RESUMEN

In cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD), the amyloid ß (Aß) peptide deposits along the vascular lumen, leading to degeneration and dysfunction of surrounding tissues. Activated coagulation factor XIIIa (FXIIIa) covalently cross-links proteins in blood and vasculature, such as in blood clots and on the extracellular matrix. Although FXIIIa co-localizes with Aß in CAA, the ability of FXIIIa to cross-link Aß has not been demonstrated. Using Western blotting, kinetic assays, and microfluidic analyses, we show that FXIIIa covalently cross-links Aß40 into dimers and oligomers (kcat/Km = 1.5 × 105 m-1s-1), as well as to fibrin, platelet proteins, and blood clots under flow in vitro Aß40 also increased the stiffness of platelet-rich plasma clots in the presence of FXIIIa. These results suggest that FXIIIa-mediated cross-linking may contribute to the formation of Aß deposits in CAA and Alzheimer's disease.

Asunto(s)

Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Proteínas Sanguíneas/metabolismo , Angiopatía Amiloide Cerebral/metabolismo , Factor XIIIa/metabolismo , Fragmentos de Péptidos/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/análisis , Plaquetas/metabolismo , Plaquetas/patología , Proteínas Sanguíneas/análisis , Angiopatía Amiloide Cerebral/patología , Factor XIIIa/análisis , Fibrina/análisis , Fibrina/metabolismo , Humanos , Fragmentos de Péptidos/análisis , Plasma Rico en Plaquetas/metabolismo , Agregación Patológica de Proteínas/metabolismo , Agregación Patológica de Proteínas/patología , Multimerización de Proteína

RESUMEN

To ascertain the current status of anesthesia care for electroconvulsive therapy (ECT) on a statewide basis, 54 facilities identified as providing ECT in the State of Pennsylvania were sent a specially designed 127-item questionnaire. Of 27 (50%) respondents, 25 (93%) included anesthesia personnel (anesthesiologists, nurse anesthetists, and anesthesia residents) on the treatment team and 2 (7%) did not. The questionnaire included items concerning pretreatment evaluation, preparation of patients, anesthesia administration, postanesthetic considerations, treatment locale, and patient profile. The items were derived from the American Psychiatric Association (APA) Task Force Report on Electroconvulsive Therapy, the Guidelines for Patient Care in Anesthesiology of the American Society of Anesthesiologists (ASA), the Standards for Nurse Anesthesia Practice of the American Association of Nurse Anesthetists (AANA), and items that reflected guidelines of the ASA and AANA. The responses of each profession were compared to its own organizational guidelines and to the other guidelines. The professions did not adhere to their own guidelines; the lowest compliance was for psychiatrists to items derived from the APA. Items derived from the APA generally received lower responses from all professions in the study. The study documents the present-day anesthetic coverage of ECT in the State of Pennsylvania, and reflects an almost complete change over a 10-year period (1978-1988) to a two-member team for ECT: a psychiatrist for electroconvulsive treatment and an anesthetist or anesthesiologist for the anesthesia management.