Evidence for a role of endothelin 1 and protein kinase C in nitroglycerin tolerance.

We sought to examine mechanisms responsible for increased vasoconstriction that occurs during development of nitroglycerin tolerance. Rabbits were treated for 3 days with nitroglycerin patches (0.4 mg/hr), and their aortic segments were studied in organ chambers. This treatment resulted in attenuated in vitro relaxations to nitroglycerin and increased contractile sensitivity to angiotensin II, serotonin, phenylephrine, KCl, and a direct activator of protein kinase C, the phorbol ester phorbol 12,13-dibutyrate. The protein kinase C antagonists calphostin C (100 nM) and staurosporine (10 nM) corrected the hypersensitivity to constrictors in tolerant vessels, yet had minimal effects on constrictions in control vessels. Paradoxically, constrictions caused by endothelin 1 were decreased in nitrate-tolerant vessels. Immunocytochemical analysis revealed intense endothelin 1-like and big endothelin 1-like immunoreactivity in the media of nitroglycerin-tolerant but not of control aortas. The enhanced vasoconstriction to angiotensin II, serotonin, KCl, and phenylephrine could be mimicked in normal vessels by addition of subthreshold concentrations of endothelin 1, and this effect was prevented by calphostin C. We propose that increased autocrine production of endothelin 1 in nitrate tolerance sensitizes vascular smooth muscle to a variety of vasoconstrictors through a protein kinase C-mediated mechanism.

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

The synthesis of a GSK 2nd generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

Una nueva rábita en la playa de Guardamar del Segura: la rábita de El Moncayo

Se publican las noticias que ha arrojado la excavación en 2004 de unos muros situados en la denominada playa de El Moncayo. Los hallazgos se sitúan a unos 3 kilómetros al Sur del casco urbano de Guardamar del Segura; a unos 135 m. en dirección Norte está la Torre del Descargador (torre almenara de los siglos IV/X y V/XI), a unos 3,5 kilómetros se localiza El Castillo de Guardamar (de los siglos VIII a.C. al XIX) y, un poco más al Norte, a unos 4 kilómetros, en las proximidades de la desembocadura del Segura, los oratorios o rábitas de las dunas de Guardamar. Se dan a conocer los restos arquitectónicos y cerámicos aparecidos en la excavación del 2004 que se interpretan como de restos del recinto de una rábita o mezquitilla (cuando se excave más se verá si está aislada o hay más edificios similares), se presentan unos apuntes al hilo de la orientación de la rábita de El Moncayo y un estudio de la moneda andalusí hallada en la excavación de El Moncayo (datables entre en 429/1037-8 y 433/1041-2).

XI. Catalogue of Harvard graduates, [ca. 1810]

This paper notebook contains a handwritten, alphabetical listing of graduates of the Harvard Classes of 1642 to 1809 presumably compiled from the published Triennial Catalogues.

Eulogy of George Washington, ca. 1800

This manuscript, which White entitled A faint sketch of the character, history & services of the Immortal Washington, appears to be a draft of the eulogy on Washington that he delivered publicly in Methuen and which was printed by Seth H. Moore and published by in February 1800.

Outlines of Holden Chapel, [ca. 1801]

Pen and ink drawings with measurements of the interior ground plot, arch, and side of Holden Chapel.

Mammals of the Chicago area / by Colin C. Sanborn, Assistant, Division of Mammals.

no.8(1925)

Draft of "A list of the books belonging to the late Library of Harvard College [...]," ca. 1764

This list appears to be a draft of the list in Folder 1. Although most of the entries match, there are some discrepancies.

Library catalogue notes of Isaac Smith, ca. 1789

Thirteen slips of paper with fragments of handwritten alphabetical lists created by Isaac Smith presumably in his capacity as Harvard Librarian. Most of the entries are surnames or single-word subjects. For example, one slip with "M" entries includes: milway, miracles, miraculous, Mitchell, and Mitchell. Some of the lists have struck-through words or have entries annotated with numbers and the abbreviations "o" and "bk." The verso of one leaf has a brief, undated note regarding the transfer of books between Mr. Hilliard and Mr. Smith.

Student notebook of Thomas Prince, ca. 1707

Paper notebook in Latin on classical Greek grammar. The name "Thomas Prince" appears on the first page. The manuscript is undated. Based on the signature, this volume is assumed to have belonged to Thomas Prince, Sr., although it is undated and may have indeed belonged to Thomas Prince, Jr.