Splanchnic ischaemia and its role in multiple organ failure

Multiple organ failure remains the leading cause of death in the intensive care unit. Increasing numbers of investigators have focused their attention on the role of gastrointestinal tract in the pathogenesis of this syndrome. Their data indicate that inadequate gut perfusion leads to a measurable imbalance between oxygen delivery and the needs of the tissues, i.e., ischaemia. Gut ischaemia of sufficient duration impairs gastrointestinal tract barrier function, facilitating the passage of enteric bacterial endotoxin into the circulation. It has been hypothesized that production of tumor necrosis factor α, and other biologic mediators by endotoxin–stimulated macrophages, triggers a generalized and uncontrolled inflammatory response that ultimately leads to multiple organ failure.
Preliminary evidence suggests that survival can be improved significantly if gut ischaemia is promptly identifed and aggressively treated by administration of fluids and inotropic drugs, using gastric intramucosal pH as the therapeutic endpoint. Future studies are needed to determine whether additional treatment modalities can improve outcome once the inflammatory response has fully developed.     

Tumor cell-enhanced sensitivity of vascular endothelial cells to photodynamic therapy

Effective antitumor photodynamic therapy (PDT) may be related to damage of vasculature within the tumor. The purpose of this study was to determine if tumor cells secrete factors that stimulate proliferation of human umbilical vein endothelial cells (HUVEC) and result in enhanced sensitivity of HUVEC to aluminum-sulfonated phthalocyanine (AISPc)-PDT. Three human tumor cell lines—pharyngeal squamous carcinoma, colonic carcinoma, and mammary carcinoma—were used in this study. Co-culture of HUVEC and either squamous carcinoma or colonic carcinoma, but not mammary carcinoma, significantly increased HUVEC proliferation and AlSPc-PDT mediated cell damage. In addition, supernatant from squamous carcinoma and colonic carcinoma cultures also stimulated HUVEC proliferation and sensitivity to AISPc-PDT. Both supernatant and cell lysate from squamous carcinoma cells contained angiogenic factors consistent with basic and acidic fibroblast growth factors, as evidenced by Western blot analysis and BALB/c 3T3 fibroblast cell proliferation assays. Collectively, these results suggest that selected tumor cell lines produce angiogenic factors that induce HUVEC proliferation and subsequently enhance sensitivity to AISPc-PDT. © 1994 Wiley-Liss, Inc.     

Z-3-(2-羟基丁烯基)苯酞的合成研究

研究目的探讨苯酞类天然产物的合成方法及其生物活性。研究方法以邻苯二甲酐为底物，首先引入丁烯基，再进行烯丙位氧化，制得目标化合物。结果通过丁基锂反应，得到了具有药物活性的丁烯基苯酞，然后利用SeO2烯丙位氧化，首次合成了Z－3－（2－羟基丁烯基）苯酞。结论此合成方法原料易得，方法简便，为苯酞类化合物的合成研究提供了一个新的途径。     

Does ageing have an effect on midbrain premotor nuclei for vertical eye movements?

Currently, there is debate in the clinical literature as to whether defects in vertical gaze are a consequence of normal ageing or a component of an underlying neurodegenerative disorder. Although pathological changes have been demonstrated in diseased subjects, no study to date has addressed the question of normal ageing effects. In this retrospective study, we examined 23 neurologically and pathologically normal subjects (age 18-91). Using an unbiased, frame-based sampling method, we quantified neuronal and glial cell densities in 10 young (<50) and 13 aged (>65) subjects in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), the key premotor substrate in the vertical gaze pathway. We found no statistically significant difference in neuronal density, glial cell density, or neuron-to-glial cell ratios between the young and the aged. We conclude, therefore, that neuronal loss, neuronal atrophy, or gliosis in the riMLF are not consequences of normal ageing.     

Single-dose and steady-state pharmacokinetics of sabeluzole in senile dementia of Alzheimer type patients

Summary The single- and repeated-dose pharmacokinetics of sabeluzole have been determined in six elderly patients with [senile] dementia of the Alzheimer type.After a single oral dose of 10 mg sabeluzole, the peak plasma concentration was attained at 1 to 4 h; it averaged 42 ng·ml^–1. On repeated dosing (10 mg b. d.), steady-state was virtually attained after 3 days of treatment. Steadystate mean trough and peak plasma concentrations fluctuated between 53 and 94 ng·ml^–1. The mean terminal half-life after a single dose and at steady-state was of the order of 33 h.Sabeluzole was well tolerated and at the end of treatment, no systematic changes in blood haematology, biochemistry or urinalysis were seen.     

The haemodynamic response to the insertion of the laryngeal mask airway: a comparison with laryngoscopy and tracheal intubation

The haemodynamic response to the insertion of the laryngeal mask airway (LMA) was assessed and compared to that of laryngoscopy and tracheal intubation in a study of forty patients (ASA 1) randomly allocated into two groups and anaesthetised using a standard balanced anaesthetic technique. The results show that the changes in all cardiovascular parameters measured following LMA insertion were significantly less (P<0.05) when compared with those following laryngoscopy and tracheal intubation. We conclude that airway management with the LMA may be used to avoid the haemodynamic response to tracheal intubation where such a response is undersirable.     

缬沙坦与苯那普利拉对SHR肾小球系膜细胞的保护作用

目的：观察ARB－valsartan及ACEI－benazeprilat能否抑制由AngⅡ、PDGF引起的SHR肾小球系膜细胞的增殖与肥大。且比较单用时作用孰强孰弱，联合应用后有无协同效应。方法；采用经典SHR系膜细胞培养技术，细胞中加入各种因子和（或）药物，以^3H-leucine或^3H-thymidine掺入后的cpm值反映蛋白或DNA合成。采用t test检验差异的显著性。结果：1、系膜细胞在AngⅡ、PDGF刺激后引起的增殖与肥大，均可被valsartan及benazeprilat抑制。2、比较发现单一用药在同一浓度下，valsartan较benazeprilat能更有效地抑制细胞的增殖与肥大。3、联合用药在同一浓度valsartan benazeprilat均比单用valsartan或benazeprilat效果明显。结论：1、valsartan与benazeprilat均能抑制SHR系膜细胞的增殖与肥大。2、valsartan在抗系膜细胞增殖与肥大作用稍强于benazeprilat。3、在一定浓度条件下联合用药对抗系膜细胞的增殖与肥大作用，较单一用药效果明显。     

Pharmacology of KB‐R7943: A Na+–Ca2+ exchange inhibitor

The Na⁺–Ca²⁺ exchange (NCX) system plays a pivotal role in regulating intracellular Ca²⁺ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB‐R9743 (KBR) that appears to exhibit selectivity for Ca²⁺‐influx‐mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology of KBR and provide a brief summary of studies with other NCX inhibitors, such as SEA0400 (SEA) and SN‐6 (SN). Potential clinical usefulness of KBR and other NCX inhibitors is still controversial but the reviewed findings may be helpful in designing more selective and clinically useful NCX inhibitors for the treatment of cardiac, neuronal and kidney diseases.