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Biomedical subjects

S Kanoh

Publications and source records attributed to S Kanoh.

At least 127 records · Page 7Linked to original sources

Interactions between bacterial pyrogen and proteolipid extracted from the cerebrum (I).

As proteolipid of the myelin sheath and its parent glial membrane may possible interact with bacterial pyrogen (lipopolysaccharide, LPS) during penetration into the brain, we investigated the interaction of LPS with proteolipid derived from the cerebrum of rabbits, rats and chickens. Intravenous administration of LPS (1 microgram/kg) produced a febrile response in rabbits, but not in rats and chickens. Marked hyperthermia was observed in these three species after intracisternal administration of LPS (0.01-0.1 microgram/kg). Dinitrophenol (30 mg/kg s.c.) induced a high fever in these three species tested, particularly in the chickens. The pyrogenicity of LPS given intravenously to rabbits was inactivated by incubation of LPS with proteolipid in vitro. Inactivation effects of proteolipid extracted from the three species was in the order of: chickens, rats and rabbits. In rats, the inactivation effects of proteolipid from the adult animal were more potent than in the case of newborn animals. The febrile response induced by dinitrophenol and leucocytic pyrogen in rabbits, however, was not suppressed by incubation with proteolipid extracted from the rabbit brain. These results suggest that proteolipids do play an important role in the mechanism of penetration of LPS into the brain.

Animals↗

Interactions between bacterial pyrogen and proteolipid extracted fom the cerebrum (II).

Our previous finding that the cerebral proteolipid could inactivate the pyrogenicity of lipopolysaccharide (LPS) in vitro was also studied by Sephadex LH-20 column chromatography and the following results were obtained. When rabbit cerebral proteolipid was chromatographed, two main protein peaks were obtained. One appeared in the chloroform (C)/methanol (M) 6:1 and the other C/M 4:1 effluent, designated as fraction IV and fraction V, respectively. When the incubation mixture of proteolipid and LPS was chromatographed, a new protein peak appeared in the C effluent. The new protein peak was suggested to be a complex of proteolipid protein and LPS, because pyrogenicity could be detected in the protein fractions only after treatment with 2% SDS. Fraction V but not fraction IV inactivated the pyrogenicity of LPS in vitro. By re-chromatography of the incubation mixture of fraction V and LPS, a complex of protein and LPS was also eluted in the C effluent. On the other hand, by rechromatography of the incubation mixture of fraction IV and LPS, such a complex was not detected in the C effluent. The present results suggest that the proteolipid apoprotein eluted in the C/M 4:1 effluent on a Sephadex LH-20 column plays an important role in the inactivation of the pyrogenicity of LPS.

Animals↗

[The antipyretic effects of aminopyrine and sodium acetylsalicylate on endotoxin-induced fever in rabbits (author's transl)].

The antipyretic effects of aminopyrine and sodium acetylsalicylate on endotoxin-induced fever in rabbits were studied relative to the route and dose of administration. Intravenous administration of aminopyrine produced a marked antipyretic effect, intracisternal administration produced a lesser effect and i.v. was the effective route. Similar results were obtained in the nonfebrile rabbits. On the contrary, the intracisternal administration of sodium acetylsalicylate reduced the body temperature to the same degree both in febrile and nonfebrile rabbits, but sodium acetylsalicylate given i.v. to nonfebrile rabbits did not reduce the body temperature. 4-aminoantipyrine and N-acetyl-4-aminoantipyrine, the major metabolites of aminopyrine had a lesser effect in the febrile rabbits. Antipyretic effects of sodium salicylate, the metabolite of sodium acetylsalicylate were similar to the effects of sodium acetylsalicylate. These data suggest that the antipyretic effects of aminopyrine may not be involved in the CNS, while the antipyretic effects of salicylate may be due to a direct action on the CNS.

Aminopyrine↗

Development changes in the febrile response to endotoxin in rabbit.

The pyrogenicity of E. coli endotoxin (lipopolysaccharide, LPS) was measured at both 25 degrees C and neutral temperatures (Tn) in day -1 to adult rabbits. Intravenous injection of endotoxin (0.5 micrograms/kg) produced febrile response at Tn in day -1 rabbits, but not at 25 degrees C. A similar response was observed when endotoxin was injected s.c. (1.0 micrograms/kg) or intracisternally (0.0001 micrograms/kg). The mean magnitude of the rise of rectal temperature increased with the advance of age. Propranolol abolished the endotoxin-fever in day 3 rabbits. The inhibitory effect of propranolol was incomplete in day 14 rabbits and was not seen in day 28 rabbits. The inhibitory effect of phentolamine was not observed in day 3 and day 28 rabbits, but the blocker reduced the febrile response in day 14 rabbits. No shivering activity was evident in day 3 rabbits after injection of endotoxin. In the day 7 and 14 rabbits, shivering was less significant and of shorter duration than in the case of day 28 rabbits. The endotoxin caused no significant decrease in ear skin temperature in day 3 rabbits. A decrease in ear skin temperature was observed in rabbits older than 14 days. Thus, pyrogenic sensitivity is apparent even in day -1 rabbits. The mechanism of the heat production underlying endotoxin-fever gradually shifted from the nonshivering thermogenesis mediated by catecholamines to shivering thermogenesis during the first month of life.

Animals↗

[Acute and chronic effects of pyrogen on mitochondrial monoamine oxidase (MAO) activity and respiratory activity in the rabbit liver (author's transl)].

Pyrogen acted on mitochondrial outer membrane or structure to increase the penetration of substrate to mitochondrial MAO. Mitochondrial respiratory activity did not change significantly after acute administration of pyrogen. With chronic administration of pyrogen, the ADP/O ratio of liver mitochondria was increased. These results suggest that the acute administration of pyrogen affects the mitochondrial outer membrane, while the chronic administration affects both the outer and inner membranes.

Animals↗

[Studies on the relationship between the endotoxin induced fever and the antipyretic effect of reserpine in rabbits (author's transl)].

It has been well documented that fever could be mediated with endogenous pyrogen released from reticuloendothelial system(RES) by administration of bacterial endotoxin(LPS) intravenously to rabbits. On the contrary, reserpine which has various pharmacological activities by depleting catecholamines decreases the normal body temperature as well as endotoxin induced fever. In this paper, we focussed our attention on the effect of reserpine on the production of endogenous pyrogen with relation to the antipyretic effect in endotoxin fever and obtained the following results: Endogenous pyrogen could be detected by intravenous administration of LPS(0.5 micrograms/kg) during the fever. However, endogenous pyrogen was undetectable with intracisternal administration of LPS(0.01 microgram/body) which provoked long-lasting fever. Reserpine (1 mg/kg, i.v.) decreased both body temperature induced by intracisternal administration of LPS(0.01 microgram/body) or intravenous administration of LPS(0.5 microgram/kg), however the degree was more extensive in cases of LPS-induced fever. Pretreatment of rabbits with reserpine (1 mg/kg, i.v.) suppressed the fever induced by an intravenous administration of LPS(0.5 microgram/kg), but did not suppress the release of endogenous pyrogen. These data suggest that endogenous pyrogen may not be an important factor in the pathogenesis of endotoxin fever.

Animals↗

[Studies on absorption and metabolism of drugs in febrile animals. (III). Antipyretic effect of acetylsalicyclic acid and aminopyrine and their plasma concentrations in febrile rabbits induced with lipopolysaccharide (author's transl)].

The present investigation was an attempt to clarify the mechanism of combined effect of acetylsalicylic acid (ASA) and aminopyrine (AMI) in febrile rabbits as induced by lipopolysaccharide (LPS). In addition, the possible synergic effect of both agents was studied in relation to the plasma concentration. In febrile rabbits, the plasma concentration of ASA (500 mg/kg, p.o.) was a higher level than in the control, but the concentration of salicylic acid (SA), the metabolite of ASA, was similar to that in the control. The plasma concentration of AMI (100 mg/kg, p.o.) in febrile rabbits was lower than in the control. A dose-dependent antipyretic effect was seen in the successive doses from 125 to 500 mg/kg of ASA, and a similar tendency was also observed in AMI from 25 to 100 mg/kg. To observe the synergic effect of ASA and AMI, we prepared the following three combinations: I (ASA/AMI; 125 plus 75 mg/kg), II (ASA/AMI; 250 plus 50 mg/kg) and III (ASA/AMI; 375 plus 25 mg/kg). Plasma concentrations of ASA, SA and AMI were measured after oral administration of the preparations and these concentrations were lower than in the separate administration of ASA ans AMI. The antipyretic effect of the three preparations was weaker than the expected value, respectively.

Administration, Oral↗