Mathematical Models of Diuresis after Oral Administration of Tizolemide, Furosemide and Placebo to Healthy Adults

Urine volumes and flows as functions of time after oral administration of placebo, furosemide 80 mg and tizolemide 100 mg to sixteen healthy male adults at 08.00 a.m. are described through mathematical models. Accumulated urine volumes after dosing, V, as functions of time, t, are accounted for by sigmoid functions and urine flows are described as dV/dt. No significant differences were found between the 24-hour urine volume mean values after furosemide (2457 ml) and tizolemide (2283 ml) and both were significantly higher than the corresponding mean value after placebo (1369 ml) (p &lt; 0.001). Peak diuresis after dosing occurs about 1.5 hours for furosemide, 4 hours for tizolemide and 6 hours for placebo. Fourteen hours after dosing, urine volume amounts to 90% of the 24-hour urine volume after furosemide and to 76% after tizolemide, so that both substances may be regarded as diurnal diuretics. </jats:p

The interactions of epigallocatechin-3-gallate with human whole saliva and parotid saliva

Correlation between the cluster energy and its population and dynamics can provide a better understanding of the complicated energy landscape of disordered metallic systems. We propose a method to analyze the cluster energy distribution for different kinds of short-range order (local clusters) in liquid and glass systems. By applying this analysis to an interesting and important glass forming system-Cu64.5Zr35.5 we observe a direct correlation between the energy and dynamics of the cluster in this realistic glass-forming system. This study suggests that dynamic arrest originates from the environment-dependent energetics of local clusters. (C) 2010 American Institute of Physics. [doi:10.1063/1.3464164]National Natural Science Foundation of China [20773100

Frequency-Dependent Focal Adhesion Instability and Cell Reorientation Under Cyclic Substrate Stretching

The adhesion-based cell mechanosensitivity plays central roles in many physiological and pathological processes. Recently, quantitative understanding of cell responses to external force has been intensively pursued. However, the frequency dependent cell responses to the substrate stretching have not yet been fully understood. Here we developed a multiscale modeling framework for studying cell reorientation behaviors under substrate stretching, in which the mechano-chemical coupling at molecular, subcellular, and cellular scales was considered. The effect of matrix stiffness was also considered in a FEM based mechano-chemical coupling simulation. We showed that the collapsing time of focal adhesion decreases with the increasing of the loading frequency, however, the cell reorientation time exhibits a biphasic frequency-dependent behavior. Our results suggested that this biphasic behavior might be caused by the competition between the frequency-dependent collapsing of focal adhesions and the less frequency-dependent formation of stress fibers aligning away from the loading direction. At the low loading frequency, the collapsing of focal adhesion dominates the reorientation process, however, at the high loading frequency the polymerization of stress fiber dominates the reorientation. Moreover, we showed that the compliance of matrix may help accelerate the cell reorientation because focal adhesion is prone to be instable on soft matrix

A Highly Photostable Hyperbranched Polyglycerol-Based NIR Fluorescence Nanoplatform for Mitochondria-Specific Cell Imaging

Considering the critical role of mitochondria in the life and death of cells, non-invasive long-term tracking of mitochondria has attracted considerable interest. However, a high-performance mitochondria-specific labeling probe with high photostability is still lacking. Herein a highly photostable hyperbranched polyglycerol (hPG)-based near-infrared (NIR) quantum dots (QDs) nanoplatform is reported for mitochondria-specific cell imaging. Comprising NIR Zn-Cu-In-S/ZnS QDs as extremely photostable fluorescent labels and alkyl chain (C-12)/triphenylphosphonium (TPP)-functionalized hPG derivatives as protective shell, the tailored QDs@hPG-C-12/TPP nanoprobe with a hydrodynamic diameter of about 65 nm exhibits NIR fluorescence, excellent biocompatibility, good stability, and mitochondria-targeted ability. Cell uptake experiments demonstrate that QDs@hPG-C-12/TPP displays a significantly enhanced uptake in HeLa cells compared to nontargeted QDs@hPG-C-12. Further co-localization study indicates that the probe selectively targets mitochondria. Importantly, compared with commercial deep-red mitochondria dyes, QDs@hPG-C-12/TPP possesses superior photostability under continuous laser irradiation, indicating great potential for long-term mitochondria labeling and tracking. Moreover, drug-loaded QDs@hPG-C-12/TPP display an enhanced tumor cell killing efficacy compared to nontargeted drugs. This work could open the door to the construction of organelle-targeted multifunctional nanoplatforms for precise diagnosis and high-efficient tumor therapy

Label-free multiplex immunoassay of AFP, CEA and CA19-9 by integrated microfluidic biosensor based on imaging ellipsometry

This study describes the development of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate 19-9(CA19-9) multiplex immunoassay by integrated microfluidic device based on imaging ellipsometry (IMBIE). Different strategies for AFP, CEA and CA 19-9 simultaneous immunoassay on the same aldehyde-substrate were developed. Unifying the reaction steps of CA19-9 for antigen direct detection, CEA for secondary antibody (rabbit-antiCEA) addition, AFP for secondary (rabbit antiAFP) and an enhancer (goat IgG) application, and comprehensively considering the dynamic ranges and detection sensitivities, we combined these three markers into multiplex analysis in serial format.The sensitivities and dynamic ranges for CA19-9, CEA and AFP were 10.0U/mL, 1.0 ng/mL, 1.0 ng/mL and 2.0-100.0 U/mL, 0.1-64.0 ng/mL, 1.0-128.0 ng/mL, respectively. The intra-assay and inter-assay (coefficient variations) CVs of CA19-9, CEA and AFP were between 1.6-8.9% and 2.1-7.8%. The specificities tested for both cross-reaction and heterogeneous proteins of CA19-9, CEA and AFP were not more than 6.7%. Quantitative detection of 49 sera from gastric patients demonstrated that the accuracy for gastric cancer diagnosis was 83.4%. The total detection time is only 60min for an automated process. The proposed assay has the potential for practical application

Bioactive calcium silicate extracts regulate the morphology and stemness of human embryonic stem cells at the initial stage

Embryonic stem cells (ESCs) are undifferentiated cells that have the capacity to self-renew and differentiate into a variety of cells and provide cell sources for regenerative medicine or biological specimens for cytotoxicity tests. Calcium silicate (CS), a bioactive silicate ceramic, can stimulate the osteogenic differentiation of various types of stem cells, but its role in regulating the biological phenotypes of ESCs remains unclear. Here, the impact of CS on human ESCs was investigated using CS-supplemented medium. The cytotoxicity of CS to hESCs and its effects on apoptosis, growth, proliferation, and differentiation were quantified systematically. Morphological analysis of hESC colonies indicated that the bioactive ions released from CS have little cytotoxicity to hESCs at two CS concentrations. Immunofluorescence and flow cytometry analyses showed that apoptosis was time-independent at early or late stages of hESC growth. In contrast, CS ion extracts regulated hESC differentiation in a time-dependent manner: ESC stemness was preserved by enhancing Oct-4, Sox-2, and Nanog gene expression at day 3, while the cells tended to differentiate at day 6. Combined tests on gene and protein levels further indicated that hESCs tended to differentiate into mesoderm in the presence of CS ion extracts, especially at low CS concentrations. These results demonstrate the effects of CS extracts on hESC stemness and differentiation at the molecular and cellular levels, suggesting that CS-based biomaterials could serve as a potential regulator for ESCs in regenerative medicine