Photoelectric recording of mechanical responses of cardiac myocytes

A method to monitor contraction of isolated myocytes by transmicroscopic photometry is illustrated. Two photodiodes are mounted inside an inverse microscope used for visual control of a cell. Illumination of one diode varies in proportion to changes in cell length. The contraction signal is amplified in a comparator circuit. Spatial resolution of the device is in the order of 1 m which corresponds to about 5% of cell shortening in the fully activated state of contraction. The method was tested on isolated myocytes from guinea-pig ventricle. Optical records of contraction in response to action potentials or during voltage clamp compare well with the contractile behaviour of multicellular preparations.     

The application of co-culture in assisted reproduction: 10 years of experience with human embryos

Co-culture techniques using fetal bovine uterine fibroblasts or bovine oviductal epithelial cells have improved embryonic development prior to replacement in humans. In initial co-culture trials, embryo development and implantation rates increased after just 1 day in culture. The most overt characteristics noted following co-culture were improved blastomere development and characteristics, reduced fragmentation, and the appearance of swollen blastomeres. In addition, an increase in the incidence of zona thickness variation was detected. Improved development of polyspermic and supernumerary embryos to the blastocyst stage was noted in initial trials. Retrospective analysis indicated that certain patient subgroups benefit the most from co-culture. As a result, co-culture is now applied routinely to patients that have previously failed attempts at in-vitro fertilization (IVF) and/or have endocrine imbalances such as polycystic ovarian syndrome and elevated day 3 concentrations of follicle stimulating hormone (FSH). The use of co-culture prior to or following cryopreservation has also proven to be beneficial to human embryos. The proposed beneficial mechanisms thought to improve embryonic development include a secretory and/or a scavenging role. Evidence describing the postulated benefits is discussed.     

The importance of water quality for media preparation

The variability in pregnancy rates achieved among in-vitro fertilization (IVF) clinics may be partially attributable to the disparate quality of the water used in the preparation of culture media. The removal of contaminants in the water is of paramount importance since water constitutes the predominant component in any media formulation. To assist in the selection, operation and maintenance of a water purification system, the level of contaminants must be carefully monitored. Conductivity and resistance are used to measure the purity of natural and ultrapure water respectively. Feed water is analysed by an assortment of direct chemical means to determine the necessary system filtration steps. In general, high quality water can be produced by combined reverse osmosis and electrodeionization of treated tap water. Processed water is supplied to an ultrapure water system to provide final polished water. A detailed water processing protocol is presented along with quality assurance guidelines to ensure the consistent production of high quality ultrapure water suitable for in-vitro human embryo culture.     

Energy-dependent extrusion of cyclic 3′,5′-adenosine-monophosphate

Summary In reticulocyte-rich suspensions of red blood cells from rats extrusion of cAMP as a regulatory mechanism of intracellular cAMP was investigated.In response to isoprenaline and/or the phosphodiesterase inhibitors Ro 20-1724 and rolipram extrusion of cAMP increases dependent on the concentration of the drugs and time of exposure. However, these drugs exert their effects on the extrusion of cAMP only indirectly, i.e. via increased intracellular levels of cAMP, since the respective EC₅₀-values of the drugs for intracellular accumulation and extrusion of cAMP are identical (isoprenaline: 50 nM; rolipram: 1 M; Ro 20-1724: 15 M).The dependence of the rate of extrusion on intracellular levels of cAMP is characterized by a typical concentration-effect relationship from which a maximal capacity of cAMP extrusion of 3–6 nmol/10 min/10⁹ cells and a half maximal effective intracellular cAMP concentration of 40–50 nmol/10⁹ cells can be derived. This relationship has been inferred from either kinetic or steady-state approaches. At rapidly changing intracellular levels of cAMP an apparent time lag of extracellular cAMP accumulation is obligatorily conditioned by this relationship. Vasodilating drugs which lower the ATP content of the cells as well as the uncoupler of oxidative phosphorylation, FCCP, inhibit the extrusive process (papaverine > FCCP > dipyridamole > dilazep hexobendine carbocromene) leading to a 3–5-fold increase of the intrato extracellular concentration gradient of cAMP.It is concluded that extrusion of cAMP is a saturable and energy-dependent process which regulates the intracellular cAMP concentration independent of the activities of adenylate cyclase and phosphodiesterase.This work was supported by a grant from the Deutsche Forschungsgemeinschaft     

4β-hydroxycholesterol as an endogenous CYP3A marker in cancer patients treated with taxanes

Aim

Taxanes are anti-cancer agents used to treat several types of solid tumours. They are metabolized by cytochrome P450 (CYP) 3A, displaying a large pharmacokinetic (PK) variability. In this study, we evaluated the endogenous CYP3A4 marker 4β-hydroxycholesterol (4β-OHC) as a potential individual taxane PK predictor.

Methods

Serum 4β-OHC and cholesterol concentrations were determined in 291 paclitaxel and 151 docetaxel-treated patients, and were subsequently correlated with taxane clearance.

Results

In the patients treated with paclitaxel, no clinically relevant correlations between the 4β-OHC or 4β-OHC : cholesterol ratio and paclitaxel clearance were found. In the patients treated with docetaxel, 4β-OHC concentration was weakly correlated with docetaxel clearance in males (r = 0.35 P = 0.01, 95% CI 0.08, 0.58). Of the 10% patients with taxane outlier clearance values, 4β-OHC did correlate with docetaxel clearance in males (r = 0.76, P = 0.03, 95% CI 0.12, 0.95).

Conclusion

There was no clinical correlation between paclitaxel clearance and the CYP3A4 activity markers 4β-OHC or the 4β-OHC : cholesterol ratio. A weak correlation was observed between 4β-OHC and docetaxel clearance, but only in males. This endogenous CYP3A4 marker has limited predictive value for taxane clearance in patients.     

Epitaxial and large area Sb2Te3 thin films on silicon by MOCVD

Antimony telluride (Sb₂Te₃) thin films were prepared by a room temperature Metal–Organic Chemical Vapor Deposition (MOCVD) process using antimony chloride (SbCl₃) and bis(trimethylsilyl)telluride (Te(SiMe₃)₂) as precursors. Pre-growth and post-growth treatments were found to be pivotal in favoring out-of-plane and in-plane alignment of the crystallites composing the films. A comprehensive suite of characterization techniques were used to evaluate their composition, surface roughness, as well as to assess their morphology, crystallinity, and structural features, revealing that a quick post-growth annealing triggers the formation of epitaxial-quality Sb₂Te₃ films on Si(111).

Highly oriented antimony telluride thin films are prepared by room temperature metalorganic chemical vapor deposition on Si(111).     

Potent Triazole Bisphosphonate Inhibitor of Geranylgeranyl Diphosphate Synthase

相似文献   

Emergency department presentation changes due to the coronavirus disease pandemic in Nova Scotia,Canada

<正>Multiple studies have reported decreased emergency department(ED) patient volumes during the coronavirus disease(COVID-19) pandemic,^[1-6] including areas most affected by the virus.^[7]Most existing studies have investigated general trends in ED presentations and have not examined the impact of COVID-19 on different types of EDs, specific ED patient groups, or illness presentations.     

A concise synthesis of pawhuskin A

Pawhuskin A is an isoprenylated stilbene that was isolated from Dalea purpurea and reported to have affinity for the opioid receptor in vitro. It has been synthesized through a convergent sequence that joins a prenylated aldehyde with a geranylated phosphonate in a stereoselective Horner-Wadsworth-Emmons condensation to afford the target E olefin isomer. This synthesis confirms the structure assigned to the natural product and establishes a route that may be used to explore its biological activity and to prepare more active analogues.