Momordica charantia (bitter melon) reduces plasma apolipoprotein B-100 and increases hepatic insulin receptor substrate and phosphoinositide-3 kinase interactions

Aqueous extracts or juice from unripened fruit of Momordica charantia (bitter melon) has traditionally been used in the treatment of diabetes and its complications. Insulin resistance is characterized by significant down-regulation of hepatic insulin signalling as documented by attenuated phosphorylation of insulin receptor (IR), IR substrates 1 and 2, phosphoinositide-3 kinase, protein kinase B, and over-expression of phosphotyrosine phosphatase 1B. We recently demonstrated that bitter melon juice (BMJ) is a potent inhibitor of apoB secretion and TAG synthesis and secretion in human hepatoma cells, HepG2, that may be involved in plasma lipid- and VLDL-lowering effects observed in animal studies. The aim of this study was to evaluate the effects of BMJ on plasma apoB levels and hepatic insulin signalling cascade in mice fed high-fat diet (HFD). Female C57BL/6 mice (4-6 weeks old) were randomized into three groups receiving regular rodent chow, HFD and HFD+BMJ. The data indicate that BMJ not only improves glucose and insulin tolerance but also lowers plasma apoB-100 and apoB-48 in HFD-fed mice as well as modulates the phosphorylation status of IR and its downstream signalling molecules. Investigating the biochemical and molecular mechanisms involved in amelioration of diabetic dyslipidaemia by BMJ may lead to identification of new molecular targets for dietary/alternative therapies.     

Clinical adaptation of a pharmacokinetic model of Propofol plasma concentrations in children

BACKGROUND: A previously published pharmacokinetic simulation suggested a simple manual infusion regimen to achieve propofol plasma concentrations of 3 microg.ml(-1). This study investigated if a simple variation in propofol infusion rates is able to achieve distinct propofol plasma concentrations and whether these are close to the propofol plasma concentrations predicted by the Kataria model. METHODS: With Research Ethics Board approval and written parental consent, a total of 17 healthy children requiring general anaesthesia were enrolled. Following inhalational induction of anaesthesia, a propofol bolus of 5 mg.kg(-1) was given and anaesthesia maintained using an adaptation of the McFarlan continuous propofol infusion regimen to achieve three distinct depths of propofol anaesthesia. Weight and propofol infusion data were used to calculate simulated propofol concentrations using the Kataria dataset and the TIVA simulation program. The performance of the infusion regimen was assessed by calculating the median performance error, median absolute performance error, wobble, and divergence. RESULTS: Measured propofol concentrations were (mean +/- sd) 7.15 +/- 1.4, 4.3 +/- 0.85, and 2.85 +/- 0.53 microg.ml(-1) against simulation values of 6.6, 4.1, and 2.8 microg.ml(-1), respectively, at 30, 50, and 70 min using the Kataria dataset. These differences were not significant. Formal assessment of the infusion regimen's performance was acceptable. CONCLUSION: The manual propofol infusion regimen achieved three distinct depths of propofol anaesthesia. The manual infusion regimen produced higher plasma propofol concentrations than predicted during the early part of the infusion period but was more accurate for later time points.     

A theoretical model for evaluation of the design of a hollow-fiber membrane oxygenator

Geometric data are fundamental to the design of a contactor. The efficiency of a membrane contactor is mainly defined by its mass-transfer coefficient. However, design modifications also have significant effects on the performance of membrane contactors. In a hollow-fiber membrane oxygenator (HFMO), properties such as priming volume and effective membrane surface area (referred to as design specifications) can be determined. In this study, an extensive theoretical model for calculation of geometric data and configuration properties, and, consequently, optimization of the design of an HFMO, is presented. Calculations were performed for Oxyphan^? hollow-fiber micro-porous membranes, which are frequently used in current HFMOs because of their high gas exchange performance. The results reveal how to regulate both the transverse and longitudinal pitches of fiber bundles to obtain a lower rand width and a greater number of windings. Such modifications assist optimization of module design and, consequently, substantially increase the efficiency of an HFMO. On the basis of these considerations, three values, called efficiency factors, are proposed for evaluation of the design specifications of an HFMO with regard with its performance characteristics (i.e. oxygen-transfer rate and blood pressure drop). Moreover, the performance characteristics of six different commercial HFMOs were measured experimentally, in vitro, under the same standard conditions. Comparison of calculated efficiency factors reveals Quadrox^? is the oxygenator with the most efficient design with regard with its performance among the oxygenators tested.     

SCHWIND AMARIS准分子激光联合丝裂霉素C行LASEK术矫治远视的研究

目的：评估SCHWIND AMARIS准分子激光在LASEK术中矫治远视手术中的有效性,安全性和可预测性。

方法：回顾性研究LASEK术联合使用丝裂霉素C矫治远视患者33例66眼,平均年龄35.42±1.12岁(范围 18～56a)。每位患者予SCHWIND AMARIS准分子激光行LASEK术。术后对其可预测性、安全性、有效性及主观验光情况进行评估,并分析客观验光、裸眼视力、最佳矫正视力及不良反应。

结果：平均屈光度为3.2±1.6D(0～7D),术前及术后平均等效球镜分别为2.34±1.76D(-1.25～7D)及0.30±0.84D(-0.2～0.8D)(P=0.001)。术后6～12mo,平均远视为0.63±0.84D(-1.75～2.76D)。平均散光度为0.68±0.43D(0～2D),61眼(78.2%)和31眼(39.7%)散光度分别在±1D和±0.50D范围内。安全指数和有效性指数分别为1.08和1.6。

结论：应用SCHWIND AMARIS准分子激光联合丝裂霉素C行LASEK术矫治远视具有良好的视觉和屈光结果,而且无严重并发症。     

Incorporating synaptic time-dependent plasticity and dynamic synapse into a computational model of wind-up

“Wind-up”, a condition related to chronic pain, is a form of plasticity in spinal dorsal horn that can be observed during electrical stimulation of pain receptors at low frequencies (0.3–3 Hz). In this paper, we present a computational model to explain several aspects of wind-up. The core of this model is the interplay of spike-time-dependent plasticity (STDP), short-term synaptic plasticity (STP), and different propagation velocities of the three afferent fibers (C, , and ). We utilize Izhikevich’s simple spiking neuron to model a dorsal horn neuron (DHN) of the spinal cord. To achieve the expected results, the model parameters need to adapt to the frequency response which is motivated by biological results. The adaptation is performed by a genetic algorithm (GA), and the resulting optimized values interestingly lie in biological ranges. Based on the proposed model, we suggest that STP may be the origin of the band-pass behavior of wind-up between 0.3 and 3 Hz; while the STDP-based long-term plasticity can be responsible for the synaptic potentiation leading to wind-up, or similar phenomena such as central sensitization. Understanding the mechanisms underlying wind-up generation might allow clarification of the molecular mechanisms of pain signaling and development of strategies, such as transcutaneous electrical nerve stimulation (TENS), for pain treatment.