PMID- 22577153
OWN - NLM
STAT- MEDLINE
DCOM- 20121126
LR  - 20131121
IS  - 1758-1117 (Electronic)
IS  - 0023-6772 (Linking)
VI  - 46
IP  - 3
DP  - 2012 Jul
TI  - Management of adverse side-effects after chemotherapy in macaques as exemplified 
      by streptozotocin: case studies and recommendations.
PG  - 178-92
LID - 10.1258/la.2012.011077 [doi]
AB  - The chemotherapeutic streptozotocin is used for induction of diabetes in animal 
      models including non-human primates. Being a cytotoxic nitrosourea compound, it 
      can be associated with adverse events (AEs), mainly nausea and emesis, 
      nephrotoxicity, elevated liver transaminase levels, pulmonary oedema and, most 
      prominently, metabolic acidosis: these can be severe in some cases. The incidence 
      and gravity are to some extent related to the characteristics of the individual 
      animal, diagnostic tools, prompt recognition of symptoms and supportive measures. 
      Careful animal selection, dose adaptation and supportive actions such as renal 
      protective hydration are the main tools in managing AEs, but do not fully 
      eliminate unavoidable and sometimes life-threatening conditions. In our centre we 
      have built experience in a cohort of 78 cynomolgus and rhesus macaques in which 
      six cases manifested severe AEs (8%). This experience has prompted implementation 
      of strategies for early detection and management of adverse effects, together 
      with an animal refinement programme. We present here specific pretreatment 
      regimens, post-infusion laboratory evaluations, and flow charts to assess/treat 
      metabolic acidosis and precipitating factors. Case reports of the six animals 
      with severe AEs are presented to illustrate management of AEs, especially 
      metabolic acidosis, and criteria for early euthanasia where appropriate. We 
      conclude that improved monitoring and validated tools allow for optimal 
      management of adverse effects in an early stage of their manifestation. Reduced 
      morbidity and mortality not only improve individual animal wellbeing but also 
      avoid model-induced confounding that diminishes the translational value of the 
      experimental protocol.
FAU - Graham, Melanie L
AU  - Graham ML
AD  - Schulze Diabetes Institute, Department of Surgery, University of Minnesota, 
      Minneapolis, MN 55455, USA. graha066@umn.edu
FAU - Mutch, Lucas A
AU  - Mutch LA
FAU - Kittredge, Jessica A
AU  - Kittredge JA
FAU - Rieke, Eric F
AU  - Rieke EF
FAU - Robinson, Nicholas A
AU  - Robinson NA
FAU - Zolondek, Elizabeth K
AU  - Zolondek EK
FAU - Faig, Aaron W
AU  - Faig AW
FAU - Dufour, Theresa A
AU  - Dufour TA
FAU - Munson, James W
AU  - Munson JW
FAU - Schuurman, Henk-Jan
AU  - Schuurman HJ
LA  - eng
PT  - Journal Article
DEP - 20120510
PL  - England
TA  - Lab Anim
JT  - Laboratory animals
JID - 0112725
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Insulin)
RN  - 5W494URQ81 (Streptozocin)
SB  - IM
MH  - Acidosis/chemically induced/*therapy
MH  - Animals
MH  - Antibiotics, Antineoplastic/*adverse effects
MH  - Cohort Studies
MH  - Diabetes Mellitus, Experimental/complications
MH  - Disease Models, Animal
MH  - Female
MH  - Insulin/therapeutic use
MH  - Macaca fascicularis/*metabolism
MH  - Macaca mulatta/*metabolism
MH  - Male
MH  - Streptozocin/*adverse effects
EDAT- 2012/05/12 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/05/12 06:00
PHST- 2012/05/12 06:00 [entrez]
PHST- 2012/05/12 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - la.2012.011077 [pii]
AID - 10.1258/la.2012.011077 [doi]
PST - ppublish
SO  - Lab Anim. 2012 Jul;46(3):178-92. doi: 10.1258/la.2012.011077. Epub 2012 May 10.