Maxsim2—Real-time interactive simulations for computer-assisted teaching of pharmacokinetics and pharmacodynamics

We developed a computer program for use in undergraduate and graduate courses in pharmacology, pharmacokinetics and pharmacodynamics. This program can also be used in environmental and toxicological studies and preclinical simulation, to facilitate communication between modeling pharmacokineticists and project leaders or other decision-makers in the pharmaceutical industry. The program simulates the drug delivery and transport by means of (I) a six-compartment physiological pharmacokinetic flow model, (II) a system of traditional compartment models, or (III) a target-mediated drug disposition system. The program also can be used to simulate instantaneous equilibria between concentration and pharmacodynamic response, or as temporal delays between concentration and response. The latter is done by means of turnover models (indirect response models). Drug absorption, distribution, and elimination are represented by differential equations, which are described by organ and tissue volumes or other volumes of distribution, blood flows, clearance terms, and tissue-to-blood partition coefficients. The user can control and adjust these parameters by means of a slider in real time. By interactively changing the parameter values and simultaneously displaying the resulting concentration–time and/or response–time profiles, users can understand the major mechanisms that govern the disposition or the pharmacological response of the drug in the organism in real time. Schedule dependence is typically seen in clinical practice with a non-linear concentration–response relationship, and is difficult to communicate except via simulations. Here, we sought to illustrate the potential advantages of this approach in teaching pharmacology, pharmacokinetics, and pharmacodynamics to undergraduate pharmacy-, veterinary-, and medical students or to project teams in drug discovery/development.     

Conscious and anaesthetised Göttingen mini-pigs as an in-vivo model for buccal absorption – pH-dependent absorption of metoprolol from bioadhesive tablets

The potential of buccal mucosa as a site for systemic absorption has attracted increased attention in recent years creating a need for new predictive in-vivo models. The aim of this study was to evaluate anaesthetised and conscious Göttingen mini-pigs as a model for buccal drug absorption by testing pH-dependent absorption of metoprolol from a solid dosage form. Buccal tablets buffered to pH 6.2 and pH 8.9, oral liquid and intravenous injection were tested in four conscious and anaesthetised Göttingen mini-pigs in a non-randomised cross-over study. Blood samples were collected and processed before analysis by ultra-performance liquid chromatography with tandem mass spectrometry detection. An ex-vivo flow retention model was applied to study release and retention of the bioadhesive buccal tablets. The T_max obtained from the two buccal conscious groups (55?±?5 and 35?±?5?min) were significantly different to the buccal anaesthetised groups (120?±?0 and 165?±?15?min) for buccal tablet pH 6.2 and pH 8.9, respectively. Also, the absolute bioavailability from the anaesthetised buccal tablet pH 8.9 (20.7?±?4.0%) had a significant increase compared to all other buccal tablet groups. In conclusion, this study showed a pH-dependent absolute bioavailability of metoprolol when administrated as bioadhesive buccal tablets to anaesthetised mini-pigs. The anaesthesia was found to delay the time to reach maximal plasma concentration of metoprolol as compared to the conscious pig model when administrated as buccal tablets.     

Effect of titanium–magnesium catalyst morphology on the properties of polypropylene upon propylene polymerization in a liquid monomer

The effect of the particle size of an IK-8-21 domestic titanium-magnesium catalyst on the properties of polypropylene (PP) produced during the polymerization of propylene in a liquid monomer is studied. Catalysts with particle sizes of 20 to 64 μm are shown to have high activity and identical sensitivity to hydrogen and allow PP to be obtained with a narrow distribution of particles over size, high isotacticity, and close values of crystallinity, melting temperature, and physicomechanical properties. A slight decrease in the activity and bulk density of PP powder is observed when the average size of catalyst particles is increased from 20 to 43 μm. A more notable reduction in the activity and bulk density of PP powder is observed for catalyst with particle sizes of 62 to 64 μm. IK-8-21 catalyst is not inferior to its foreign analogues with respect to the properties of the resulting PP.     

Evaluation of Three-Dimensional Bioprinted Human Cartilage Powder Combined with Micronized Subcutaneous Adipose Tissues for the Repair of Osteochondral Defects in Beagle Dogs

Cartilage lesions are difficult to repair due to low vascular distribution and may progress into osteoarthritis. Despite numerous attempts in the past, there is no proven method to regenerate hyaline cartilage. The purpose of this study was to investigate the ability to use a 3D printed biomatrix to repair a critical size femoral chondral defect using a canine weight-bearing model. The biomatrix was comprised of human costal-derived cartilage powder, micronized adipose tissue, and fibrin glue. Bilateral femoral condyle defects were treated on 12 mature beagles staged 12 weeks apart. Four groups, one control and three experimental, were used. Animals were euthanized at 32 weeks to collect samples. Significant differences between control and experimental groups were found in both regeneration pattern and tissue composition. In results, we observed that the experimental group with the treatment with cartilage powder and adipose tissue alleviated the inflammatory response. Moreover, it was found that the MOCART score was higher, and cartilage repair was more organized than in the other groups, suggesting that a combination of cartilage powder and adipose tissue has the potential to repair cartilage with a similarity to normal cartilage. Microscopically, there was a well-defined cartilage-like structure in which the mid junction below the surface layer was surrounded by a matrix composed of collagen type I, II, and proteoglycans. MRI examination revealed significant reduction of the inflammation level and progression of a cartilage-like growth in the experimental group. This canine study suggests a promising new surgical treatment for cartilage lesions.     

Biosynthesis of prostaglandin E1 by human seminal vesicles

[1-¹⁴C] 8,11,14-Eicosatrienoic acid was converted into prostaglandin E₁ when incubated with a homogenate of human seminal vesicles. No conversion could be detected with homogenates of human prostate or testis.     

PEPT study of particle cycle and residence time distributions in a Wurster fluid bed

Particle cycle and residence time distributions are critical factors in determining the coating quality in the Wurster process. Positron emission particle tracking experiments are performed to determine the cycle and residence times of particles in different regions of a Wurster fluid bed. The results show that particles tend to recirculate in and sneak out below from the Wurster tube. The experiments also show that a larger batch size leads to a shorter cycle time and a narrower cycle time distribution (CTD). It is possible to avoid recirculations and obtain a shorter cycle time and a narrower CTD by selecting the operating conditions appropriately or via equipment design. Experiments using binary mixtures of particles with a diameter ratio of 1.5 show that large particles have a longer cycle time than small particles and that the cycle time is shorter for mixtures with approximately equal amounts of small and large particles. © 2014 American Institute of Chemical Engineers AIChE J, 61: 756–768, 2015     

Removal of estrogenicity in Swedish municipal sewage treatment plants

The human estrogen receptor alpha-test, hosted in a yeast strain, was used to quantify estrogenicity in three-week composite samples of untreated and treated effluents from 20 Swedish municipal sewage treatment plants. The treatment plants were selected to represent different treatment processes regarding chemical precipitation and microbial procedures. The discharge from Swedish domestic sewage treatment plants contained estrogenic compounds corresponding to <0.1-15 ng estradiol equivalents/L. Low levels of estrogenic activity were also found in a river receiving municipal effluents, 3.5-35 km downstream the outlet from a sewage treatment works. The range of estrogenicity in untreated, raw sewage effluents was found to be 1-30 ng estradiol equivalents/L. Generally, wastewater treatment reduced the estrogenicity and extended biological treatment was most effective in its removal. Activated sludge treatment tended to be more effective than trickling filters, whereas chemical precipitation using iron or aluminium salts without biological treatment showed little effectivity. The study showed that treatment methods in current use are able to eliminate or largely reduce estrogenicity in domestic wastewater.     

爱立信IMS weShare分享每一天(系列之二)如何提供出色的用户体验?

爱立信IMS weShare业务有20%的开发与用户视觉体验相关(用户界面、图标、标签以及进度条),其它的80%则主要致力于设备间的系统.与此相对比,用户的体验则完全(100%)有赖于其可接触的事物.