Despite recent advances in surgical techniques, adhesion formation remains a leading cause of persistent infertility following reconstructive tubal surgery. Recently, we reported that reduction of fibroproliferative inflammation by nonsteroidal anti-inflammatory drugs was an effective method of modifying peritoneal healing. Although the pharmacologic activity of these drugs is mediated through arachidonic acid metabolism, their mechanism of action in altering postoperative peritoneal healing remains unknown. In this grant, we plan to determine the cellular events leading to postoperative adhesion formation and at what point nonsteroidal anti-inflammatory drugs modify this process. In specific, we plan to perform the following studies in a dose-response and time response format: 1) Identification of the changing cellular patterns accompanying the formation of adhesions during re-epithelialization and the results of pharmacologic pertubation of fibroproliferative inflammation on that response. 2) Determine the pattern of arachidonic acid metabolism, collagen and proteoglycan secretion in cellular elements central to peritoneal re-epithelialization with and without inhibitors of arachidonic acid metabolism or corticosteroids. 3) Quantitative assessment of de novo inflammation in vivo (using eye chamber) to explant postoperative peritoneal repair cells and the effects of pharmacologic modifiers of arachidonic acid metabolism on that response. Through elucidation of the biochemical events and cellular elements involved in adhesion formation and their respective responses to pharmacologic manipulations, strategies should be forthcoming allowing the design of clinically effective methods for adhesion-free surgery.

Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Los Angeles County-University of S Cal Medical Center
Department
Type
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90033
Fukasawa, M; Bryant, S M; Orita, H et al. (1989) Modulation of proline and glucosamine incorporation into tissue repair cells by peritoneal macrophages. J Surg Res 46:166-71
Fukasawa, M; Bryant, S M; diZerega, G S (1988) Superoxide anion production by postsurgical macrophages. J Surg Res 45:382-8
Greenwald, D; Nakamura, R; diZerega, G (1988) Determination of pH and pKa in human peritoneal fluid. Curr Surg 45:217-8
Shimanuki, T; Nishimura, K; Montz, F J et al. (1987) Localized prevention of postsurgical adhesion formation and reformation with oxidized regenerated cellulose. J Biomed Mater Res 21:173-85
Fukasawa, M; Bryant, S M; Nakamura, R M et al. (1987) Modulation of fibroblast proliferation by postsurgical macrophages. J Surg Res 43:513-20
Orita, H; Campeau, J D; Nakamura, R M et al. (1986) Modulation of fibroblast proliferation and transformation by activated macrophages during postoperative peritoneal reepithelialization. Am J Obstet Gynecol 155:905-11
Shimanuki, T; Nakamura, R M; diZerega, G S (1986) A kinetic analysis of peritoneal fluid cytology and arachidonic acid metabolism after abrasion and reabrasion of rabbit peritoneum. J Surg Res 41:245-51
Orita, H; Campeau, J D; Gale, J A et al. (1986) Differential secretion of plasminogen activator activity by postsurgical activated macrophages. J Surg Res 41:569-73
Shimanuki, T; Nakamura, R M; diZerega, G S (1985) In vivo modulation of leukotaxis by non-steroidal anti-inflammatory drugs. Agents Actions 17:80-3
Montz, F J; diZerega, G S (1985) Genital tuberculosis in an elderly woman with the primary symptoms of pelvic prolapse: case report. Am J Obstet Gynecol 152:42-3

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