ObjectiveTo preliminarily investigate three different lipid matrices consisting of two natural homolipids from Capra hircus (goat fat) and Bovine Spp. (tallow fat) and one semi-synthetic lipid (Softisan? 142) separate...ObjectiveTo preliminarily investigate three different lipid matrices consisting of two natural homolipids from Capra hircus (goat fat) and Bovine Spp. (tallow fat) and one semi-synthetic lipid (Softisan? 142) separately structured with Phospholipon? 90G (P90G) as potential delivery systems for poorly water soluble drugs.MethodsThe structured lipid matrices were characterized by differential scanning calorimetry (DSC) and employed to prepare solid lipid microparticles (SLMs) by the melt homogenization method using gradient concentrations of polysorbate 80 and at different emulsification times of 2, 5 and 10 min using a Silverson mixer. The SLMs were analyzed for morphology and particle size, thermal properties, stability studies and determination of injectability.ResultsThe results showed that SLM production was optimum at 5 % of lipid matrices, 1.5 % of polysorbate 80 and emulsification time of 5 min. Increase in polysorbate 80 concentrations decreased the particle size of the SLMs. The SLMs were well formed, spherical, smooth and non-porous with particle sizes in the ranges of (13.90 ± 2.10) μm - (0.09 ± 0.01) μm for SLMs produced from the structured - tallow fat; (13.40 ± 1.30) μm - (0.10 ± 0.01) μm for the structured - goat fat and (13.40±2.00) μm - (2.10± 1.00)μm for the structured Softisan? 142 lipid matrices. DSC traces showed that Softisan? 142 was the most crystalline of all three bulk matrices due to its high enthalpy (?7.962 mW/mg) while tallow fat was the least (?5.067 mW/mg) but addition of P90G to the matrices lowered their enthalpies mostly in the structured goat fat matrices. The SLMs when stored at 4-6 ° were most stable and syringeable with 27 G needle.ConclusionsThis suggests that structured goat fat matrices with the enthalpy of ?2.813 mW/mg will mostly favour drug loading of some poorly soluble drugs more than tallow fat (?4.892 mW/mg) and Softisan? 142 (?5.501 mW/mg).展开更多
在安全性要求极高的一些车辆系统中,基于事件触发的CAN(Controller Area Network)已经不能满足要求。一种采用CAN的解决方法就是将标准CAN扩展成时间触发的协议。TTCAN(Time-Triggered CAN)就是这样一个扩展并且已经成为国际标准协议。...在安全性要求极高的一些车辆系统中,基于事件触发的CAN(Controller Area Network)已经不能满足要求。一种采用CAN的解决方法就是将标准CAN扩展成时间触发的协议。TTCAN(Time-Triggered CAN)就是这样一个扩展并且已经成为国际标准协议。本文对TTCAN进行大概的描述并介绍如何用mb90f543G来实现其第一层次扩展的方法。展开更多
Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective vi...Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundamental to analyze the mechanism of drug resistance and develop a strategy to minimize resistance. Objective: The molecular evolution of drug resistance of one patient who had received reverse transcriptase inhibitors for a long time and had treatment which replaced Nevirapine with Indinavir was analyzed, with the aim of observing the drug resistance evolution pathway. Methods: The patient, XLF, was followed-up for six successive times. The viral populations were amplified and sequenced by single-genome amplification. All the sequences were submitted to the Stanford HIV Drug Resistance Database for the analysis of genotypic drug resistance. Results: 149 entire protease and 171 entire reverse transcriptase sequences were obtained from these samples, and all sequences were identified as subtype B. Before the patient received Indinavir, the viral population only had some polymorphisms in the protease sequences. After the patient began Indinavir treatment, the variants carrying polymorphisms declined while variants carrying the secondary mutation G73S gained the advantage. As therapy was prolonged, G73S was combined with M46I/L90M to form a resistance pattern M46I/G73S/L90M, which then became the dominant population. 97.9% of variants had the M46I/G73S/L90M pattern at XLF6. During the emergence of protease inhibitors resistance, reverse transcriptase inhibitors resistance maintained high levels. Conclusion: Indinavirresistance evolution was observed by single-genome amplification. During the course of changing the regimen to incorporate Indinavir, the G73S mutation occurred and was combined with M46I/L90M.展开更多
文摘ObjectiveTo preliminarily investigate three different lipid matrices consisting of two natural homolipids from Capra hircus (goat fat) and Bovine Spp. (tallow fat) and one semi-synthetic lipid (Softisan? 142) separately structured with Phospholipon? 90G (P90G) as potential delivery systems for poorly water soluble drugs.MethodsThe structured lipid matrices were characterized by differential scanning calorimetry (DSC) and employed to prepare solid lipid microparticles (SLMs) by the melt homogenization method using gradient concentrations of polysorbate 80 and at different emulsification times of 2, 5 and 10 min using a Silverson mixer. The SLMs were analyzed for morphology and particle size, thermal properties, stability studies and determination of injectability.ResultsThe results showed that SLM production was optimum at 5 % of lipid matrices, 1.5 % of polysorbate 80 and emulsification time of 5 min. Increase in polysorbate 80 concentrations decreased the particle size of the SLMs. The SLMs were well formed, spherical, smooth and non-porous with particle sizes in the ranges of (13.90 ± 2.10) μm - (0.09 ± 0.01) μm for SLMs produced from the structured - tallow fat; (13.40 ± 1.30) μm - (0.10 ± 0.01) μm for the structured - goat fat and (13.40±2.00) μm - (2.10± 1.00)μm for the structured Softisan? 142 lipid matrices. DSC traces showed that Softisan? 142 was the most crystalline of all three bulk matrices due to its high enthalpy (?7.962 mW/mg) while tallow fat was the least (?5.067 mW/mg) but addition of P90G to the matrices lowered their enthalpies mostly in the structured goat fat matrices. The SLMs when stored at 4-6 ° were most stable and syringeable with 27 G needle.ConclusionsThis suggests that structured goat fat matrices with the enthalpy of ?2.813 mW/mg will mostly favour drug loading of some poorly soluble drugs more than tallow fat (?4.892 mW/mg) and Softisan? 142 (?5.501 mW/mg).
文摘在安全性要求极高的一些车辆系统中,基于事件触发的CAN(Controller Area Network)已经不能满足要求。一种采用CAN的解决方法就是将标准CAN扩展成时间触发的协议。TTCAN(Time-Triggered CAN)就是这样一个扩展并且已经成为国际标准协议。本文对TTCAN进行大概的描述并介绍如何用mb90f543G来实现其第一层次扩展的方法。
基金National Natural Science Foundation of China (30830088 and 30800938)The National Key and Special Projects on Major Infectious Disease Grant (2008 ZX10001-004)
文摘Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundamental to analyze the mechanism of drug resistance and develop a strategy to minimize resistance. Objective: The molecular evolution of drug resistance of one patient who had received reverse transcriptase inhibitors for a long time and had treatment which replaced Nevirapine with Indinavir was analyzed, with the aim of observing the drug resistance evolution pathway. Methods: The patient, XLF, was followed-up for six successive times. The viral populations were amplified and sequenced by single-genome amplification. All the sequences were submitted to the Stanford HIV Drug Resistance Database for the analysis of genotypic drug resistance. Results: 149 entire protease and 171 entire reverse transcriptase sequences were obtained from these samples, and all sequences were identified as subtype B. Before the patient received Indinavir, the viral population only had some polymorphisms in the protease sequences. After the patient began Indinavir treatment, the variants carrying polymorphisms declined while variants carrying the secondary mutation G73S gained the advantage. As therapy was prolonged, G73S was combined with M46I/L90M to form a resistance pattern M46I/G73S/L90M, which then became the dominant population. 97.9% of variants had the M46I/G73S/L90M pattern at XLF6. During the emergence of protease inhibitors resistance, reverse transcriptase inhibitors resistance maintained high levels. Conclusion: Indinavirresistance evolution was observed by single-genome amplification. During the course of changing the regimen to incorporate Indinavir, the G73S mutation occurred and was combined with M46I/L90M.
