Phospholipase C-γ as a Potential Therapeutic Target for Graves' Orbitopathy.

BACKGRUOUND: Phospholipase C-γ (PLC-γ) plays a crucial role in immune responses and is related to the pathogenesis of various inflammatory disorders. In this study, we investigated the role of PLC-γ and the therapeutic effect of the PLC-specific inhibitor U73122 using orbital fibroblasts from patients with Graves' orbitopathy (GO). METHODS: The expression of phospholipase C gamma 1 (PLCG1) and phospholipase C gamma 2 (PLCG2) was evaluated using polymerase chain reaction in GO and normal orbital tissues/fibroblasts. The primary cultures of orbital fibroblasts were treated with non-toxic concentrations of U73122 with or without interleukin (IL)-1ß to determine its therapeutic efficacy. The proinflammatory cytokine levels and activation of downstream signaling molecules were determined using Western blotting. RESULTS: PLCG1 and PLCG2 mRNA expression was significantly higher in GO orbital tissues than in controls (P<0.05). PLCG1 and PLCG2 mRNA expression was significantly increased (P<0.05) in IL-1ß, tumor necrosis factor-α, and a cluster of differentiation 40 ligand-stimulated GO fibroblasts. U73122 significantly inhibited the IL-1ß-induced expression of proinflammatory molecules, including IL-6, IL-8, monocyte chemoattractant protein-1, cyclooxygenase-2, and intercellular adhesion molecule-1 (ICAM-1), and phosphorylated protein kinase B (p-Akt) and p38 (p-p38) kinase in GO fibroblasts, whereas it inhibited IL-6, IL-8, and ICAM-1, and p-Akt and c-Jun N-terminal kinase (p-JNK) in normal fibroblasts (P<0.05). CONCLUSION: PLC-γ-inhibiting U73122 suppressed the production of proinflammatory cytokines and the phosphorylation of Akt and p38 kinase in GO fibroblasts. This study indicates the implications of PLC-γ in GO pathogenesis and its potential as a therapeutic target for GO.

Prognosis of choroidal melanoma and the result of ruthenium brachytherapy combined with transpupillary thermotherapy in Korean patients.

BACKGROUND/AIMS: To evaluate the clinical features and prognosis of choroidal melanoma in Korean patients and the results of treatment with ruthenium (Ru) 106 plaque brachytherapy. METHODS: The medical charts of 111 patients diagnosed with choroidal melanoma who underwent Ru brachytherapy with trans-pupillary thermotherapy or local resection (61 patients) or who underwent other treatments (26 primary enucleations, 22 γ-knife radiotherapies and two lamellar sclerouvectomies) were reviewed retrospectively. RESULTS: The mean largest basal diameter (LBD) was 11.4±3.2 mm and the mean apical height was 7.8±2.9 mm. Compared with the collaborative ocular melanoma study, mean tumour height was skewed toward higher values (6.2 vs 4.8 in medium tumours, p<0.0001; 10.9 vs 9.5 mm in large tumours, p=0.034) and the LBD in large tumours was skewed toward smaller values (13.6 vs 17.3, p<0.0001). The estimated 5-year metastasis-free rate was 73.9% and the disease-specific survival rate was 84.6%. For the 61 patients that were treated with Ru brachytherapy, the 5-year metastasis-free and disease-specific survival rates were 79.0% and 87.7%, respectively, and the 5-year incidence of enucleation was 25.4%. The mean tumour regression at 6, 12 and 18 months after brachytherapy was 80.2%, 73.1% and 69.2%, respectively. CONCLUSIONS: Choroidal melanomas in Korean patients tend to grow vertically with a relatively large apical height and a small LBD. The prognosis of choroidal melanomas overall as well as prognosis after Ru brachytherapy were similar to those seen in previous studies with Caucasian patients. The enucleation rate after brachytherapy seems to be higher in Korean patients, for which a greater initial tumour height seems to be partly responsible.

Effect of degumming condition on the solution properties and electrospinnablity of regenerated silk solution.

The application of silk on tissue engineering scaffolds has been studied intensively because silk has an electrospinning technique using a good blood compatibility, excellent cytocompatibility and biodegradability. Silk consists of two polymers, fibroin and sericin. In spite of importance of sericin, most studies were focused on the fibroin only and the effect of residual sericin on the electrospinning performance of silk has not been considered. In this study, regenerated silk with different residual sericin contents was prepared by controlling the degumming conditions. The effects of the degumming conditions on the solution properties and electrospinning performance of silk were examined. The fast protein liquid chromatography (FPLC) measurements confirmed that the molecular weight of the regenerated silk decreased slightly with increasing residual sericin content. More molecular aggregation of silk occurred with increasing sericin content, resulting in an increase in the solution turbidity of formic acid. All silk formic acid solutions exhibited almost Newtonian fluid behavior and the viscosity increased with increasing sericin content. Interestingly, the dope solution viscosity of silk increased remarkably at sericin contents <1% (or degumming ratio >25%) leading to significant improvements in electrospinnability and an increase in the fiber diameter of the silk web.