Gram-negative endotoxaemia
department or school: Medicine, Faculty of
department or school: Anesthesiology, Pharmacology and Therapeutics, Department of
data provider: DSpace
degree campus: UBCV
creator: Tuchek, John Michael
issued: 2010-06-13T17:02:28Z
issued: 1983
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Endotoxins arelipopolysaccharide (LPS) complexes extractable from the outer membrane of gram negative bacilli. These complexes comprise the 0-antigen of gram-negative bacteria and are used in the serological typing of these organisms. The release of endotoxins from gram-negative bacteria is believed to be a contributing factor to the high mortality rate associated with gram-negative septic shock in humans. Indeed, the sequelae of gram-negative septic shock seen clinically can be reproduced in experimental animals by the parenteral administration of purified endotoxin. The clinical management of gram-negative septicaemia would, perhaps, be much more effective if agents capable of antagonizing the actions of endotoxin in vivo could be used in combination with appropriate antibiotic therapy. The work reported in this thesis has utilized both biochemical and physiological approaches to obtain more insight into the mechanism of action of E. coli endotoxin with the ultimate hope of finding an effective antagonist for this toxic substance. In vivo studies with rats and guinea pigs have indicated that elevations in plasma lysosomal enzyme activities can be used as a measure of the severity of endotoxic shock. The lysosomal enzymes examined in this study included acid phosphatase, N-acetyl-β-glucosaminidase and cathepsin D. Interestingly, when the investigation of these enzymes was extended to include patients in gram-negative septic shock, it was found that the plasma of the patients also contained lysosomal enzyme activities that were significantly elevated relative to controls. Furthermore, the average plasma activity of cathepsin D in gram-negative septic shock patients was found to be significantly higher than that seen in the plasma of patients in other forms of shock. Thus, these preliminary studies indicate that measurements of plasma cathepsin D activity may have diagnostic and possibly prognostic value in clinical gram-negative septic shock. Other in vivo investiga…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/25667
note: GRAM-NEGATIVE ENDOTOXAEMIA by JOHN MICHAEL TUCHEK B . S c , The University of Saskatchewan, 1969 M.Sc., The University of Saskatchewan, 1978 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DOCTOR OF PHILOSOPHY DEGREE in THE FACULTY OF GRADUATE STUDIES Department of Pharmacology, Faculty of Medicine We accept this thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA JULY 1983 0 John Michael Tuchek, 1983 I n p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f t h e r e q u i r e m e n t s f o r an a d v a n c e d d e g r e e a t t h e U n i v e r s i t y o f B r i t i s h C o l u m b i a , I a g r e e t h a t t h e L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e and s t u d y . I f u r t h e r a g r e e t h a t p e r m i s s i o n f o r e x t e n s i v e c o p y i n g o f t h i s t h e s i s f o r s c h o l a r l y p u r p o s e s may be g r a n t e d by t h e h e a d o f my d e p a r t m e n t o r by h i s o r h e r r e p r e s e n t a t i v e s . I t i s u n d e r s t o o d t h a t c o p y i n g o r p u b l i c a t i o n o f t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l n o t be a l l o w e d w i t h o u t my w r i t t e n p e r m i s s i o n . D e p a r t m e n t o f ^Pk^^M t i ^ o /o The U n i v e r s i t y o f B r i t i s h C o l u m b i a 1956 Main Mall V a n c o u v e r , Canada V6T 1Y3 D a t e y ^ n ^ W e v ^ ( i i ) ABSTRACT Endotoxins are 1 ipopolysaccharide (LPS) complexes extractable from the outer membrane of gram negative b a c i l l i . These complexes comprise the 0-antigen of gram-negative bacteria and are used in the serological typing of these organisms. The release of endotoxins from gram-negative bacteria is believed to be a contributing factor to the high mortality rate associa-ted with gram-negative septic shock in humans. Indeed, the sequelae of gram-negative septic shock seen c l i n i c a l l y can be reproduce…
has type: Thesis/Dissertation
date issued: 1984-05
is shown at: 10.14288/1.0448021
language: eng
degree discipline: Pharmacology and Therapeutics
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/25667