PMID- 15179237
OWN - NLM
STAT- MEDLINE
DCOM- 20040617
LR  - 20190711
IS  - 0022-5282 (Print)
IS  - 0022-5282 (Linking)
VI  - 56
IP  - 5
DP  - 2004 May
TI  - Therapeutic potential of exogenous ubiquitin during resuscitation from severe 
      trauma.
PG  - 991-9; discussion 999-1000
AB  - BACKGROUND: Recent studies suggest that extracellular ubiquitin could have a 
      physiologic role in immunodepression in sepsis and trauma. The therapeutic 
      potential of exogenous ubiquitin after trauma has not been examined. To fill this 
      gap, we designed a series of experiments in a clinically relevant trauma model. 
      METHODS: Forty minutes after femur fractures and hemorrhage, swine received 1.3 
      mg of ubiquitin per kilogram or bovine serum albumin intravenously followed by 
      fluid resuscitation to maintain systemic hemodynamics. Leukocyte function and the 
      immunomodulatory capacity of serum were assessed measuring endotoxin-evoked tumor 
      necrosis factor-alpha (TNF alpha) production ex vivo. TNF alpha and ubiquitin 
      were quantified with enzyme-linked immunosorbent assay. RESULTS: Intravenous 
      ubiquitin had no significant hemodynamic effect in normal animals. After injury, 
      ubiquitin significantly reduced fluid requirements by at least 60% (p < 0.05). 
      The injury was associated with transient immunodepression, as reflected by 
      reduced endotoxin-evoked TNF alpha production by 40% to 50%. With ubiquitin, this 
      response remained depressed for 100 to 160 minutes (p < 0.05), but fully 
      recovered to baseline with albumin. CONCLUSION: Ubiquitin is apparently safe and 
      effective for reducing fluid requirements as a measure of diffuse capillary leak. 
      This immunomodulatory property suggests a new therapeutic approach after injury 
      in particular, and for infectious and noninfectious inflammation in general.
FAU - Majetschak, Matthias
AU  - Majetschak M
AD  - Daughtry Department of Surgery, Divisions of Trauma and Surgical Critical Care, 
      Ryder Trauma Center, University of Miami School of Medicine, Miami, Florida, USA. 
      mmajetschak@med.miami.edu
FAU - Cohn, Stephen M
AU  - Cohn SM
FAU - Obertacke, Udo
AU  - Obertacke U
FAU - Proctor, Kenneth G
AU  - Proctor KG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Trauma
JT  - The Journal of trauma
JID - 0376373
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Ubiquitin)
RN  - 27432CM55Q (Serum Albumin, Bovine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - *Disease Models, Animal
MH  - Drug Evaluation, Preclinical
MH  - Drug Monitoring/methods
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Femoral Fractures/*complications
MH  - Fluid Therapy/*methods
MH  - Hemorrhage/*drug therapy/etiology/metabolism/physiopathology
MH  - Humans
MH  - Immune Tolerance/drug effects
MH  - Infusions, Intravenous
MH  - Male
MH  - Random Allocation
MH  - Resuscitation/*methods
MH  - Serum Albumin, Bovine/therapeutic use
MH  - Single-Blind Method
MH  - Swine
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/drug effects/metabolism
MH  - Ubiquitin/pharmacology/physiology/*therapeutic use
EDAT- 2004/06/05 05:00
MHDA- 2004/06/18 05:00
CRDT- 2004/06/05 05:00
PHST- 2004/06/05 05:00 [pubmed]
PHST- 2004/06/18 05:00 [medline]
PHST- 2004/06/05 05:00 [entrez]
AID - 00005373-200405000-00009 [pii]
AID - 10.1097/01.ta.0000127770.29009.5a [doi]
PST - ppublish
SO  - J Trauma. 2004 May;56(5):991-9; discussion 999-1000. doi: 
      10.1097/01.ta.0000127770.29009.5a.