Özkan Karaman

Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma.

Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n=6), Group 2 (ovalbumin induced asthma only, n=10), Group 3 (ovalbumin induced asthma + MSCs, n=10), and Group 4 (MSCs only, n=10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma.

Risk factors in wheezing infants.

Abstract Background: Some lifestyle factors may be important for the occurrence of wheezing and there are considerable differences around the world.

Retrospective evaluation of epidermal skin prick tests in patients living in Aegean region

Sensitization to aeroallergens of Aegean region is not well decumented. In this study we evaluated the epidermal skin prick test results of the patients who applied to allergy outpatient department retrospectively. Epidermal skin prick test of the 5055 patients were evaluated. Of these patients 2638 (52 %) were female, 2417 (48 %) male, 1213 (24 %) adult and 3842 (76 %) pediatric patient, 1163 (23 %) patients were allergic rhinitis, 2477 (49 %) were bronchial asthma, 505 (10 %) were allergic rhinitis with bronchial asthma, 556 (11 %) were chronic urticaria, 253 (5 %) were wheezy infant and 101 (2 %) patients were atopic dermatitis, 2932 (58 %) had atopy history in their first and second degree relatives. Patients were aged between 3.5 months and 79 years (mean 14.1 3.2 years and median 11 years). In epidermal skin prick tests sensitization to house dust mites (D. farinae, D. pteroniyssinus), pollens (grass, cereals and trees), moulds, animal danders, foods (especially in early childhood) and cockroach were evaluated. Our data indicate that allergens that may be the cause of the high prevalence of allergic diseases in Izmir are probably produced by pollens and mites.

Anti-inflammatory effects of curcumin in a murine model of chronic asthma

BACKGROUND Curcumin, a dietary pigment responsible for the yellow colour of curry, has been used for the treatment of inflammatory diseases and exhibits a variety of pharmacological effects. METHODS Forty-two BALB/c mice were divided into six groups: I, II, III, IV, V, and control group. All groups except the controls were sensitised and challenged with ovalbumin. Group I received nebulised saline in challenge period. Mice in groups II, III, IV, and V were administered curcumin at a dose of 10 mg/kg, curcumin 20 mg/kg, dexamethasone 1 mg/kg, and dimethyl sulfoxide 1 mg/kg, respectively, intraperitoneally once a day for the final 5 days of the challenge period. Animals were sacrificed 24 h after the last drug administration and the airway samples were evaluated histologically by light microscopy. RESULTS All histological parameters in Group III improved similar to Group IV when compared to Group I. In Group II, only thickness of epithelium was significantly lower compared with regard to Group I. All variables except epithelium thicknesses were found to be significantly better in Group III compared to Group II. CONCLUSIONS In our study, we demonstrated that curcumin administration alleviates the pathological changes of chronic asthma. Curcumin might be a promising therapy for asthma in the future.

Effects of Curcumin on Lung Histopathology and Fungal Burden in a Mouse Model of Chronic Asthma and Oropharyngeal Candidiasis

BACKGROUND AND AIMS Oropharyngeal candidiasis (OPC) is one of the most common local side effects of current therapy in chronic asthma. New therapeutic options with fewer side effects and reverse chronic changes are needed. Curcumin, as a promising antiinflammatory and antifungal agent, could be a candidate of alternative therapy in asthma. This study aimed to determine the efficacy of orally administrated curcumin on lung histopathology, serum nitric oxide levels and fungal burden in a murine model of asthma and OPC. METHODS Thirty five BALB/c mice were divided into five groups: I, II, III, IV (placebo) and V (control). All groups except the control were sensitized and challenged with ovalbumin. OPC model was established after the model of chronic asthma. Lung histology, serum nitric oxide levels and fungal burden were evaluated after 5 days of treatment with curcumin, dexamethasone, curcumin-dexamethasone combination and placebo. Evaluation of lung histology included subepithelial smooth muscle and epithelial thickness and number of goblet and mast cells by using light microscopy. RESULTS All histological parameters improved in curcumin group similar to dexamethasone group. Curcumin and dexamethasone-curcumin combination were also as effective as dexamethasone on decreasing nitric oxide levels. Oral fungal burden was significantly lower in curcumin-treated group than dexamethasone. CONCLUSIONS In our study we demonstrated that curcumin administration alleviates the pathological changes in asthma and decreases the fungal burden. Curcumin may have a potential effect on treating chronic asthma and decreasing the frequency of the OPC.

Effects of Ginkgo biloba on airway histology in a mouse model of chronic asthma.

Platelet-activating factor (PAF) is an inflammatory mediator involved in the pathophysiology of asthma, suggesting a therapy antagonizing its effects may play a role in the disease treatment. The aim of the study was to determine the effects of Ginkgo biloba, a PAF antagonist, on lung histology. Thirty-five BALB/c mice were divided into five groups; A, B, C, D, and the control. All mice except controls were sensitized and challenged with ovalbumin. Mice in group A (placebo) received saline; group B received G. biloba, 100 mg/kg; group C received G. biloba, 150 mg/kg; and group D received dexamethasone, 1 mg/kg via orogastric gavage for 7 consecutive days. Chronic structural changes and airway remodeling were evaluated by using light and electron microscopy in all groups. Evaluation of lung histology indicated that the number of goblet cells, mast cells, thicknesses of epithelium, and basement membrane were significantly improved in groups B and C when compared with group A. There was no statistically significant difference in thicknesses of subepithelial smooth muscle between groups A, B, and C. When doses of G. biloba were compared with each other, only the number of goblet cells was significantly lower in group C than in group B. When G. biloba and dexamethasone groups were compared with each other, thicknesses of basement membrane and subepithelial smooth muscle were found to be lower in group D than in groups B and C. G. biloba alleviates all established chronic histological changes of lung except smooth muscle thickness in a mouse model of asthma.

Evaluation of montelukast in 8 to 14 year old children with mild persistent asthma and compared with inhaled corticosteroids.

OBJECTIVES To determine the clinical effectiveness, tolerability and reliability of montelukast and to compare this drug with inhaled corticosteroids. METHODS We performed a randomized, 14-week, 2-period, prospective parallel group study. After a 2-week run-in period, patients received treatment for 12 weeks. Sixty-three clinically stable outpatients aged 8 to 14 years with a history of mild persistent asthma for at least 1 year and a forced expiratory volume in one second (FEV1) greater than 80 % of the predicted value were evaluated. RESULTS Montelukast produced improvement in airway obstruction, daily symptom scores, total daily as-needed beta-agonist use, nocturnal awakenings, percentage of days and percentage of patients with asthma exacerbations, and urinary leukotriene E4 levels. These beneficial effects were similar to those produced by inhaled corticosteroids. There were no significant adverse effects requiring treatment discontinuation. CONCLUSIONS Montelukast may be a well-tolerated and effective therapeutic option in 8 to 14-year-old patients with mild persistent asthma.

Systemic lupus erythematosus presenting with normocomplementemic urticarial vasculitis in a 4-year-old girl

cytoclastic vasculitis of dermal vessels are the hallmarks of urticarial vasculitis.1 Urticarial vasculitis has been reported to be associated with connective tissue diseases, such as systemic lupus erythematosus (SLE), mixed cryoglobulinemia, drug reactions, hepatitis B antigenemia and malignant disease.1,2 Hypocomplementemic urticarial vasculitis (HUV) has been reported to be more strongly associated with SLE and patients with this form of urticarial vasculitis have been determined to have more severe multisystem disease in comparison with patients who have normocomplementemic urticarial vasculitis (NUV).3,4 In a recently published broadbased report, the average age at which urticarial vasculitis was diagnosed was 43 and 51 years for patients with HUV and NUV, respectively.1 In addition, in that study, the youngest patients with HUV and NUV were 15 and 7 years, respectively. In the present study, we report on a 4-year-old girl with NUV whose symptoms began at the age of 1 year and whose clinical picture progressed to SLE at the age of 4 years.

Role of vascular endothelial growth factor antagonism on airway remodeling in asthma.

BACKGROUND Vascular endothelial growth factor (VEGF) is an important mediator of the neoangiogenesis component of remodeling in asthma. OBJECTIVE To evaluate the influence of VEGF blockage on airway remodeling, specifically epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness, in a mouse model of chronic asthma. METHODS We used 30 BALB/c mice. The control group was not exposed to ovalbumin or any medication (group 1). Other groups were exposed to intraperitoneal and inhaled ovalbumin to achieve chronic asthma. Each of these groups received intraperitoneal saline (group 2), intraperitoneal dexamethasone (group 3), or intraperitoneal bevacizumab (group 4). Histomorphologic examination for epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness was performed from the middle zone of the left lung. RESULTS Treatment with anti-VEGF caused significant reduction in epithelial, subepithelial muscle, and basement membrane thickness compared with untreated asthmatic mice (P = .001, P = .03, and P = .009, respectively). Goblet and mast cell numbers were significantly lower in mice treated with anti-VEGF than in untreated mice (P = .02 and P = .007, respectively). Dexamethasone treatment resulted in improvement of all histomorphologic markers, except goblet cell number. Influences of dexamethasone and anti-VEGF on epithelial and basement membrane thickness and mast and goblet cell numbers did not differ (P > .05), but subepithelial muscle layer was thinner in the former (P = .003). CONCLUSION VEGF blockage may provide adjunctive therapeutic options as steroid-sparing agents for more effective treatment of remodeling in asthma.

Change of mean platelet volume values in asthmatic children as an inflammatory marker

BACKGROUND Asthma is the most common chronic disease of childhood in industrialised countries. T helper-2 (Th-2) cells, mast cells and eosinophils have a role in inflammation of asthma. Recently it was shown that platelets also play a role in asthma. Mean platelet volume shows platelet size and reflects platelet activation. OBJECTIVE The aim of this retrospective study is to evaluate levels of mean platelet volume in asthmatic patients during asymptomatic periods and exacerbations compared with healthy controls. METHODS The study consisted of 100 asthmatic patients (male/female: 55/45, mean age: 8.2±3.3) and 49 age and sex matched healthy children as a control group. RESULTS Mean platelet volume values of asthmatic patients during asymptomatic period were 7.7±0.8fL while mean platelet volume values in asthmatics during exacerbation were 7.8±0.9fL. Comparison of mean platelet volume values of asthmatic patients and healthy controls both in acute asthmatic attack and asymptomatic period showed no difference (p>0.05). Comparison of mean platelet volume values at asthmatic attack and asymptomatic period also had no difference (p>0.05). The presence of atopy, infection, eosinophilia, elevated immunoglobulin E, and severity of acute asthmatic attack did not influence mean platelet volume values. CONCLUSION The results of our study suggest that mean platelet volume values may not be used as a marker in bronchial asthma, although prospective studies with larger number of patients are needed to evaluate the role of mean platelet volume in asthma.