Protective Effects of Antioxidants Against Uraemia-Induced Lipid Peroxidation and Glutathione Depletion in Humans

Abstract: The effects of uraemias and antioxidant therapy for 40 days with vitamin A, vitamin C and vitamin E on blood and erythrocyte sulfhydryl (glutathione, GSH) content and on erythrocyte glutathione-S transferase (GST), glutathione reductase (GSR) and glutathione peroxidase activities were studied in six uraemic patients maintained on haemodialysis. In addition, the effect of antioxidant therapy on erythrocyte lipid peroxidation was determined, and erythrocyte haemoglobin content was measured. Uraemic patients in dialysis exhibited significant decreases in blood and erythrocyte GSH content as well as significant decreases in the activities of GST, GSR and GSH-peroxidase relative to control subjects. Furthermore, the uraemic patients had elevated erythrocyte malondialdehyde levels. Blood and erythrocyte GSH content from uraemic patients was significantly elevated after 20 days of antioxidant treatment and remained elevated thereafter throughout the remaining 20 days of the study (130% and 173%, respectively). Antioxidant therapy also produced significant increases in GSR and GSH-peroxidase activities after 20 days of treatment which remained relatively constant thereafter. No significant change in GST activity was observed. Erythrocyte malondialdehyde levels, as an index of oxidative tissue damage, exhibited a significant decrease (70%) in the patients after 40 days of antioxidant therapy. A gradual increase in erythrocyte haemoglobin content was observed following treatment of the uraemic subjects (45% at day 40). The results suggest that antioxidant therapy may protect against oxidative stress associated with uraemia.     

Microvascular corrosion casting of normal tissue, transitional mucosa and adenocarcinoma in the human colon.

The microcirculatory architecture of normal tissue, transitional mucosa and adenocarcinoma of the human colon was investigated with microvascular corrosion casting (MVCC) combined with scanning electron microscopy (SEM). The study showed that the capillaries within the normal mucosa were arranged in a regular hexagonal pattern around the mucosal glands and that the microvessels of transitional mucosa mostly had lost the typical hexagonal pattern and become slightly wider in diameter. The microvessels in the tumor periphery were increased in number and disorganized, and presented large variation in morphology with claw-like formations, widened sinuses, diverticula and appendixoid patterns. Microvessels were lacking in the central areas of tumors. These morphological alterations may serve as additional indicators of tumor development.     

三个统一:21世纪中医学发展取向的思考

21世纪中医学的发展，面临着理顺民族性表述方式与国际性科学内涵关系的问题，因此必须辩证地把握结构与机能、实证科学手段与人文精神、过程与结果之间的谐调统一，这样既符合中医学术体系特征，又能与当代生命科学研究保持一致。     

T cell adhesion to extracellular matrix molecules secreted by endothelial cells cultured on a substrate of type IV collagen

T cell emigrating from the bloodstream into lymphoid organs or sites of inflammation in the connective tissue must adhere to, and traverse, the subendothelial basement membrane (BM). The goal of the current investigation was to develop a method to study the adhesion of T cells to endothelial cell (EC)-derived extracellular matrix (ECM) as a model for the interaction of T cells with the subendothelial BM in vivo. To be certain that we were truly measuring T cell adhesion to ECM molecules secreted by the EC, it was necessary to culture the EC on a substrate to which T cells could not attach. Non-tissue culture-treated microtiter plate wells which had been coated with type IV collagen (tIVC), a major constituent of BM in vivo, were found to be suitable for this purpose since EC, but very few T cells, adhered to such wells. After incubating the EC on a substrate of tIVC in non-treated wells for a period of 48 h, the EC were gently removed from their underlying ECM and T cell adhesion to that ECM was examined. Using this system, it was observed that approximately 15-40% of human peripheral blood T cells specifically adhered to ECM molecules produced by the EC. This method should be useful as a model for the interactions of T cells and other leukocytes with the vascular BM in vivo.     

Phase II trial of gallium nitrate,amonafide and teniposide in metastatic non-small cell lung cancer

Summary Fifty-five patients with metastatic non-small cell lung cancer (NSCLC) were entered into this phase II randomized study for evaluating three new agents: gallium nitrate, amonafide and teniposide. The patients had to have ECOG performance status 0 or 1, no prior chemotherapy, and adequate hematological, hepatic and renal functions. Forty-seven patients were eligible and evaluable. Fourteen were randomized to receive gallium nitrate, 18 to amonafide and 15 to teniposide. Seventy-four percent of eligible patients were male. The majority of patients (89%) had an ECOG performance status 1. ECOG grade 4 toxicity occurred twice in patients on gallium nitrate, seven times on amonafide and 18 times on teniposide. The cause of death was attributed to amonafide in one patient (from sepsis) and to teniposide in two patients (due to infection and leukopenia). There was no objective response in all the patients entered. The overall survival times ranged from 2 weeks to 156 weeks with a median of 23 weeks. There were no survival differences among the three treatment arms. We conclude that gallium nitrate, amonafide and teniposide are inactive in metastatic NSCLC and do not warrant any further testing in this disease.The contents of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.     

Acute appendicitis—a clear-cut case in men,a guessing game in young women

Background: The aggressive surgical approach to patients suspected of having acute appendicitis for fear of perforation, and the inaccuracy of available diagnostic methods lead to an unacceptably high negative appendicectomy rate, especially in young women, in whom gynecological disorders frequently mimic appendicitis. Our objectives were to determine the value of diagnostic laparoscopy in women of child-bearing age to reduce the number of negative laparotomies and establish the correct diagnosis to allow prompt and appropriate treatment. Methods: 161 consecutive adult female patients under 50 years of age with a clinical diagnosis of acute appendicitis underwent diagnostic laparoscopy prior to the planned appendicectomy. If an inflamed appendix was found, appendicectomy was usually done through a muscle-splitting McBurney incision. Other diagnoses were treated accordingly. A normal appendix was not removed. Results were compared to a group of 42 similar patients in whom the laparoscopy was omitted for various reasons, to 23 postmenopausal women, and to all 137 male adults, directly operated by the McBurney approach. Results: After laparoscopy, 55% of the patients required appendicectomy for appendicitis while in 23% a gynecological diagnosis was made in spite of previous examination by a gynecologist. Fourteen percent had a negative laparoscopy. There were no false-negative results. The negative appendicectomy rate after laparoscopy was 5% due to two false positives and eight laparoscopy failures. In the group of fertile females who escaped laparoscopy the negative appendicectomy rate was 38%. The respective rates for postmenopausal women and men were 4% and 8%. Conclusions: All women of child-bearing age suspected of having acute appendicitis should undergo diagnostic laparoscopy prior to the planned appendicectomy, regardless of the certainty of the preoperative diagnosis. This is currently the only way to reduce the negative appendicectomy rate and establish a correct diagnosis allowing prompt and appropriate treatment. In male patients and postmenopausal women one may proceed directly to emergency appendicectomy.     

肝素雾化治疗小儿哮喘性疾病的疗效观察

应用肝素雾化治疗小儿哮喘性疾病（包括以喘为主的支气管肺炎）１６例，其咳喘症状消失和肺部体征消失时间校对照组快，总显效率高。文中还就７例肝素雾化治疗前后血气结果对照，进一步阐述肝素雾化有利于改善通气功能，促进二氧化碳排出和炎症吸收，从而解除支气管痉挛的机理。具有疗效显著，安全可靠，无任何副作用的特点，值得临床推广应用。     

Quantitative autoradiography of 11 different transmitter binding sites in the basal forebrain region of the rat--evidence of heterogeneity in distribution patterns.

The distribution of 12 different binding sites for acetylcholine, L-glutamate, GABA, 5-hydroxytryptamine, dopamine and noradrenaline was measured with quantitative receptor autoradiography in four regions of the rat basal forebrain (medial septal nucleus including vertical and horizontal limbs of the diagonal band of Broca, magnocellular preoptic nucleus, substantia innominata and basal nucleus of Meynert, ventral pallidum). L-Glutamate binding sites represent the largest portion of the analysed receptors in all regions, followed by muscarinic2, 5-hydroxytryptamine1 and GABAA receptors. Muscarinic1, dopamine1, dopamine2 and 5-hydroxytryptamine2 receptors and alpha 1-, alpha 1A- and alpha 1B-adrenoceptors represent the minor receptor populations. The largest portion of the dopamine receptors is represented by the dopamine1 subtype, and the alpha 1B subtype dominates the alpha 1-adrenoceptor group. A heterogeneity of the distribution patterns of the different receptors throughout the basal forebrain regions is found. A comparison of the patterns shows that alpha 1-adrenoceptors have a similar regional distribution to that of the muscarinic2 receptors, but both receptor types have reciprocal distributions compared with the 5-hydroxytryptamine1 receptors. The results indicate that one transmitter may exert different effects in the basal forebrain regions depending on the densities of the respective receptor subtypes. Moreover, similar or reciprocal distribution patterns of some, but not all, analysed receptors point to a non-random association (co-distribution) of the different transmitter systems in the basal forebrain regions.     

THE SCIENCES OF CLINICAL PRACTICE

The Robert Wood Johnson Commission on Medical Education focused on evidence that, in the midst of the genetic revolution in medicine, medical students all too often are not engaged by the science component of their education. Medical education is being driven by social as well as these intellectual forces to make fundamental changes. In the USA, the rich array of scientific talent can be used more effectively, and there is a new significance for the behavioural, social, probabilistic, and information sciences. The Report discusses the general changes under way in the USA and includes examples from the eight schools in the Robert Wood Johnson Foundation's Preparing Physicians for the Future: A Program in Medical Education .
Another report explores the reasons why the general changes under way in North American medical education are difficult to bring about. Educating Medical Students is the report of the Assessing Change in Medical Education: The Road to Implementation (ACME-TRI) project of the Association of American Medical Colleges. This project, funded by the Charles E. Culpeper Foundation, explored the recurring problems in medical students' education that have been reported from the 1930s. The ACME-TRI report documents that most medical schools have not solved these recurring problems, summarizes the schools' views of the barriers to solving these problems, and identifies strategies to assist schools in overcoming or minimizing the barriers they have identified.
Together, the Robert Wood Johnson Commission report and the ACME-TRI report provide a context in which to consider the complex issues facing medical education in the 21st century.