was a positive correlation between the positive results for enterotoxin B, S. aureus-specific IgE antibodies and Th1 cytokine profiles (Spearman's rank correlation test, r = 0.89, p < 0.05). CONCLUSION: Our results indicate that AD patients with low total IgE levels differ in immunopathogenesis from AD patients with high circulating levels of total IgE AD.

Serum TARC and CTACK concentrations in children with atopic dermatitis, allergic asthma, and urticaria.

BACKGROUND: Thymus and activation-regulated chemokine (TARC/CCL17) and cutaneous T cell-attracting chemokine (CTACK/CCL27) belong to the CC chemokine family, which plays an important role in immune-inflammatory processes. It has been demonstrated that serum concentrations of TARC and CTACK are increased in patients with various allergic diseases. AIM: To compare serum TARC and CTACK concentrations between children with different clinical manifestation of mast cell-dependent diseases, such as atopic allergy and urticaria. METHODS: A total of 87 children including 26 with mild to severe atopic dermatitis (AD), 43 children with controlled allergic asthma symptoms (treated and untreated with anti-inflammatory drugs), and 18 children with urticaria were recruited into the study. The control group consisted of 31 healthy non-atopic children. RESULTS: Serum concentrations of TARC and CTACK were significantly higher in children with AD than in healthy controls. No significant differences in serum concentrations of the chemokines between asthmatics, urticaria patients, and healthy controls were found. The severity of AD symptoms significantly correlated with serum CTACK and TARC concentrations. CONCLUSION: These findings, in conjunction with earlier data, indicate that differences may exist in circulating concentrations of TARC and CTACK, between patients with atopic allergy and urticaria.

Nutritional Status and Selected Adipokines in Children with Irritable Bowel Syndrome.

BACKGROUND: The aim of this study was to assess the nutritional status and serum concentrations of adipokines in children with irritable bowel syndrome (IBS) and healthy controls. We also sought to evaluate their relation to metabolic parameters. METHODS: We studied 33 IBS patients (11 girls, 22 boys) aged 5-17 years and 30 healthy age-matched controls (11 girls, 19 boys). The analysis included anthropometric measurements, body composition parameter measurements using bioimpedance, and biochemical tests and measurements of serum concentrations of leptin, adiponectin, chemerin, and omentin-1. RESULTS: The results of the anthropometric measurements were comparable between the patients and the controls. The patients had higher triglycerides, HOMA-IRs, and chemerin concentrations than the healthy subjects. The HDL cholesterol and omentin-1 levels were lower than in the controls. Leptin and adiponectin did not differ significantly between the groups. An analysis of the receiver operator curves (ROCs) showed that serum concentrations of chemerin ≥ 232.8 ng/mL had 30% sensitivity and 87% specificity when they were used to differentiate between children with IBS and healthy subjects. In the case of serum omentin-1 concentrations ≤ 279.4 ng/mL, the sensitivity and specificity were 60% and 80%, respectively. CONCLUSIONS: The nutritional status of children with IBS did not differ from that of the healthy controls. We found significant differences in serum chemerin and omentin-1 concentrations between IBS patients and healthy children. These adipokines could be used as IBS biomarkers as they demonstrate good specificity and moderate sensitivity. The serum concentrations of chemerin and omentin-1 in IBS patients were related to nutritional status and insulin resistance.

[Dementia--distribution and diagnostic criteria]. / Otepienia--podzial i kryteria diagnostyczne.

The ageing of the population makes the health problems of elderly people a major issue in the work of various specialists. More and more people show cognitive functions disorders from minor to considerable ones. The most common cause of dementia is Alzheimer's disease. The diagnostic criteria of dementia in the course of Alzheimer's disease or the criteria of vascular dementia are described in this article. Although we mention the scales focused on cognitive functions disorders.

Exocrine Pancreatic Function in Girls with Anorexia Nervosa.

OBJECTIVES: To assess pancreatic exocrine function in patients with anorexia nervosa using a breath test with 13C-labeled mixed triglycerides (MTG-BT) and to determine the relationship between the test results and selected biochemical and hormonal parameters. MATERIAL AND METHODS: Anthropometric measurements, biochemical and hormonal parameters (serum leptin, soluble leptin receptor (sLR), acylated and desacylated ghrelin, free leptin index (FLI)), and MTG-BT were performed in a group of 31 girls with the restrictive type of AN, as well as 38 healthy girls (C). RESULTS: The average cumulative dose of 13C-triglycerides recovered with exhaled air (%CD) was similar in both study groups, while the average time from 13C-triglycerides administration to peak 13CO2 excretion in expired air (time to peak (TTP)) was significantly longer in patients with AN compared to C. In both groups, %CD correlated negatively with FLI. TTP correlated negatively with sLR and FLI in the AN and with serum insulin and HOMA-IR values in the C. CONCLUSIONS: In girls with AN, the pancreatic efficiency of lipase secretion was found to be normal, while the kinetics of this enzyme secretion were disturbed. These changes may result from disorders in the functioning of the adipose-insular and islet-acinar axes.

Chemokine receptors on peripheral blood T lymphocytes in children on peritoneal dialysis.

BACKGROUND: Immune cell dysfunction is listed among complications resulting from chronic kidney disease (CKD). It could be associated with T-cells, which play a role in the lymphocytic migration and infiltration. However, the data on chemokine receptors expression on T-cells in patients with CKD particularly treated with peritoneal dialysis (PD) are still limited. METHODS: The study aimed at multiparameter flow-cytometric analysis of the absolute numbers and percentage of T-cell subsets with surface chemokine receptors (CCR4, CCR5, CCR7, CXCR3, and CXCR4) or receptors' combinations in 47 children treated with PD. RESULTS: We found lower absolute numbers of total T lymphocytes, lymphocytes with surface CCR5, CXCR4+CCR5, CXCR3+CCR5 antigens and T-cells with CCR4, CCR4+CD4, CXCR3, CXCR3+CD4, and CD8 receptors. Lymphocytes T with CD4, CCR7, CD28+CCR7, CXCR3+CD8 antigens showed higher percentage in children on PD as compared to healthy children and opposite percentage values of CCR4+, CCR4+CD4+, CXCR3+ T lymphocytes were diminished. Mean fluorescent intensity for CCR7+, CCR7+CD45RO+, CCR7+CD28+, CXCR4+CD4+, CCR5+CD4+, CCR4+, CCR4+CD4+ T-cells was lower in the PD group than in healthy children. The analysis of correlation between T lymphocyte subpopulations with chemokine receptors and other parameters revealed positive correlation of CCR7+ and CCR7+CD28+ T-cells and weekly creatinine clearance, negative correlation between the percentage of CD45RO+CCR7 antigen positive T-cells and KT/Vurea. SUMMARY: In conclusion, we could not confirm the phenomenon of earlier senescence of T-cells in children with CKD on PD treatment. This still requires further investigation. The higher percentage of T-cells with CCR7 surface receptor could be responsible for the increase of proliferation activity in this group of children.

Cytokine production by peripheral blood CD4+ and CD8+ T cells in atopic childhood asthma.

There are conflicting studies on T cell cytokine production in childhood asthma. In this study intracellular cytokine expression of IL-2, IL-4, IL-10, IL-13, IFN-γ, and TNF-α in CD4(+) and CD8(+) T cells in children with atopic asthma were measured by flow cytometry. Results. A significant increase in the percentage of CD4(+) and CD8(+) T cells producing IL-4 and IL-13 and decrease in the percentage of CD4(+) producing IFN-γ in asthmatic children was found. The percentage of CD4(+)/IL-13(+) was significantly higher in severe asthma than in children with intermittent disease symptoms. Severity of asthma was associated with increased both serum IgE and frequencies of CD4(+)/IL-13(+) T cells, as well as duration of disease. Moreover, a decrease in FEV(1), FEV(1)/FVC was observed in relation to the severity of asthma. Changes in cytokine profile in CD8(+) subpopulation didn't depend on the severity of the disease. Conclusions. Increased production of IL-4 and IL-13 in both CD4(+) and CD8(+) T cells accompanied by decreased IFN-γ expression in CD4(+) T cells may be evidence that both lymphocyte subpopulations are implicated in the pathogenesis of asthma. Relationship of CD4(+)/IL-13(+) T cells with disease activity suggests that this lymphocyte subset may have a prominent role in childhood asthma.

Chalcones and dihydrochalcones augment TRAIL-mediated apoptosis in prostate cancer cells.

Chalcones and dihydrochalcones exhibit chemopreventive and antitumor activity. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a natural endogenous anticancer agent. We examined the cytotoxic and apoptotic effect of chalcones and dihydrochalcones on TRAIL-mediated apoptosis in LNCaP prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was detected using annexin V-FITC by flow cytometry and fluorescence microscopy. The DeltaPsim was evaluated using DePsipher staining by fluorescence microscopy. Our study showed that two tested chalcones (chalcone and 2',6'dihydroxy-4'-methoxychalcone) and three dihydrochalcones (2',6'-dihydroxy-4'4-dimethoxydihydrochalcone, 2',6'-dihydroxy-4'-methoxydihydro- chalcone, and 2',4',6'-trihydroxydihydrochalcone, called phloretin) markedly augmented TRAIL-induced apoptosis and cytotoxicity in LNCaP cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer.

The concentration of insulin-like growth factor-1 in pregnancies complicated by pregnancy-induced hypertension and/or intrauterine hypotrophy.

OBJECTIVES: The aim of the study was to compare Insulin-like Growth Factor-1 (IGF-1)concentration in pregnancies complicated by pregnancy-induced hypertension and/or intrauterine hypotrophy, and its correlation with maternal pressure and umbilical artery pulsatility and resistance indices. MATERIAL AND METHODS: 65 pairs pregnant-newborn were included to four groups: I - control, II - PIH, III - Hypotrophy, IV - PIH and Hypotrophy. In the study we analyzed cord blood IGF-1 concentration, newborns antropometry, umbilical artery pulsatility and resistance indices and maternal pressure before delivery. RESULTS: The concentration of IGF-1 was the lowest in IV group of hypotrophic newborns from pregnancies complicated by pregnancy-induced hypertension. In this group of patients there was strong negative correlation between IGF-1 concentration and maternal systolic and diastolic pressure. CONCLUSIONS: There is a strong negative correlation between IGF-1 concentration and maternal systolic pressure in group of hypotrophic newborns from pregnancies complicated by pregnancy-induced hypertension.