The lack of information concerning individual variation in content and activity of human liver microsomal protein is one of the most important obstacles for designing personalized medicines. We demonstrated that the mean value of microsomal protein per gram of liver (MPPGL) was 39.46 mg/g in 128 human livers and up to 19-fold individual variations existed. Meanwhile, the metabolic activities of 10 cytochrome P450 (CYPs) were detected in microsomes and liver tissues, respectively, which showed huge individual variations (200-fold). Compared with microsomes, the activities of liver tissues were much suitable to express the individual variations of CYP activities. Furthermore, individual variations in the in vivo clearance of tolbutamide were successfully predicted with the individual parameter values. In conclusion, we offer the values for MPPGL contents in normal liver tissues and build a new method to assess the in vitro CYP activities. In addition, large individual variations exist in predicted hepatic clearance of tolbutamide. These findings provide important physiological parameters for physiologically-based pharmacokinetics models and thus, establish a solid foundation for future development of personalized medicines.
Asthma is a dynamic disease, in which lung mechanical and inflammatory processes interact in a complex manner, often resulting in exaggerated physiological, in particular, inflammatory responses to exogenous triggers. We hypothesize that this may be explained by respiratory disease-related systems instability and loss of adaptability to changing environmental conditions, manifested in highly fluctuating biomarkers and symptoms. Using time series of inflammatory (eosinophils, neutrophils, FeNO), clinical and lung function biomarkers (PEF, FVC,FEV1), we estimated this loss of adaptive capacity (AC) during an experimental rhinovirus infection in 24 healthy and asthmatic human volunteers. Loss of AC was estimated by comparing similarities between pre- and post-challenge time series. Unlike healthy participants, the asthmatic’s post-viral-challenge state resembled more other rhinovirus-infected asthmatics than their own pre-viral-challenge state (hypergeometric-test: p=0.029). This reveals loss of AC and supports the concept that in asthma, biological processes underlying inflammatory and physiological responses are unstable, contributing to loss of control.
Integrated fabrics with a smart heating control system (HCS) are attractive in warming and thermotherapy for human healthcare management. Metal nanofibers (NFs) networks with high flexibility, conductivity and gas permeability are ideal functional materials for wearable electronics. Herein, a novel sandwich-structural (Ag NFs/fabrics/Pt NFs) textile for a HCS is constructed, where a Ag NF network film was functioned as a wearable heater and Pt NF network arrays were functioned as wearable temperature sensors. Conductivity and mechanical stability of the metal NFs were enhanced by crosslinking the free-standing fiber networks, resulting in high thermo-stability, thermal resistance (163.5 °C W−1 cm2) and temperature sensitivity (0.135% °C−1) of the HCS. The HCS can simultaneously realize heating and temperature distribution detection, demonstrating only 0.57% average error between the simulated resistance-to-temperature diagram of Pt NF arrays and actual temperature mapping. In addition, the HCS can be stuck on the skin for thermochromic fabrics, real-time heating and temperature detection/control through a Bluetooth device in a smartphone wirelessly.
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