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Biomedical subjects

A Morimoto

Publications and source records attributed to A Morimoto.

At least 163 records · Page 9Linked to original sources

Activation of brain regions of rats during fever.

The central nervous structures involved in febrile responses were investigated in conscious rats by means of the 2-deoxy-D-[14C]glucose autoradiographic technique. An intravenous injection of endogenous pyrogen prepared from rabbit white blood cells induced a significant rise in the rectal temperature of rats accompanied by a decrease in the skin temperature. According to autoradiographs, significant increases in metabolic activity were observed in the lateral preoptic area, posterior part of dorsomedial thalamus, posterior hypothalamus and the red nucleus during an induced fever. Because of the close relationship between metabolic activity and brain function, these regions are considered to compose the neural components directly or indirectly related with the febrile responses.

Animals↗

Changes in [14C]deoxyglucose incorporation into rat brain regions during heat-seeking behavior in the cold environment.

The central nervous structures involved in behavioral thermoregulatory responses during cold exposure were investigated in conscious rats by means of the 2-deoxy-D-[14C]glucose ([14C]-DG) autoradiographic technique. According to autoradiographs, many brain regions with significant increases or decreases in [14C]-DG incorporation were observed during thermoregulatory behavior. When animals were only exposed to cold, significant increases in [14C]-DG incorporation were observed in the caudate putamen, lateral preoptic area, medial forebrain bundle, ventromedial hypothalamus (VMH), posterior hypothalamus, ventroposteromedial thalamus (VPM), dorsomedial thalamus (MD), substantia nigra (SN) and red nucleus (RN). Lower activities were observed in the hippocampus and the medial habenula. However, when animals performed the behavioral thermoregulation (heat seeking behavior) significant increases were noted in the sulcal prefrontal cortex, sensory-motor cortex, and MD, while decreases were noted in the piriform cortex, VMH, VPM, medial habenula, SN and RN, compared with those in the group without the thermoregulatory behavior.

Animals↗

Suppression of non-shivering thermogenesis in the rat by heat-seeking behaviour during cold exposure.

Changes in rectal temperature (Tre) during cold exposure (0 +/- 1 degrees C) were observed in three groups of rats: heat-seeking, no-behaviour and semi-restrained groups. Significant increases in Tre were observed in the no-behaviour and the semi-restrained groups during cold exposure. In the heat-seeking behaviour group Tre remained constant during cold exposure. The increased Tre in the semi-restrained group during cold exposure was markedly attenuated by the systemic injection of beta-blocker (propranolol: 10 mg/kg, I.P.), indicating that this increase of Tre was caused by activation of non-shivering thermogenesis (n.s.t.). Furthermore, the rise in Tre in the semi-restrained group was preceded by a greater increase in the temperature of the interscapular brown adipose tissue. Using the autoradiographic [14C]deoxyglucose technique, it was revealed that the enhanced n.s.t. in the no-behaviour and the semi-restrained groups was accompanied by a significant increase of metabolic activity in the anterior part of the ventromedial hypothalamus. We conclude that during cold exposure motionlessness of slightly restrained animals increase n.s.t. when thermoregulatory behaviour to gain heat is not available. This increased n.s.t. is mediated by activation of hypothalamic function.

Animals↗

Effect of amine on temperature-responsive neuron in slice preparation of rat brain stem.

Using slice preparations we investigated the effect of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) on thermoresponsive neurons in the hypothalamus, midbrain, and the medulla oblongata. NE inhibits the activities of most of the warm-responsive neurons (11 out of 13 neurons) but 5-HT activates the warm-responsive neurons (10 out of 11 neurons) in the hypothalamus. However, the direction of neuronal response of the midbrain was opposite of that in the hypothalamus when 5-HT was applied. In the medulla oblongata, 5-HT facilitates both warm- and cold-responsive neurons and NE facilitates or inhibits these neurons in equal proportions. Furthermore, the dose-response relationships were determined using slice preparations. In the hypothalamus and the midbrain, NE and 5-HT started to effect the warm-responsive neurons at the minimum concentration of 5 X 10(-6) M, whereas the maximum responses were obtained at the concentration of 5 X 10(-5) M. In the medulla oblongata, NE or 5-HT changed the activities of the warm-responsive neurons in the range of 5 X 10(-5) to 10(-3) M or 10(-6) to 10(-5) M, respectively. It is concluded that the thermoresponsive neurons respond to 5-HT and NE in different ways, at both various levels in the central nervous system and the applied concentration of amines.

Action Potentials↗

Stimulation of ventromedial hypothalamus induces cold defense responses in conscious rabbits.

The involvement of the ventromedial hypothalamus (VMH) in thermoregulatory responses, which include heat production and heat loss responses, was investigated by the method of electrical stimulation. Electrical stimulation of the VMH caused a rise in rectal temperature, accompanied by the enhancement of heat production: O2 consumption and shivering. In addition, a reduction in heat loss was observed, including decreases in skin temperature (Ts), respiratory rate, and body surface area resulting from a huddled posture. In this study, stimulation of the lateral hypothalamus and other regions near the VMH had no effect on thermoregulatory responses. beta-Blocker (propranolol, 1 mg/kg iv) injected 20 min before stimulation lessened O2 consumption by approximately 10% and attenuated the reduction in Ts during VMH stimulation, whereas alpha-blockade (phentolamine, 1 mg/kg iv) was ineffective. These results indicate that most of the increase in O2 consumption during VMH stimulation was due to the occurrence of shivering but that some component of it could be due to nonshivering thermogenesis. They also indicate that the VMH, either directly or by converging influences, is involved in the activation of thermoregulatory responses to cold stress.

Adrenergic beta-Antagonists↗

Rat endogenous pyrogen and fever.

Rat endogenous pyrogen (EP), prepared from the white blood cells of lipopolysaccharide-pretreated rats, produced a fever in both rabbits and rats. The effects of human, rabbit, and rat EP on the body temperatures of rabbits and rats were investigated to clarify differences in the febrile response to each kind of EP. The latency to fever onset and the time to peak fever induced by rat EP in rabbits and rats were significantly greater than those induced by human and rabbit EP. The maximum elevation of the body temperature induced by rat EP in both animals was almost identical to that induced by human and rabbit EP. In a comparison of the febrile responses to various EPs between rabbits and rats, the latency to fever onset, the time to peak, and the maximum elevation of fever in rats were approximately half those observed for rabbits. Furthermore, the threshold dosage to induce a fever response in rats was greater than that necessary for rabbits. It is concluded that rat EP could be obtained by in vitro techniques and that rats have the physiological mechanisms to develop a fever through production of EP.

Animals↗

Dehydration enhances endotoxin fever by increased production of endogenous pyrogen.

The febrile responses in rats to an intravenous injection of the bacterial endotoxin Salmonella typhosa were investigated under normally hydrated and dehydrated conditions. When endotoxin was injected intravenously into the dehydrated rats, a biphasic-patterned fever resulted, whereas in normal rats an intravenous injection of endotoxin did not induce fever. No significant differences in febrile responses to the intravenous endogenous pyrogen (EP), prostaglandin E2, and intracerebroventricular prostaglandin E2 between normal and dehydrated rats were observed. When the blood plasma obtained from rats with endotoxin-induced fever under dehydrated conditions was transferred to the normal rats, a significant rise in the body temperature was induced. The effect of hydration by an administration of the hypotonic solution after dehydration was examined in endotoxin-induced fever and in changes of the basic blood parameters. It is concluded that febrile responses to endotoxin during dehydrated condition are caused by an increased production of EP. The migration of leukocytes from circulation to any other tissue will be an important factor in producing EP under dehydrated conditions. Furthermore, under dehydrated condition, EP may be produced by numerous macrophages in tissues in vivo, where many kinds of leukocytes migrate and exchange signals with each other in developing an immune response.

Animals↗

Fever in rats during normal and dehydrated conditions.

The effect of endogenous pyrogen (EP, from rabbit) and endotoxin (Salmonella typhosa) on rectal temperature (Tre) was investigated in normal and dehydrated rats of both sexes. Intraperitoneal injection of either EP or endotoxin did not affect body temperature. In addition, no changes in Tre were observed when endotoxin was injected intravenously in normally hydrated male rats, but significant falls in Tre occurred in normal female rats. However, intravenous injection of EP produced fever in both sexes, but females generally showed smaller responses. A second intravenous injection of endotoxin, given 3 days after the first injection, always produced fever in normally hydrated rats. The pattern of this febrile response was monophasic. In contrast to the response in normal rats, intravenous endotoxin produced significant fevers with a biphasic pattern in dehydrated rats of either sex, but the febrile responses of male rats were greater than those of female rats. On the other hand, there were no significant differences between febrile responses to intravenous EP exhibited by normal and dehydrated animals. These results show that rats of both sexes possess physiological mechanisms capable of producing a fever following intravenous injections of EP.

Animals↗

[14C]deoxyglucose incorporation into rat brain regions during hypothalamic or peripheral thermal stimulation.

The central nervous structures involved in thermoregulatory responses induced by hypothalamic or peripheral thermal stimulation were investigated in conscious rats by means of the 2-deoxy-D-[14C]glucose ([14C]-DG) autoradiographic technique. According to autoradiographs, many brain regions with significant increases or decreases in [14C]-DG incorporation were observed during thermoregulatory responses. Based on the present changes in [14C]-DG incorporation of brain regions obtained from two kinds of thermal stimulation, the following conclusions were drawn. 1) The medial preoptic area and the medial forebrain bundle are common sites for development of thermoregulatory responses being activated during cooling and warming. 2) The anterior hypothalamic area is activated during hypothalamic or peripheral warming and not during cooling. 3) The ventromedial hypothalamus, dorsomedial thalamus, caudate-putamen, globus pallidus, pars compacta of the substantia nigra, red nucleus, and the midbrain reticular formation are activated with hypothalamic or peripheral cooling. 4) The lateral preoptic area, suprachiasmatic nucleus, ventroposteromedial thalamus, pars reticulata of the substantia nigra, and the hippocampus change their activities only during peripheral cooling and warming.

Animals↗

Activation of brain regions in rats during food-intake operant behavior.

The central nervous structures involved in bar pressing and feeding behavior during food-intake operant behavior were investigated in rats by the [14C]-deoxyglucose ( [14C]-DG) autoradiographic technique. During bar pressing behavior, the [14C]-DG incorporation increased in the sensory-motor cortex, ventromedial thalamus, zona incerta, pars reticulata of substantia nigra, ligular cortex of the cerebellum and the reticular formation of the medulla. On the other hand, an increase of the [14C]-DG incorporation induced by feeding behavior was observed in the fornix, medial forebrain bundle, parietal cortex, trigeminal nuclei and the solitary nuclei.

Animals↗

Ototoxicity of the anticancer drug cisplatin. An experimental study.

Cisplatin was administered to guinea pigs. Hearing function was tested using ABR, and morphological studies were conducted by scanning and transmission electron microscopy. The following findings were made. (1) The susceptibility to cochlear damage by cisplatin was dose dependent. (2) At the same dose, damage was most severe in the lower turns, particularly in the second turn. This tallies with the high tone loss. (3) Mainly the outer hair cells are the site of the damage and the inner hair cells are rarely damaged. (4) The first row of the outer hair cells tend to be more severely damaged. (5) Variation of the stria vascularis was moderate compared with the damage to the organ of Corti. (6) A tendency of recovery was observed in ABR in some animals after they were given 2 mg/kg/day cisplatin intramuscularly consecutively for 8 days.

Animals↗

Direct effects of endogenous pyrogen on medullary temperature-responsive neurons in rabbits.

The effect of endogenous pyrogen (E.P.) injected directly into the tissue near the recording site were examined on the activities of the medullary temperature-responsive (TR) neurons in rabbits anesthetized with urethane. Endogenous pyrogen prepared from rabbit's whole blood was administered by a fine glass cannula (100-200 micrometer in diameter) in a fluid volume of 1 to 4 microliter. The cannula was fixed to the manipulator in parallel with a microelectrode and their tips were less than 0.05 mm apart. In rabbits with the intact preoptic/anterior hypothalamic (PO/AH) region, 4 warm-responsive neurons out of 7 were inhibited and 6 cold-responsive neuron out of 7 were excited by the direct administration of the E.P. In rabbits with lesions of the PO/AH, 5 warm-responsive neurons out of 9 were inhibited and 6 cold-responsive neurons out of 8 were facilitated by E.P. Antipyretics administered locally after the E.P. antagonized the pyretic effect, causing a return of the discharge of TR neuron to the control rate within 2.4 +/- 1.2 (mean +/- S.D.) min. The medullary TR neuron itself has the ability to respond to the E.P. and contributes to the development of fever.

Animals↗

Nitrogen balance and hepatic gluconeogenesis in rats fed on diets containing various proportions of carbohydrate and fat.

This study was conducted to investigate the effects of various proportions of dietary carbohydrate and fat in diet on protein and carbohydrate metabolism. The growth rate, nitrogen balance, urinary and serum urea levels, and the activities of key ureogenic and gluconeogenic enzymes in the livers were examined in the weanling and growing rats. The rats were raised on a 20% casein diet containing various proportions of carbohydrate and fat, viz. 30% and 50%, 50% and 30%, 60% and 20% or 70% and 10% as calorie percent, respectively, for 10 days. For both weanling and growing rats, the growth rate was unaffected by the alteration in the proportions of carbohydrate and fat in the diets. However, in the rats fed on the 30% carbohydrate-50% fat diet, the urinary excretion of nitrogen and urea were reduced in both groups and these findings were reflected in the reduced serum urea level. Arginase activity decreased. In contrast, glucose-6-phosphatase activity was enhanced in the animals of the 30% carbohydrate-50% fat diet group as compared to the other groups. These results suggest that a low carbohydrate-high fat diet causes the reduction of urea formation and the enhancement of glucose formation at a fixed level of protein in the diets in weanling as well as in growing rats.

Aging↗

Synthesis and structure-activity relationships of 7 beta-[2-(2-aminothiazol-4-yl)acetamido]cephalosporin derivatives. IV. Synthesis of 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetic acid derivatives and related compounds.

In an effort to improve the antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)acetamido]-cephalosporins by introducing a methoxyimino group into the 7-acyl side chain, geometrically isomeric 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetic acids and their derivatives were selectively synthesized. Structurally related acid derivatives were also synthesized. A facile and practical synthesis of an important starting material, 2-(2-chloroacetamidothiazol-4-yl)-(Z)-2-methoxyiminoacetic acid, for the preparation of SCE-1365 which is now under extensive clinical trial was achieved.

Anti-Bacterial Agents↗