Dose related effect of endotoxin on the reticulo endothelial system (RES), the sinusoidal cells in the liver, and on hepatocytes from rats.
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Biomedical subjects
Publications and source records attributed to N Freudenberg.
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Escape of endotoxin from the intraintestinal site was investigated in experimental models of intestinal ischemia and during intraabdominal infection in rats. Following the instillation of Salmonella abortus equi endotoxin (S-form) into the proximal large bowel, we recorded the presence of the lipopolysaccharide molecule in the bowel wall, the intestinal lymph nodes, the peritoneal cavity, and in the liver sinusoids by immunohistochemical methods. At 3, 6, 12, 24, and 48 hr after the operative procedure, peritoneal fluid, blood, and tissue samples were taken. Survival rates were similar between the two test-groups (occlusion of the superior mesenteric artery [SMA] and cecal ligation and puncture [CLP]) and were not influenced by the amount of the injected endotoxin. There was no detectable morbidity in the sham-operated control animals with endotoxin doses up to 20 mg. Endotoxin could only be detected at 24 and 48 hr in the SMA group in the liver as well as in the peritoneal sediment and in intestinal lymph nodes. CLP and control samples remained negative throughout the observation period. Bacteria were found intraperitoneally within 12 to 24 hr in the SMA group and within 3 to 12 hr in the CLP group.
Restenosis and occlusion of atherosclerotic arteries are prevented by a newly developed arterial prosthesis consisting of a pliable and elastic wire mesh tube positioned to the balloon of an angioplasty catheter. As the balloon is inflated the prosthesis dilates and provides the arterial wall with a new mechanical support. This new device was successfully implanted in ten patients having an iliac artery stenosis and improved the therapeutic result of the preceding angioplasty. There were no complications.
A new cutting biopsy needle has been used to obtain histologically useful material while causing the minimum of trauma. It permits biopsies of organs, but its small external diameter of 0.8 or 0.95 mm makes it possible to carry out transperitoneal puncture of the stomach, colon or liver and of the retroperitoneal space, using a ventral approach. Tissue samples were obtained in 96% of 63 patients. The risk of complications is no higher than for conventional needles used for cytology. The accuracy with which the material can be obtained is therefore the most important problem. The position of the area to be biopsied should determine whether the biopsy is to be aided by sonography or CT. Biopsies of organs can be appropriately carried out under ultrasound control, but processes in the pelvis and in retroperitoneal-paravertebral and extra-peritoneal positions are best biopsied under CT control.
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The view that individual behavior change is the primary goal of health education presents several serious problems. Although individual behavior does contribute to health and disease, social organization is perhaps a more powerful influence. The use of behavior change as the primary tool for health education raises grave ethical issues. Health education which seeks to change individual behavior has also failed to have a significant impact on public health. An alternative strategy is health education for social change. The goal of this approach is to involve people in collective action to create health promoting environments and life-styles. Several contemporary models for and principles characteristic of health education for social change are described.
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There was a marked decrease in the RES phagocytic activity during the first 12 hours after injection of high concentrations of endotoxin in rats. Phagocytic activity then increased considerably, reaching maximum values on days 3 to 5 and it was still higher than in control animals 20 days later. Parallel studies on 3H thymidine incorporation showed a significant increase in the rate of DNA-synthesis of reticulum cells of the liver during the 5 days period following endotoxin injection. Peak values were obtained on day 2 when the number of labelled cell were 50 times higher than in the controls. A likely reason for the increased DNA-synthesis is a repair of RES following endotoxin induced damage but it may also represent an endotoxin induced proliferation of reticulum cells that may at least partly account for the enhanced phagocytic activity.
Aortic endothelium of normal and endotoxin treated rats was investigated in "Häutchen" preparations by light microscopy, autoradiography, DNA cytophotometry, and enzyme histochemistry. In the endothelium of control rats the following cell populations were found: 1. Endothelial cells (90% of all cells in endothelium), characterized by the alignment of the longitudinal axis of their nuclei, their light microscopic morphology, their DNA content resp. DNA synthesis, and by their enzymatic activity; 2. mononuclear cells (10% of all cells in endothelium), identified as mature blood monocytes, mononuclear phagocytes (macrophages), and as lymphocytes; 3. granulocytes (less than 1% of all cells in endothelium). The presence of mononuclear cells and granulocytes in the normal endothelium appears to be the expression of a physiological repair process in endothelium. After endotoxin application one can observe an endothelial damage and then a repair process. During the repair of endothelium the following processes occurred: An increase of DNA synthesis particularly of endothelial cells, an aggregation of platelets on the endothelial surface, an increase in number of granulocytes and at last an increase in number of activated mononuclear cells. Participation of mononuclear cells in the physiological as well as in the pathological repair process of endothelium was shown by the present investigation. The process of transformation of mononuclear cells into endothelial cells is discussed at the same time.