RESUMEN
Salmonella typhimurium is a highly transmissible pathogen in rabbits that causes significant losses. Danofloxacin shows excellent efficacy against S. typhimurium infections. However, there are few reports of the pharmacokinetic/pharmacodynamic (PK/PD) modeling of danofloxacin against this pathogen. The aim of this study was to evaluate the in vivo PK/PD relationship of danofloxacin in rabbits infected with S. typhimurium. We used the reduction of bacterial burden in the blood, liver, spleen, and lung as the target PD endpoints, and determined the PK/PD indexes that best correlated with the efficacy and its corresponding magnitude. Danofloxacin was administrated orally to experimentally S. typhimurium-infected rabbits once daily for three successive days. The concentrations of danofloxacin in the serum and the bacterial burden in the blood, liver, spleen, and lung were determined. The PK/PD relationships of danofloxacin against S. typhimurium were evaluated using a Sigmoid Emax model. The results showed that the area under the concentration-time curve from 0 to 24 h/minimum inhibitory concentration (AUC24 h/MIC) ratio correlated well with the in vivo antibacterial effectiveness in different organs, with an r2 of 0.8971, 0.9186, 0.9581, and 0.8708 in the blood, liver, spleen, and lung, respectively. The AUC24 h/MIC ratios for the bactericidal effect (3 × Log10 colony forming units/mL reductions) were 121.30, 354.28, 216.64, and 228.66 in the blood, liver, spleen, and lung, respectively, indicating that the in vivo effectiveness of danofloxacin against S. typhimurium using bacterial reduction in different organs as PD endpoints was not identical. This study illustrated that the selection of the target organ for bacterial reduction determination had little effect on best PK/PD parameter determination, but is critical for parameter magnitude calculation in antimicrobial PK/PD modeling, and furthermore, has an impact on the rational dosage optimization process.
RESUMEN
<p><b>OBJECTIVE</b>To probe into the mechanism of acupuncture analgesia.</p><p><b>METHODS</b>Type-I collagenase was injected to destroy the structure of collagen fibers in the acupoint. Paw withdrawing latency and mast cell degranulation rate in the acute adjuvant arthritis rat were investigated. Effects of acupuncture at "Zusanli" (ST 36) with twirling or thrusting-lifting manipulation on acupuncture analgesia and mast cells were compared when the structures of collagen fibers in the acupoint were destroyed or not.</p><p><b>RESULTS</b>When the structures of collagen fiber were destroyed, the analgesic effects of both acupuncture manipulations were attenuated and the degranulation rate of mast cells caused by acupuncture were significantly inhibited.</p><p><b>CONCLUSION</b>Collagen fibers and mast cells in the acupoint play an important role in acupuncture analgesia. Collagen fibers participate in transmission and transform process of acupuncture signs from the acupoint to the target organ, and the degranulation of mast cells is positively correlated with acupuncture analgesia.</p>