Effect of heparin on high glucose induced proliferation and expression of matrix metalloproteinases in normal human mesangial cells

Background The pathogenesis of diabetic nephropathy (DN) is a complex pathophysiological process. Its precise mechanism is not fully known. In recent years it has been recognized that synthesis of various extracelluar matrix (ECM) components may increase, and that degradation of ECM may decrease in DN. It was reported heparin could inhibit mesangial cells proliferation in vitro. The main aim of this study is to explore whether heparin inhibits proliferation of mesangial cells grown in high glucose concentration and to measure the effect of heparin on matrix metalloproteinases (MMPs) expression in mesangial cells. Methods The medium contained either low glucose (5 mmol/L) or high glucose (25 mmol/L). The concentrations of heparin in the culture medium were 0, 25, 50, 100, 200 or 400 μg/mL. A metabolic (WST-1) assay was used to measure mesangial cell proliferation and Western blot analysis was used to measure MMPs expression of mesangial cells. Results Normal human mesangial cell (NHMC) proliferation was higher in high glucose (HG) medium than in low glucose (LG) medium. They showed a 1.93 fold expansion after 72 h in high glucose in contrast to a 1.63 fold expansion in low glucose. In the presence of heparin, mesangial cells proliferation was inhibited, which was more obvious at high glucose concentrations than at low glucose concentrations. In high glucose, with heparin concentration of 50, 100, 200 and 400 μg/mL, the mesangial cells showed a 0.61 fold, 0.52 fold, 0.52 fold and 0.41 fold reductions in cell number compared to cells grown without heparin. In low glucose, only concentrations of 200 μg/mL and 400 μg/mL showed reduction in cell number, namely 0.54 fold and 0.45 fold, when compared to cells grown without heparin. In Western blot analysis, MMP₁, MMP₂, MMP₃ and MMP₉ was expressed by mesangial cells expressed in both high and low glucose concentrations, which was more prominent in high glucose medium. Incubation of heparin further increased expression of MMP₁, MMP₂, MMP₃ and MMP₉. Conclusions This study suggests that glucose can accelerate mesangial cell proliferation while heparin can reduce proliferation, being more obvious at high glucose concentrations. Higher glucose concentrations led to increased MMP expression, which may take part in the regulation of mesangial matrix synthesis and degradation. Addition of heparin resulted in a corresponding increase in MMP expression, most notably at high glucose concentrations, indicating a potentially renoprotective role in DN. Foundation item: Project (30370663) supported by the National Natural Science Foundation of China     

The pharmacokinetics of water-in-oil-in-water-type multiple emulsion of a new tacrolimus formulation

We developed a water-in-oil-in-water (W/O/W)-type multiple emulsion of a new tacrolimus formulation. A potential approach to avoid the complications of systemic immunosuppression and simultaneously enhance immunosuppressive efficacy is to deliver immunosuppressive agents locally to the site of the target organs. The W/O/W emulsion is dispersed oil drops containing smaller water droplets that allow the delivery of drugs preferentially to the reticuloendothelial system (RES). Since the liver and the spleen are primary components of the RES, and the brain and the kidney have a poor RES, we hypothesized that a W/O/W emulsion of tacrolimus would prossess the pharmacokinetic benefits of local immunosuppression. We evaluated this hypothesis in a rat model. The tacrolimus levels of whole blood, the liver, spleen, brain, and kidney in rats given intravenous emulsions of tacrolimus (W/O/W group) were compared with a group administered tacrolimus alone (T group). There were no significant differences between the pharmacokinetic parameters of W/O/W group and T group based on whole blood data. However, the W/O/W group had significantly decreased tacrolimus levels in the brain and kidney, and significantly increased levels in the liver and spleen compared with the T group. These data suggest that the W/O/W emulsion is applicable as an intravenous drug carrier for local immunosuppression.     

Thermal and optical properties of epoxy/zirconia hybrid materials synthesized via in situ polymerization

Epoxy/zirconia hybrid materials were synthesized from a bisphenol-A type epoxy resin, zirconium-tetra-n-propoxide and acetic acid via in situ polymerization. Acetic acid was used to control the hydrolysis and condensation reaction of the zirconium-tetra-n-propoxide. As a result, the zirconia produced by the in situ polymerization was uniformly dispersed into the epoxy matrix on a nano scale or less, and the hybrid materials exhibited an excellent optical transparency. With the increasing zirconia contents, the storage modulus in the rubbery region increased and the peak area of tanδ in the glass transition temperature region decreased. These results indicate that their heat resistance of the hybrid materials could be improved by hybridization with zirconia. Furthermore, the refractive indices of the hybrid materials were significantly improved with the increasing zirconia contents.     

Autonomous mobile robot based on behavior decision skill and control skill of the operator

This paper introduces a human skill base control algorithm using artificial neural networks and fuzzy reasoning for an autonomous mobile robot. Neural networks are used to select a suitable motion control pattern in actual environments. The back propagation algorithm adjusts the weights of the neural networks so that the selected motion control pattern corresponds to the action, which is obtained by the operator's behavior decision skill. To realize the selected motion control pattern, the orientation angle and the speed of the mobile robot are determined by fuzzy reasoning in which fuzzy rules are also automatically tuned so as to simulate the operator's control skill. We have implemented and tested the proposed control algorithm on an autonomous mobile robot and some experimental results demonstrate the effectiveness of the proposed control algorithm for the autonomous mobile robot. © 2000 Scripta Technica, Electr Eng Jpn, 131(2): 30–39, 2000     

Neuroprotection,Growth Factors and BDNF-TrkB Signalling in Retinal Degeneration

Neurotrophic factors play key roles in the development and survival of neurons. The potent neuroprotective effects of neurotrophic factors, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF) and nerve growth factor (NGF), suggest that they are good therapeutic candidates for neurodegenerative diseases. Glaucoma is a neurodegenerative disease of the eye that causes irreversible blindness. It is characterized by damage to the optic nerve, usually due to high intraocular pressure (IOP), and progressive degeneration of retinal neurons called retinal ganglion cells (RGCs). Current therapy for glaucoma focuses on reduction of IOP, but neuroprotection may also be beneficial. BDNF is a powerful neuroprotective agent especially for RGCs. Exogenous application of BDNF to the retina and increased BDNF expression in retinal neurons using viral vector systems are both effective in protecting RGCs from damage. Furthermore, induction of BDNF expression by agents such as valproic acid has also been beneficial in promoting RGC survival. In this review, we discuss the therapeutic potential of neurotrophic factors in retinal diseases and focus on the differential roles of glial and neuronal TrkB in neuroprotection. We also discuss the role of neurotrophic factors in neuroregeneration.     

Design of quaternary Ir-Nb-Ni-Al refractory superalloys

We propose a method for developing new quaternary Ir-Nb-Ni-Al refractory superalloys for ultra-high-temperature uses, by mixing two types of binary alloys, Ir-20 at. pct Nb and Ni-16.8 at. pct Al, which contain fcc/L1₂ two-phase coherent structures. For alloys of various Ir-Nb/Ni-Al compositions, we analyzed the microstructure and measured the compressive strengths. Phase analysis indicated that three-phase equilibria—fcc, Ir₃Nb-L1₂, and Ni₃Al-L1₂—existed in Ir-5Nb-62.4Ni-12.6Al (at. pct) (alloy A), Ir-10Nb-41.6Ni-8.4Al (at. pct) (alloy B), and Ir-15Nb-20.8Ni-4.2Al (at. pct) (alloy C) at 1400 °C; at 1300 °C, three phase equilibria—fcc, Ir₃Nb, and Ni₃Al—existed in alloys A and C and four-phase equilibria—fcc, Ir₃Nb, Ni₃Al, and IrAl-B2—existed in alloy B. The fcc/L1₂ coherent structure was examined by using transmission electron microscopy (TEM). At a temperature of 1200 °C, the compressive strength of these quaternary alloys was between 130 and 350 MPa, which was higher than that of commercial Ni-based superalloys, such as MarM247 (50 MPa), and lower than that of Ir-based binary alloys (500 MPa). Compared to Ir-based alloys, the compressive strain of these quaternary alloys was greatly improved. The potential of the quaternary alloys for ultra-high-temperature use is also discussed.     

Transversal merge operation: a nondominated coterie construction method for distributed mutual exclusion

A coterie is a set of subsets (called quorums) of the processes in a distributed system such that any two quorums intersect with each other and is mainly used to solve the mutual exclusion problem in a quorum-based algorithm. The choice of a coterie sensitively affects the performance of the algorithm and it is known that nondominated (ND) coteries achieve good performance in terms of criteria such as availability and load. On the other hand, grid coteries have some other attractive features: 1) a quorum size is small, which implies a low message complexity, and 2) a quorum is constructible on the fly, which benefits a low space complexity. However, they are not ND coteries unfortunately. To construct ND coteries having the favorite features of grid coteries, we introduce the transversal merge operation that transforms a dominated coterie into an ND coterie and apply it to grid coteries. We call the constructed ND coteries ND grid coteries. These ND grid coteries have availability higher than the original ones, inheriting the above desirable features from them. To demonstrate this fact, we then investigate their quorum size, load, and availability, and propose a dynamic quorum construction algorithm for an ND grid coterie.     

Data fitting with a spline using a real-coded genetic algorithm

To obtain a good approximation for data fitting with a spline, frequently we have to deal with knots as variables. The problem to be solved then becomes a continuous nonlinear and multivariate optimization problem with many local optima. Therefore, it is difficult to obtain the global optimum. In this paper, we propose a method for solving this problem by using a real-coded genetic algorithm. Our method can treat not only data with a smooth underlying function, but also data with an underlying function having discontinuous points and/or cusps. We search for the best model among candidate models by using the Bayes Information Criterion (BIC). With this, we can appropriately determine the number and locations of knots automatically and simultaneously. Five examples of data fitting are given to show the performance of our method.     

Surface‐discharge electrode design methods for ACPDPs

Abstract— In order to lower development costs and to shorten development time, small panels, under 10‐in on the diagonal, are used for the experiments to improve the luminous efficiency of plasma‐display panels. However, it is difficult to show the same results as those of large panels, over 40 in. on the diagonal. In this paper, first, we show that the luminous efficiency and the voltage margin of mini‐panels are not obtained with large panels by using an actual 46‐in. PDP. The reason is that the resistance in the large panels is larger than that in the mini panels and the voltage drop in the large panels are larger than in mini‐panels. Therefore, we conclude that the bus electrode width and the transparent electrode width are important factors in the design of large PDPs. Next, we show the technique of designing large panels by using a database obtained from mini‐panels. The estimated cell‐design results show good agreement with an actual 46‐in. PDP in luminous efficiency and minimum sustain voltage. We show that a desired large PDP can be obtained by using the cell design proposed in the present paper.