Platelets modulate gastric ulcer healing: Role of endostatin and vascular endothelial growth factor release

Bleeding and delayed healing of ulcers are well recognized clinical problems associated with the use of aspirin and other nonsteroidal antiinflammatory drugs, which have been attributed to their antiaggregatory effects on platelets. We hypothesized that antiplatelet drugs might interfere with gastric ulcer healing by suppressing the release of growth factors, such as vascular endothelial growth factor (VEGF), from platelets. Gastric ulcers were induced in rats by serosal application of acetic acid. Daily oral treatment with vehicle, aspirin, or ticlopidine (an ADP receptor antagonist) was started 3 days later and continued for 1 week. Ulcer induction resulted in a significant increase in serum levels of VEGF and a significant decrease in serum levels of endostatin (an antiangiogenic factor). Although both aspirin and ticlopidine markedly suppressed platelet aggregation, only ticlopidine impaired gastric ulcer healing and angiogenesis as well as reversing the ulcer-associated changes in serum levels of VEGF and endostatin. The effects of ticlopidine on ulcer healing and angiogenesis were mimicked by immunodepletion of circulating platelets, and ticlopidine did not influence ulcer healing when given to thrombocytopenic rats. Incubation of human umbilical vein endothelial cells with serum from ticlopidine-treated rats significantly reduced proliferation and increased apoptosis, effects reversed by an antibody directed against endostatin. Ticlopidine treatment resulted in increased platelet endostatin content and release. These results demonstrate a previously unrecognized contribution of platelets to the regulation of gastric ulcer healing. Such effects likely are mediated through the release from platelets of endostatin and possibly VEGF. As shown with ticlopidine, drugs that influence gastric ulcer healing may do so in part through altering the ability of platelets to release growth factors.

The Power of the Placement of Public Sculpture

The Power of the Placement of Public Sculpture explores the aesthetic effects public sculpture has on the environment around it. The work presented includes a discussion of case studies in select American and international communities. Relevance is brought to the topic through the documentation of the placement of a fabricated eight-foot avocado sculpture displayed on the University of Denver campus. Reflection on the experience exposes additional questions and demonstrates the importance of the placement of a public sculpture.

Power of attorney for Joseph Chip, 1804 December 21

Handwritten draft of a power of attorney, in Croswell's hand, authorizing John Jones to act for mariner Joseph Chip.

Power of Attorney, [?] Wellington for Thomas Durant, Sept. 22, 1787

Signed by Thomas Durant and witnessed by Ebenezer Bradish. It is possible that Shapleigh used this document as a guide when drafting his own power of attorney documents.

Power of Attorney, Samuel Shapleigh for Thomas Adams, Jan. 12, 1791

Signed by Thomas Adams and witnessed by Abraham Biglow and Daniel Clarke Sanders.

Power of Attorney, Samuel Shapleigh for James Otis Prentiss, Aug. 18, 1791

Document also contains what appears to be a bill for medical services rendered by Prentiss, a doctor, to William Boman.

[Power of attorney between Stephen Sewall and Thomas Wigglesworth], 1794 August 21

This one-page printed form appoints Thomas Wigglesworth as the "true and lawful Attorney" for Stephen Sewall. The form is notarized by Samuel Barrett and witnessed by Barrett and his daughter Peggy Barrett.

Power of Attorney, Samuel Shapleigh for Thomas Thompson, May 18, 1791

Signed by Thomas Thompson and witnessed by Thaddeus Mason Harris and Otis(?) Clarke.