Regulatory volume decrease in a renal distal tubular cell line (A6) II. Effect of Na+ transport rate

A6 epithelia, a cell line originating from the distal tubular part of the kidney ofXenopus laevis, were cultured on permeable supports and mounted in an Ussing-type chamber. Cell thickness (T _c), short-circuit current (I _sc) and transepithelial conductance (G _t) were recorded while tissues were bilaterally incubated in NaCl solutions and the transepithelial potential was clamped to zero. Effects of inhibition and stimulation of transepithelial Na⁺ transport on cell volume and on its regulation during a hyposmotic challenge were investigated. Under control conditions a slow spontaneous decrease ofT _c described by a linear baseline was recorded. The reduction of the apical osmolality from 260 to 140 mosmol/kg did not alter cell volume significantly, demonstrating a negligible water permeability of the apical barrier. The inhibition of Na⁺ uptake by replacing apical Na⁺ byN-methyl-d-glucamine (NMDG⁺) did not affect cell volume under isotonic conditions. An increase ofT _c by 12.1% above the control baseline was recorded after blocking active transport with ouabain for 60 min. The activation of Na⁺ transport with insulin or oxytocin, which is known to activate the apical water permeability in other epithelia, did not alter cell volume significantly. The insensitivity of cell volume to alterations in apical Na⁺ uptake or Na⁺ pump rate confirms the close coupling between apical and basolateral transport processes. The blockage of basolateral K⁺ channels by 5 mM Ba²⁺ elicited a significant increase inT _c of 16.3% above control. Quinine, a potent blocker of volume-activated K⁺ channels, did not changeT _c significantly. Basolateral hypotonicity elicited a rapid rise inT _c followed by a regulatory volume decrease (RVD). An RVD was also recorded after blocking apical Na⁺ uptake as well as after stimulating apical Na⁺ uptake with oxytocin or insulin. Inhibition of active transport with ouabain as well as blocking K⁺ efflux at the basolateral side with Ba²⁺ or quinine abolished the RVD. The inhibition of the RVD by ouabain seems to be caused by a depletion of cellular K⁺, whereas the effects of Ba²⁺ and quinine are most likely due to the blockage of the basolateral K⁺ pathway.     

Metallothionein induction protects swollen rat primary astrocyte cultures from methylmercury-induced inhibition of regulatory volume decrease

Metallothionein (MT) proteins have been postulated to play a role in the detoxification of heavy metals. Since methylmercury (MeHg) preferentially accumulates in astrocytes, and MT-1 and MT-2 are astrocyte-specific MT isoforms, we investigated the ability of MTs to attenuate MeHg-induced cytotoxicity. The toxic effects of MeHg on astrocytes were investigated in a model of regulatory volume decrease (RVD) in which the cells are swollen by exposure to a hypotonic buffer. Preexposure to CdCl₂ (1 μM) for 72, 96 or 120 h, prior to acute exposure to hypotonic buffer and McHg (10 μM) led to a time-dependent increase in the intracellular levels of astrocyte MT proteins. The acute MeHg-induced inhibition of RVD was significantly, and almost fully reversed by preexposure to CdCl₂. This reversal was time-dependent, 120-h preexposure to CdCl₂ producing the greatest reversibility. Furthermore, the ability of astrocytes to efficiently volume regulate in the presence of MeHg-containing hypotonic buffer was highly correlated (r = 0.99) with the intracellular levels of MT proteins. The release of [³H]taurine, an osmolyte involved in the RVD process was also measured. The inhibitory effect of MeHg on [³H]taurine in swollen cells was significantly, and fully reversed by CdCl₂ preexposure. The study suggests that astrocytes induced to express high levels of MT proteins are resistant to the acute inhibitory effect of McHg on RVD.     

肝硬化腹水患者限钠治疗利弊关系的商榷

目的：探讨与评介肝硬化腹水限钠治疗的利弊关系。方法：对血浆钠〈１３５ｍｍｏｌ／Ｌ的２７例肝硬化腹水患者分限钠（１３９例）与不限钠（８８例）两组，观察腹水消失时间及限钠诱发低渗性脑病发生情况。     

螺旋CT在进展期胃癌诊断中的价值

目的：探讨螺旋CT扫描在胃癌诊断及TNM分期中的价值。方法：46例胃癌行低张服水螺旋CT检查，其结果与术后病理对照。结果：46例进展期胃癌病灶显示45例(敏感性98％)；13例病变胃外侵犯CT显示10例(敏感性77％)；39例淋巴结转移CT显示30例(敏感性77％)；10例远处转移显示8例(敏感性80％)结论：螺旋CT扫描可用作进展期胃癌的辅助诊断及TNM分期。     

How do kinases contribute to tonicity-dependent regulation of the transcription factor NFAT5?

NFAT5 plays a critical role in maintaining the renal functions. Its dis-regulation in the kidney leads to or is associated with certain renal diseases or disorders, most notably the urinary concentration defect. Hypertonicity, which the kidney medulla is normally exposed to, activates NFAT5 through phosphorylation of a signaling molecule or NFAT5 itself. Hypotonicity inhibits NFAT5 through a similar mechanism. More than a dozen of protein and lipid kinases have been identified to contribute to tonicity-dependent regulation of NFAT5. Hypertonicity activates NFAT5 by increasing its nuclear localization and transactivating activity in the early phase and protein abundance in the late phase. The known mechanism for inhibition of NFAT5 by hypotonicity is a decrease of nuclear NFAT5. The present article reviews the effect of each kinase on NFAT5 nuclear localization, transactivation and protein abundance, and the relationship among these kinases, if known. Cyclosporine A and tacrolimus suppress immune reactions by inhibiting the phosphatase calcineurin-dependent activation of NFAT1. It is hoped that this review would stimulate the interest to seek explanations from the NFAT5 regulatory pathways for certain clinical presentations and to explore novel therapeutic approaches based on the pathways. On the basic science front, this review raises two interesting questions. The first one is how these kinases can specifically signal to NFAT5 in the context of hypertonicity or hypotonicity, because they also regulate other cellular activities and even opposite activities in some cases. The second one is why these many kinases, some of which might have redundant functions, are needed to regulate NFAT5 activity. This review reiterates the concept of signaling through cooperation. Cells need these kinases working in a coordinated way to provide the signaling specificity that is lacking in the individual one. Redundancy in regulation of NFAT5 is a critical strategy for cells to maintain robustness against hypertonic or hypotonic stress.     

多层螺旋CT小肠低张造影对壶腹癌的诊断价值

目的:探讨多层螺旋CT低张造影在壶腹癌诊断中的应用价值.方法:对22例经手术病理证实的壶腹癌CT表现进行回顾性分析,采用低张(肌注10-20mg 654-2)后行螺旋薄层CT增强扫描.结果:常规平扫仅1例在钩突水平十二指肠降部内侧壁见圆形结节影,余21例均未见确切病灶.低张后增强扫描所有病例均见轻中度和/或明显强化局限性管壁增厚影或强化软组织结节影,肿块直径0.3cm-2.2cm;所有病例均见胆总管扩张,肝内胆管扩张形态均呈软藤状,并伴胆囊增大.术前正确诊断21例,1例误诊为炎症.结论:螺旋CT低张增强扫描在壶腹癌的诊断中具有重要价值.     

Fluid balance concepts in medicine: Principles and practice

The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water (TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment (mainly sodium salts) and in the intracellular compartment (mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume (EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance.     

Poorly selective cation channels in the apical membrane of A6 cells

This paper describes a Ca²⁺-blockable, poorly selective cation pathway in the apical membrane of A6 epithelia. This pathway has properties that resemble the cation-selective channels in the toad urinary bladder and frog skin. Transepithelial short circuit currents (I _sc) and power density spectra (PDS) of the fluctuations in current were recorded. The basolateral surface of the tissues was exposed to Cl^– or SO ₄ ^2– solutions with Na⁺ as the major cation. Ca²⁺-blockable inward oriented currents and Lorentzian noise were recorded with isotonic (215 mosmol/kg) mucosal Cl^– and hypotonic (144 mos-mol/kg) serosal SO ₄ ^2– solution with Na⁺, K⁺, Rb⁺ or Cs⁺ as the major mucosal cation. Experiments with mucosal K⁺ demonstrated that the cation-selective channel was markedly activated by serosal hypotonicity. Effects of an increased electrical driving force were excluded on the basis of the results obtained with microelectrode experiments and transepithelial voltage clamping. Cell volume expansion induced by isotonic replacements of serosal sucrose by glycerol or urea also activated the cation-selective pathway. Furthermore, the presence of Cl^– in the mucosal solution was a prerequisite for a sustained response to hypotonicity or replacements of the organic compounds. Moreover, we found that the cationselective channels are mainly expressed in the cells during the early period of epithelial growth.     

肺心病神志改变17例临床分析

本文对17例肺心病所致神志改变进行了临床分析,认为以肺性脑病引起者最为常见,但低钠、低渗血症引起者也占相当比例。因其治疗方面存在较大的差异,故须及时监测血气和血电解质以助鉴别。