Role of the GABAB receptor in alcohol-seeking and drinking behavior

The present paper summarizes experimental data demonstrating the reducing effect of direct agonists and positive allosteric modulators (PAMs) of the γ-aminobutyric acid_B (GABA_B) receptor on different alcohol-related behaviors. Different lines of evidence indicate that direct agonists, including baclofen, effectively suppress acquisition and maintenance of alcohol drinking behavior, relapse-like drinking, and alcohol's reinforcing, rewarding, stimulating, and motivational properties in rats and mice. More recently, the discovery of a positive allosteric modulatory binding site, together with the synthesis of in vivo effective ligands, opened a new avenue of research in GABA_B pharmacology. Accumulating lines of evidence suggest that PAMs retain baclofen's capcity to suppress alcohol consumption and alcohol's reinforcing and motivational properties in rats; these effects occur at doses far from those producing behavioral toxicity.     

Mechanisms underlying the nociceptive responses induced by platelet-activating factor (PAF) in the rat paw

Platelet-activating factor (PAF) is an inflammatory mediator widely known to exert relevant pathophysiological functions. However, the relevance of PAF in nociception has received much less attention. Herein, we have investigated the mechanisms underlying PAF-induced spontaneous nociception and mechanical hypersensitivity in the rat paw. PAF injection (1-30 nmol/paw) resulted in a dose-related overt nociception, whilst only the dose of 10 nmol/paw produced a significant and time-related mechanical hypersensitivity. Local coinjection of PAF antagonist WEB2086 significantly inhibited both spontaneous nociception and mechanical hypersensitivity. Moreover, the coinjection of the natural IL-1β receptor antagonist (IRA) notably prevented both PAF-induced nociceptive responses, whilst these responses were not altered by anti-TNFα coinjection. Interestingly, pretreatment with the ultrapotent vaniloid agonist resiniferotoxin, coinjection of the TRPV1 receptor antagonist SB366791, or mast cell depletion with compound 48/80 markedly prevented PAF-induced spontaneous nociception. Conversely, PAF-elicited mechanical hypersensitivity was strikingly susceptible to distinct antineutrophil-related strategies, namely the antineutrophil antibody, the selectin blocker fucoidin, the chemokine CXCR2 receptor antagonist SB225002, and the C5a receptor antibody anti-CD88. Notably, the same antineutrophil migration strategies significantly prevented the increase of myeloperoxidase activity induced by PAF. The mechanical hypersensitivity caused by PAF was also prevented by the cyclooxygenase inhibitors indomethacin or celecoxib, and by the selective β₁ adrenergic receptor antagonist atenolol. Collectively, the present results provide consistent evidence indicating that distinct mechanisms are involved in the spontaneous nociception and mechanical hypersensitivity caused by PAF. They also support the concept that selective PAF receptor antagonists might constitute interesting targets for the development of new analgesic drugs.     

机械心瓣关闭速率的实时激光诊断

针对现行激光 扫掠法测量关闭 速率不具备实 时性的弱点， 本文采 用计数 型信号 处理 技术及 微机 高速数据采集方 法，构成了机械 心瓣关闭速率 激光诊断的实 时信 号处理 系统。利 用该 系统的 实时性 ，由大量的实时 数据可获得 心瓣 关闭 速率 的统计 特性 。本文 在介 绍激 光扫 掠方 法的 基础 上，介 绍了实时信号处 理系统的原理 及构成，并给出 了单叶碟型机械 心瓣关闭速率的 实测结果。     

冬虫夏草对大鼠小肠黏膜机械屏障功能影响的研究

目的:探讨冬虫夏草对大鼠小肠黏膜机械屏障功能的影响。方法:实验分为正常对照组、内毒素灌胃组和内毒素灌胃+冬虫夏草组。内毒素灌胃组于实验开始第1天给予内毒素5 EU/kg灌胃,内毒素灌胃+冬虫夏草组每天给予冬虫夏草5 g/(kg.d)混悬液灌胃,对照组给予等量的等渗盐水灌胃,三组均自由进食和饮水。分别于灌胃第4、7、10天取8只大鼠,取小肠黏膜行流式细胞仪检测黏膜细胞的增殖指数(PI),透射电镜检测黏膜上皮细胞间紧密连接宽度,免疫组化染色检测黏膜增殖细胞核抗原(PCNA)。结果:内毒素灌胃+冬虫夏草组大鼠肠黏膜细胞的PI、PCNA比例和肠黏膜上皮细胞间的紧密连接第7天即恢复至正常水平,与内毒素灌胃组相比,有显著性差异。结论:冬虫夏草可促进大鼠小肠黏膜细胞的增殖,维持小肠黏膜上皮细胞间紧密连接的完整性,保护肠黏膜的机械屏障功能。     

10. Entwicklung der Maschinennaht und Vergleich mit der manuellen Naht in der Chirurgie

Summary Mechanical sutures in surgery were first used in 1908 by Hültl. Since then they have found a large field of application in thoracic and abdominal surgery because of their ease in handling and consequent reduction of duration of operation, as well as reduction of contamination from hollow organs. Safety, diminished tissue trauma and early function of anastomotic continuity are other advantages that recommend the use of staplers over hand sutures.Zusammenfassung Die Maschinennaht in der Chirurgie, zuerst angewendet im Jahre 1908 von H. Hültl. in Budapest, empfiehlt sich oft als ein Verfahren erster Wahl in der Thorax- und Bauchchirurgie. Die Vorteile der chirurgischen Klammernaht beruhen auf vereinfachter Handhabung, verkürzter Dauer des Eingriffes und der Öffnung keimbesiedelter Hohlorgane, selbständiger Nahtsicherheit, vorsichtiger Gewebebehandlung und früher Anastomosenfunktion. Die Klammernahtgeräte haben die Entwicklung neuer Operationsmethoden erlaubt, besonders dank technisch immer mehr verbesserten Instrumenten.

     

Molecular interactions, internal structure and drug release kinetics of rationally developed polymer–lipid hybrid nanoparticles

This paper presents the first study of molecular interactions of ingredients and internal nanostructure in relation to drug loading and release mechanisms/kinetics of rationally designed solid polymer–lipid hybrid nanoparticles (PLN). The PLN were prepared by using a rationally selected composition that was found in our previous work to provide optimized interactions of verapamil hydrochloride (VRP) with dextran sulfate sodium (DS) and then the VRP–DS complex with dodecanoic acid (DA). The solid-state properties of the components, their molecular interactions and the morphology, particle size and internal structure of PLN were determined by use of differential scanning calorimetry, powder X-ray diffraction, ¹³C nuclear magnetic resonance, Fourier transform infrared spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering. The distribution of VRP in PLN was examined by TEM imaging using a cationic gold tracer. Drug release studies were conducted in various media. Drug loading as high as 36% and loading efficiencies up to 99% were achieved in the rationally formulated PLN. Hydrogen bonding between drug, polymer and lipid and a uniform distribution of amorphous VRP within the solid lipid matrix were evident. Sustained drug release from the PLN was mainly controlled by ion exchange and diffusion processes. The results demonstrated that strong molecular interactions among the drug, the polymer and the lipid in the optimized formulation were responsible for the improved drug loading and release performance of the PLN.     

Development and Characterization of Active Gelatin Films Loaded with Rapeseed Meal Extracts

The use of industrial waste as a material for the development of natural innovative and active packaging is economically and environmentally appealing. The aim of this study was to develop and characterize active gelatin films incorporating rapeseed oil industry waste. Water (RM-WE) and methanolic (RM-MWE) extracts of rapeseed meal (RM) were used as active agents in film formulations. The active films were produced by a casting technique. The physicochemical, mechanical, optical, morphological, radical scavenging, and antibacterial properties of the films were analyzed. The addition of RM-WE and RM-MWE in the concentrations range between 4 and 12% promoted an increase of Young’s modulus (YM) and radical scavenging properties of films investigated by the direct QUick, Easy, New, CHEap and Reproducible procedure using 2,2-diphenyl-1-picrylhydrazyl (QUENCHER_DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (QUENCHER_ABTS) radicals. The antibacterial properties of films were examined against five bacterial strains: E. coli, S. enterica, M. luteus, L. monocytogenes, and S. aureus. Additionally, color and opacity of the control and fortified films differed significantly. The gelatin films with RM extracts are resistant to the microbial spoilage and could be used to produce active packaging for food that is vulnerable to rancidity effects.     

心脏反搏辅助装置研究进展

目前,全球心力衰竭患者的发病率及病死率逐年增加。机械辅助循环已成为治疗心力衰竭的主要方法之一,其中反搏法辅助心脏的实验研究及临床应用已成为热点,具有代表性的主动脉球囊反搏已成为目前临床最常用的治疗心功能不全的短期机械辅助装置。近年来,主动脉旁反搏装置及其它各种新型反搏装置的研发也取得了快速发展,现对反搏原理、发展历史及各种不同反搏装置的进展进行综述。     

Contribution of skin biometrology to the diagnosis of the Ehlers–Danlos syndrome in a prospective series of 41 patients

Background/purpose: The diagnosis of the Ehlers–Danlos syndrome (EDS) is primarily clinical. Clinical signs result from modifications of the rheological properties of the skin: thickness, extensibility and hydration. Our main objective was to demonstrate what skin biometry can contribute to the diagnosis and evaluation of the different types of EDS.
Methods: Forty-one patients clinically diagnosed with EDS were paired by age and sex to 41 healthy subjects with no known dermatologic disease, in particular connective tissue diseases. We measured skin thickness, extensibility, hydration and sebum secretion by skin ultrasonography, use of a Cutometer^®, a Corneometer^® and a Sebumeter^®.
Results: The skin is thinner in all three disease types (classical, hypermobility and vascular). It is more extensible only in the classical type, and more hydrated and fatty in the hypermobility type.
Conclusion: Non-invasive measurement of skin thickness and elasticity are quantitative parameters that can be used to better diagnose EDS. Moreover, the sebaceous rate can help to diagnose the hypermobility type whereas the immediate retraction distinguishes the classical form from vascular and hypermobile types.     

Effects of compressive loading on biomechanical properties of disc and peripheral tissue in a rat tail model

Intervertebral disc degeneration induced by mechanical compression is an important issue in spinal disorder research. In this study, the biomechanical aspect of the rat tail model was investigated. An external loading device equipped with super-elastic TiNi springs was developed to apply a precise load to the rat tail. By using this device, rat tail discs were subjected to compressive stress of 0.5 or 1.0 MPa for 2 weeks. Discs in the sham group received an attachment of the device but no loading. After the experimental period, first the intact tail with peripheral tissues (PT) such as tendon and skin and then the retrieved disc without PT were subjected to a uniaxial tension–compression test; biomechanical characteristics such as range of motion (ROM), neutral zone (NZ), and hysteresis loss (HL) were evaluated. Furthermore, the load-bearing contribution of PT in the intact tail was estimated by comparing the load–displacement curves obtained by the mechanical tests performed with and without PT. The experimental findings revealed that the continuous compressive stress induced reduction in disc thickness. The intact tail demonstrated decreases in ROM and NZ as well as increases in HL. On the other hand, the retrieved disc demonstrated increases in ROM, NZ, and HL. Further, a significant increase in the load-bearing contribution of PT was indicated. These findings suggest that the load-bearing capacity of the disc was seriously deteriorated by the application of compressive stress of 0.5 or 1.0 MPa for 2 weeks.