A remarkable blood pressure rise associated with elevated plasma catecholamines was observed at the onset of arrhythmia when a toxic dose of ouabain was administered into dogs. The mechanism of this phenomenon may be explained as the release of endogenous catecholamines from the adrenal glands and peripheral sympathetic nerve endings brought about by a toxic dose of ouabain. Central catecholamine does not appear to be related with the above phenomenon.
Hemolytic anemia was induced in dogs with repeated intravenous injections of p-methylphenylhydrazine (MPH), phenylhydrazine (PH) or nitrite for five days (10 mg/kg day each). Both erythrocyte number and hemoglobin concentration were decreased more by MPH than by PH or nitrite. Reticulocytes were also increased more by MPH than by PH or nitrite. Phagocytosis of MPH-injured erythrocytes by macrophages was observed in vitro. Erythrocyte number was decreased about 30 % by MPH upon repeated intraperitoneal administration of anti-macrophage serum compared to about 45 % effect without anti-macrophage serum. Those results show that MPH-induced hemolytic anemia is caused by macrbphagic phagocytosis of MPH-injured erythrocytes.
Hepatic injury and hepato-accumulation of (+)rugulosin, an anthraquinoid mycotoxin from Renicillium rugulosum Thom, were investigated in mice. Subcutaneously administered (+) rugulosin to ddYS mice induced an elevation of glutamate-poxaloacetate transaminase in the serum, a depression of mitochondrial function and an accumulation of monoribosomes in the liver. Tracer experiments revealed that the administered toxin preferencially accumulated into the liver, especially into the mitochondrial and microsomal fractions. Lethal toxicity test as well biochemical assay revealed that (+) rugulosin is a slow acting hepatotoxin.
The quantitative analysis of nociceptive reaction produced by i.m. injection of some algesic derivatives of penicillin and cephalosporin was carried out with rabbits. A half ml of the drug solution was injected into the antebrachial muscle of rabbits, and a characteristic behavior was scored by measuring the length of time during which the animals lifted a forelimb of the injected side. Since the response to 25% carbenicillin solution was reduced either by premedication with 1 or 3 mg morphine/kg i. v.in a dose dependent manner or by utilizing 0.5% lidocaine solution as a solvent for carbenicillin, the observed behavior may be regarded as the manifestation of pain experience in the animals. Carbenicillin, sulbenicillin and cephalothin produced the pronounced pain response, while cephazolin was relatively less noxious in rabbits. Timoxicillin, a new wide-spectrum penicillin, was the least painful among the sodium salt of antibiotics tested. Cephaloridine, which is not a sodium salt but a betaine form, showed no detectable pain response. The present results are consistent with many clinical experiences with respect to pain produced by these intramuscular remedies. The method described here seems useful for screening the compounds which are presumed to possess algesic activity.
The time course of concentrations of glutamate in plasma was examined following a single dose of 1 g/kg body weight of monosodium glutamate (MSG) by intraperitoneal or subcutaneous injection or peroral intubation in 10-day, 23-day and 4-month-old mice of ICR strain. Ad libitum dietary administration in shorter period of time and effects of food accompaniment were also investigated. Levels of plasma glutamate rapidly elevated and reached maximum from 10 to 30 minutes after administration of an aqueous solution of MSG and then returned to normal levels by 90 minutes. Peak values in peroral intubation were significantly lower than those in intraperitoneal or subcutaneous injection, especially in infants and weanlings. Food accompaniment markedly suppressed elevations of plasma glutamate. In dietary administration, maximum levels of plasma glutamate, which were remarkably low as compared with those in food accompaniment, never exceeded 5-fold of base-line values.