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Biomedical subjects

A Kawabata

Publications and source records attributed to A Kawabata.

At least 91 records · Page 5Linked to original sources

Mechanism of the analgesic effect of neurotropin.

Neurotropin, an extract from the inflamed skin of vaccinia virus-inoculated rabbits, has been observed clinically to be effective for treating pain in patients with lumbago, SMON and other neuropathies. In the present study, we examined the mechanism of the antinociceptive effect of neurotropin in mice in relation to administration routes, opioids, and noradrenergic or GABAergic drugs, by the tail pressure method. The antinociceptive effects of neurotropin were large when administered by the i.p. and intracisternal (i.cist.) routes, but comparatively small in the case of the intrathecal (i.th.) route. Neurotropin may thus act at the supraspinal level rather than on the spinal cord. The antinociceptive effect of neurotropin was not blocked by naloxone, and no cross-tolerance developed between neurotropin and morphine. The effect of neurotropin was blocked by phentolamine and reserpine, but not by atropine. Its effect was enhanced by GABA, muscimol, aminooxyacetic acid and diaminobutyric acid, but not by baclofen, and blocked by bicuculline methiodide. From these results, the antinociceptive action of neurotropin appears to be non-opioid in nature, and may possible be mediated by the noradrenergic and GABAergic systems, but unrelated to the cholinergic system.

Analgesics↗

The abnormal open-field behavior of SART-stressed rats and effects of some drugs on it.

As part of an investigation on the behavioral characteristics of SART-stressed animals, an animal model of autonomic imbalance, the open-field behavior of SART-stressed (repeated cold-stressed) rats was studied and compared with that of rats exposed to other types of stress. In addition, the effects of several drugs on it were also studied. As compared with normal rats, SART-stressed rats exhibited increased locomotor activity, rearing and center-field penetration, together with decreased grooming and increased defecation, whereas they showed no significant changes in spontaneous movements in the daytime as measured by an Animex activity meter. These behavioral abnormalities were remarkably different from those due to 1-hr cold, 48-hr cold and repeated restraint stresses. These abnormal forms of open-field behavior due to SART stress were considerably inhibited by chlorpromazine, imipramine and neurotropin at doses having no corresponding influence on normal rats; and they were partially inhibited by alprazolam, diazepam and carpipramine at doses exerting considerable influence on normal rats. The above results show that SART-stressed rats exhibit open-field behavioral abnormalities that are different from those of rats exposed to other types of stress. Such abnormalities include excessive activity, which is considered to be caused by excessive emotionality.

Alprazolam↗

Catecholamine levels in the brain of SART (repeated cold)-stressed rats.

1 The catecholamine levels in the brains of SART (specific alternation of rhythm in temperature)-stressed (repeated cold-stressed) rats with vagotonic-type dysautonomia, were examined by high performance liquid chromatography with electrochemical detection techniques. 2 The cerebral cortex, hypothalamus and hippocampus of the SART-stressed rats had increased levels of noradrenaline. All brain areas examined showed increased levels of dopamine. 3 These increased catecholamine levels were still maintained by day 10 of SART stress. 4 Among brain areas examined, the hypothalamus showed most rapid change. 5 Cold-stressed rats showed increased noradrenaline levels only in the basal ganglia and dopamine levels in the hippocampus. 6 Rats suffering from restraint and water immersion stress showed decreased noradrenaline levels and increased dopamine levels. 7 These results suggest that SART-stressed animals are in a disease state differing from that of other so-called stressed animals, and changes in the hypothalamus give rise to the various symptoms in SART-stressed animals.

Animals↗

Electrocorticogram in rats loaded with SART stress (repeated cold stress).

The electrocorticogram (ECoG) in a SART (specific alternation of rhythm in temperature)-stressed (repeatedly cold-stressed) rat, which is regarded as an experimental model for clinical vagotonic-type dysautonomia, was investigated in the present study by the power spectral technique. 1) Analysis of ECoG in SART-stressed rats during the resting-arousal state indicated a decrease in total power and a decrease in relative power in the delta band, and also an increase in relative power in the theta, alpha and beta bands. 2) In the slow-wave sleeping state, the ECoG of SART-stressed rats indicated a marked increase in total power, an increase in the delta band and decreases in theta, alpha and beta bands. 3) Electric stimulation of the posterior-hypothalamic area evoked alterations of ECoG similar to those caused by SART stress. ECoG response to electric stimulation in SART-stressed rats was less than that in unstressed rats. 4) Lesioning of the posterior-hypothalamic areas prevented SART stress-induced ECoG alterations. SART-stressed rats thus appear to be at a higher consciousness level on awakening but to sleep more soundly. They seem to exhibit greater fluctuation in brain activity than normal rats. There is also the possibility that the posterior-hypothalamic area is responsible to some degree for ECoG alterations in SART-stressed rats.

Animals↗

Changes of total acetylcholine content and the activity of related enzymes in SART (repeated cold)-stressed rat brain and duodenum.

In SART-stressed rats regarded as pathologically diseased model animals with vagotonic-type autonomic imbalance, a decrease of total acetylcholine (T-ACh) content and enhancements of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities were recognized in the basal ganglia and hypothalamus. In contrast, in the duodenum, an increase in T-ACh content and a decrease in AChE activity were found, while CAT activity showed no change. These findings suggest that in both brain areas of basal ganglia and hypothalamus in SART-stressed rats, ACh neurons may be activated.

Acetylcholine↗

Changes of tissue blood flow in mice loaded with SART (repeated cold) stress or restraint and water immersion stress and the effect of administered neurotropin.

In order to explore the peripheral microcirculation and to obtain an outline of autonomic innervation in SART (specific alternation of rhythm in temperature)-stressed (repeated cold-stressed) animals, which are regarded as model animals for clinical vagotonic-type dysautonomia, peripheral tissue blood flow was determined in mice, using the hydrogen clearance method. SART-stressed mice showed a decrease in gastric blood flow, no change in hepatic blood flow and an increase in dermal blood flow. In the mice exposed to the restraint and water immersion stress (RWIS), a type of acute stress, in contrast with SART stress which is a subacute type, remarkable decreases were observed in gastric, hepatic and dermal blood flows. Changes of both gastric and dermal blood flow in SART-stressed mice were dose-dependently prevented and maintained within normal limits by the treatment with Neurotropin, a sedative analgesic which is an extract isolated from vaccinia virus-inoculated and inflamed skin of rabbits. In RWIS-loaded mice, Neurotropin exhibited a great preventive effect on changes of blood flow in the stomach, a slight effect in the liver, and no effect in the cutis. When mice were loaded with SART stress after left-cervical vagotomy, SART stress failed to elicit any decrease in gastric blood flow. In SART-stressed mice treated with 6-hydroxydopamine, gastric and dermal blood flows tended to show a further decrease and increase, respectively, over and above the changes caused by SART stress. From these results, it is suggested that SART-stressed mice may have decreased gastric parasympathetic tone, a decrease in sympathetic tone and also other anomalies such as increased tension of the sympathetic cholinergic vasodilator nerves in the cutis.

Animals↗

Effect of ginseng-20S-prosapogenin on tissue blood flow measured by the hydrogen clearance method in sympathicotonic- or parasympathicotonic-type stressed mice.

An attempt was made to investigate the preventive effects of 20S-prosapogenin (20S-PG), a partial hydrolyzate of diol saponins isolated from Panax ginseng, on changes of peripheral tissue blood flow in diseased model animals with vagotonic-type autonomic imbalance [SART (specific alternation of rhythm in temperature)-stressed (repeated cold-stressed) mice developed by us], and sympathicotonic-type stressed mice [restraint and water immersion-stressed (R WIS) mice], using the hydrogen clearance method. Decreases in gastric blood flow in both body and pyloric regions of the stomach and increases in dermal blood in both the shoulder and lumbar region in SART-stressed mice were prevented to a considerable extent by daily treatments with 20S-PG, 2.5-10 mg/kg/d. Similarly, the marked decrease in gastric blood flow following R WIS loading was significantly blocked by 10 mg/kg/d of 20S-PG. 20S-PG had a minor preventive effect on decreases in hepatic and dermal blood flow in R WIS mice. The preventive effect of 20S-PG on changes in tissue blood flow, recognized in model animals with autonomic imbalance not only in the vagotonic state but also in the sympathicotonic state, is therefore regarded with considerable interest and may provide a clue to explain the pharmacological action of ginseng.

Animals↗

Mechanism of Glyoxylate Decarboxylation in the Glycolate Pathway in Euglena gracilis Z : Participation of Mn-Dependent NADPH Oxidase in Chloroplasts.

The mechanism for decarboxylating the carboxyl carbon of glycolate was studied in Euglena gracilis Z, which liberates more than 70% of the carboxyl carbon as CO(2) during glycolate metabolism.In the isolated mitochondria of E. gracilis, glycolate was oxidized to glyoxylate, 25% of which was aminated to glycine, with the remaining unchanged in the presence of glutamate; in the absence of the amino donor, glyoxylate was not changed. Irrespective of the presence or absence of the amino donor, no decarboxylation took place in Euglena mitochondria. In Euglena chloroplasts glyoxylate was actively decarboxylated by the action of hydrogen peroxide generated by the reaction of a Mn(2+)-dependent NADPH oxidase. This enzyme was purified 120-fold over the crude extract and some of its properties studied. Oxidation of one molecule of NADPH was accompanied by the formation of one molecule of H(2)O(2); the NADPH oxidation was not attributable to the action of l-ascorbate peroxidase, the sole peroxidase present in E. gracilis. Specific participation of chloroplasts and mitochondria in glycolate metabolism is discussed.

Journal Article↗

Carcinogenic effect of N-bis-(2-hydroxypropyl)nitrosamine in newborn rats.

The carcinogenic effect of N-bis(2-hydroxypropyl)nitrosamine (BHP) was studied in newborn Wistar rats. Tumors were induced in the lung (adenoma), pancreas (adenoma), kidney (nephroblastoma), and ovary (benign granulosa cell tumor) at 24 weeks after the treatment and in the lung (adenoma and adenocarcinoma), liver (hemangioma, hemangioendothelioma, and hepatocellular carcinoma), pancreas (adenoma), kidney (renal cell carcinoma and nephroblastoma), thyroid (adenocarcinoma) and ovary (benign and malignant granulosa cell tumors) at 52 weeks. The highest incidence of tumor was seen in the liver of rats applied BHP within 24 hours after birth. These results indicate that newborn Wistar rats are more susceptible to BHP than are adult rats.

Animals↗

Carcinogenic effect of N-bis(2-hydroxypropyl)nitrosamine by a single administration in rats.

The carcinogenic effect of a single intraperitoneal injection of N-bis)2-hydroxypropyl)nitrosamine (BHP) was studied in male Wistar rats. Lung tumors (adenomas and adenocarcinomas) had the highest incidence (100%). Fewer neoplasms were induced in the thyroid (adenomas and adenocarcinomas, 36%), kidney (renal cell carcinomas, 8%), and the sigmoid colon (adenomas and adenocarcinomas, 9%). No pancreatic neoplasms were found.

Adenocarcinoma↗

Effect of dose on the carcinogenic activity of orally administered N-bis(2-hydroxypropyl)nitrosamine in rats.

The carcinogenic activity of orally administered N-bis(2-hydroxypropyl)-nitrosamine (DHPN) in male Wistar rats was evaluated with respect to its dose. DHPN was administered at two doses, 100 ppm and 500 ppm, in the drinking water to rats for 25 to 52 weeks. Tumors developed in the lung, liver, and thyroid of rats receiving 100 ppm DHPN and in the lung, liver thyroid, esophagus, kidney, and urinary bladder of rats receiving 500 ppm DHPN. The principal target organ was the lung in rats receiving either 100 or 500 ppm DHPN, indicating that the carcinogenic action of these doses of DHPN was similar to that of higher doses previously reported. Histologically, the tumors were adenoma, adenocarcinoma, squamous cell carcinoma, and combined carcinoma of the lung, hepatocellular carcinoma and hemangioma of the liver, adenoma and adenocarcinoma of the thyroid, squamous cell papilloma and carcinoma of the esophagus, renal cell and transitional carcinoma of the kidney, and transitional cell carcinoma of the urinary bladder. No pancreatic tumors were observed.

Adenocarcinoma↗