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Biomedical subjects

P Kuna

Publications and source records attributed to P Kuna.

At least 37 records · Page 2Linked to original sources
PubMed2000

[New aspects of use inhaled steroids in treatment of children with bronchial asthma].

The development of potent glucocorticoids (GC) delivered topically via metered dose inhalers (MDI) have revolutionized the way we care for asthmatic children. Steroids can improve asthma symptoms, baseline pulmonary function, and reduce bronchial hyperresponsiveness (BHR) to the extent no other asthma medication can. In addition, the fact that small quantities of GC are delivered topically, the incidence of adverse effects is greatly diminished. Inhaled GC therapy has become first line therapy for all children even with mild persistent asthma, and their early use in life is known as "early intervention". The results from many studies suggest that the longer the time from the initiation of symptoms, and subsequent treatment with inhaled GC, the less effective this form of therapy may be. Also, early intervention and long-term therapy may offer the potential to effect long-term outcome. Unfortunately, systemic absorption does occur, and with that comes the potential for adverse effects. Growth suppression and bone metabolism effects remain the most feared, controversial, and inadequately addressed issues facing long-term inhaled GC therapy. In general, the development of adverse effects from inhaled GC therapy is dependent on the dose and the frequency with which the inhaled GC is given. They can also be minimized by using a spacer device, turbuhaler, mouth rinsing. It is important to define maximally safe and effective doses of the available inhaled GC and corresponding delivery systems.

Administration, Inhalation↗
PubMed2000

[Hypersensitivity to cockroach allergen among children with bronchial asthma living in the Łódź district].

Asthma morbidity increase every year, especially among children. The cause of this is multifactorial, but exposure to high levels of indoor allergens is thought to be one important factor, since we spend the large fraction (appx. 90%) of time indoors. Next to other popular indoor allergens (i.e. dust mites), many studies underline the importance of cockroach allergen. The purpose of this study was to evaluate the prevalence and importance of cockroach allergen in asthma among children in Łódź district. One hundred and sixty children, age 4-17, with bronchial asthma, were participated in this study. Each patient was examined, had skin prick test with common and cockroach allergens, measured total IgE level and undergone spirometry. Children with positive skin test to cockroach allergen had also measured specific IgE level to this antigen (immunoassay, CAP system). Our results showed that the most common allergen (by skin test), among these children, was dust mite 51.3%, followed by pollen 48.8% and cockroach allergen 24.3%. Among children with hypersensitivity to cockroach allergen 62% had also positive skin test with house dust mite and 59% with pollen. Average time of asthma duration in patients sensitive to cockroach antigen was 4 years and was similar to that of patients sensitive to dust mites and pollen. In children with cockroach sensitivity 13% had mild asthma, 26% moderate and 61% had severe asthma. We concluded that children with cockroach hypersensitivity have severe asthma more often than children with dust and pollen sensitivity. Class 3 and 4 in specific IgE levels correlated with severity of asthma. Our results showed that in children of Łódź distict, cockroach allergen is very important factor of sensitivity, next to dust mites and pollen. Hypersensitivity to cockroach antigen seems to influence the course and severity of asthma in children.

Adolescent↗
PubMed2000

[The role of leukotrienes and the effect of leukotriene receptor antagonists in allergic rhinitis].

Allergic rhinitis is associated with persistent inflammation of nasal mucosa. Characteristic feature of this inflammation is an accumulation of eosinophils. These cells are the major source of cysteinyl leukotrienes--potent pro-inflammatory mediators responsible for nasal blockade, rhinorrhoea and hyperresponsiveness. Because leukotriene receptor antagonists inhibit activity of endogenous leukotrienes and decrease tissue eosinophilia it is speculated that these drugs may be useful also in the management of allergic rhinitis. This article is an overview of the publication on the role of leukotrienes in allergic rhinitis and the effect of leukotriene receptor antagonists.

Humans↗
PubMed1999

[The role of leukotrienes in inflammation and leukotriene inhibitors].

Over recent years it has become widely accepted that asthma is a chronic persistent inflammatory condition regulated by a variety of inflammatory cells and mediators such as leukotrienes. It has been shown that there are increased levels of cysteinyl leukotrienes in biological fluids from patient with chronic asthma and in acute bronchospasm experimentally induced by allergen or other stimuli. The evidence suggests that blocking the formation or action of cysteinyl leukotrienes may be benefit in the treatment of chronic inflammatory diseases. In this article the leukotriene pathway, the biological role of these lipid mediators and their antagonists are widely characterised. There are three groups of leukotriene inhibitors: 5-lipooxygenase inhibitors, FLAP (activating protein) inhibitors and Cys-Lt1 receptor antagonists. On Polish market two representative drugs are currently: montelukast and zafirlukast, both leukotriene receptor antagonists. They bind competitively and selectively to Cys-Lt1 receptors blocking the pro-inflammatory effects of the cysteinyl leukotrienes. They offer protection against cold, dry air or exercise-induced bronchoconstriction significantly greater than placebo. These agents produce a modest improvement in lung function, symptom control and reduce the need for short acting inhaled beta2-agonist therapy. Some guidelines suggest that they may be considered as an alternative treatment to low dose inhaled corticosteroid therapy and cromones therapy of mild persistent asthma. It seems likely that aspirin-sensitive asthmatic patients may be benefited by LTD4-antagonists. These drugs have the great advantage of efficacy by oral administration and they do not appear any class-specific side effects. Also some basic information about zileuton--5-lipooxygenase inhibitor are given. Due to its induction of hepatic enzyme activity zileuton is not available in Poland, but it is important agent in evaluation of the leukotriene inhibitors in some models of inflammation. The introduction of leukotriene antagonists is undoubtedly an important breakthrough in asthma therapy.

Acetates↗
PubMed1998

Audiological abnormalities in the Klippel-Feil syndrome.

Klippel-Feil syndrome (KFS) is defined as a short neck with decreased movement and low posterior hairline. Radiologically, there is a failure of cervical segmentation. Deafness is a well known associated feature and may be of sensorineural, conductive, or mixed type. The audiological assessment of 44 patients with KFS is reported. Thirty five were found to have abnormalities on audiological testing. The presence of other features in these patients, reviews of data from other reports, and the need for further study are discussed.

Adolescent↗
PubMed1998

RANTES induces nasal mucosal inflammation rich in eosinophils, basophils, and lymphocytes in vivo.

RANTES is a CC chemokine that causes chemotaxis of eosinophils, basophils, and lymphocytes in vitro. The objective of this study was to investigate the effect of RANTES on the influx of inflammatory cells into the nasal mucosa of 12 allergic patients. In the first phase, each patient was challenged with RANTES or diluent on two subsequent days. RANTES caused a significant (p < 0.05) influx of eosinophils as compared with the diluent. The number of eosinophils were 5,548 +/- 1,532/ml and 462 +/- 206/ml after RANTES and diluent challenge, respectively, at the peak of the response at 2 h. There was also a significant influx of metachromatic cells and lymphocytes, but not monocytes, neutrophils, or epithelial cells after RANTES challenge. In the second phase, the patients were first challenged with an allergen and 24 h later, challenged with RANTES or diluent. In the allergen-primed mucosa RANTES induced a significantly higher influx of eosinophils, basophils, and lymphocytes. Further, RANTES caused migration of monocytes and neutrophils, and shedding of epithelial cells. The influx of the inflammatory cells was associated with symptoms of rhinitis. We conclude that RANTES induces a clinically symptomatic inflammatory response in vivo by causing chemotaxis of eosinophils, basophils, and mononuclear cells.

Adult↗
PubMed1998

[Clinical efficacy and safety of spiramycin and clarithromycin in the treatment of outpatients with lower respiratory tract infections].

Macrolide antibiotics have a broad spectrum of activities against the common pathogens responsible for lower respiratory tract infections, therefore for over 40 years they have been useful in treatment of these diseases. The aim of this open randomised multicentre trial is to compare the efficacy and safety of spiramycin, one of the first macrolides, to clarithromycin, a new generation macrolide, in their normal condition of use in patient presenting with acute non-complicated lower respiratory tract infections. 55 adult non-hospitalised patients with clinical diagnosis of bronchitis or pneumonia were randomised to receive either spiramycin 3 MIU twice daily or clarithromycin 500 mg twice daily for 7 or 10 days. For clinical evaluable patients, successful outcome was noted for 96.15% (25/26) spiramycin-treated patients and 96.43% (27/28) clarithromycin-treated patients. Clinically significant improvement in signs and symptoms was comparable between treatment groups. 2 patients in the spiramycin group (7.69%) and 3 in clarithromycin group (10.71%) complained of adverse events which severity was mild or moderate and did not require interruption of conducting antibioticotherapy. Efficacy and safety analysis showed that the two macrolides were equally effective and well-tolerated, at the given doses, for the treatment of lower respiratory tract infections and may play important role in out-patient therapy of these diseases.

Adult↗
PubMed1998

[Longterm effects of steroid therapy].

Asthma is a chronic inflammatory disease of the airways play. Anti-inflammatory drugs the fundamental role in the treatment of asthma and among them steroids are the most important. However, oral steroids may cause many serious side effects. A major breakthrough in the treatment of asthma was introducing inhaled steroids. Inhaled steroids have much less side effects than oral steroids, although they have the same anti-inflammatory activity. Long term effect of inhaled steroids can be divided into wanted and unwanted outcome. The desirable anti-inflammatory effect of steroids is reflected by lowering of bronchial hyperresponsiveness and a better control of asthma symptoms. Inhaled corticosteroid may have systemic side effects similar to those observed with oral steroids such as 1) adrenal suppression, 2) effect on bone metabolism, 3) growth suppression in children, 4) impaired skin collagen synthesis, 5) cataract, 6) metabolic disturbances, 7) effect on central nervous system. Topical side effects of inhaled corticosteroid such as oral candidiasis, dysphonia and cough effect about 10 to 30% of patients taking those drugs. Summing up it is advisable to use inhaled corticosteroid in the lower effective dose.

Administration, Inhalation↗
PubMed1997

Monocyte chemotactic and activating factor/monocyte chemoattractant protein in bronchoalveolar lavage fluid from patients with atopic asthma and chronic bronchitis. Relationship to lung function tests, bronchial hyper-responsiveness and cytology of bronchoalveolar lavage fluid.

Monocyte chemotactic and activating factor/monocyte chemoattractant protein (MCAF/MCP1) is a member of beta (C-C) subfamily of chemokines. The biological roles played by MCAF/MCP1 in a number of inflammatory and non-inflammatory disease states is not well known. Several studies have confirmed that inflammation is present in the airways of subjects with atopic asthma (AA) and in chronic bronchitis (CHB). The aim of the current study was to examine associations among MCAF/MCP1 and bronchoalveolar lavage fluid (BALF) cells and disease severity as measured by airway caliber and bronchial hyperresponsiveness in patients with AA and CHB. Thirty-two patients with AA, 32 patients with CHB and 14 patients of a control group took part in this study. ELISA test was used to assess MCAF/MCP1 in BALF. The levels of MCAF/MCP1 (mean +/- S.E.M.) were 107 +/- 15.8 pg/ml in patients with AA, 393.4 +/- 105.9 pg/ml in CHB and 36.4 +/- 10.9 pg/ml in the control group (P < 0.05). Significant correlations with clinical parameters were found in both group of patients with disease. In conclusion, MCAF/MCP1 possesses proinflammatory properties and their biological effect can in part account for the persistance of inflammation in the bronchial mucosa of AA and CHB.

Adult↗
PubMed1997

[The influence of heparin on histamine level in plasma during the early reaction phase of asthma].

Heparin, well known anticoagulant, can also modulate inflammatory and immunologic processes. Some investigators suggest that heparin inhibits mast cell degranulation. Mast cells play very important role in early phase of asthmatic reaction, releasing many proinflammatory mediators including histamine. The purpose of study was to determine the effect of heparin on early asthmatic response and on histamine level in plasma after allergen challenge. Eleven patients with mild and moderate asthma were studied in a double blind placebo controlled manner. Sodium heparin or placebo were taken via nebulizer, and 15 minutes later allergen challenge (Dpt./grass pollen) was performed. FEV1 was measured at 5, 15, 30 and 60 minutes after challenge and PC20 for allergen was calculated. Peripheral blood was collected before and 30 minutes after challenge to assess histamine concentration in plasma by an immunoenzymatic assay. We observed that heparin significantly decreased early asthmatic response in all patients. After challenge with the same concentration of allergen FEV1 fell 36% for placebo and 8% for heparin. Heparin also prevented rise in histamine level in plasma after allergen challenge. The concentration of histamine before and after challenge were respectively 9.55 +/- 4.08 and 13.06 +/- 3.86 nM for placebo (p < 0.05) and 8.88 +/- 1.50 and 11.18 +/- 1.84 nM for heparin (p > 0.05). There was no correlation between FEV1 and histamine level before and after challenge. Our results suggest that heparin diminishes allergen induced early phase of asthmatic recreation by inhibition of mast cells degranulation.

Administration, Inhalation↗
PubMed1997

[Regulation of immunoglobulin E synthesis].

Immunoglobulin E plays a central role in the pathogenesis of allergic diseases. Therefore an understanding of mechanisms which regulate production of IgE is very important. Recent studies have demonstrated that the induction of IgE synthesis in B cells requires two signals. The first one, IgE isotype-specific, is delivered by interleukins 4 or 13 and results in epsilon germ line transcription. The second B-cell-activating factor is responsible for switch recombination and expression of mature epsilon RNA transcripts. This signal is delivered by lymphocytes T, but these cells can be replaced by Epstein-Barr virus infection, protein gp39 (CD40L), monoclonal antibodies to CD40 and CD58, membrane-TNF-alpha, as well as corticosteroids. Besides this a variety of factors can modulate the IgE synthesis. Interleukin-2, -5, -6, -9, -10, MIP1-alpha, RANTES and sCD23 enhance the production of IgE whereas PAF, PGE2, IL-8, -12 and 18, IFN-alpha and gamma, TGF-beta, sIL-4R, IL-1Ra, and probably sIL-1R inhibit it. In this article, we review current knowledge about the mechanisms underlying the synthesis of IgE in humans, including molecular events and clinical attempts at reduction of the total IgE level in patients with allergic diseases.

B-Lymphocytes↗
PubMed1997

[The effect of heparin on release of histamine from basophils under the influence of MCAF/MCP-I in patients with bronchial asthma].

The clinical studies show that heparin, well known as an anticoagulant, inhibits early asthmatic response (EAR) and bronchial hyperactivity after allergen challenge in allergic patients. We have previously shown that heparin attenuates also the late phase of allergic reaction (LAR) Recently it has been shown that heparin modulates mastocyte mediator release. This could explain the beneficial role of heparin in EAR. The goal of this study was to explore the protective mechanism of heparin on LAR. Basophils are important cells in the development of LAR. We studied the effect of heparin on histamine release from basophils induced by anti-IgE and monocyte chemotactic-activating factor/monocyte chemotactic protein (MCAF/MCP-I). MCAF belongs to the chemokine family and is the most potent histamine releasing factor. Basophils were isolated from peripheral blood of 12 asthmatic patients. The cells were incubated with heparin in various concentrations: 10, 25, 50 and 100 U. Histamine was measured by spectrophotofluorometric method. We observed that incubation of basophils with heparin inhibits histamine release as shown in the table: [table: see text] Preincubation of anti-IgE or MCAF/MCP-I with heparin did not induce any changes in histamine release. The suggest that action of heparin depends on interaction with the cells but not with the agonists.

Asthma↗
PubMed1997

[The effect of heparin on eosinophil chemotaxis induced by Rantes and FMLP].

Eosinophils are important cells of inflammatory infiltration in respiratory tract of asthmatics patients. Rantes is a potent chemotactic agent for eosinophils. It belongs to the chemokine family. Heparin has been reported to diminish size of allergen skin tests and decrease response to allergen bronchoprovocation in allergic asthma. We have found that heparin diminished late phase of allergic reaction and inhibits allergen induced increase in specific and nonspecific bronchial hyperresponsiveness. In order to explore the mechanism involved in these protective effects we studied the influence of heparin on eosinophil chemotaxis induced by Rantes and FMLP. Eosinophils were isolated from peripheral blood of 12 asthmatic donors. Chemotaxis was evaluated using polycarbonate filters in 48-well chemotactic chamber. The table shows the results (*) p < 0.05. [table: see text] Ten minutes exposure of eosinophils to heparin was sufficient for inhibition. Removal to heparin by washing the cells ablated observed effects. Preincubation of Rantes or FMLP with heparin did not induce any significant changes in eosinophil chemotaxis. Heparin alone did not posess any chemotactic activity for eosinophils. Our results suggest that heparin ameliorate allergic inflammation by inhibition of eosinophil flux and this inhibition is a surface phenomenon.

Asthma↗
PubMed1996

Human C1q induces eosinophil migration.

Eosinophils (Eo) play a significant role in allergic inflammation and the host's immunity to parasitic infections. Although the presence of C1q-binding cell surface molecule(s) (C1q-R) on Eo had been previously implicated by the ability of C1q to augment IgG-dependent, Eo-mediated killing of schistosomula, little is known about the structure or the function of this receptor. The present studies were therefore undertaken to immunochemically demonstrate and to examine the biology of Eo C1q-R. Eo were purified to homogeneity (>90%) and viability (>98%) from hypereosinophilic donors by Percoll density gradient. Western blot analysis using antibodies to cC1q-R and gC1q-R showed distinct bands corresponding to cC1q-R (60 kDa) and gC1q-R (33 kDa) when immunoblotted with their respective antibodies. The Eo C1q-R was tested for its ability to induce chemokinesis and/or chemotaxis as assessed by the modified Boyden microchamber assay utilizing 5-micrometer-pore polycarbonate membranes and using C1q, cC1q, or gC1q (10 micrograms/ml) as agonists. The known chemotactic factors C5a and RANTES (10(-8)M) were used as positive controls. The results showed that at this concentration, cC1q was most efficient in its ability to induce Eo migration (20 +/- SEM 12, n = 4) followed by C1q (107 +/- SEM 7, n=7) and gC1q (77 +/- SEM 10, n = 10). When checkerboard analysis was performed, the data indicated that the observed phenomenon was likely to be due largely to chemokinesis. As expected, C5a (145 +/- SEM 15, n = 7) and RANTES (145 +/- SEM 43, n = 7) were both chemotactic. Furthermore, incubation of Eo with 50 micrograms of either C1q, gC1q, or cC1q (1 hr, 37 degrees C) did not cause release of eosinophil cationic protein as measured by RIA, nor did it enhance the expression of CD11b or CD29 as assessed by FACS analysis. The data presented in this paper show that Eo express both cC1q-R and gC1q-R and may participate in Eo function by providing a primary signal for locomotion.

Blood Proteins↗
PubMed1996

Chemokines in seasonal allergic rhinitis.

Monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), RANTES, and macrophage inflammatory protein (MIP)-1 alpha are chemokines known to activate basophils (MCAF/RANTES) and eosinophils (RANTES/MIP-1 alpha). IL-8 inhibits MCAF-induced histamine release from basophils. We questioned whether a relationship exists between the levels of these chemokines and various inflammatory mediators released from mast cells, eosinophils, and basophils as assessed in nasal secretions obtained from patients during the allergy season and out of season. Samples were assessed for MCAF/MCP-1, RANTES, MIP-1 alpha, IL-8, histamine, tryptase and eosinophil cationic protein (ECP) in three subject groups: subjects with allergic rhinitis (n = 18), atopic subjects without rhinitis (n = 9), and healthy individuals (n = 6). Statistically significant differences were apparent only in the subjects with symptoms as follows. MCAF/MCP-1 increased during the season from 336 +/- 47 pg/ml to 829 +/- 137 pg/ml (p < 0.001), whereas IL-8 decreased from a baseline of 1932 +/- 335 pg/ml to 1070 +/- 202 pg/ml (p < 0.028). The ratio of IL-8 to MCAF/MCP-1 decreased during the symptomatic season from the baseline of 6.66 +/- 1.06 seen during winter to 1.3 +/- 0.22 during ragweed season (p < 0.001). Histamine increased from 6.3 +/- 1.5 to 89 +/- 15.5 ng/ml (p < 0.001), ECP increased from 20.6 +/- 6.4 to 237.1 +/- 50.2 ng/ml (p < 0.001), and tryptase increased from 2.34 +/- 0.6 to 9.7 +/- 2.3 U/ml (p < 0.001). Most samples did not have detectable quantities of MIP-1 alpha or RANTES. We also found a correlation between the level of MCAF/MCP-1 and IL-8 and the level of histamine or IL-8 and ECP. Our results suggest that the chemokines MCAF/MCP-1 and IL-8 may participate in the pathogenesis of allergic rhinitis, contributing to the attraction of the proinflammatory cells and mediator release, which might be very important during the late phase of the allergic reaction. Furthermore, the ratio of certain chemokines, such as MCAF/MCP-1 and IL-8 may reflect the magnitude of the reaction, as does the presence of histamine and ECP.

Basophils↗
PubMed1996

[Mast cells and cytokines--a new insight on the participation of mast cells in inflammatory reactions].

Tissue mast cells are multifunctional immune cells and have been implicated in allergic and inflammatory reactions. They used to be regarded merely as a source of histamine, prostaglandins and leukotrienes which mediated the symptoms of the acute allergic reaction but more recent work has indicated they are involved in many inflammatory reactions. The discovery of production and secretion of a unique array of cytokines by these cells has suggested new ways in which they could influence to the development of inflammation. Many experiments have disclosed that mast cells owning to cytokines can not only initiate but also regulate and modulate this process. With the results come the realisation that these cytokines might represent important effector molecules in a variety of pathologic and physiologic processes where mast cells involvement had been postulated but an understanding of the mechanisms remained obscure. The aim of this article is introduction the biology of mast cells and presentation the information concern production and secretion of cytokines by these cells like also influence of these biologically active molecules on inflammatory process.

Cytokines↗