Biomedical subjects

A Edward

Publications and source records attributed to A Edward.

4 recordsLinked to original sources

PubMed2001

Predicted permeability of the cornea to topical drugs.

PURPOSE: To develop a theoretical model to predict the passive, steady-state permeability of cornea and its component layers (epithelium, stroma, and endothelium) as a function of drug size and distribution coefficient (phi). The parameters of the model should represent physical properties that can be independently estimated and have physically interpretable meaning. METHODS: A model was developed to predict corneal permeability using 1) a newly developed composite porous-medium approach to model transport through the transcellular and paracellular pathways across the epithelium and endothelium and 2) previous work on modeling corneal stroma using a fiber-matrix approach. RESULTS: The model, which predicts corneal permeability for molecules having a broad range of size and lipophilicity, was validated by comparison with over 150 different experimental data points and showed agreement with a mean absolute fractional error of 2.43, which is within the confidence interval of the data. In addition to overall corneal permeability, the model permitted independent analysis of transcellular and paracellular pathways in epithelium, stroma and endothelium. This yielded strategies to enhance corneal permeability by targeting epithelial paracellular pathways for hydrophilic compounds (phi < 0.1 - 1), epithelial transcellular pathways for intermediate compounds, and stromal pathways for hydrophobic compounds (phi > 10 - 100). The effects of changing corneal physical properties (e.g., to mimic disease states or animals models) were also examined. CONCLUSIONS: A model based on physicochemical properties of the cornea and drug molecules can be broadly applied to predict corneal permeability and suggest strategies to enhance that permeability.

Administration, Topical↗

PubMed2000

Dimethylsulfoniopropionate in giant clams (Tridacnidae).

The tridacnid clams maintain symbiotic associations with certain dinoflagellates (termed zooxanthellae). Tridacnids are thus candidates to have high tissue concentrations of dimethylsulfoniopropionate (DMSP), a tertiary sulfonium compound that is not synthesized by animals but is commonly produced by dinoflagellates. This study establishes that DMSP is about an order of magnitude more concentrated in the light-exposed and shaded mantle and gills of Tridacna maxima and T. squamosa than in any other known animal tissues. The DMSP concentration in the light-exposed, siphonal mantle--the location of most zooxanthellae--is an inverse function of body size, paralleling an inverse relation between apparent density of zooxanthellae (measured as pheophytin concentration) and body size. The shaded mantle and gills are high in DMSP despite having low densities of zooxanthellae, indicating that high DMSP concentrations occur in molluscan tissue, not just in algal cells. DMSP is almost an order of magnitude less concentrated in the adductor muscle than in other tissues. The high DMSP concentrations found in tridacnids, by providing abundant substrate for formation of volatile dimethylsulfide, probably explain the peculiar tendency of tridacnids to rapidly develop offensive odors and tastes after death: a serious problem for their exploitation as food. Tridacnids are the one group of animals in which DMSP concentrations are high enough in some tissues to be in the range capable of perturbing enzyme function at high physiological temperatures. Thus, tridacnids may require enzyme forms adapted to DMSP.

Animals↗

PubMed1992

Streptococcus peritonitis with urticaria.

Peritonitis following urticaria on two occasions in a 46-year-old white female treated with CAPD for nine years is reported. On both occasions an episode of urticaria and pruritus occurred 24 hr before the dialysate became cloudy, and the patient experienced abdominal pain, nausea, and vomiting. The culture of the peritoneal dialysis effluent grew gamma Streptococcus with the first episode. To our knowledge this is the first report of CAPD peritonitis preceded by urticaria where the skin findings were most likely related to the peritoneal infection.

Female↗

PubMedDate not supplied

A new approach to optimizing urea clearances in hemodialysis and continuous ambulatory peritoneal dialysis.

Recent studies suggest that the relationship of the net normalized protein catabolic rate (which is the normalized protein equivalent of nitrogen appearance [nPNA]) to the weekly clearance of urea normalized to total body water (Kt/V urea) in patients on continuous ambulatory peritoneal dialysis (CAPD) is curvilinear, rather than linear, as has been thought. The authors have reexamined the relationship of nPNA to weekly Kt/V urea in a CAPD population by cross-sectional analysis to see if the curvilinear definition of the relationship is as good as or better than the usual linear description. They also examined this relationship in the hemodialysis populations at the Dialysis Clinics Inc. in Columbia, Missouri, and in the Renal Kidney Disease Program in Minneapolis, Minnesota. It seems obvious that there should be a plateau of nPNA in each therapy because extension of linear regressions would predict protein intakes of normal individuals exceeding 8 g/kg/body weight/day. The authors compared their findings to other published results. Intuitively and analytically, the curvilinear relationships seem likely. The authors observed that the nPNA plateau is achieved at lower Kt/V in patients on CAPD than in those on hemodialysis, which is compatible with the peak concentration hypothesis. Asymptotes for CAPD and hemodialysis are similar. Weekly Kt/V urea requirements to achieve nPNA values at 95% of the asymptote are greater than those usually delivered. However, such nearly complete elimination of uremic appetite suppression may not be practical or necessary for achieving acceptable nutritional status and long-term survival in most patients. Optimum therapy may be well above adequate therapy relative to minimizing appetite suppression by uremia.

Appetite↗