Prostaglandin E2 systemic production in patients with asthma with and without aspirin hypersensitivity.

Background: A special regulatory role for prostaglandin E2 has been postulated in aspirin-induced asthma. A study was undertaken to investigate the effects of aspirin on the systemic production of prostaglandin E2 and cysteinyl leucotrienes in patients with asthma.

Methods: The urinary concentrations were determined of two main prostaglandin E2 metabolites (13,14-dihydro-15keto-PGE2 using a commercial enzyme immunoassay and 9,15-dioxo-11alpha-hydroxy-2,3,4,5-tetranor-prostane-1,20-dioic acid by gas chromatography/mass spectrometry) and leucotriene E4 using an immunoassay.

Rapid and inexpensive detection of alpha1-antitrypsin deficiency-related alleles S and Z by a real-time polymerase chain reaction suitable for a large-scale population-based screening.

alpha(1)-Antitrypsin (AAT) deficiency is one of the most common genetic disorders in Caucasians, leading to early onset pulmonary emphysema and/or liver disorders. Accumulating data suggest that AAT deficiency is commonly under-recognized or misdiagnosed by physicians. The need for a rapid, timesaving, and relatively inexpensive but reliable detection method for the two most common deficiency alleles was developed using real-time polymerase chain reaction (PCR) genotyping.

[Allelic variant 6' at locus D13S317 in a paternity casework; a semi-automatic genotyping problem].

During a routine paternity casework, performed with automated genotyping using an AmpFISTR Identifiler kit, an inconsistency affecting maternal segregation of D13S317 allele was encountered, manually detected as a variant allele in the mother and child. Alleles of the putative father were transmitted in 13 out of 15 autosomal STR loci, but in CSF1PO locus, there was an apparent mutation. We, therefore, directly sequenced the variant D13S317 allele in the mother and the child and compared the results to the available data on variant alleles within this STR locus.

The alpha-chain of high-affinity receptor for IgE (FcepsilonRIalpha) gene polymorphisms and serum IgE levels.

Background: The high-affinity receptor for immunoglobulin-E (IgE) (FcepsilonRI) plays a major role in the pathogenesis of allergy, but there are only two published studies on its alpha subunit (FcepsilonRIalpha) genetic variability in allergic diseases.

Aims Of The Study: Mutational screening in the region of the FcepsilonRIalpha gene promoter and the first exon with subsequent genetic variability assessment in allergic patients and a random population sample.

Methods: Allergic subjects were individuals with asthma or urticaria.

Valine/Leucine247 polymorphism of beta2-glycoprotein I in patients with antiphospholipid syndrome: lack of association with anti-beta2-glycoprotein I antibodies.

In antiphospholipid syndrome (APS) the presence of anti-beta2-glycoprotein I (beta2GPI) antibodies is strongly associated with thromboembolic complications. It has been suggested that the common beta2GPI Valine/Leucine247 (Val/Leu247) polymorphism could be found more commonly in APS and might influence the generation of anti-beta2GPI antibodies. Therefore we studied beta2GPI Val/Leu247 single-nucleotide polymorphism (SNP) by PCR in 338 patients with various autoimmune diseases (46 with secondary and 84 with primary APS) and 147 sex and age-matched healthy controls.

Antithrombotic effects of aspirin based on PLA1/A2 glycoprotein IIIa polymorphism in patients with coronary artery disease.

Objective: The diallelic glycoprotein IIIa polymorphism P1A1/A2 was attributed to be an inherited risk factor for coronary events. Whether this polymorphism affects response to aspirin in patients with coronary artery disease is not known.

Methods: We assessed thrombin generation (prothrombin fragment F1+2) in consecutive blood samples collected from bleeding-time wounds in 28 men with coronary artery disease; P1A2 carriers, n=9; P1A1/A1, n=19.

[Interleukin-1beta C+3953T gene polymorphism and peripheral arterial occlusive disease in Polish population].

The proinflammatory cytokines, like interleukine-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), have been suggested to play a role in the development of atherosclerotic conditions, e.g. peripheral arterial occlusive disease (PAOD).

The broken balance in aspirin hypersensitivity.

Aspirin was introduced into medicine over a century ago and has become the most popular drug in the world. Although the first hypersensitivity reaction was described soon after aspirin had been marketed, only recently a phenomenon of cysteinyl leukotriene overproduction brought new insights on a balance between pro- and anti-inflammatory mediators derived from arachidonic acid. We describe the most common clinical presentations of aspirin hypersensitivity, i.

Familial aggregation of aspirin-induced urticaria and leukotriene C synthase allelic variant.

Background: We have reported that in patients with chronic idiopathic urticaria (CIU) who reacted adversely to aspirin, the frequency of the (-444)C allele of the leukotriene C(4) synthase gene (LTC4S) was higher than in patients who tolerated aspirin well.

Objectives: To study the pattern of aspirin-induced urticaria (AIU) in two families, with special interest on the polymorphisms of LTC4S (AA, AC, CC) and the glutathione S-transferase M1 and P1 genes (GSTM1 and GSTP1).

Methods: Of 74 patients with CIU and a history of aspirin hypersensitivity studied by us, two patients (probands) gave a family history of aspirin intolerance.

Towards a multidisciplinary and integrated strategy in the assessment of adverse health effects related to air pollution: the case study of Cracow (Poland) and asthma.

Complex interaction between anthropogenic activities, air quality and human health in urban areas, such as in Cracow sustains the need for the development of an interdisciplinary and integrated risk-assessment methodology. In such purpose, we propose a pilot study performed on asthmatics and based on a combined use of a biomarker, such as metallothionein 2A (MT-2A) in the characterization of human exposure to one or a mixture of pollutants and of Geographical Information Systems (G.I.

Aspirin resistance.

Aspirin protects many though not all patients from acute cardiovascular events. It is generally accepted that such prophylactic effect depends mainly on the antithrombotic action involving inhibition of thromboxane A(2) production and platelet aggregation. In many patients aspirin failure to protect against cardiovascular event is obvious, as their symptoms simply cannot be controlled by the administration of a single drug.

Anti-thrombotic action of clopidogrel and P1(A1/A2) polymorphism of beta3 integrin in patients with coronary artery disease not being treated with aspirin.

Individual variability in response to clopidogrel is known but its mechanism is poorly understood. We examined the relationship between glycoprotein IIIa polymorphism P1(A1/A2) and anti-thrombotic actions of clopidogrel. Clopidogrel (75 mg/d; 2 weeks) was administered to 48 normolipemic patients with coronary artery disease.

Prediction of the excessive perioperative bleeding in patients undergoing coronary artery bypass grafting: role of aspirin and platelet glycoprotein IIIa polymorphism.

Objective: The presence of the glycoprotein IIIa allele PlA2 is associated with enhanced thrombin formation and an impaired antithrombotic action of aspirin, which could favor coronary thrombosis. We wondered whether PlA1/A2 genetic polymorphism could affect the postoperative bleeding in patients undergoing coronary artery bypass grafting. We also aimed to assess the effects of aspirin pretreatment and to ascertain the value of platelet function studies as predictors of postoperative bleeding.

Aspirin resistance.

Treatment failures occur with any drug and aspirin is no exception. Evidence is growing to indicate that there are subpopulations that do not respond to antithrombotic action of aspirin. The term 'aspirin resistance' has been used to describe a number of different phenomena, including inability of aspirin to: (i) protect against cardiovascular events despite its regular intake; (ii) to affect various laboratory tests, reflecting platelet activity.

Genetic polymorphisms in chronic obstructive pulmonary disease.

Etiology of chronic obstructive pulmonary disease remains unknown but, despite some inconsistencies in reports on inflammatory cells, mediators and proteases involved in the pathogenesis of chronic obstructive pulmonary disease, genetic risk factors were proposed as a cause of susceptibility to the disease. Results of many studies suggested polygenic inheritance, with the genetic component consisting of several genes of a small effect each, rather than of single major gene. We are going to review the clinical importance of alpha-1 antitrypsin, glutathione S-transferase, microsomal epoxide hydrolase, matrix metalloproteinase, tumor necrosis factor-a, alpha-1 antichymotrypsin, alpha 2-macroglobulin, cytochrome P4501A1, heme oxygenase-1 genes polymorphisms associated with susceptibility and progression of the chronic obstructive pulmonary disease.

Exhaled eicosanoids following oral aspirin challenge in asthmatic patients.

Background: Biochemical analysis of expiratory breath condensate is an emerging non-invasive technique for assessment of airway inflammation.

Objective: We wondered whether application of expiratory breath condensate could facilitate diagnosis of aspirin-intolerant asthma and reproduce eicosanoids mediators' abnormalities described in this disease.

Methods: We measured prostaglandins (PGs) E(2), F(2 alpha), 9 alpha 11 beta F(2) and iso-F(2) by gas-chromatography/mass-spectrometry and cysteinyl leukotrienes (cys-LTs) by radioimmunoassay in breath condensates of asthmatic patients undergoing oral aspirin challenge.

[Hereditary hemochromatosis: molecular diagnosis and effect of treatment].

Hereditary hemochromatosis is a genetic disorder, inherited as an autosomal recessive trait, characterized by iron overload. A single mutation (C282Y) in the HFE gene is found in more than 90% of these patients. We report the case of a 50-year-old man, with clinical symptoms of hemochromatosis, who was found to be homozygous for the C282Y mutation.

Functional effects and gender association of COX-2 gene polymorphism G-765C in bronchial asthma.

Background: Prostaglandins, generated via the COX pathways, are essential mediators of inflammation in bronchial asthma. The promoter polymorphism of COX-2 gene (G-765C), which might affect binding of transcription factors, has recently been described

Objective: To study distribution and function of the genetic COX-2 variant in patients with asthma compared with healthy controls.

Methods: Three groups of adults were studied: (1) patients with aspirin-induced asthma (AIA; n=112), (2) asthmatic patients who tolerated aspirin (ATA; n=198), and (3) a random population sample from city of Krakow (n=547).