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Biomedical subjects

Brigita Sitkauskiene

Publications and source records attributed to Brigita Sitkauskiene.

13 recordsLinked to original sources

Changes in cough reflex sensitivity after cessation and resumption of cigarette smoking.

Previous studies have shown that healthy cigarette smokers have diminished cough reflex sensitivity compared to healthy nonsmokers. We have recently demonstrated that cough reflex sensitivity is enhanced soon after smoking cessation, suggesting that diminished cough sensitivity in smokers results from chronic cigarette smoke-induced desensitization of airway cough receptors. In this study, we evaluated cough reflex sensitivity to capsaicin (C(5)) in 11 chronic smokers who had discontinued smoking for at least 2 weeks, and then resumed smoking. Two weeks after smoking cessation there was a significant enhancement of cough reflex sensitivity; mean (+/-SEM) log C(5) decreased from 1.77+/-0.18 to 1.47+/-0.14 (p=0.01). All subjects resumed smoking after 2-12 weeks of abstinence. Repeat capsaicin cough challenge was performed 14-23 days after resumption of smoking. Mean log C(5) increased compared to the last value obtained during the smoking cessation period: 1.42+/-0.15 vs. 1.77+/-0.16 (p=0.0004). Mean log C(5) after resumption of smoking returned to almost exactly the baseline value. Our findings suggest that the sensitivity of airway cough receptors is a dynamic phenomenon, promptly affected and modulated by changes in environmental conditions, such as the presence or absence of cigarette smoke.

Administration, Cutaneous↗

Dyspnea perception and reversibility of methacholine-induced unlimited airway narrowing in asthmatics.

The hypothesis was that asthmatics might experience impaired perception of dyspnea and salbutamol-induced reversibility during unlimited airway narrowing. A total of 38 asthmatics (18 to 59 years of age) were examined. All patients underwent the methacholine challenge test. According to the dose-response curve to methacholine, they were categorized as having either unlimited airway narrowing (UAN group) (n = 20) or response plateau (RP group) (n = 18). Reversibility of methacholine-induced bronchoconstriction was measured 20 minutes after the inhalation of 400 microg of salbutamol to compare postbronchodilator FEV1 with baseline FEV1. Dyspnea perception was evaluated using the Borg Scale to calculate a perception score at a 20% decrease in FEV1 (PS20) and the slope alpha of the regression line between the changes in Borg scores and the reduction in FEV1 as percentage of the baseline value. Subjects in the UAN group exhibited significantly lower PS20 compared with the RP group (1.45+/- 0.23 vs. 2.84 +/- 0.35, p = 0.002); the mean of the slope values was higher in the RP group than it was in the UAN group (0.150 +/- 0.015 vs. 0.095 +/- 0.006, p = 0.003). Salbutamol-induced reversibility was significantly lower in the UAN group (81 +/- 1.4 % of baseline FEV1) compared with patients from the RP group (91 +/- 1.1% of baseline FEV1; p < 0.001). In conclusion, asthmatics during methacholine-induced unlimited airway narrowing exhibit diminished perception of dyspnea and lower bronchial reversibility to the baseline 20 minutes after inhalation of salbutamol. This suggests that more careful monitoring of the lung function for timely recognition of asthma deteriorations and adequate bronchodilatory therapy during severe acute attacks should be recommended for such patients.

Adolescent↗

[Genetic features during chronic obstructive pulmonary disease].

Chronic obstructive pulmonary disease is one of the leading causes of mortality, which is caused by the interaction of genetic susceptibility with environmental factors (especially smoking); however, genetic features of chronic obstructive pulmonary disease still remain unknown. The only proven genetic risk factor is severe deficiency of plasma protease inhibitor, alpha-1 antitrypsin. A large number of candidate genes for chronic obstructive pulmonary disease have already been identified in many experimental and clinical studies; however, polygenic etiology of chronic obstructive pulmonary disease is the main reason for conflicting molecular and genetic findings. This review describes the correlation between single nucleotide polymorphism of alpha-1 antitrypsin, alpha-1 antichymotrypsin, microsomal epoxide hydrolase-1, matrix metalloproteinases-1,-9,-12, glutathione S-transferases, heme oxygenase-1, tumor necrosis factor-alpha, transforming growth factor-beta, interleukins-1,-4,-13, beta2-adrenergic receptor, G-globulin genes and chronic obstructive pulmonary disease. Regions on chromosomes 1, 2, 12, and 17 are indicated as candidate chromosomal regions influencing the decrease in spirometric parameters. Genome-wide scan shows direct evidence for linkage of decreased FEV1/FVC ratio to one or more genes on chromosome 2q influencing the development of airflow obstruction. Genetic markers on chromosome 12p suggest evidence for linkage of FEV1 to this region, and observations on chromosome 1p show the relationship between FVC and genes of this region. All these findings also need to be proven, and linkage analysis among combinations of gene candidates for chronic obstructive pulmonary disease has to be done.

Genetic Linkage↗

Airway allergen exposure stimulates bone marrow eosinophilia partly via IL-9.

BACKGROUND: Interleukin (IL)-9 is a Th2-derived cytokine with pleiotropic biological effects, which recently has been proposed as a candidate gene for asthma and allergy. We aimed to evaluate the therapeutic effect of a neutralizing anti-IL-9 antibody in a mouse model of airway eosinophilic inflammation and compared any such effect with anti-IL-5 treatment. METHODS: OVA-sensitized Balb/c mice were intraperitoneally pretreated with a single dose (100 microg) of an anti-mouse IL-9 monoclonal antibody (clone D9302C12) or its vehicle. A third group was given 50 microg of a monoclonal anti-mouse IL-5 antibody (TRFK-5) or its vehicle. Animals were subsequently exposed to OVA on five days via airways. Newly produced eosinophils were labelled using 5-bromo-2'-deoxyuridine (BrdU). BrdU+ eosinophils and CD34+ cell numbers were examined by immunocytochemistry. After culture and stimulation with OVA or PMA+IC, intracellular staining of IL-9 in bone marrow cells from OVA-exposed animals was measured by Flow Cytometry. The Mann-Whitney U-test was used to determine significant differences between groups. RESULTS: Anti-IL-9 significantly reduced bone marrow eosinophilia, primarily by decrease of newly produced (BrdU+) and mature eosinophils. Anti-IL-9 treatment also reduced blood neutrophil counts, but did not affect BAL neutrophils. Anti-IL-5 was able to reduce eosinophil numbers in all tissue compartments, as well as BrdU+ eosinophils and CD34+ progenitor cells, and in all instances to a greater extent than anti-IL-9. Also, FACS analysis showed that IL-9 is over-expressed in bone marrow CD4+ cells after allergen exposure. CONCLUSIONS: Our data shows that a single dose of a neutralizing IL-9 antibody is not sufficient to reduce allergen-induced influx of newly produced cells from bone marrow to airways. However, in response to allergen, bone marrow cells over-express IL-9. This data suggest that IL-9 may participate in the regulation of granulocytopoiesis in allergic inflammation.

Animals↗

The role of beta(2)-adrenergic receptors in inflammation and allergy.

Essential role of beta(2)-adrenoreceptor (beta(2)AR) in airway relaxation is well established. Nevertheless, beta(2)AR seems playing an actual role in allergy and inflammation. Interaction between beta(2)AR and proinflamatory cytokines in airway smooth muscle has been revealed. Being located on proinflamatory cells, beta(2)ARs may influence function of these cells in vivo. It was clear established, that stimulation of beta(2)AR inhibits release of proinflamatory mediators from mast cells, influences T-cell growth and function, eosinophil survival and function, including GM-CSF- or PAF-induced degranulation. Stimulation of beta(2)ARs, located on alveolar macrophages and epithelial cells, has ambiguity influence on their regulation and function, including phagocytosis and mediator secretion, in vivo. Vascular responses, resulting in inhibition of plasma exudation were confirmed, but modulation of sensory nerves via beta(2)AR is not certain yet. beta(2)AR-agonists are effective in treatment of immediate allergic reactions, but desensitisation of beta(2)ARs on inflammatory cells may result in paradoxical effects, especially in asthma. In summary, it is clear that beta(2)ARs may play an anti-inflammatory role in vitro. Unfortunately, in vitro data have shown limited applicability in vivo; therefore further research in this field is required.

Adrenergic beta-2 Receptor Agonists↗

[Autoimmunity in pathogenesis of chronic obstructive pulmonary disease].

For years, smoking induced inflammatory reaction, comprised mainly of neutrophils and macrophages, has been accepted to be the major component in pathogenesis of chronic obstructive pulmonary disease. New developments in molecular and cell biology have provided scientists with new knowledge and understanding of inflammatory processes in lung. Recent reports have underlined the role of autoimmunity and T lymphocytes as a potential important factor, which takes place in the pathogenesis of chronic obstructive pulmonary disease. This article reviews potential mechanism of T cell mediated immune response in chronic obstructive pulmonary disease.

Antibody Formation↗

[Peculiarities of induced sputum inflammatory cell counts in allergic versus non-allergic asthma].

OBJECTIVE: According to the Global Initiative for Asthma (GINA, updated 2004), although non-allergic asthma has a different clinical profile than allergic asthma, it is not a distinct immunopathological entity. We aimed to investigate the peculiarities of inflammatory cell counts in induced sputum from patients with allergic and non-allergic asthma. METHODS: We investigated 41 steroid naive patients (mean age 51.8+/-1.5 years) with mild persistent asthma. Depending on the results of allergic anamnesis and skin prick test, patients were divided into the two groups: 21-with allergic asthma, 20-with non-allergic asthma. Spirometry, bronchial provocation test with methacholine (PD20) and sputum induction with hypertonic saline were performed. Cytospins of induced sputum were stained with May-Grunwald-Giemsa for differential cell counts. RESULTS. In samples from non-allergic asthmatics we detected a significantly higher number of total cells (1.97+/-0.33 vs 1.23+/-0.11x10(6)/ml, p<0.01), neutrophils (1.34+/-0.18 vs 0.41+/-0.06x10(6)/ml, p<0.01) and lymphocytes (0.36+/-0.04 vs 0.15+/-0.03x10(6)/ml, p<0.01), than in samples from allergic asthmatics. Number of eosinophils and macrophages did not significantly differ between two groups. In non-allergic asthmatics, number of lymphocytes correlated with PD20 (Rs=0.41, p<0.05); in allergic asthmatics, number of eosinophils in induced sputum correlated with PD20 (Rs=0.71, p<0.05). CONCLUSIONS: Our data suggest that lymphocytes might play a more important role in pathogenesis of non-allergic asthma, while eosinophils -- in allergic asthma.

Adult↗

[Lymphocyte subsets in patients with recurrent upper airway infections].

UNLABELLED: The aim of our study was to evaluate the digressions of lymphocyte subsets in patients with recurrent upper airway infectious diseases. METHODS: We studied 35 patients (mean of age 11.1+/-2.1 years) with recurrent upper airway infections. The first group consisted of patients, who had acute upper airway infections: rhinitis, pharyngitis, laryngitis and tracheitis more than 6 times per last year, sinusitis or otitis more than 4 times per last year. The control group comprised of 9 healthy subjects. Subsets of lymphocytes (CD3+, CD4+, CD8+, CD4+/CD8+, CD16+/56+ and CD19+) were detected by FACS Calibur cytometer. RESULTS: We found a significantly lower count of CD4+ lymphocytes in the patients' group compared to the control group (37.5+/-1.2 vs 45.7+/-3.1% of total lymphocytes, p<0.01). We did not find any significant differences of other lymphocyte subsets between patients and control groups. CONCLUSION: We propose that patients with recurrent upper airway infections have alterations of the cellular immunity -- decreased amount of CD4+ lymphocytes.

Acute Disease↗

[Consensus on asthma diagnosis and treatment in children and adults].

Asthma is a chronic airway disease that is a growing problem of public health. The current consensus is based on the Global Initiative for Asthma (GINA) and other guidelines for asthma, and adapted for Lithuania. This Consensus provides physicians with recommendations for asthma management in children and adults.

Adolescent↗

Perception of dyspnea in asthmatics with normal lung function.

UNLABELLED: The perception of dyspnea varies widely among asthmatics and it is influenced by many factors. The aims of our study were to investigate the perception of dyspnea during methacholine-induced bronchoconstriction in asthmatics with normal lung function and to evaluate the influence of bronchial responsiveness, age and gender to dyspnea perception in these patients. A total of 192 outpatients (aged 16-77 years) with stable asthma and normal lung function were examined. Methacholine challenge test was performed to each patient. The provocative dose of methacholine that reduces forced expiratory volume in 1 sec. (FEV1) by 20% (PD20) was estimated. Dyspnea perception of bronchoconstriction was evaluated using a Borg Scale and calculating the perception score corresponding to a fall in FEV1 of 20% (PS20). According to PS20+/-1 standard deviation subjects were divided into three groups: hypoperceivers, normoperceivers and hyperperceivers. From the hypoperceivers group we set up asthmatics with PS20=0 and defined them as nonperceivers. We found out that 43 (22.4%) patients were hypoperceivers, 116 (60.4%)--normoperceivers and 33 (17.2%)--hyperperceivers. The nonperceivers presented 6.3% (n=12) of all subjects. PD20 positively correlated with PS20 (r=0.252, p<0.001). Hypoperceivers showed significantly higher bronchial hyperesponsiveness (PD20=174+/-28 microg) comparing with hyperperceivers (PD20=323+/-50 microg, p=0.013). Bronchial responsiveness to methacholine of nonperceivers (PD20= 106+/-31 microg, range 15-253 microg) was the highest and PD20 was significantly lower comparing with normoperceivers (p=0.005) and hyperperceivers (p=0.001). Age and gender had no significant effect on the perception of bronchoconstriction. CONCLUSION: The part of asthmatics with normal lung function has impaired perception of dyspnea. Dyspnea perception depends on bronchial responsiveness, but not on age and gender of these patients.

Adolescent↗

Eotaxin-2 regulates newly produced and CD34 airway eosinophils after allergen exposure.

BACKGROUND: Eosinophils develop from CD34+ bone marrow progenitors, and evidence increasingly suggests that these progenitors are recruited to the airways in atopic asthmatics after allergen challenge. Moreover, it has been shown that the number of CD34+ progenitors in bronchial tissue correlates with asthma severity. To date, however, little is known about how these cells are recruited into the airways. OBJECTIVE: Our aim was to evaluate the role of 2 chemokines, eotaxin-I and/or eotaxin-2, in the recruitment of newly produced and CD34+ eosinophils to the airways after allergen exposure. METHODS: BALB/c mice sensitized and exposed to ovalbumin were pretreated intraperitoneally or intranasally with a neutralizing anti-eotaxin-1 and/or anti-eotaxin-2 antibody.A thymidine analogue, 5-bromo-2'-deoxyuridine (BrdU), was used to mark newly produced cells. Bronchoalveolar lavage (BAL), blood, and bone marrow were collected 24 hours after the final exposure. RESULTS: Anti-eotaxin-1 and/or anti-eotaxin-2 given intranasally(ie, locally to airways) significantly decreased BAL eosinophils. This decrease was paralleled with a decrease in both BrdU+and CD34+ eosinophils. In contrast, systemically administered(ie, intraperitoneally) anti-eotaxin-1 and/or anti-eotaxin-2 resulted in a significant decrease in BAL eosinophils only when the combined treatment was of a sufficiently high dosage to produce measurable concentrations in the airways.Furthermore, neither of the treated groups showed any significant decrease in blood or bone marrow eosinophils. CONCLUSION: Both eotaxin-1 and eotaxin-2 are involved locally within the airways in the regulation of the recruitment of newly produced and CD34+ eosinophils after allergen exposure.

Allergens↗

Regulation of bone marrow and airway CD34+ eosinophils by interleukin-5.

The aim of this study was to evaluate the effect of a neutralizing anti-interleukin (IL)-5 monoclonal antibody (TRFK-5) on bone marrow and airway CD34(+) and immature eosinophils. A focus was to determine the effect of the timing of treatment. Balb/c mice were ovalbumin-sensitized and subsequently exposed to ovalbumin for 5-10 d via airway route. Animals were treated intraperitoneally with TRFK-5 or its isotype control (50 microg) once at different time points. Newly produced eosinophils were labeled using 5-bromo-2'-deoxyuridine (BrdU). BrdU(+) and CD34(+) eosinophil numbers were examined by immunocytochemistry. TRFK-5 reduced bone marrow immature eosinophils within 3 d. This effect was closely related to a reduction of BrdU(+) and CD34(+) bone marrow eosinophils, and reduced numbers of blood eosinophils. However, bronchoalveolar lavage (BAL) eosinophilia was not attenuated to the same degree. The effect of TRFK-5 was most prominent in the extended allergen-exposure protocol, where the treatment was given in the middle of the exposure, with strongly reduced bone marrow CD34(+) and immature bone marrow eosinophils, blood eosinophils as well as BAL BrdU(+) eosinophils, and BAL CD34(+) eosinophils. These data argue that anti-IL-5 downregulates eosinophilopoiesis within 3 d by action in the bone marrow, by inhibition of the early stages of eosinophil maturation from CD34(+) cells.

Allergens↗

[Wiskott-Aldrich syndrome: the possibilities of diagnosis and treatment].

Wiskott-Aldrich syndrome is congenital X-linked immunodeficiency characterized by frequent infections, thrombocytopenia with small platelets, eczema and increased risk of autoimmune disorders and malignancies. This article is review of Wiskott-Aldrich syndrome actual diagnostics and treatment problems. Diagnostics problems exist due to clinical heterogenity of this syndrome, which is caused by mutations of the responsible gene. Recent 15-year studies showed, that bone marrow transplantations or use of cord blood as a source of stem cells prolonged median survival from 6.5 to 11 years. However, widespread use of splenectomy, intravenous immune globulin and prophylactic antibiotics did not change survival or appearance of infections, bleeding and autoimmune diseases. An attractive option for Wiskott-Aldrich syndrome is gene therapy, which leads to complete cure.

Anti-Bacterial Agents↗