Teyfik Turgut

The effects of low dose leukotriene receptor antagonist therapy on airway remodeling and cysteinyl leukotriene expression in a mouse asthma model

Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling. The cysteinyl leukotrienes (LTC4, D4 and E4) are known to play important roles in the pathobiology of asthma. To evaluate the effect of low dose montelukast (MK) on the development of airway remodeling using a chronic murine model of allergic airway inflammation with subepithelial fibrosis, BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on days 0 and 14, received intranasal OVA periodically on days 14-75. MK treated mice received montelukast sodium intraperitoneally on days 26-75. The OVA sensitized/challenged mice developed an extensive eosinophil cell inflammatory response, goblet cell hyperplasia, mucus occlusion, and smooth muscle hypertrophy of the airways. In addition, in OVA sensitized/challenged mice, dense collagen deposition/fibrosis was seen throughout the lung interstitium surrounding the airways, blood vessels, and alveolar septae. The cysteinyl leukotriene 1 (CysLT1) receptor antagonist, MK significantly reduced the airway eosinophil infiltration, goblet cell hyperplasia, mucus occlusion, and lung fibrosis except airway smooth muscle hypertrophy in the OVA sensitized/challenged mice. The OVA sensitized/challenged mice had significantly increased epithelial desquamation compared with control mice. MK markedly reduced epithelial desquamation of airways in OVA/MK treated animals compared with OVA sensitized/challenged mice. MK treatment did not affect the levels of CysLT in lung tissue. Our results show that the important role of cysteinyl leukotrienes in the pathogenesis of asthma. Lower dose of CysLT1 receptor antagonism has a significant anti-inflammatory effect on allergen-induced lung inflammation and fibrosis but not airway smooth muscle hypertrophy in an animal model of asthma.

Changes in Serum Cytokine Levels in Active Tuberculosis With Treatment

It has been reported that IFN-γ, TNF-α, and IL-12 stimulate, and that IL-10, TGF-β, and IL-4 suppress the protective immune response against tuberculosis. We aim to evaluate changes in the serum levels of pro and antiinflammatory cytokines in active pulmonary tuberculosis (APTB) and the possible effects of treatment on these changes. Serum IL-12p40, IL-4, IL-10, TNF-α, IFN-γ, and TGF-β1 levels were determined in 20 APTB cases (group 1) before and 2, 4, and 6 months after therapy. The same parameters were also determined in 9 inactive pulmonary tuberculosis (IPTB) cases (group 2) and 9 healthy controls (HC, group 3). Before treatment, the mean serum IFN-γ, TNF-α, and IL-10 levels in group 1 were statistically higher than those in group 2 (P = .001, P = .024, P = .016, resp) or group 3 (P = .003, P = .002, P = .011, resp). The levels in group 1 decreased significantly after treatment (P = .001 for IFN-γ, P = .004 for TNF-α, P = .000 for IL-10). The serum levels of IL-12p40 were significantly higher in group 1 than in group 3 (P = .012) and decreased insignificantly after treatment. There was no difference in serum IL-4 and TGF-β1 levels among the groups (P > .05). Because the serum IL-12p40, IL-10, TNF-α, and IFN-γ levels were high in APTB, we believe that these cytokines have important roles in the immune response to Mycobacterium tuberculosis (M tuberculosis). These parameters could be used in follow-up as indicators of the success of APTB therapy.

Evaluation of the anti‐inflammatory effect of infliximab in a mouse model of acute asthma

Background and objective:  To evaluate the potential role of anti‐tumour necrosis factor (TNF)‐α mAb (infliximab) on the inflammatory response in a mouse model of acute asthma.

Glutathione and nitrite in induced sputum from patients with stable and acute asthma compared with controls.

BACKGROUND Oxidative stress is believed to play an important role in the pathogenesis of asthma. Determining the reduced glutathione (GSH) and nitric oxide (NO) contents of the airway is useful when investigating oxidative stress in the lung. OBJECTIVE To explore antioxidant defenses by measuring sputum GSH levels and to evaluate oxidant stress by measuring sputum nitrite (NO2-) levels in asthma patients. METHODS Sputum GSH, NO2-, cell counts, and plasma NO2- contents were evaluated in 11 patients with stable asthma, 10 patients with acute asthma attacks, and 11 controls. RESULTS The highest GSH content in sputum samples was in stable asthma patients compared with the other groups (P < .001), and patients with exacerbations of asthma had a greater GSH content than controls (P < .001). Mean sputum NO2- content was significantly lower in controls than in acute (P = .001) and stable (P < .001) asthma patients. There was no significant difference in sputum NO2- contents between acute and stable asthma patients, although there was a trend toward higher levels in acute asthma patients (P = .38). CONCLUSIONS Sputum induction can be used to obtain bronchial secretions for the evaluation of GSH and NO2- contents. Oxidative stress is chronic and probably less severe in patients with stable asthma. Glutathione and NO2- may serve as markers for determining the extent of the oxidative processes in asthma, which is characterized by chronic airway inflammation.

The prevalence of chronic obstructive pulmonary disease in Elazig, Eastern Turkey

BACKGROUND To investigate the prevalence of Chronic Obstructive Pulmonary Disease (COPD) in the urban and rural areas of the Elazig Region of Turkey. METHODS A questionnaire was conducted and spirometric measurements were made, based on the BOLD protocol. A total of 1270 individuals, over 18 years of age, were included in the study, comprising 610 individuals from the city center and 660 from the rural area. The questionnaire included demographics, symptoms and possible risk factors. The description and staging of COPD were in accordance with GOLD (Global Initiative for Chronic Obstructive Lung Disease). RESULTS Of the 1270 cases, 1206 (94.9%) were able to complete the questionnaire and undergo spirometric analysis. Of these 1206 cases, 1188 (98.5%) were used in the final assessment; the remainder were excluded due to errors in the spirometric analysis. Of the cases included in the study, 43.2% (25.9% female; 56.7% male) were current smokers. The prevalence of COPD at ≥ 18 years old was 4.5% (female 2.5%; male 6%); the prevalence at ≥ 45 years old was 11.5% (female 5.9%; male 15.1%). The majority of the COPD cases were at stages I and II (22.6% and 66%, respectively). The prevalence of COPD was higher among current and former smokers (5.8%) than non-smokers (2.8%). In general, the risk factors for COPD were found to be age, male gender, smoking, living in a rural area, and low income. CONCLUSIONS The prevalence of COPD in Elazig, Turkey was highest among the elderly and smokers, and constituted primarily stages I and II of the disease.

Sleep Quality Is Related to Disease Activity in Patients With Ankylosing Spondylitis: A Polysomnographic Study.

BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory disease that is associated with poor sleep quality. ObjectivesThe present study aimed to investigate the relationship between disease activity and sleep quality in patients with AS and to evaluate the potential effect of anti–tumor necrosis factor (TNF) treatment on sleep quality and pattern. MethodsFifty-nine patients with AS were consecutively included in the study. Twenty-eight patients (47.5%) were receiving anti-TNF, and 31 (52.5%) patients were receiving only nonsteroidal anti-inflammatory drugs (NSAIDs). Demographic and treatment characteristics, spinal mobility measurements, disease activity measurements, and sleep questionnaire results of each patient were recorded. Each patient underwent a polysomnography examination for the evaluation of sleep patterns. ResultsWhen compared with the patients on NSAID treatment, patients receiving anti-TNF treatment had significantly greater total sleep time and sleep efficiency (P = 0.003 and P < 0.001, respectively). They had a significantly lower (better) Pittsburgh Sleep Quality Index, sleep onset latency, number of awakenings, and arousal index (P < 0.001, for all). Moreover, they had a significantly shorter superficial sleep period (stage 1) and a significantly longer rapid eye movement sleep period (P < 0.001 and P = 0.02, respectively). Higher indexes of disease activity (Bath AS Disease Activity Index, Bath AS Functional Index, and visual analog scale) were reflecting poorer sleep quality. ConclusionsSleep quality and pattern was markedly better in patients with AS on anti-TNF compared with the patients on NSAID treatments. Increased disease activity can impair the quality of sleep in AS. Improved sleep quality and pattern in patients on anti-TNF treatment may be related to improved disease activity.