Purpose.: Dry eye syndrome (DES) is characterized by an increase in tear osmolarity and induction of the expression and nuclear localization of an osmoprotective transcription factor (nuclear factor of activated T-cells 5 [NFAT5]) that plays an important role in providing protection against hyperosmotic tears. In this study, we screened medicines already in clinical use with a view of finding compounds that protect cultured human corneal epithelial cells against hyperosmolarity-induced cell damage. Methods.: Viable cell number was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and cellular NFAT5 level was measured by immunoblotting. The rat model for DES was developed by removal of the lacrimal glands, with an assessment of corneal surface damage based on levels of fluorescein staining and epithelial apoptosis. Results.: Some nonsteroidal anti-inflammatory drugs (NSAIDs), including diclofenac sodium (diclofenac), were identified during the screening procedure. These NSAIDs were able to suppress hyperosmolarity-induced apoptosis and cell growth arrest. In contrast, other NSAIDs, including bromfenac sodium (bromfenac), did not exert such a protective action. Treatment of cells with diclofenac, but not bromfenac, stimulated both the nuclear localization and expression of NFAT5 under hyperosmotic conditions. In the rat model for DES, topical administration of diclofenac (but not bromfenac) to eyes reduced corneal surface damage without affecting the volume of tear fluid. Conclusions.: Diclofenac appears to protect cells against hyperosmolarity-induced cell damage and NFAT5 would play an important role in this protective action. The findings reported here may also indicate that the topical administration of diclofenac to eyes may be therapeutically beneficial for DES patients.
Abstract The number of patients with dry eye disease (DED) is increasing, and DED has become an urgent public health problem. A comorbidity of mental disorders has been reported in DED patients. We hypothesized that physical and psychological stressors impair tear secretion. To examine the relationship between stress loading and decreased tear secretion, we established a stress-induced DED mouse model, which permitted us to address the underlying mechanism of pathogenesis and resilience. Enriched environment (EE) was an effective intervention to prevent and alleviate stress-induced decreased tear secretion. Because stress loading resulted in decreased brain-derived neurotrophic factor (BDNF) expression while EE resulted in increased expression, we focused on the role of BDNF in tear secretion. Using two distinct Bdnf gene knockdown mice, we evaluated whether BDNF was a deterministic factor in regulating tear secretion in healthy and stressed conditions. Bdnf knockdown mice showed decreased basal tear secretion and loss of stress tolerance by EE for tear secretion. These results suggest that BDNF expression is related to tear secretion and to the pathology of DED.
SUMMARY 1. Both natriuretic and hypotensive effects of brain natriuretic peptide (BNP), a novel peptide identified in porcine brain, were investigated in anaesthetized DOCA‐salt rats and control rats. 2. An intravenous injection of two different doses (0.5 and 5.0 nmol/kg) of BNP produced a rapid and marked natriuresis and hypotension in DOCA‐salt rats. 3. In particular, significant differences of responsiveness were observed between DOCA‐salt and control rats when administered the lower dose of BNP. 4. It was suggested that DOCA‐salt rats might be relatively more susceptible to BNP.
Transcatheter arterial embolization (TAE) was performed in 20 patients from April, 1982 to February, 1984. These patients had unresectable hepatomas due to extreme tumor extension and/or advanced accompanying cirrhosis. Angiographically, solitary hypervascular mass was seen in 8 patients, solitary mass with daughter nodules in 10, and central portal vein obstruction was in 6 patients ; 3 in the portal vein trunk and 2 in the first branch of the portal vein.Embolic material was gelatin sponge permeated with MMC 20mg and contrast material. Under fluoroscopic guidance, these embolic materials were infused into the feeding artery through the catheter which was inserted distally to the proper hepatic artery.Eight patients out of 20 were died until March 31, 1984. Four patients out of 8 showed proximal obstruction of the portal vein by tumor thrombus. Twelve patients are alive. Three patients out of 6 more than one year after the initial TAE are alive. Two patients with recurrent or metastatic tumor after hepatectomy are also alive.
