Methamphetamine (METH) abuse produces serious neurotoxicity to the central nervous system along with long-term cognitive dysfunction. Resveratrol, a natural polyphenol, has broad application prospects in the treatment of neurodegenerative diseases. Therefore, this study was conducted to investigate whether resveratrol might alleviate METH-induced memory deficits in vivo. We found that multiple exposures to METH significantly impaired cognitive functions and caused long-lasting memory deficits (p < .05). Pretreatment of resveratrol (10 or 100 mg/kg) remarkably attenuated METH-induced memory impairment in mice (p < .05). Bioinformatics analysis results showed that resveratrol might alleviate memory deficits by inhibiting METH-induced oxidative damage and apoptosis. Molecular docking showed that resveratrol had hydrogen bonding interactions with Kelch-like ECH associated protein 1 (Keap1), a repressor protein of the classic antioxidant Keap1-Nrf2 pathway. Further results validated oxidative stress parameters, apoptosis, and expression of Keap1 were significantly increased, while the translocation and activation of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus and expression of its downstream proteins were greatly decreased in the hippocampus after METH exposure (p < .05). These changes caused by METH could be prevented by resveratrol (p < .05). Therefore, these findings suggested that the prevention of resveratrol on memory dysfunction induced by METH was possibly related to the activation of the Keap1-Nrf2 pathway and reduction of apoptosis. Supplementation of resveratrol could be a potential treatment for preventing the neurotoxicity of METH in the future. Practical applications As one of the worst commonly abused psychostimulants, methamphetamine (METH) addiction produces serious complications including cognitive impairment and memory deficits. Resveratrol is a natural polyphenol that has important nutritional supplements and protective effects in the treatment of many neurodegenerative diseases.
BackgroundMarbofloxacin is a veterinary fluoroquinolone with high activity against Pasteurella multocida. We evaluated it’s in vivo activity against P. multocida based on in vivo time-kill data in swine using a tissue-cage model. A series of dosages ranging from 0.15 to 2.5 mg/kg were administered intramuscularly after challenge with P. multocida type B, serotype 2.ResultsThe ratio of the 24 h area under the concentration-time curve divided by the minimum inhibitory concentration (AUC24TCF/MIC) was the best PK/PD index correlated with the in vivo antibacterial effectiveness of marbofloxacin (R2 = 0.9279). The AUC24TCF/MIC necessary to achieve a 1-log10 CFU/ml reduction and a 3-log10 CFU/ml (90% of the maximum response) reduction as calculated by an inhibitory sigmoid Emax model were 13.48 h and 57.70 h, respectively.ConclusionsMarbofloxacin is adequate for the treatment of swine infected with P. multocida. The tissue-cage model played a significant role in achieving these PK/PD results.
In this paper, a gradient-driven non-linear optimization algorithm has been introduced and applied in numerically simulation of a nickel-chromium alloy at elevated temperature. The Chaboche unified constitutive model has been used to describe the cyclic plasticity and viscoplasticity of this alloy. Optimisation algorithm has facilitated a step-by-step method to obtain the initial material parameters, while a non-linear least-square approach were used to obtain the optimised material parameters. Uniaxial experiments were carried to obtain the full cyclic stress-strain and stress relaxation data at 450°C. Satisfactory results have been obtained for the simulation of the transient and steady state cyclic stress-strain and stress relaxation behaviour.
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