The effect of latanoprost and brimonidine on rabbit subconjunctival fibroblasts

PURPOSE: Subconjunctival fibroblasts play a critical role in scarring and treatment failure in fistulizing surgery for glaucoma. The proliferation of subconjunctival fibroblasts appears to be modulated by topical glaucoma medications. This study was conducted to evaluate the effects of latanoprost and brimonidine on subconjunctival fibroblast proliferation in rabbit eyes. METHODS: Twelve pigmented Dutch-belted rabbits were divided into treatment groups of four: latanoprost 0.005%, brimonidine 0.2%, or balanced saline solution (BSS) each were administered to one treatment group, both eyes of each rabbit, twice a day, 6 days a week for 10 weeks. The eyes were then enucleated along with the conjunctiva, fixed, processed, and evaluated by light microscopy and immunohistochemistry using anti-proliferating cell nuclear antigen (PCNA) and anti-muscle-specific actin antibody (HHF-35). Fibroblast cell counts were performed at magnification x40. RESULTS: In all groups, few inflammatory cells were seen in the subconjunctival space under light microscopy. PCNA staining revealed a statistically significant increase in the mean number of labeled fibroblasts in the group receiving brimonidine compared with the control (BSS) group. The group receiving latanoprost also had a significantly higher mean number of labeled fibroblasts than the groups receiving brimonidine or BSS. Only a few fibroblasts stained positively with the anti HHF antibody. Eyes treated with latanoprost, however, had significantly higher numbers of positively labeled cells than eyes treated with brimonidine or BSS. CONCLUSION: When applied to rabbit eyes, latanoprost and brimonidine appear to increase the number of positively labeled proliferating subconjunctival fibroblasts.     

Analysis of posterior spinal wiring in a validated rabbit model

Mamillary and spinous process base wiring did not improve L5-L6 posterolateral fusion rate, stiffness, or strength in a previously established rabbit model. Specimen radiography significantly underestimated fusion rate when compared with manual palpation (37% versus 68%). Fused specimens were significantly stiffer (67.2 N/mm versus 41.1 N/mm) and stronger (177 N versus 121 N) in tension than were nonfused specimens. Deep wound infection, detected only at the time of sacrifice, apparently was more common with internal fixation (43% versus 21%). Noninfected specimens were significantly stiffer (63.3 N/mm versus 43.0 N/mm) and stronger (176 N versus 107 N) than were infected specimens.     

Detection of stromelysin and collagenase in synovial fluid from patients with rheumatoid arthritis and posttraumatic knee injury.

OBJECTIVE. To quantify stromelysin and collagenase in synovial fluid (SF) from patients with rheumatoid arthritis (RA) or traumatic knee injury. METHODS. Stromelysin and collagenase were measured in the SF of 33 patients with RA or posttraumatic knee injury, using specific double-antibody sandwich enzyme-linked immunosorbent assays. Stromelysin was fractionated from representative SF, and the molecular form was identified by immunoblot analysis. RESULTS. The stromelysin concentration was approximately 20-fold higher than the collagenase concentration in the fluids from patients with RA and approximately 8-fold higher in the fluids from patients with traumatic injury. For both metalloproteinases, there was a higher enzyme concentration in RA SF than in the SF from patients with trauma (stromelysin 40.1 +/- 26 micrograms/ml [mean +/- SD] in RA SF, 8.5 +/- 15 micrograms/ml in trauma SF; collagenase 2.2 +/- 3.3 micrograms/ml in RA SF, 1.1 +/- 2.3 micrograms/ml in trauma SF). The majority of the stromelysin within the SF bound to reactive red-agarose and was identified as prostromelysin based on electrophoretic mobility and immunoblotting with monospecific antibodies. CONCLUSION. The finding of high levels of stromelysin in SF from patients with RA supports the proposal that this enzyme may play a role in the connective tissue degradation observed in this disease.     

Intratumoral inflammation is associated with more aggressive prostate cancer

Purpose

Inflammation may play a role in the development and progression of many cancers, including prostate cancer. We sought to test whether histological inflammation within prostate cancer was associated with more aggressive disease.

Methods

The slides of prostatectomy specimens were reviewed by a board-certified pathologist on 287 men from a Veterans Affairs Medical Center treated with radical prostatectomy from 1992 to 2004. The area with the greatest tumor burden was scored in a blinded manner for the degree of inflammation: absent, mild, or marked. We used logistic and Cox proportional hazards regression analysis to examine whether categorically coded inflammation score was associated with adverse pathology and biochemical progression, respectively.

Results

No inflammation was found in 49 men (17 %), while 153 (53 %) and 85 (30 %) had mild and marked inflammation. During a median follow-up of 77 months, biochemical recurrence occurred among 126 (44 %) men. On multivariate analysis, more inflammation was associated with greater risk of positive margins, capsular penetration, and seminal vesicle invasion (all p < 0.05). Marked inflammation was associated with increased PSA recurrence risk when adjusting for preoperative features only (HR 2.08, 95 % CI 1.02–4.24), but not after adjusting for pathologic features.

Conclusions

Inflammation within prostate cancer was associated with more advanced disease, although it is unclear whether aggressive disease caused increased inflammation or inflammation caused aggressive disease.     

Potent Irreversible Inhibitors of LasR Quorum Sensing in Pseudomonas aeruginosa

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