BACKGROUND AND AIM: In clinical sepsis research nearly all immune-modulators have demonstrated no benefit in regard to the 28-day mortality rate. Other endpoints such as quality of life have become more attractive, but clinically relevant animal models analyzing an equivalent to quality of life by measurement of sickness behavior are extremely rare. The concept of clinic modeling randomized trials was used in an animal trial to model clinical complexity and conditions of a randomized clinical trial. METHODS: 80 adult male Wistar rats were randomly assigned to (1) control: anesthesia and sham operation, (2) sepsis: laparotomy and peritoneal infection with human stool bacteria, (3) sepsis with antibiotic prophylaxis: cefuroxime/metronidazole and (4) sepsis with antibiotic plus a cytokine prophylaxis with granulocyte-colony stimulating factor (GCSF). Endpoints were physiological and behavioral parameters. RESULTS: The combination of antibiotics plus G-CSF was most effective in reducing mortality. All infected animals showed reduced open field activity acutely after infection, and recovery was improved during the 9 day follow-up in rats with prophylactic treatments. In the social interaction test, but not in the elevated plus-maze anxiety test, prophylaxis was also efficient, especially with antibiotics and G-CSF. CONCLUSIONS: The results show that improving sickness behavior in septic rats with G-CSF plus antibiotics may be a promising approach.
BACKGROUND AND AIM: In clinical sepsis research nearly all immune-modulators have demonstrated no benefit in regard to the 28-day mortality rate. Other endpoints such as quality of life have become more attractive, but clinically relevant animal models analyzing an equivalent to quality of life by measurement of sickness behavior are extremely rare. The concept of clinic modeling randomized trials was used in an animal trial to model clinical complexity and conditions of a randomized clinical trial. METHODS: 80 adult male Wistar rats were randomly assigned to (1) control: anesthesia and sham operation, (2) sepsis: laparotomy and peritoneal infection with human stool bacteria, (3) sepsis with antibiotic prophylaxis: cefuroxime/metronidazole and (4) sepsis with antibiotic plus a cytokine prophylaxis with granulocyte-colony stimulating factor (GCSF). Endpoints were physiological and behavioral parameters. RESULTS: The combination of antibiotics plus G-CSF was most effective in reducing mortality. All infected animals showed reduced open field activity acutely after infection, and recovery was improved during the 9 day follow-up in rats with prophylactic treatments. In the social interaction test, but not in the elevated plus-maze anxiety test, prophylaxis was also efficient, especially with antibiotics and G-CSF. CONCLUSIONS: The results show that improving sickness behavior in septic rats with G-CSF plus antibiotics may be a promising approach.
Authors: Allan C Calsavara; David H Rodrigues; Aline S Miranda; Priscila A Costa; Cristiano X Lima; Márcia C Vilela; Milene A Rachid; Antônio L Teixeira Journal: Neurotox Res Date: 2012-12-06 Impact factor: 3.911
Authors: Lisiane Tuon; Clarissa M Comim; Fabricia Petronilho; Tatiana Barichello; Ivan Izquierdo; João Quevedo; Felipe Dal-Pizzol Journal: Intensive Care Med Date: 2008-04-30 Impact factor: 17.440
Authors: M Klinkhammer-Schalke; M Koller; B Steinger; C Ehret; B Ernst; J C Wyatt; F Hofstädter; W Lorenz Journal: Br J Cancer Date: 2012-02-07 Impact factor: 7.640