Biomedical subjects
Publications and source records attributed to L Bertók.
Five mg of bacterial endotoxin (LPS) can provoke a serious leukocytic pulmonary infiltration in rats. The same dose of radiation-detoxified LPS (RD-LPS; 150 kGy 60Co-gamma irradiated) can produce only slight pulmonary infiltration. However, 100 micrograms RD-LPS--as pretreatment--can prevent the LPS-induced leukocytic infiltration of the lung.
150 min ligature of the superior (cranial) mesenteric artery (intestinal ischemia) significantly decreases serum T4 level and completely inhibits the response of the thyroid gland to exogenous TSH in rats. 300 min ligature of the hind limbs (tourniquet shock) decreases serum T4 level and the T4 response of thyroid gland to exogenous TSH in rats. The probable reasons for altered function of the thyroid gland in enteroendotoxemic shock conditions are discussed.
Chemiluminescence (CL) of peritoneal cells was investigated one and five days after injection of toxic and radio-detoxified endotoxin. The CL was triggered by toxic and radio-detoxified endotoxin. The radio-detoxified endotoxin has less pronounced in vivo activating effect than the toxic endotoxin. As triggering agent the toxic endotoxin was more effective than the radio-detoxified endotoxin. However, the radio-detoxified endotoxin has preserved some in vivo activating and in vitro triggering effect.
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Endotoxin (LPS) and radio-detoxified endotoxin (RD-LPS: 150 kGy 60Co-gamma irradiated) preparations were compared in mice (C57Bl X CBA: F1/Rapo) for capacity to enhance the immune response against sheep red blood cells and to induce the production of antibody against autologous (bromelain-treated) erythrocytes. As RD-LPS retains its capacity to stimulate immune response against heterologous antigen, it may be used as an immuno-adjuvant. The LPS preparation gave rise to a significant increase of autoreactive cells. However, RD-LPS activated the autoantibody forming cells only to a very small degree.
Circulating endotoxin is an important factor in the pathogenesis and clinical symptoms of endotoxin shock. The effect of extracorporeal activated charcoal hemoperfusion was investigated in experimental endotoxin shock of dogs produced by i.v. injection of Escherichia coli 089 endotoxin (1 mg/kg body weight). The endotoxin was labeled with 99mTc. The aorta and vein cava caudalis of anesthetized dogs were cannulated through the arteria and vein femorales. The cannulae were contacted to the hemoperfusion charcoal cartridge. The efficiency of hemoperfusion was tested from the blood samples, and the endotoxin content of blood was measured biologically (in lead acetate-treated rats) and isotopically (99mTc radioactivity) at 15, 30, 60, 90, and 120 min after injection. It was demonstrated that extracorporeal activated charcoal hemoperfusion can eliminate the majority of circulating endotoxin from the blood within 30 min.
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The immunity enhancing adjuvant activity of radiodetoxified endotoxin (RD-LPS) on the potency of "C" type foot-and-mouth (FMD) vaccine was tested in different animal species. The suitable quantity of RD-LPS (20 micrograms per mouse) adjuvated a small than a high dose of FMD antigen. In cattle and sheep the adjuvant effect of oil + RD + LPS surpassed only slightly that of oil alone. The effect of RD-LPS in the pig was very pronounced when applied in small doses but further studies in larger animal populations have to confirm this result.
High incidence of cardiovascular collapses during clinical treatments with the cytostatic Vinca derivative formyl-leurosine (F-leurosine) prompted efforts to analyse in experimental models the haemodynamic mechanisms underlying the cardiodepression induced by large doses of the drug. A variety of cardiovascular variables was measured in 38 dogs narcotized with sodium pentobarbital. It was found that i.v. administration of F-leurosine (2 mg/kg) elicits, after a very short latency (less than 5 min), considerable decreases of arterial and pulmonary blood pressure, ventricular contractile force, cardiac output, ventricular filling pressure, coronary blood flow, and myocardial O2 consumption. Calculated systemic and pulmonary vascular resistance increased, while coronary resistance did not change. The later phase of F-leurosine action (greater than 1 hour) was associated with a permanent circulatory depression, a compromised coronary autoregulatory capacity, and serious histological injuries in the heart. Autonomic blocking drugs could not prevent these effects. It is concluded that the F-leurosine-induced rapid primary (pharmacologic) depression is followed by toxic manifestations of a more serious, secondary cardiac damage caused by the direct action of the drug cellular membranes.
A bacterial inoculum was positioned intraperitoneally and retroperitoneally in animals who had been treated with various antibiotic programs. The results indicate that the retroperitoneal tissue is more resistant to severe infectious complications than the general peritoneal cavity.
The influence of different endotoxins (lipopolysaccharides, LPS) obtained from Serratia marcescens 08, Escherichia coli 089, and their derivatives, detoxified either by partial hydrolysis or irradiation, on serum and hepatic lipids and on serum lipase activity in C57Black mice was studied. Endotoxic LPS elevated the serum total lipids and lipoproteins, particularly the very-low-density lipoproteins, and induced a reversible accumulation of triglycerides in the liver. Since nontoxic preparations did not cause such alterations, it is assumed that the toxicity of LPS is an essential factor in causing lipid metabolism disorder. A nearly identical increase in the lipase activity was detected in 5 to 10 hr in the sera of experimental animals treated by both toxic and nontoxic preparations. Results indicated the potential advantage of using detoxified derivatives of bacterial endotoxins in human therapy.
Cytotoxicity of a mixed pyrogen preparation and its components as well as native and radiodetoxified lipopolysacharides (LPS) was determined with established HEp-2 cell cultures and by measuring plating efficiency. This proved to be more sensitive to the damaging effect of both microbe-containing LPS (Escherichia coli) and purified LPS. Microorganisms without this compound (Lactobacillus casei, Streptococcus faecalis) seem to be more infifferent on cells, even Saccharomyces cerevisiae has a marked augmenting effect on cell plating. Divergence in null-toxicity between the established cultures and plating efficiency makes it possible to presume that the primary effect of microorganisms on epithelial cells is medited by LPS, and the subsequent liberation of lysosomal proteinases is responsible for major biological effects.
We have demonstrated that, while the shock-inducing dose of parent (toxic) endotoxin significantly decreases the serum T4 level of rats and inhibits the T4 response given to exogenous thyroid stimulating hormone (TSH), the radio-detoxified (60Co-gamma, 150 kGy) endotoxin preparation does not inhibit the response to exogenous TSH and decreases serum T4 level to a lesser extent than untreated endotoxin.
Radio-detoxified endotoxin (Tolerin), produced by 60Co-gamma irradiation of Escherichia coli 089 endotoxin, can protect dogs against the acute cardiotoxic side-effects of formyl-leurosine, a semi-synthetic Vinca derivative with promising antineoplastic potency. Formyl-leurosine induces a rapid decrease in arterial blood pressure and diminishes the contractile force of the myocardium in the anaesthetized dog. These responses indicate a direct pharmacologic relaxant effect of the drug on the heart and vasculature smooth muscle. The early cardiovascular depression is of short duration and is unaffected by Tolerin. Tolerin can prevent, however, the secondary, more dangerous phase of circulatory depression that is associated with the severe cardiotoxic manifestations of the drug, as demonstrated by hemodynamic and morphologic (light and electronmicroscopic) patterns.
E. coli endotoxin (LPS) depresses the hepatic microsomal mono-oxygenase activity. Radio-detoxified LPS (TOLERIN: 60 Co irradiated endotoxin preparation) decreases this biotransforming activity to a smaller extent. Phenobarbital, an inducer of this mono-oxygenase system, failed to induce in LPS-treated animals. In radio-detoxified LPS-treated rats, phenobarbital induced the mono-oxygenase and almost fully restored the biotransformation.
The effects of parent endotoxin and radiodetoxified endotoxin on human peripheral lymphocytes were compared in experiments in vitro. Radiodetoxified endotoxin is able to exceed the degree of the stimulation induced by parent endotoxin and its stimulatory effect. At the same time, no change was observed in the presence of autologous serum. Radiodetoxified endotoxin did not inhibit the phytohaemagglutinin-induced proliferative response.
A 18 mg/kg dose of dianhydrodulcitol, a lymphotropic cytostatic agent produced the same death rate among germfree as a 12 mg/kg dose did in conventional mice. Pretreatment with the same dose of an irradiated immunomodulatory endotoxin preparation had increased the sensitivity to these dianhydrodulcitol doses in the same degree in germfree as in conventional mice. A study of the lymphoid organs and the intestinal wall indicate that both in germfree and conventional mice the dianhydrodulcitol sensitivity increasing effect of the endotoxin preparation was due to its stimulation of the lymphoid system. The higher resistance of germfree mice to dianhydrodulcitol is ascribed to their lack of a normal intestinal flora.
The effect of the endotoxin of a noncapsulated Haemophilus influenzae strain isolated from bronchitis was studied on the respiration of mice. Inhalation of the H. influenzae endotoxin resulted in heavy attacks of dyspnoea with non-specific histological changes in the lung. The endotoxin elicited no direct response in isolated organs, but produced cytotoxic changes in HEp-2 tissue cultures. The experiments led to the conclusion that the clinical signs and the histological changes may be explained by the direct damaging effect of endotoxin on the cells and by the released mediator substances.