Effects of Intraperitoneal Injection of Allogeneic Bone Marrow-derived Mesenchymal Stem Cells on Bronchiolitis Obliterans in Mice Model.

Bone marrow-derived mesenchymal stem cells (BMSCs) can ameliorate a variety of lung diseases such as asthma, lung fibrosis, and acute lung injury by its anti-inflammatory and immunmodulatory effects. In this study, we developed a mouse model of bronchiolitis obliterans (BO) and evaluated the effects of the intraperitoneal administration of BMSCs on lung histopathology and cytokine levels. 25 BALB/c mice were divided into four groups; control group (Group I), BO developed and 1x106 BMSCs-injected group (Group II), non-BO, 1x106 BMSCs-injected group (Group III), and BO developed and saline-injected group (Group IV). Histological and immunohistochemical findings of the lung tissue and the migration of BMSCs to the lung were evaluated using light and confocal microscopy techniques. Confocal microscopy evaluations showed that there was no noteworthy amount of BMSCs in the lung tissue of group III while significant amount of BMSCs was detected in group II. Wall thicknesses of terminal bronchiole and periterminal bronchiolar collagen deposition were significantly lower in group II compared to the group IV (p<0.05). Furthermore, according to the immunohistochemical staining results, CD3, CD4, CD8, CD20, CD68 and neutrophil elastase positive immune cells of group II were stained more positive than group IV cells (p<0.05). IFN-γ IL-2 and TNF-α levels in bronchoalveolar lavage fluid (BALF) were significantly lower in group II compared to group IV (p<0.05). The findings of this study indicate that intraperitoneally administered BMSCs have potent effects on histopatological changes of the lung tissue and cytokine levels in the murine model of BO.

Resveratrol ameliorates 2,4-dinitrofluorobenzene-induced atopic dermatitis-like lesions through effects on the epithelium.

Background. Resveratrol is a natural polyphenol that exhibits anti-inflammatory effects. The aim of this study was to investigate the effects of resveratrol treatment on epithelium-derived cytokines and epithelial apoptosis in a murine model of atopic dermatitis-like lesions. Material and Methods. Atopic dermatitis-like lesions were induced in BALB/c mice by repeated application of 2,4-dinitrofluorobenzene to shaved dorsal skin. Twenty-one BALB/c mice were divided into three groups: group I (control), group II (vehicle control), and group III (resveratrol). Systemic resveratrol (30 mg/kg/day) was administered repeatedly during the 6th week of the experiment. After the mice had been sacrificed, skin tissues were examined histologically for epithelial thickness. Epithelial apoptosis (caspase-3) and epithelium-derived cytokines [interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP)] were evaluated immunohistochemically. Results. Epithelial thickness and the numbers of IL-25, IL-33, TSLP and caspase-3-positive cells were significantly higher in group II compared to group I mice. There was significant improvement in epithelial thickness in group III compared with group II mice (p < 0.05). The numbers of IL-25, IL-33, and TSLP-positive cells in the epithelium were lower in group III than in group II mice (p < 0.05). The number of caspase-3-positive cells, as an indicator of apoptosis, in the epithelium was significantly lower in group III than in group II mice (p < 0.05). Conclusion. Treatment with resveratrol was effective at ameliorating histological changes and inflammation by acting on epithelium-derived cytokines and epithelial apoptosis.

Effects of Quercetin Treatment on Epithelium-derived Cytokines and Epithelial Cell Apoptosis in Allergic Airway Inflammation Mice Model.

Quercetin is a dietary flavonoid which has anti-inflammatory effects. This study aimed to evaluate the influence of quercetin on histopathological aspects and airway epithelium in  allergic airway  inflammation mice model. Twenty-eight BALB/c mice were randomly divided into four groups: Group I (control), Group II (untreated mice with allergic airway inflammation), Group III (allergic airway inflammation quercetin-treated [16mg/kg/day]), Group IV (allergic airway inflammation dexamethasone-treated [1mg/kg/day]). Ovalbumin was administered intraperitoneally and via inhalation to achieve allergic airway inflammation mice model and treatments were also given intraperitoneally. Epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness were examined on samples isolated from lung. Immunohistochemical evaluationof lung tissues was performed using  IL-25, IL-33, thymic stromal lymphopoietin (TSLP), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases(caspase)-3 antibodies. IL-4, IL-25, IL-33, TSLP were quantified in bronchoalveolar lavage (BAL) and OVAspecific IgE levels was measured in serum by standard ELISA protocols. IL-25, IL-33, thymic stromal lymphopoietin (TSLP) and cysteine-dependent aspartate-specific proteases (caspase)-3. Quercetin treatment led to lower epithelial thickness, subepithelial smooth muscle thickness, goblet and mast cell numbers compared to untreated  mice with allergic airway inflammation (p<0.05). However, quercetin treatment was not effective on improving basal membane thickness. Immunohistochemical scores of IL-25, IL-33, TSLP, caspase-3 and TUNEL were lower in quercetin-treated mice  t compared to untreated mice with allergic airway inflammation (p<0.05). IL-4, IL-25, IL-33, TSLP levels in BAL and OVA-specific IgE in serum were lower in quercetin treated mice compared to untreated mice (p<0.05). These findings suggest that quercetin improves chronic histopathological changes except basal membrane thickness in lung tissue and its beneficial effects on inflammation might be related to modulating epithelium derived cytokines and epithelial apoptosis.

Cyclosporin treatment improves skin findings in omenn syndrome.

Omenn syndrome is a combined immunodeficiency characterized by a generalized erythematous skin rash, enlarged lymph nodes, hepatosplenomegaly, severe susceptibility to infections, eosinophilia, and hyperimmunoglobulinemia E. A 3-month-old girl was admitted to our hospital with a history of recurrent sepsis. Physical examination revealed severe erythroderma, hepatosplenomegaly, lymphadenopathy, and failure to thrive. Laboratory findings revealed leukocytosis, lymphocytosis with high CD3 T-cells, a high CD4:CD8 ratio, absence of CD19 B-cells, high eosinophil count, and low immunoglobulin levels. A heterozygote RAG1 gene mutation was found. She had itchy, scaling, ichthyosiform erythroderma and protracted diarrhea. Cyclosporin treatment up to 10 mg/kg effectively resolved erythroderma and lowered total eosinophil counts, and she gained weight during treatment. Since extensive erythroderma with generalized itching causes patient discomfort in Omenn syndrome, cyclosporin treatment can be considered while waiting for treatment with hematopoietic stem cell transplantation.

Survival of an infant with homozygous surfactant protein C (SFTPC) mutation.

Lung diseases caused by surfactant protein C (SFTPC) mutations are inherited as autosomal traits with variable penetrance and severity or as sporadic disease caused by a de novo mutation on one allele. Here, we report the case of a child surviving with a homozygous surfactant protein C mutation after aggressive clinical management unlike his six siblings who died in infancy. This presentation raises the suspicion of an autosomal recessive inheritance that is discussed in this report.

[Effects of Imipenem, Tobramycin and Curcumin on Biofilm Formation of Pseudomonas aeruginosa Strains]. / Pseudomonas aeruginosa Suslarinda Imipenem, Tobramisin ve Curcuminin Biyofilm Olusumu Üzerine Etkisi.

Aminoglycoside antibiotics and imipenem are reported to stimulate exopolysaccharide alginate production and cause an increased biofilm volume in Pseudomonas aeruginosa. Recently, some remarkable studies have been conducted on the effects of curcumin (Turmeric), which is the fenolic form of Curcuma longa plant, on virulence factors of P.aeruginosa. In this study, we aimed to investigate the effects of MIC and sub-MIC concentrations of imipenem, tobramycin, and curcumin on biofilm formation of P.aeruginosa strains. P.aeruginosa strains (n= 2) used in this study were isolated from deep oropharyngeal swab samples of two cystic fibrosis patients. Antimicrobial susceptibilities of the two strains to imipenem, tobramycin, and curcumin were investigated by broth microdilution method, and biofilm production was assessed by using crystal violet staining method. In our study, MIC values of imipenem, tobramycin and curcumin for strain-1 were 8 µg/ml, 8 µg/ml and 16 µg/ml, respectively, while those values were 4 µg/ml, 8 µg/ml and 16 µg/ml for strain-2. Biofilm optical density values of the strain-1 and strain-2 before being treated with the test substances were 0.937 and 0.313 (control: 0.090), respectively, Biofilm optical densities of the both strains showed an increase following treatment with MIC concentrations of imipenem and tobramycin. The treatment of the strains with MIC and sub-MIC concentrations of curcumin led to no significant increase in biofilm optical density. The data obtained in this study supported the promising inhibitory effect of curcumin on P.aeruginosa biofilms. However, further more comprehensive studies are required to provide satisfactory data about the use of curcumin to treat P.aeruginosa infections characterized by biofilm formation.

Immunoglobulin abnormalities and effects of enzyme replacement therapy in children with Gaucher disease.

Hyperimmunoglobulinemia is documented in patients with Gaucher disease of all ages. We investigated the frequency of hyperimmunoglobulinemia in 12 pediatric patients with type I and III Gaucher disease and the effects of enzyme replacement therapy on these abnormalities. The incidence of hyperimmunoglobulinemia was 77%, 66%, and 60% at the diagnosis, before and after ERT, respectively. Immunoglobulin G abnormalities were the most commonly seen isotype abnormality. After enzyme replacement therapy normalization of IgA and IgM levels were recorded but decline in IgG levels was less likely to occur. This study indicated the higher frequency of hyperimmunoglobulinemia in pediatric Gaucher patients.