偏头痛与卵圆孔未闭的研究进展

偏头痛是临床常见的慢性致残性的神经系统疾病,超过半数的患者会因为偏头痛的发作而影响正常生活。近年来,大量研究表明偏头痛与卵圆孔未闭之间存在着一定的联系,但因为卵圆孔未闭发病率较高且引发偏头痛发作的病理机制不明,两者之间的因果关系尚存争议,经皮卵圆孔封堵术是否为治疗卵圆孔未闭合并偏头痛的有效治疗手段亦成为研究热点。该文将围绕卵圆孔未闭与偏头痛的相关性、两者间可能存在的发病机制以及封堵术治疗偏头痛的疗效展开综述。     

Prodrugs of 5-Iodo-2′-Deoxyuridine for Enhanced Ocular Transport

Problems associated with the use of 5-iodo-2-deoxyundine (IDU) in the treatment of herpes simplex keratitis can be attributed largely to the polar nature of IDU resulting in its poor permeability across the lipoidal epithelial layer of the corneal membrane. Five aliphatic 5-esters of IDU were synthesized and evaluated as prodrugs for potential use in the treatment of deep ocular infections such as stromal keratitis, iritis, and even retinitis. A parabolic relationship between in vitro corneal membrane permeability and carbon chain length of prodrugs is evident. For a given prodrug, enzymatic hydrolysis proceeded most readily in iris–ciliary body, followed by cornea and aqueous humor. An increase in carbon chain length made the prodrugs more enzymatically labile but more resistant to chemical hydrolysis at pH 7.4 and 34°C. The 5-butyryl ester of IDU exhibited an approximately fourfold increase in aqueous humor IDU concentration relative to IDU at 25 min following instillation of 25-µl 5 mM solutions.     

Gas-to-liquid permeation in silicon-containing, crosslinked, glassy copotymers of methyl methacrylate

Copolymers of methyl methacrylate with disiloxane derivatives have been proposed as biomaterials for contact lens applications. Although glassy, these copolymers exhibit high oxygen permeability and adequate wettability so that they can be used for manufacture of hard, extended wear lenses. CrossHnked copolymers of poly(methyl methacrylate-co-1,3-bis(methacryloxymethyl)-1,1,3,3-tetramethyl-disiloxane), P(MMA-co-BMTDS), containing from 0.085 to 0.53 mole fraction of BMTDS were prepared and tested for oxygen permeation using a novel apparatus which simulates the atmosphere/lens/cornea conditions. The gas-to-liquid dissolved oxygen permeability, P_gd, was determined and it was found to increase with BMTDS content Permeability values for P(MMA-co-BMTDS) at 34°C were significantly higher than for pure homopolymer PMMA, although these copolymers were glassy at this temperature. The increased oxygen permeation was attributed to increased oxygen solubility in the copolymers due to the presence of the -Si-0-bonds.     

门静脉的体表定位及其临床意义

目的：为超声波检查门静脉或经皮经肝门静脉穿刺提供解剖学基础。方法：在４０例成人尸体标本上观测了门静脉的行程及其分叉位置的体表投影。结果：门静脉肝外段与身体的垂线呈约４０°角；门静脉分叉位置在经右半胸宽中点的垂线与右锁骨中线上肝高中点的水平线的交点附近；门静脉右支分为前、后支的位置在剑突尖平面下方约２ｃｍ，右锁骨中线上肝高的中点附近；门静脉左支分出第１外侧支的位置在剑突尖稍下方的右侧约２ｃｍ。结论：在右腋中线剑突尖平面下方约２ｃｍ经皮经肝穿刺至锁骨中线，导管即可进入门静脉右支内     

A multiple-pathway model for the diffusion of drugs in skin

A mathematical model for the diffusion of drugs in skin is presented.The penetration of the drug by both transcellular and intercellularpathways, as well as its interchange between these pathways,is considered. A pharmacologically motivated asymptotic limitis identified and analysed to obtain, in particular, an analyticalexpression for the flux of drug to the blood at steady state.Relevant model data is discussed, and some numerical resultsare also presented.     

Differential effects of phosphoramidon and captopril on NK1 receptor-mediated plasma extravasation in the rat trachea

We sought to confirm the identity of the tachykinin receptor subtype that mediates plasma extravasation in the rat trachea, and assess the respective contributions of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) in regulating this tachykinin-induced response. To achieve these aims, we determined the relative potencies of several natural tachykinins and receptor-selective synthetic agonists, both before and after inhibiting NEP with phosphoramidon and ACE with captopril. We also determined the effects of these peptidase inhibitors, and the NK-1 receptor antagonist L-703,606, on the plasma extravasation produced by capsaicin, which releases tachykinins endogenously from sensory nerve endings. We found that the rank order of potency for producing plasma extravasation in the rat trachea was NK-1 receptor agonist ([Sar⁹, Met(O₂)¹¹] SP)>substance P>neurokinin A> neurokinin B. The NK-2 ([Nle¹⁰]NKA (4–10)) and NK-3 ([MePhe⁷]NKB) receptor agonists were without effect. We observed no change in the relative potencies of these peptides after giving rats phosphoramidon or captopril, which suggests that the different peptide potencies are not simply the consequence of different rates of enzymatic degradation. Nevertheless, the responses to substance P and neurokinin A were clearly potentiated in rats given phosphoramidon, indicating that NEP effectively degrades tachykininsin vivo. No significant potentiation was evident for any peptide in rats given captopril. Similarly, the plasma extravasation produced by capsaicin was potentiated in rats given phosphoramidon, but not in those given captopril. Pretreating rats with L-703,606 abolished the response to capsaicin. We conclude from these observations that NK-1 receptors mediate tachykinin-induced plasma extravasation in the rat trachea, and that NEP regulates this response with little or no contribution from ACE.     

Transport of Ca2+ ions in the mitochondria of Ehrlich's ascites tumor cells

The pattern of Ca²⁺ accumulation by tumor mitochondria (MC) was investigated under various experimental conditions. In the absence of penetrating anions tumor MC were shown to take up Ca²⁺ in only one fifth the amount taken up by liver MC. In the presence of acetate this difference was greater still. Inorganic phosphate (P_in) abolished the observed defects of Ca²⁺ transport and increased the Ca²⁺ capacity of the tumor MC considerably. By contrast with liver MC, P_in also had a stabilizing effect on membrane permeability of the tumor MC; this may be the cause of the increasee Ca²⁺ capacity of these MC.Department of Bioenergetics, Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. (Presented by Academician of the Academy of Medical Sciences of the USSR S. E. Severin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 8, pp. 202–205, August, 1977.     

Advection and Diffusion of Substances in Biological Tissues With Complex Vascular Networks

For highly diffusive solutes the kinetics of blood–tissue exchange is only poorly represented by a model consisting of sets of independent parallel capillary–tissue units. We constructed a more realistic multicapillary network model conforming statistically to morphometric data. Flows through the tortuous paths in the network were calculated based on constant resistance per unit length throughout the network and the resulting advective intracapillary velocity field was used as a framework for describing the extravascular diffusion of a substance for which there is no barrier or permeability limitation. Simulated impulse responses from the system, analogous to tracer water outflow dilution curves, showed flow-limited behavior over a range of flows from about 2 to 5 ml min^–1 g^–1, as is observed for water in the heart in vivo. The present model serves as a reference standard against which to evaluate computationally simpler, less physically realistic models. The simulated outflow curves from the network model, like experimental water curves, were matched to outflow curves from the commonly used axially distributed models only by setting the capillary wall permeability–surface area (PS) to a value so artifactually low that it is incompatible with the experimental observations that transport is flow limited. However, simple axially distributed models with appropriately high PSs will fit water outflow dilution curves if axial diffusion coefficients are set at high enough values to account for enhanced dispersion due to the complex geometry of the capillary network. Without incorporating this enhanced dispersion, when applied to experimental curves over a range of flows, the simpler models give a false inference that there is recruitment of capillary surface area with increasing flow. Thus distributed models must account for diffusional as well as permeation processes to provide physiologically appropriate parameter estimates. © 2000 Biomedical Engineering Society. PAC00: 8719-j, 8710+e     

老年冠心病慢性闭塞病变的介入治疗探讨

目的探讨老年冠心病患者采用经皮冠状动脉介入(PCI)治疗的中短期疗效。方法对102例住院老年患者采用股动脉穿刺后,行球囊扩张,造影显示扩张满意后植入合适支架。术后随访6-32个月。结果102例患者术后临床症状均完全或基本完全缓解。本组患者有19例多支病变患者至少有一支慢性完全闭塞血管经努力而未能开通,无法植入支架。102例患者通过随访6-32个月,其中32例患者接受了冠脉造影复查,有17例患者分别于术后6个月至16个月又出现胸痛、胸闷症状。超声心动图检查射血分数(EF),心功能术后较术前明显改善,P<0.05。结论对冠状动脉慢性完全闭塞的老年患者,无论核素或超声检查是否存在存活心肌,均应尽量进行闭塞病变的介入治疗,以期改善患者的远期预后。     

卡巴胆碱抑制肿瘤坏死因子所致微血管内皮细胞通透性增高

目的探讨卡巴胆碱对肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）诱导的增加微血管通透性的作用。方法采用FITC标记白蛋白漏出法、考马斯亮蓝染色法观察卡巴胆碱对TNF-α诱导微血管内皮细胞通透性，细胞形态和细胞骨架变化的影响。结果与对照组比较，TNF-α明显增加微血管内皮细胞通透性（P〈0．05），诱导细胞皱缩，细胞间隙增大和细胞骨架排列紊乱。给予卡巴胆碱可以明显抑制TNF-α诱导微血管内皮细胞通透性增加，并呈剂量依赖性，同时可以使细胞间隙明显减小，细胞骨架排列有序。结论卡巴胆碱可能通过抑制TNF-α对细胞骨架的损伤，进而抑制微血管通透性增加。