The entorhinal cortex: an examination of cyto- and myeloarchitectonic organization in humans

The entorhinal cortex (ERC) has been implicated in the pathophysiology of Alzheimer's disease, schizophrenia and other disorders affecting cognitive functions. While powerful anatomical and histochemical methods (immunohistochemistry, in situ hybridization, etc.) may be applied (although with limitations) to postmortem human brain, each analysis should utilize a cytoarchitectonic approach to provide appropriate comparisons within the subdivisions of the ERC. Accordingly, we describe here the normal cyto- and myeloarchitecture of the human ERC as a prerequisite for the accompanying study of this region in schizophrenia. Our parcellation of this cortex differs from previous treatments in three ways. First, we adopted specific criteria of inclusion to define each subdivision of the region. Although distinctive ERC features are most prominent in the intermediate portion of this region, at least one of these features was considered the minimum necessary criterion to include adjacent tissue in the entorhinal area. Second, we used morphometric measurements (neuronal size and density as well as subdivisional volume and laminar thickness) to support our qualitative evaluation. Third, we have applied to the human ERC the conventional cytoarchitectonic nomenclature of the entorhinal cortex used previously in studies of non-human primates. This allows a more accurate extrapolation of the available numerous experimental anatomical, physiological and psychological data on this region to the human. As in the monkey, the five main subareas were recognized in the human (prorhinal, lateral, intermediate, sulcal and medial) but three required further subdivision (intermediate, sulcal and medial). The morphometric results obtained suggested a progression of the human entorhinal cortex from the peripheral to the central subareas, with the intermediate subarea (281) as the most complete entorhinal subdivision. Compared with non-human primates, the human ERC not only retains the basic periallocortical organization but also demonstrates further evolution. Taken together with available experimental data on the connectivity of this brain region, these results provide an anatomical basis for evaluating the ERC in human behavior.      

Inhibition of the intrinsic factor X activating complex by protein S: evidence for a specific binding of protein S to factor VIII

Protein S is a vitamin K-dependent nonenzymatic anticoagulant protein that acts as a cofactor to activated protein C. Recently it was shown that protein S inhibits the prothrombinase reaction independent of activated protein C. In this study, we show that protein S can also inhibit the intrinsic factor X activation via a specific interaction with factor VIII. In the presence of endothelial cells, the intrinsic activation of factor X was inhibited by protein S with an IC50 value of 0.28 +/- 0.04 mumol/L corresponding to the plasma concentration of protein S. This inhibitory effect was even more pronounced when the intrinsic factor X activation was studied in the presence of activated platelets (IC50 = 0.15 +/- 0.02 mumol/L). When a nonlimiting concentration of phospholipid vesicles was used, the plasma concentration of protein S (300 nmol/L) inhibited the intrinsic factor X activation by 40%. Thrombin-cleaved protein S inhibited the endothelial cell-mediated factor X activation with an IC50 similar to that of native protein S (0.26 +/- 0.02 mumol/L). Protein S in complex with C4b-binding protein inhibited the endothelial cell-mediated factor X activation more potently than protein S alone (IC50 = 0.19 +/- 0.03 mumol/L). Using thrombin activated factor VIII, IC50 values of 0.53 +/- 0.09 mumol/L and 0.46 +/- 0.10 mumol/L were found for native protein S and thrombin-cleaved protein S, respectively. The possible interactions of protein S with factor IXa, phospholipids, and factor VIII were investigated. The enzymatic activity of factor IXa was not affected by protein S, and interaction of protein S with the phospholipid surface could not fully explain the inhibitory effect of protein S on the factor X activation. Using a solid-phase binding assay, we showed a specific, saturable, and reversible binding of protein S to factor VIII with a high affinity. The concentration of protein S where half-maximal binding was reached (B1/2max) was 0.41 +/- 0.06 mumol/L. A similar affinity was found for the interaction of thrombin-cleaved protein S with factor VIII (B1/2max = 0.40 +/- 0.04 mumol/L). The affinity of the complex protein S with C4B-binding protein appeared to be five times higher (B1/2max = 0.07 +/- 0.03 mumol/L). Because the affinities of the interaction of the different forms of protein S with factor VIII correspond to the IC50 values observed for the intrinsic factor X activating complex, the interaction of protein S with factor VIII may explain the inhibitory effect of protein S on the intrinsic factor X activating complex.(ABSTRACT TRUNCATED AT 400 WORDS)     

大鼠肝脏缺血再灌注损伤后5′核苷酸酶和乳酸脱氢酶活化变化的研究

目的 探讨大鼠肝脏经过UW、Celsior和HTK三种不同类型保存液低浊保存和常温再灌注后5′核苷酸酶和乳酸脱氢酶活性的变化。方法 将大鼠肝脏在UW、Celsior和HTK液中低温4℃保存0、8、16、和24h后,采用离体连续灌注模型,用Krebs-Henseleit液37℃连续循环灌注90min,灌注结束后取肝脏组织标本测定5′核苷酸酶和乳酸脱氢酶活性,并测定胆汁分泌量的变化。结果 经过16和24h的UW和Celsior低温保存后的肝组织5′核式酸酶和乳酸脱氢酶的活性出现降低;HTK组8h就出现降低,UW和Celsior组经过24h的低温保存后,胆汁分泌量开始明显;在HTK组16h后,胆汁分泌量就显著降低。结论 5′核苷酸酶和乳酸脱氢酶的活性随着低温缺血时间的延长逐渐降低;UW和Celsior液以肝窦内皮细胞和肝实质细胞的保护作用均强于HTK。     

大鼠肝脏缺血再灌注损伤后5′核苷酸酶和乳酸脱氢酶活性变化的研究

目的探讨大鼠肝脏经过UW、Celsior和HTK三种不同类型保存液低温保存和常温再灌注后5′核苷酸酶和乳酸脱氢酶活性的变化.方法将大鼠肝脏在UW、Celsior和HTK液中低温4℃保存0、8、16和24 h后,采用离体连续灌注模型,用Krebs-Henseleit液37℃连续循环灌注90 min,灌注结束后取肝脏组织标本测定5′核苷酸酶和乳酸脱氢酶活性,并测定胆汁分泌量的变化.结果经过16和24 h的UW和Celsior低温保存后的肝组织5′核苷酸酶和乳酸脱氢酶的活性出现降低;HTK组8 h就出现降低.UW和Celsior组经过24 h的低温保存后,胆汁分泌量开始明显降低;在HTK组16 h后,胆汁分泌量就显著降低.结论 5′核苷酸酶和乳酸脱氢酶的活性随着低温缺血时间的延长逐渐降低;UW和Celsior液对肝窦内皮细胞和肝实质细胞的保护作用均强于HTK.     

Survival after out-of-hospital cardiac arrest,Viet Nam: multicentre prospective cohort study

ObjectiveTo investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam.MethodsWe did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis.FindingsOf 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54–9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03–8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33–12.74).ConclusionImprovements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.