Two Distinct Modes of Hypoosmotic Medium-Induced Release of Excitatory Amino Acids and Taurine in the Rat Brain In Vivo

A variety of physiological and pathological factors induce cellular swelling in the brain. Changes in cell volume activate several types of ion channels, which mediate the release of inorganic and organic osmolytes and allow for compensatory cell volume decrease. Volume-regulated anion channels (VRAC) are thought to be responsible for the release of some of organic osmolytes, including the excitatory neurotransmitters glutamate and aspartate. In the present study, we compared the in vivo properties of the swelling-activated release of glutamate, aspartate, and another major brain osmolyte taurine. Cell swelling was induced by perfusion of hypoosmotic (low [NaCl]) medium via a microdialysis probe placed in the rat cortex. The hypoosmotic medium produced several-fold increases in the extracellular levels of glutamate, aspartate and taurine. However, the release of the excitatory amino acids differed from the release of taurine in several respects including: (i) kinetic properties, (ii) sensitivity to isoosmotic changes in [NaCl], and (iii) sensitivity to hydrogen peroxide, which is known to modulate VRAC. Consistent with the involvement of VRAC, hypoosmotic medium-induced release of the excitatory amino acids was inhibited by the anion channel blocker DNDS, but not by the glutamate transporter inhibitor TBOA or Cd²⁺, which inhibits exocytosis. In order to elucidate the mechanisms contributing to taurine release, we studied its release properties in cultured astrocytes and cortical synaptosomes. Similarities between the results obtained in vivo and in synaptosomes suggest that the swelling-activated release of taurine in vivo may be of neuronal origin. Taken together, our findings indicate that different transport mechanisms and/or distinct cellular sources mediate hypoosmotic medium-induced release of the excitatory amino acids and taurine in vivo.     

Nutritional and genetic contributions to serum cholesterol concentration in a children's follow-up study

In the Finnish multicentre study of cardiovascular risk in young Finns in 1980, 1983 and 1986, 2429, 2052 and 1841 9 to 18-year-old children and adolescents participated. In 1980, subjects of eastern origin living in the west had, despite their western diet, higher serum cholesterol concentrations than subjects both residing in and originating from the west. In males, eastern origin increased the eastlwest difference in serum cholesterol concentrations. Between 1980 and 1986 the mean serum total cholesterol of the study cohorts decreased by 5.5% and simultaneously the east/west differences in serum cholesterol concentrations disappeared in boys. The study suggests that genetic background is a separate factor determining serum total cholesterol level, but with declining serum cholesterol concentrations the effect of the genetic factor does not become manifest.     

Astrocytic swelling in cerebral ischemia as a possible cause of injury and target for therapy

In this viewpoint article, I summarize data showing that the astrocytic swelling that occurs early after the acute CNS pathologies ischemia and traumatic brain injury is damaging. We have proposed that one reason may be the release of excitatory amino acids (EAA) via volume-activated anion channels (VRACs) that are activated by such swelling. This release could be a target for therapy, which could involve blocking the astrocytic swelling or the release mechanisms. The transport mechanisms likely causing the early astrocytic swelling are therefore summarized. In terms of targeting the release mechanisms, we have found a potent inhibitor of VRACs, tamoxifen, to be strongly neuroprotective in focal ischemia with a therapeutic window of 3 h after initiation of the ischemia. The question, however, of whether neuroprotection by tamoxifen can be solely attributed to VRAC inhibition in astrocytes has yet to be resolved.     

中国和英国精神科医生对儿童多动行为症状的评估比较

目的 :比较不同文化背景的精神专科医生在评估多动症儿童各种症状表现时的一致程度 ,探讨文化对儿童多动症诊断可能产生的影响。方法 :使用单独或集体行为观察清单 ,让两地的精神科医生对儿童多动症的各种表现进行症状评估 ;所有的评估者均观察同一录像带上患儿的行为表现 ;对其评定结果进行统计和比较。结果 :儿童独自活动观察量表的 12项中有 11项症状条目评定结果类似 ,有 3项英国医生的评分高于中国医生 ,有 9项中国医生评分高于英国医生 ,其中 1项具有显著性差异。结论 :对行为表现和症状认知的文化差异可能使流行病学的研究出现不同的结果 ,即使使用统一的诊断标准和症状评分量表作为诊断工具 ,不同文化背景的国家 ,儿童多动症的患病率仍然可不一致     

Colorectal liver metastases: Current management and future perspectives

The liver is the commonest site of metastatic disease for patients with colorectal cancer, with at least 25% developing colorectal liver metastases (CRLM) during the course of their illness. The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology (cross sectional, nuclear medicine and interventional), Oncology, Liver surgery, Colorectal surgery, and Histopathology. Patient management is based on assessment of sophisticated clinical, radiological and biomarker information. Despite incomplete evidence in this very heterogeneous patient group, maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure. To this end, liver resection is maximised by the use of downsizing chemotherapy, optimisation of liver remnant by portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and combining resection with ablation, in the context of improvements in the functional assessment of the future remnant liver. Liver resection may safely be carried out laparoscopically or open, and synchronously with, or before, colorectal surgery in selected patients. For unresectable patients, treatment options including systemic chemotherapy, targeted biological agents, intra-arterial infusion or bead delivered chemotherapy, tumour ablation, stereotactic radiotherapy, and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability. Currently evolving areas include biomarker characterisation of tumours, the development of novel systemic agents targeting specific oncogenic pathways, and the potential re-emergence of radical surgical options such as liver transplantation.     

多层螺旋CT评价先天性单冠状动脉畸形

目的 探讨16层螺旋CT（MSCT）冠状动脉造影诊断先天性单冠状动脉畸形的价值。资料与方法 回顾性分析4例先天性单冠状动脉患者的MSCT和常规X线冠状动脉造影（CCA）资料。对比两者在显示和诊断此病中的差异。仿真内镜技术用于评价异位开口及其与邻近正常冠状动脉开口的关系,多平面重建、曲面多平面重建、最大密度投影、容积成像等重建方法则用于评价变异冠状动脉的行径及其与邻近大血管的关系。结果 4例患者变异的冠状动脉全部为MSCT造影所显示并明确诊断。MSCT显示3例患者的左主干起源于右冠状动脉的近段,其中1例在CCA中左主干仅近段局部显影,未能明确诊断,另2例左冠状动脉虽显影,但较淡。1例右冠状动脉起源于左主干的末端,CCA则误为起源于回旋支。MSCT显示2例异常开口冠状动脉的近段狭窄,3支异常冠状动脉穿过主动脉根部和肺动脉或右室流出道的间隙,1支绕主动脉根部后方走行,而CCA均不能明确诊断。结论 MSCT显示先天性单冠状动脉明显优于CCA,凡疑及冠状动脉变异的患者,可首选非创伤性的MSCT冠状动脉造影检查。     

重组人BAFF112-285的制备及活性分析

目的 制备具有功能活性的重组人TNF家族的B细胞激活因子(B cell activating factor belonging to the TNF family,BAFF)胞外区112—285氨基酸残基段(rhBAFF112—285)，为BAFF的深人研究奠定基础。方法 提取人HL-60细胞总RNA，经RT—PCR扩增编码人BAFF胞外区112—285氨基酸残基(BAFF112—285)的cDNA，行序列测定后，构建于原核表达载体pQE—80L并转化大肠杆菌DH5α，经IPTG诱导表达rhBAFF112—285，Ni^2 —NTA层析纯化，进而经^3H—TdR掺人实验检测其免疫学活性。结果 RT—PC双扩增得到了525bp的DNA片段，序列分析与GenBank中报道的编码人BAFF112—285的cDNA序列一致，该胞外区片段在大肠杆菌中获得了高效表达，表达水平达细菌总蛋白的45．7％，经纯化后纯度可达98．4％，活性检测证实其能明显刺激外周血淋巴细胞活化。结论 利用大肠杆菌可高效表达rhBAFF112—285，所获纯化产物具有生物学活性，所获结果为进一步研究创造了条件。     

Oxygen and glucose deprivation-induced changes in astrocyte membrane potential and their underlying mechanisms in acute rat hippocampal slices.

Accumulating evidence indicates a significant astrocytic involvement in cerebral ischemia neuropathology, but little is known about the immediate astrocytic responses to ischemia insults in terms of electrophysiology and their pathologic implications. We show that astrocytes in acute rat hippocampal slices responded reversibly to more than 30 mins oxygen and glucose deprivation (OGD) treatment with depolarized membrane potentials (V(m)) in whole-cell current clamp recording. This depolarization was multiphasic, showing an initial approximately 11 mins small-amplitude depolarization plateau, followed by a 6-mins accelerated depolarization, and then a second plateau. Oxygen and glucose deprivation-induced astrocyte V(m) depolarization was only marginally inhibited, approximately 10%, by inhibition of ionotropic glutamate, gamma-aminobutyric acid, purinergic receptors, and glutamate transporters presumed to be present on astrocytes in situ, suggesting increase in extracellular [K(+)] was primarily responsible for the astrocytic V(m) change. The V(m) depolarization was five-fold greater when glycolysis was inhibited by iodoacetate in a short 8 mins OGD treatment, suggesting glycolytic ATP is critical in maintaining extracellular K(+) homeostasis in the early phase of OGD. Addition of oxidative metabolism inhibitors had much less effect. Cessation of OGD was always followed by a rapid and transient 9 mV astrocyte V(m) hyperpolarization relative to the control V(m) that was inhibited by ouabain, indicating a reactively enhanced Na(+)/K(+)-ATPase activity in post-OGD reperfusion. Altogether, hippocampal astrocytes appear to be electrophysiologically more resistant to acute ischemia insults as compared with neurons, and this should allow astrocytes to rescue endangered neurons in the face of acute ischemia insults via their various homeostatic functions.     

Botulinum toxin A in the hemiplegia upper limb: a double-blind trial

In a randomised, double-blind study, the effects of intramuscular injection of botulinum toxin type A (BtA) into the upper limb were compared with those of normal saline solution in 14 patients with cerebral palsy; their mean age was 9 years. Range of movement and function were assessed before injection and at 2 and 12 weeks after injection. BtA injection significantly increased maximum active elbow and thumb extension and significantly reduced tone at wrist and elbow. The hand grasp-and-release score improved, representing a modest functional change, but fine motor function, assessed by the ability to pick up coins, did not improve and in some cases deteriorated temporarily. The most notable subjective change was the cosmetic benefit of reduced involuntary elbow flexion. The tone-reducing effect of BtA was clinically detectable in comparison with the placebo and patients and parents perceived the change as beneficial. The median of changes in the treatment group was small but the range Was large, suggesting that BtA can be useful in selected patients.