Inhibition of cyclooxygenase 2 in mice increases production of g-csf and induces radioprotection.

Meloxicam, a selective inhibitor of cyclooxygenase 2, was tested to determine its ability to modulate hematopoiesis and to influence survival of mid-lethally gamma-irradiated mice. A single dose of meloxicam (20 mg/kg) administered to mice intraperitoneally 1 h before irradiation was shown to enhance serum levels of granulocyte colony-stimulating factor (G-CSF) during the first 24 h after irradiation, to elevate numbers of granulocytic precursor cells in bone marrow and granulocyte counts in peripheral blood on day 10 after irradiation, and to increase 30-day survival of these mice. The results provide new evidence for the protective ability of meloxicam administration to mice irradiated with mid-lethal doses and contribute to the understanding of the mechanisms of this meloxicam action by drawing attention to the possible role of increased endogenous G-CSF production.

The association of interleukin-4 haplotypes with chronic periodontitis in a Czech population.

Background: Cytokine gene polymorphisms are known to influence the susceptibility and disease course of many chronic disorders. Recently, interleukin (IL)-4 gene polymorphisms were associated with aggressive periodontitis. The aim of this study was to test differences in the distribution of the IL-4 alleles, genotypes, and haplotypes between patients with chronic periodontitis (CP) and healthy controls in a Czech population.

Haplotype analysis of the NADPH oxidase p22 phox gene in patients with bronchial asthma.

Background: Superoxide produced by airway epithelial and inflammatory cells may contribute to the pathogenesis of asthma. NADPH oxidase (an enzyme complex made up of 5 subunits) is a major source of superoxide in cells. We sought to elucidate the role of genetic variability in the gene encoding the p22(phox) subunit of the NADPH oxidase (CYBA, 16q24.

Clinical and molecular-genetic markers of ADHD in children.

Objectives: The objective was to make a contribution to deepening the knowledge of the etiopathogenesis of ADHD.

Design: In an association study design, an analysis of polymorphisms of selected genes was conducted in 119 hyperkinetic boys and a control group of boys, aged 7-13. Furthermore several psychologically determined subgroups were identified.

Haplotype analysis of the endothelial nitric oxide synthase gene in asthma.

Nitric oxide (NO) is an important mediator of physiologic processes in the airways. Evidence exists that genetic factors affect NO formation and contribute to the pathophysiology of asthma. The aims of this study were to determine the endothelial NO synthase (eNOS) haplotypes in Czech asthmatics and control subjects and examine their relation to asthma.

Association of interleukin-6 (IL-6) haplotypes with plaque-induced gingivitis in children.

Objectives: The proinflammatory cytokine interleukin-6 (IL-6) is a key regulator of the host response to microbial infection and major modulator of extracellular matrix catabolism and bone resorption. The aim of this case-control study was to test differences between children with and without gingivitis in the distribution of IL-6 alleles at positions -174, -572, and -597 and their haplotypes.

Material And Methods: A total of 455 Caucasian children, aged 11 to 13 years, were enrolled in this study.

Homeostatic action of adenosine A3 and A1 receptor agonists on proliferation of hematopoietic precursor cells.

Two adenosine receptor agonists, N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) and N6-cyclopentyladenosine (CPA), which selectively activate adenosine A3 and A1 receptors, respectively, were tested for their ability to influence proliferation of granulocytic and erythroid cells in femoral bone marrow of mice using morphological criteria. Agonists were given intraperitoneally to mice in repeated isomolar doses of 200 nmol/kg. Three variants of experiments were performed to investigate the action of the agonists under normal resting state of mice and in phases of cell depletion and subsequent regeneration after treatment with the cytotoxic drug 5-fluorouracil.

Activation of adenosine A(3) receptors potentiates stimulatory effects of IL-3, SCF, and GM-CSF on mouse granulocyte-macrophage hematopoietic progenitor cells.

Adenosine A(3) receptor agonist N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) has been tested from the point of view of potentiating the effects of hematopoietic growth factors interleukin-3 (IL-3), stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) on the growth of hematopoietic progenitor cells for granulocytes and macrophages (GM-CFC) in suspension of normal mouse bone marrow cells in vitro. IB-MECA alone induced no GM-CFC growth. Significant elevation of numbers of GM-CFC evoked by the combinations of IB-MECA with IL-3, SCF, or GM-CSF as compared with these growth factors alone has been noted.

[Definition of 24 hour ambulatory blood pressure values corresponding to office blood pressure values of 130/80 mm Hg].

Background: Ambulatory blood pressure monitoring (ABPM) provides a profile of blood pressure (BP) away from the medical environment and has been shown to be a stronger predictor of cardiovascular morbidity and mortality than office BP measurement. There are known the normal BP values for ABPM in general population with office BP value 140/90 mm Hg, but don't are known normal values for ABPM of patients with high risk hypertension which needs to have office BP below 130/80 mm Hg.

Aim Of Study: Definition of normal BP value of ABPM in patients with office BP130 and/or 80 mm Hg.

Effect of adenosine on the growth of human T-lymphocyte leukemia cell line MOLT-4.

Adenosine has been observed to suppress the growth of MOLT-4 human leukemia cells in vitro. Changes in the cell cycle, especially increased percentage of cells in S phase, prolonged generation time, and induction of apoptosis at higher adenosine concentrations have been found to be responsible for the growth suppression. Dipyridamole, a drug inhibiting the cellular uptake of adenosine, reversed partially but significantly the adenosine-induced growth suppression.

HFE C282Y gene variant is a risk factor for the progression to decompensated liver disease in chronic viral hepatitis C subjects in the Czech population.

Aim: To determine the prevalence of selected HFE polymorphisms (C282Y, H63D and S65C) among patients with chronic viral hepatitis B and C and to investigate their role in the progression of liver disease.

Methods: A total of 207 subjects with chronic B or C viral hepatitis and 243 healthy controls were enrolled in the case-control study. Cases were further classified into three groups according to the clinical stage of liver disease: (A) virus carriers; (B) compensated liver disease; and (C) decompensated liver disease.

Meloxicam, an inhibitor of cyclooxygenase-2, increases the level of serum G-CSF and might be usable as an auxiliary means in G-CSF therapy.

Hematopoiesis-modulating action of meloxicam, a cyclooxyge-nase-2 inhibitor, has been evaluated in mice. Increased serum level of granulocyte colony-stimulating factor (G-CSF) after meloxicam administration has been found in sublethally gamma-irradiated animals. In further experiments hematopoiesis-stimulating effects of meloxicam and G-CSF given alone or in combination have been investigated.

Adenosine A(3) receptor agonist acts as a homeostatic regulator of bone marrow hematopoiesis.

The present study was performed to define the optimum conditions of the stimulatory action of the adenosine A(3) receptor agonist, N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA), on bone marrow hematopoiesis in mice. Effects of 2-day treatment with IB-MECA given at single doses of 200nmol/kg twice daily were investigated in normal mice and in mice whose femoral bone marrow cells were either depleted or regenerating after pretreatment with the cytotoxic drug 5-fluorouracil. Morphological criteria were used to determine the proliferation state of the granulocytic and erythroid cell systems.

Interleukin-18 and its three gene polymorphisms relating to allergic rhinitis.

The study aimed to examine an association of three different single nucleotide polymorphisms (SNPs) of the IL-18 gene (-607 C/A, -137 G/C and -133 C/G) on chromosome 11q22 with allergic rhinitis (AR). Genotyping for the SNPs was performed using 539 patients with AR and 312 healthy control volunteers. Positivity to the skin prick test for the fungus Alternaria sp.

Analysis of the inducible nitric oxide synthase gene polymorphisms in Czech patients with atopic diseases.

Background: Nitric oxide (NO) is an important mediator of physiologic processes in the airways; it plays a significant role in the regulation of the T helper type 1/type 2 balance and contributes to the development of atopic diseases.

Objective: We analysed several polymorphisms mainly in the promoter region of the inducible NO synthase (NOS2, iNOS) gene and investigated their associations with asthma and/or atopic phenotypes.

Methods: We performed a case-control study in 994 subjects (661 patients with atopic disorders, with subgroups of 304 patients with allergic asthma, and 333 healthy individuals), matched for sex, living in the same geographical area.

Polymorphisms of the CD14 gene and atopic phenotypes in Czech patients with IgE-mediated allergy.

IgE-mediated allergy is a common chronic disorder resulting from interactions between genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localised on chromosome 5q31.1, a region linked to asthma and bronchial hyperresponsiveness.

Meloxicam, a cyclooxygenase 2 inhibitor, supports hematopoietic recovery in gamma-irradiated mice.

Meloxicam, a selective inhibitor of cyclooxygenase 2, a nonsteroidal anti-inflammatory drug with an improved side-effects profile in terms of gastrointestinal toxicity, has been found to stimulate hematopoiesis in whole-body gamma-irradiated mice. A distinct corroboration of this positive action of meloxicam is an enhancement of the recovery of hematopoietic progenitor cells committed to granulocyte-macrophage and erythroid development, which has been demonstrated in sublethally irradiated animals treated with meloxicam at a dose of 20 mg/kg administered intraperitoneally either singly 1 h before irradiation or repeatedly after radiation exposure. The results suggest that meloxicam can be added to the list of biological response modifiers that can be used in the treatment of hematopoietic damage induced by ionizing radiation.

Drugs elevating extracellular adenosine administered in vivo induce serum colony-stimulating activity and interleukin-6 in mice.

Our previous studies have shown that the combined administration of drugs elevating extracellular adenosine, i.e. dipyridamole (DP) and adenosine monophosphate (AMP), enhances murine hematopoiesis and potentiates the action of granulocyte colony-stimulating factor (G-CSF).

Association study of promoter polymorphisms within the NOS3 gene and allergic diseases.

Background: Nitric oxide (NO) is an important mediator of physiologic and pathologic processes in the airways. On this basis, we hypothesized that polymorphisms in the NOS3 gene could be associated with the disease process.

Methods: Two promoter variants (-786C/T and -691C/T) were examined in a Caucasian Czech population of allergic patients [n = 671, with a subgroup of asthmatics (n = 305)] and healthy controls (n = 334) using PCR-RFLP analyses.

The association of monoamine oxidase B functional polymorphism with postoperative pain intensity.

Objectives: The monoamine oxidase B (MAO-B) is an enzyme involved in metabolism of dopamine, benzylamine, phenylethylamine, tyramine and tryptamine. The A/G polymorphism in intron 13 of the MAO-B gene has been previously found to be associated with variability of the MAO-B enzyme activity. The aim of the present association study has been to examine the relationship between the A/G polymorphism in intron 13 and postoperative pain intensity.

Polymorphism of DRD2 gene and ADHD.

Objectives: Attention deficit hyperactivity disorder (ADHD) is a prevalent childhood disorder. Evidence from the family and twin studies suggest that ADHD is familiar and highly heritable. Association studies are frequently used for the searching of markers responsible for genetic basis of ADHD.

The association between high-activity COMT allele and alcoholism.

Objectives: The catechol-O-methyltransferase (COMT) is an enzyme involved in the metabolism of dopamine, adrenaline and noradrenaline. The Val158Met polymorphism of the COMT gene has been previously associated with a variability of the COMT activity, and alcoholism. The aim of the present association study was to examine the relationship between the Val158Met polymorphism of the COMT gene and dispositions to alcoholism.

Effects of adenosine A(3) receptor agonist on bone marrow granulocytic system in 5-fluorouracil-treated mice.

The purpose of the experiments reported was to investigate effects of N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA), a selective adenosine A(3) receptor agonist, on the granulocytic system in femoral marrow of mice depleted by the cytotoxic drug 5-fluorouracil. In the phase of the highest cell depletion IB-MECA was injected i.p.

[The relation of GERD, bronchial asthma and the upper respiratory tract].

Unlabelled: Gastroesophageal reflux disease (GERD) is one of the most common diseases affecting upper gastrointestinal tract. It is a chronic disease, whith stadily growing incidence and prevalence in west countries during last 30 years. GERD is caused by pathologic gastroesophageal reflux (GER).

Adenosine potentiates stimulatory effects on granulocyte-macrophage hematopoietic progenitor cells in vitro of IL-3 and SCF, but not those of G-CSF, GM-CSF and IL-11.

The aim of the studies was to ascertain if adenosine is able to co-operate with selected hematopoietic growth factors and cytokines, namely with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), interleukin-3 (IL-3), and interleukin-11 (IL-11), in inducing the growth of colonies from hematopoietic progenitor cells for granulocytes and macrophages (GM-CFC) from normal bone marrow cells in vitro. Adenosine was found not to produce any colonies when present in the cultures as the only potential stimulator. All the tested cytokines and growth factors were observed to induce the growth of distinct numbers of GM-CFC colonies, with the exception of IL-11.