Fatih Firinci

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.

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.

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.

Comparison of TNF antagonism by etanercept and dexamethasone on airway epithelium and remodeling in an experimental model of asthma.

BACKGROUND The aim of the study was to compare the influence of TNF antagonism and corticosteroid treatment on epithelial, smooth muscle and basement membrane component of airway remodeling in an experimental murine model of chronic asthma. METHODS We used 30 BALB/c mice. Group 1 not exposed to ovalbumin or any medication was designated as control group. Chronic asthma model was achieved in the other three groups with intraperitoneal (IP) and inhaled ovalbumin. Then, Group 2 received IP saline, Group 3 received IP dexamethasone and Group 4 received IP etanercept. Epithelial, subepithelial smooth muscle and basement membrane thickness as well as goblet cells and mast cells were examined on samples isolated from left lung. RESULTS Etanercept treatment led to thinner epithelial and basement membrane layer and lower goblet and mast cell number than untreated asthmatic mice (p<0.001, p=0.001, p=0.005 and p=0.03 respectively). Neither epithelial and basement membrane thickness nor mast cell number was different among mice treated with etanercept and dexamethasone (p=0.38, p=0.79 and p=0.51 respectively). However, etanercept group was associated with thicker subepithelial muscle layer but lower goblet cell number (p<0.001 and p=0.04 respectively) than dexamethasone group. CONCLUSIONS Corticosteroids are more effective in decreasing smooth muscle mass while TNF antagonists in reducing goblet cell number in animal model of asthma. Therefore, further research is needed to assess the synergistic use of TNF antagonism and dexamethasone for more rational remodeling control.

Anaphylaxis caused by honey ingestion in an infant.

case of a florist with rhinoconjunctivitis and asthma due to sensitisation to Freesia, which is from the same family as the gladiolus. Ordoqui 6 reported a case of a florist, who has worked with plants for 18 years. He refers respiratory symptoms upon exposure to gladiolus and carnation, with positive prick test to these plants, specific IgE by ELISA on patient serum, and positive bronchial challenges. The immuno-blotting showed two proteins of 40 and 47 kDa on carnation extract, but nothing for the gladiolus extract. In order to determinate the prevalence of occupational asthma and sensitisation to workplace allergens in greenhouse flowers and/or ornamental plant growers, Monsó 7 et al. studied a population of 39 growers, and found three cases of occupational asthma. The growers were sensitised to various moulds in one case; to gladiolus spp. in the second; and to Aspergillus and different flowers (including gladiolus) the patient cultivated in the third. In summary, we present a case of rhinoconjunctivitis and asthma due to sensitisation to gladiolus proteins, and on the basis of in vitro test, we identified three proteins of 70, 52 and 21 kDa. as the main allergens causing sensitisation in this patient, data which, to the best of our knowledge, have never been reported.

Beneficial effects of erythropoietin on airway histology in a murine model of chronic asthma

BACKGROUND Erythropoietin (EPO) is originally defined as a haematopoietic growth factor, but also has anti-inflammatory effects through cytokine modulation. This anti-inflammatory and cytokine modulating effect has not been investigated for the treatment of asthma. We aimed to determine the beneficial effects of erythropoietin on lung histology of murine model of chronic asthma. METHODS Thirty-five BALB/c mice were divided into five groups: I; II; III; IV; and control group. All groups except control group were sensitised and challenged with ovalbumin. Mice with experimentally induced asthma in Group I received saline; Group II EPO 500IU/kg; Group III EPO 1000IU/kg; and Group IV dexamethasone 1mg/kg intraperitoneally once a day in the last five days of the challenge period. Animals were sacrificed 24h after the last administration of study drugs. Histological findings of airways were evaluated by light and electron microscopic examination. RESULTS All histological parameters of asthma in the group treated with a high dose of EPO (Group III) were significantly ameliorated when compared with the group treated with saline (Group I). In comparison to the group treated with low dose of EPO (Group II) and the group treated with saline (Group I), basement membrane thicknesses and number of mast cells were significantly lower in the group treated with low dose of EPO (Group II). All histological parameters were similar between the group treated with high dose of EPO (Group III) and the group treated with dexamethasone (Group IV) except higher number of mast cells in the group treated with high dose of EPO (Group III). Additionally, the results of all histological parameters in the group treated with high dose of EPO (Group III) were significantly better when compared with the group treated with low dose of EPO (Group II). CONCLUSIONS We found that EPO ameliorated histological changes of chronic murine model of asthma. Further studies are needed to evaluate the efficacy of EPO in the treatment of asthma.

The effect of atorvastatin on lung histopathology in a murine model of chronic asthma.

INTRODUCTION Atorvastatin is a statin group medicine that reduces the level of serum cholesterol; thus it is used to treat hypercholesterolaemia. Independent of the cholesterol-lowering property of statins they also have anti-inflammatory and immunomodulating effects. This study aimed to investigate the effect of atorvastatin on histological changes in the lungs in a murine model of chronic asthma. MATERIALS AND METHODS Twenty-eight BALB/c mice in Group I, II, III and IV were divided into four groups. All the mice except the control group (Group I) were sensitised with ovalbumin. Intraperitoneal injection with saline, atorvastatin (10mg/kg), dexametazon (1mg/kg) was administered to Group II, Group III, and Group IV respectively for five consecutive days. Mice were sacrificed 24h after the last drug administration. All the histological properties of lung tissue samples from all groups were evaluated with light and electron microscopy. In addition, IL-4 and IL-5 levels of the lung tissue were measured. RESULTS When Group II and Group III (atorvastatin) were compared, thicknesses of basement membrane and subepithelial smooth muscle layer, height of epithelium, number of mast and goblet cells were significantly lower in Group III. In comparing Group III (atorvastatin) and Group IV (dexamethasone), all the improvements in histological parameters were similar. In addition, the IL-4 and IL-5 levels of the lung tissue were significantly lower in atorvastatin group (Group III) compared to placebo-treated group. CONCLUSION Atorvastatin had a beneficial effect on histological changes in a chronic murine model of asthma.

An 11-Year-Old Child with Autosomal Dominant Polycystic Kidney Disease Who Presented with Nephrolithiasis

Patients with autosomal dominant polycystic kidney disease become symptomatic and are diagnosed usually at adulthood. The rate of nephrolithiasis in these patients is 5–10 times the rate in the general population, and both anatomic and metabolic abnormalities play role in the formation of renal stones. However, nephrolithiasis is rare in childhood age group. In this paper, an 11-year-old child with autosomal dominant polycystic kidney disease presenting with nephrolithiasis is discussed.

Hyperbilirubinemia and urinary tract infection: the effect of indirect hyperbilirubinemia on the in vitro growth of uropathogen Escherichia coli in newborn urine

Abstract High serum bilirubin is antioxidant and cytoprotective. We evaluated if urine samples of hyperbilirubinemic newborns impede uropathogenic Escherichia coli growth. Bag-urine samples of hyperbilirubinemic newborns (study group) were cultured at presentation and during remission. Urine sample were obtained only once from healthy newborns (control group). Escherichia coli [2 × 104 colony-forming unit (cfu)/mL] was inoculated into the sterile urine samples and colony counts were determined after 24 h. Bilirubin levels at presentation and remission were also recorded. Escherichia coli colony counts of the control versus study groups and of the presentation versus remission samples in the study group were compared. There were 13 study and 17 control cases. Escherichia coli colony counts were not different in the study group at presentation versus remission (5.4 ± 0.7 vs. 5.5 ± 0.8 log10, respectively; p = 0.659). Escherichia coli colony count of the control group (5.2 ± 0.6 log10) was also not different from the study group. In conclusion, the urine of hyperbilirubinemic newborns did not affect the growth rate of uropathogenic E. coli.