PubMed · 4330488
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G G Nahas, C F Poyart, J P Kleisbauer, M Verosky, Y Vulliemoz. 1971-12-30. Activated lipolysis and pH changes.. https://doi.org/10.1111/j.1749-6632.1971.tb45244.x
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A novel approach to immobilize nonuniform initial drug concentration profiles in multilaminated matrix devices utilizing photopolymerization techniques is presented. Solution polymerization of 2-hydroxyethyl methacrylate (HEMA) and diethylene glycol dimethacrylate (DEGDMA) in the presence of a model compound, acid orange 8 (AO8), was conducted using UV light and photoinitiators to construct a laminated matrix device. In this process, each layer was polymerized with a different AO8 concentration to form a nonuniform initial concentration profile in the matrix devices. The AO8 diffusion coefficients measured in this work were used in a concurrently developed model to predict the effects of nonuniform AO8 concentration profiles on AO8 release patterns. The release data predicted by the model agreed well with the experimentally determined data. The results indicate that a zero-order release pattern can be approximated by employing a suitable nonuniform initial drug concentration profile.
The average polymorphonuclear neutrophil (PMN) lives only a day and then dies by apoptosis. We previously found that the calcium-dependent protease calpain is required for apoptosis in several mouse models of cell death. Here we identify calpain, and its endogenous inhibitor calpastatin, as regulators of human neutrophil apoptosis. Cell death triggered by the translation inhibitor cycloheximide is calpain-dependent, as evidenced using either a calpain active site inhibitor (N-acetyl-leucyl-leucyl-norleucinal) or agents that target calpain's calcium binding sites (PD150606, PD151746). No significant effect on cycloheximide-triggered apoptosis was found by using inhibitors of the proteasome or of other papain-like cysteine proteases, providing further evidence that the active site calpain inhibitor prevents apoptosis via its action on calpain. In addition, we find that potentiation of calpain activity by depleting its endogenous inhibitor, calpastatin, is sufficient to cause apoptosis of neutrophils. Nevertheless, apoptosis signalled via the Fas antigen proceeds regardless of the presence of calpain inhibitor. These experiments support a growing body of work, indicating an upstream regulatory role for calpain in many, but not all, forms of apoptotic cell death. They also identify calpastatin as a participant in apoptotic cell death and suggest that for at least one cell type, a decrease in calpastatin is a sufficient stimulus to initiate calpain-dependent apoptosis.
OBJECTIVE: To compare the visual outcome, neodymium:YAG (Nd:YAG) capsulotomy rates, and percentage of posterior capsular opacification (PCO) seen with polymethylmethacrylate (PMMA), silicone, and polyacrylic intraocular lens implants 3 years after surgery. DESIGN: Randomized, prospective trial. PARTICIPANTS: Ninety eyes of 81 patients were examined at a British teaching hospital. INTERVENTION: Ninety eyes were prospectively randomized to receive a PMMA, silicone, or polyacrylic (AcrySof, Alcon, Fort Worth, TX) implant. All lenses had 6-mm disc optics with PMMA haptics. A standardized surgical protocol was performed by a single surgeon using an extracapsular technique with capsulorhexis; any surgical complications were excluded and all patients had standardized postoperative medication and follow-up. MAIN OUTCOME MEASURES: Patients were seen at 6 months and 1, 2, and 3 years after surgery. At 3 years, logarithm of the minimum angle of resolution (LogMAR) visual acuity and Pelli-Robson contrast sensitivity were measured and YAG capsulotomy rates determined. Posterior capsular opacification was assessed objectively by digital retroillumination imaging using dedicated software and calculated as the percentage area of opacified capsule. RESULTS: At 3 years, the overall follow-up rate was 71%: 19 patients were available for examination with polyacrylic lens implants, 22 with silicone, and 23 with PMMA. There was a significant difference in percentage PCO at 3 years among the lens types (P = 0.0001). Polyacrylic lenses were associated with less PCO (10%) than silicone (40%) and PMMA lenses (56%). The YAG capsulotomy rate was 0% for polyacrylic, 14% for silicone, and 26% for PMMA (P = 0.05). The visual acuity and contrast sensitivity were not significantly different among the three groups if patients with age-related macular degeneration and those requiring YAG capsulotomies are excluded. CONCLUSIONS: Intraocular lenses made from polyacrylic are associated with a significantly reduced degree of PCO and lower YAG rates.