[Clinical aspects of thrombelytic therapy using streptokinase].
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Biomedical subjects
Publications and source records attributed to G Vogel.
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In order to complete previous results of the efficacy of the horse chestnut saponin escin, its activity was tested on two further models of inflammation: the rat serous peritonitis provoked by i.p. injection of formalin solution, and the rat serous pleurisy provoked by intrapleural injection of Evans Blue/carrageenan. The results showed escin to be an anti-exudative substance with regard to its exudation inhibitory effect determined by the reduction of exudative fluid. As to peritonitis the diminution of protein permeation into the abdominal cavity was determined: with increasing doses escin tended to prevent more efficiently the diffusion of small molecules than the permeation of large molecules. The hypothesis that escin has an effect on the vascular walls in the sense of a "sealing" effect on the capillaries was tested on the following model: the permeability of the plasma-lymph barrier of the hind leg of the rabbit was enhanced by injection of bradykinin. Escin antagonised the bradykinin effect dose-dependently determined by the depression of the raised lymph-flow by about 70%.
1. By means of an indirect immunofluorescent technique with reference to Weller and Coons (1954), modified for spermatozoal immunofluorescence we found antibodies against spermatozoa in the sera of: 6 of 35 female partners of couples with unexplained infertility, 5 of 35 male partners of couples with unexplained infertility, 8 of 40 prostitutes, 8 of 18 men after orchitis and vasoresection. In contrast to these findings the sera of 20 fertile women, 25 fertile men, and 20 virgins showed negative results with the test mentioned above. 2. The site of the antigen-antibody reaction was mainly the spermatozoal tail and in the second place, the equatorial segment. 3. The immunoglobulins primarily belonged to the IgG and secondly to the IgA class. 4. Our results differ partly from the findings made by other authors perhaps on account of methodical differences. 5. The clinical relevance and associated problems are discussed.
The effects of three oral doses of bedtime triazolam (0.25 mg, 0.5 mg, and 1.0 mg) a new benzodiazepine, on the laboratory sleep of insomniacs were studied in a double blind design which used the following 14 consecutive night schedule: 1-4 placebo; 5-11 drug; 12-14 placebo. Effects on sleep were measured objectively by conventional EEG/EOG/EMG sleep recordings and subjectively by questionnaires administered each morning. Side or toxic effects were assessed by screening physicals and questionnaires administered each morning and each evening and by a comparison of the prestudy vs. end-study physical exams and clinical lab tests. At the 0.5 mg dose triazolam significantly reduced several objective and subjective measures of insomnia. It had lesser effects at the 0.25 mg dose and equal or greater effects at 1.0 mg dose. There were no remarkable side or toxic effects at any dose.
Phallolysin, a protein from Amanita phalloides with cytolytic effects in vitro, was highly toxic when given intravenously to rats, mice, rabbits and guinea pigs: i.v. LD50 in rats was 85 Haemolytic Units (HU)/kg, corresponding to 0.05 mg protein/kg b.w. Death ensued from intravascular haemolysis. In rats large doses (600 HU/kg b.w.) caused cardiac death within a few minutes due to liberation of potassium from lysed cells. The serum contained lethal concentrations of potassium. There was also histological evidence of severe renal damage as a result of the haemolysis. In addition, phallolysin directly damaged the isolated guinea pig heart and the isolated rat liver, probably by its action on membranes. Given by mouth, phallolysin was not poisonous to rats.
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The influence of movements of fluid from the blood into the bowel lumen (solvent drag) on absorption of drugs from the intestine was studied in conscious rats with surgically implanted duodenal tubes. The drugs were given to the rats by intraduodenal instillation either in isotonic saline or in solutions of mannite having twice or three times the osmotic pressure of the blood. The instillation of hypertonic mannite solutions leads to concentration-dependent exsorption of fluid. The drugs tested were atropine and azoniaspiro compound XVII (azoniaspiro[3alpha-benziloyloxy-nortropan-8,1'-pyrrolidine]-chloride), both of which are poorly absorbed, and phenobarbital and nicotine, both of which are well absorbed. The criteria used to assess the rate of entry of the drugs into the blood stream were "efficacy" and "toxicity". In the case of atropine, azoniaspiro compound XVII and nicotine mortality rate and survival time were measured, while in the case of phenobarbital the latent period between instillation of the solution and onset of the hypnotic effect was used. As the tonicity of the solution was raised, so the concentration-dependent "efficacy" and "toxicity" declined. This meant that the latent period after instillation of phenobarbital lengthened, while after instillation of atropine, azoniaspiro compound XVII and nicotine in solutions of increasing tonicity the mortality fell and survival was prolonged. The only exception to this generalization was found when azoniaspiro compound XVII was instilled in triple strength mannite solution. The reasons for this exception were not ascertained. From the results it is concluded that "solvent drag" is an important factor in the absorption of drugs from the intestine. A stream of fluid passing into the lumen interferes with absorption, and this is reflected in the diminished "efficacy" and "toxicity" of the drug. Another factor which may influence the absorption of the drugs tested is the fall in concentration resulting from the inflow of fluid into the bowel lumen. This tends to flatten the concentration gradient between the bowel lumen and the blood and therefore delays absorption.
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The following experiments were carried out on the question of the "predictability" of the effect of drug combinations. A methanol extract from Viscum album causes a rise in coronary perfusion in isolated and perfused (Langendorff's method) guinea pig hearts. Administration of a methanol extract from Crataegus oxyacantha results not only in a rise in coronary perfusion, but also in a positive inotropic effect. Combined application of the drugs leads to a pure addition of effects, which are therefore "predictable". Extracts from Rhamnus frangula, Rheum sinens. and Senna lead to a dose-dependent reduction in the gastro-intestinal passage time. Combining the three extracts results in a pure addition of the effects. An extract from Potentilla anserina, which when given alone lengthens the gastrointestinal passage time, antagonises the laxative effect of extracts from Rheum sinens., Rhamnus frangula and Senna. All the effects we tested in the area of the gastro-intestinal tract behaved in a purely additive way and were therefore "predictable". When given separately the ethereal oils menthol, oleum juniperi, borneol and eugenol as well as dehydrocholic acid-Na-salt and alpha-naphthyl acetic acid-Na-salt cause, in rats, a dose-dependent increase in bile flow. Combining two or three of these substances results in a pure addition of the effects. The effects of all the test substances were therefore "predictable". When given separately valepotriate, morphine, scopolamine, ajmalicine, rescinnamine, reserpinine and reserpine, as depressants of the central nervous system (CNS), lead to a dose-dependent lengthening of hexobarbital-induced sleeping time in mice. However, when combined, these substances lead to a lengthening of hexobarbital sleeping time which is well above what was to be expected following application of the single substances. So, it can happen that the combination of the two single doses which, when taken separately produce no effect, leads to a lengthening of hexobarbital-induced sleeping time by more than 100 percent. In the case of CNS depressants, it is therefore true to say that their effect, when given in combination, was "unpredictable". It can be seen from these findings that, at least in the case of the tested extracts and single substances, which are all of plant origin, the "predictability" of the effect of the test substances in combination is the rule, and the "unpredictability" the exception. In addition the investigations may give further information concerning the methods as to how the question of "predictability" can be studied experimentally.
The hepatoprotective action of silymarin, the active principle extracted from the fruit of Silybum marianum (L.) Gaertn., in animals (dogs, rabbits, rats, mice) intoxicated with phalloidine is evident, both after protective and curative treatment. A dose of 15 mg/kg of silymarin protects every animal when given 60 min before the toxin. When injected 10 mim after phalloidine, a dose of 100 mg/kg of silymarin again provides total protection. However, as the time span between administration of the toxic substance and start of treatment increases, so the efficacy of silymarin decreases; after 30 min its curative effect is negligible. The histochemical and histoenzymological studies show that during intoxication of the mice by phalloidine, silymarin inhibits the effect of the toxic substance and regulates the functions of the hepatocyte, when given either 60 min before or 10 min after phalloidine.
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