Biomedical subjects

A Kawabata

Publications and source records attributed to A Kawabata.

At least 73 records · Page 4Linked to original sources

PubMed1992

Platelet hypoaggregability in rats exposed to SART stress (repeated cold stress).

A prolongation of bleeding time accompanied by thrombocytopenia and abnormalities in coagulation-fibrinolysis systems has been observed in laboratory animals exposed to a chronic form of environmental stress induced by severe fluctuations of air temperature, known as SART (specific alternation of rhythm in temperature) stress. In order to clarify the hemostatic profile under SART stress in more detail, the present study examined platelet aggregability in vitro as well as in vivo in stressed rats. During exposure to stress, thrombocytopenia developed from day 5, and remained up to at least day 14. In vitro aggregation of platelets stimulated by ADP or collagen was markedly decreased in stressed rats, compared with unstressed rats. Furthermore, stressed rats exhibited in vivo hypoaggregability of platelets, as estimated by the magnitude of the drop in circulating platelet counts following intravenous injection of ADP and collagen. Protein and cholesterol content in platelets remained constant after stress exposure. These results indicate that SART-stressed rats exhibit platelet dysfunctions in addition to thrombocytopenia. Considering the previous findings, the hemostatic system under SART stress appears to show a general tendency toward hemorrhage.

Adenosine Diphosphate↗

PubMed1992

L-leucyl-L-arginine, naltrindole and D-arginine block antinociception elicited by L-arginine in mice with carrageenin-induced hyperalgesia.

1. Intraplantar injection of carrageenin into the mouse hind paw produced hyperalgesia when measured by the paw pressure test (Randall & Selitto method). 2. Subcutaneous administration of L-arginine (100-1,000 mg kg-1), a possible precursor of kyotorphin which is an endogenous analgesic neuropeptide, inhibited carrageenin-induced hyperalgesia in a dose-dependent manner. This effect was blocked by subcutaneous administration of naloxone, naltrindole, a selective delta-opioid receptor antagonist (enkephalin antagonist), and D-arginine. 3. Intracerebroventricular administration of L-leucyl-L-arginine inhibited the antinociceptive effect of systemically administered L-arginine in hyperalgesic mice. 4. Intracerebroventricular administration of L-arginine (3 and 30 micrograms per mouse) and kyotorphin (300 ng-3 micrograms per mouse) produced antinociception in hyperalgesic mice. The antinociceptive effects of L-arginine but not kyotorphin were blocked by intracerebroventricular administration of D-arginine. 5. These results suggest that L-arginine-induced antinociception is mediated by activation of 'kyotorphinergic' nerves followed by activation of the 'opioidergic' (possible 'enkephalinergic') nerves in the central nervous system.

Analgesics↗

PubMed1992

[An autopsy case of massive pulmonary hemorrhage in systemic lupus erythematosus].

A 60-year-old female was admitted to our hospital because of respiratory failure. She was diagnosed as having systemic lupus erythematosus (SLE) in 1971 and had been treated with low-dose oral corticosteroids for 13 years. She developed cough, fever and anemia several days after oral corticosteroids were tapered. Initially, she had no complications such as congestive heart failure, renal failure or bleeding tendency. Respiratory failure progressed without any response to antibiotic therapy. Chest roentgenogram showed bilateral diffuse infiltrates and air bronchograms. There was no improvement even with steroid pulse therapy, and she died of multiple organ failure. Autopsy revealed massive intra-alveolar hemorrhage and interstitial pneumonitis. Deposition of immunoglobulins in the lung was not seen. To our knowledge, this is the 11th reported case of SLE associated with pulmonary hemorrhage in Japan.

Female↗

PubMed1992

[Involvement of lymph nodes and neural plexus in carcinoma of the pancreas].

We studied 428 lymph nodes attached to the head of the pancreas (13,14,17) in 18 patients with ductal carcinoma of the pancreatic head. These were classified into the small size of the lymph nodes less than 5mm (group S), the moderate size of the lymph nodes (group M) and the large size of the lymph nodes more than 10 mm (group L). The metastases were seen in 76 nodes, which consisted of 49 with group S, 14 with group M and 13 with group L. The lymph node involvement in group (14) S was found in 7 of 18 patients (38.9%), that in group (14) M was in 4 (22.2%) and that in group (14) L was in 2 (11.1%). In these involved cases, the primary tumors tended to be locate in the portion near the superior mesenteric artery, such as in the uncinate process. Invasion of extrapancreatic neural plexus was noted in 9 of 18 patients (50%). There was no significant correlation between nerve plexus invasion and lymphatic invasion by Spearman's rank correlation. In addition, any close relationship between plexus invasion and primary tumor location could not be indicated. These results suggested that neural invasion in pancreatic carcinoma is independent of lymphatic invasion, and the routes of cancer spread via the neural plexus are different from those via the lymphatic vessels. Those without liver metastases survived longer than those with liver metastases, which were characteristically multiple.

Humans↗

PubMed1991

Effects of thyrotropin-releasing hormone and a related analog, CNK-602A, on long-term potentiation in the mossy fiber-CA3 pathway of guinea pig hippocampal slices.

The effects of thyrotropin-releasing hormone (TRH) and a related analog, CNK-602A, that induces the release of catecholamines, on long-term potentiation (LTP) of the population spike in mossy fiber-CA3 pathways were investigated in guinea pig hippocampal slices. TRH augmented LTP of the population spike at concentrations of 10(-6)-10(-5) M. CNK-602A also augmented LTP at concentrations of 10(-6)-10(-5) M in a dose-dependent manner. LTP in slices of the hippocampus obtained from animals given 6-hydroxydopamine (6-OHDA) intraventricularly was significantly lower than that in non-treated animals. However, both TRH and CNK-602A (10(-6) M) augmented LTP in slices from 6-OHDA-treated animals. These findings suggest that TRH and CNK-602A augment LTP in the mossy fiber-CA3 pathway without activating noradrenergic and/or dopaminergic fibers.

Animals↗

PubMed1991

Plasma catecholamine levels in SART-stressed rats and effects of drugs on stress-induced alteration in plasma and brain catecholamine levels.

1. Plasma catecholamine (CA) levels were examined in rats exposed to SART (specific alternation of rhythm in temperature) stress, a repeated cold stress. Effects of neurotropin, a sedative analgesic, and alprazolam, an anxiolytic, on the changes in plasma and brain CA levels were then studied. 2. SART stress induced remarkable increases in plasma levels of noradrenaline (NA) and dopamine (DA). The plasma adrenaline (Adr) level also increased significantly, but the extent was smaller than that of NA or DA. 3. Repeated treatments with neurotropin reduced the stress-induced increases in plasma and brain NA and DA levels significantly and dose-dependently. 4. Repeated treatments with alprazolam markedly reduced all increases in plasma and brain CA levels. 5. The above findings suggest that SART-stressed animals are in an increasing state of sympathetic neuronal activity and in a slightly increasing state of adrenal function. Neurotropin is also suggested to have modulating effects on autonomic imbalance in both catecholaminergic and cholinergic nerves.

Alprazolam↗

PubMed1991

Effects of anti-vertigo drugs on medial vestibular nucleus neurons activated by horizontal rotation.

The effects of anti-vertigo drugs on medial vestibular nucleus (MVN) neurons were examined to assess the site and mode of action using cats anesthetized with alpha-chloralose. Single neuron activity in the MVN was extracellularly recorded using a silver wire microelectrode attached along a seven-barreled micropipette, each of which was filled with diphenhydramine, diphenidol, betahistine, glutamate or NaCl. Type I of the MVN neurons were identified according to the responses obtained when the animal placed on a turn-table was rotated sinusoidally. The effects of the drugs were examined on type I neurons which received impulses primarily from the labyrinth and sent them to the oculomotor nuclei. The microiontophoretic application of diphenhydramine, diphenidol and betahistine inhibited rotation-induced firing of type I MVN neurons. Diphenhydramine and diphenidol were more potent than betahistine. These results suggest that these drugs directly act on MVN neurons to reduce the responsiveness to rotatory stimulation.

Animals↗

PubMed1991

Changes in CNS levels of serotonin and its metabolite in SART-stressed (repeatedly cold-stressed) rats.

Central nervous system levels of serotonin (5-HT) and 5-hydroxy-indoleacetic acid (5-HIAA) in SART (specific alternation of rhythm in temperature)-stressed (repeatedly cold-stressed) rats were examined by HPLC-ECD. In SART-stressed rats, the levels of both 5-HT and 5-HIAA decreased in many brain areas. In the spinal cord, only the 5-HT level decreased. Therefore, the ratio of 5-HIAA to 5-HT increased only in the spinal cord. These results suggest that SART-stressed rats have some form of abnormality in the synthetic system of 5-HT.

Animals↗

PubMed1991

Blood coagulation and fibrinolysis in SART-stressed (repeated cold-stressed) rats and drug effects on the altered hemostatic parameters.

Blood coagulation and fibrinolytic activity was studied in SART (specific alternation of rhythm in temperature)-stressed animals found to exhibit thrombocytopenia and prolonged bleeding time, and drug effects on the abnormalities were evaluated. 1) SART-stressed rats revealed prolongation of activated partial thromboplastin and thrombin time, no change in prothrombin time, decreased plasma fibrinogen levels, and shortened euglobulin clot lysis time (ELT). Antithrombin III and alpha 2-plasmin inhibitor activity remained constant following stress exposure. 2) During stress, fibrinogen levels declined from day 5 and remained depressed up to day 14. Reduction in ELT developed in a similar manner to fibrinogen. 3) Decreased fibrinogen levels were prevented by consecutive doses of tranexamic acid, an antifibrinolytic, and Neurotropin, a sedative analgesic. Shortened ELT was counteracted by chronic treatment with Neurotropin and alprazolam, an anxiolytic. Single administrations of the above agents failed to affect either change. These results indicate that SART-stressed animals exhibit suppressed intrinsic coagulability and enhanced fibrinolytic activity, but normal extrinsic coagulability. Considering the previous report together with the above results, the hemostatic system under SART stress tends uniformly toward hemorrhage. Moreover, Neurotropin appears to improve and normalize hemostatic imbalance due to SART stress, a chronic form of stress.

Alprazolam↗

PubMed1990

Inhibition by enkephalin of medial vestibular nucleus neurons responding to horizontal pendular rotation.

Electrophysiological studies were performed to determine whether or not enkephalin modulates the activities of medial vestibular nucleus (MVN) neurons responding to horizontal pendular rotation using alpha-chloralose anesthetized cats. The effects of microiontophoretically applied drugs were examined in type I and type II neurons identified according to responses to horizontal, sinusoidal rotation; type I and type II neurons showed an increase and decrease in firing with rotation ipsilateral to the recording site and vice versa with contralateral rotation, respectively. Iontophoretic application of enkephalin suppressed spike firing induced by rotation of the animals in type I neuron, but not in type II neuron. The spike firing induced by iontophoretically applied glutamate was also inhibited during the application of enkephalin. The inhibition by enkephalin of both rotation- and glutamate-induced firing was antagonized by naloxone which was given simultaneously. These results suggest that enkephalin acts on MVN type I neuron to inhibit transmission from the vestibule, thereby controlling vestibulo-ocular reflex.

Animals↗

PubMed1990

Inhibition by intravenously administered sodium bicarbonate of neuronal activity in medial vestibular nucleus neurons.

The effects of 7% sodium bicarbonate on medial vestibular nucleus (MVN) neurons were examined to elucidate the mechanism underlying its anti-vertigo action, using alpha-chloralose-anesthetized cats. Intravenous injection of the drug at 1, 2 and 4 ml/kg every 10 min dose-dependently inhibited rotation- and glutamate-induced firing of type 1 neurons, although a low dose of the drug enhanced firing in a few neurons. However, microiontophoretic application of bicarbonate ions did not inhibit rotation- or glutamate-induced firing. After injection of the drug, the Po2 level in arterial blood did not differ from previous levels, but the bicarbonate ion levels dose-dependently increased concomitantly with an increase in pH, as compared with previous levels. These results suggest that the intravenous injection of 7% sodium bicarbonate directly inhibits the neuronal activity of the MVN, although the lower dose may enhance neuronal activity by acting on the peripheral vestibule.

Animals↗

PubMed1990

[Effects of oral administration of various non-steroidal anti-inflammatory drugs on bone growth and bone wound healing in mice].

Morphometric and microdensitometric studies on normal bone growth and bone wound healing in growing ICR strain male mice were carried out as preliminary investigations. Then the effects of oral administration of non-steroidal anti-inflammatory drugs on bone growth and bone wound healing were studied. Femur length and width, and bone mineral contents in the femur as judged by microdensitometry of the soft x-ray films of the cortical portion of the femur showed time-dependent linear increase between 3 and 6 weeks of age. Wound holes were made in the parietal bones of mice with a dental bar at 4 weeks of age, and uncalcified area in the holes was determined by image analysis of soft x-ray films. The area decreased their size with the advance in age, especially a marked decrease was observed 2 weeks after the operation. From the above results, 4 week-old male mice were employed and 8 kinds of non-steroidal anti-inflammatory drugs (indomethacin, 1 mg/kg; mefenamic acid, 10 mg/kg; flufenamic acid, 10 mg/kg; diclofenac sodium, 1 mg/kg; ibuprofen, 10 mg/kg; naproxen, 10 mg/kg; phenylbutazone, 10 mg/kg and aspirin, 50 mg/kg) and dexamethasone (1 mg/kg), a steroidal anti-inflammatory drugs were administered orally every day for 9 or 11 days except Sunday, and 15 days after the initial administration, the length and width of the femur were measured. The bone mineral contents were determined by microdensitometry of the soft x-ray film of the femur. Hydroxyproline contents of the femur were also determined. Wound holes were made in the parietal bones at 4 week-old and administered the drugs from one day before the operation for 9 days and the uncalcified area in the wound hole was determined 2 weeks after the operation with an image analyzer. The results obtained were as follows: 1. A significant inhibition of the growth in length of the femur was observed by dexamethasone, diclofenac sodium and naproxen administration for 9 and 11 days. A significant inhibition of the growth in width was also observed by dexamethasone and diclofenac sodium administration for 9 days and by dexamethasone administration for 11 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1989

Impairment of passive avoidance performance in SART-stressed mice and the action of drugs.

In order to investigate the behavioral characteristics of the SART-stressed (repeated cold-stressed) animal, a model of dysautonomia, step-down passive avoidance performance was examined in SART-stressed mice. SART-stressed mice exhibited a shortened test trial latency and a decreased incidence of maximum latency of 300 sec, but no change in the training latency. These alterations were blocked by single administration of chlorpromazine or carpipramine prior to the training trial. Repeated, but not single treatments with neurotropin and hopantenate improved the impaired performance due to SART stress. On the other hand, alprazolam and diazepam were ineffective by either mode of administration. Thus, SART-stressed mice appear to have impairment in the process of acquisition of a passive avoidance task.

Animals↗

PubMed1989

Subsensitivity to substance P in SART-stressed mice.

The sensitivity of SART-stressed (repeated cold-stressed) mice to substance P (SP) was studied. The behavioral responses to intrathecal SP in the stressed mice were less marked than those in non-stressed mice. The 50% effective dose of SP, however, did not differ between the 2 groups. Also, the antagonistic effect of intrathecal [D-Pro2, D-Trp7,9]-substance P against SP was not different. These results suggest that SART-stressed mice are subsensitive to exogenous SP and that the number but not the affinity of SP receptors may be altered.

Animals↗

PubMed1989

A characteristic pattern of active avoidance behavior in SART-stressed rats.

In SART-stressed (repeated cold-stressed) rats, shuttle-avoidance response was examined. The rats exposed to SART stress prior to training showed a high avoidance rate and no change in the intertrial response. Upon exposure to SART stress after completion of learning, the rats showed no changes in the avoidance rate and an increase in the intertrial response in the retention test. These results are in contrast to the previous observations of passive avoidance response, and the abnormal behavior in such animals may be based on excessive emotionality and/or hyperreactivity rather than alterations in the process of learning and memory.

Animals↗

PubMed1989

[Strongyloidiasis following long-term corticosteroid therapy].

A 64-year-old man who was born and raised in Fukuoka Prefecture was admitted because of dyspnea. The chest X-ray film showed multiple pulmonary cysts. Corticosteroid therapy was given because of repeated episodes of dyspnea and wheezing. He complained of epigastric pain 20 months after administration of corticosteroid therapy. Gastro-endoscopic examination showed inflammatory changes of the gastric mucosa and the biopsy specimens revealed the filariform larvae of Strongyloides stercoralis. Furthermore, the larvae were frequently detected in both sputum specimens and stools. Pyrvinium pamoate was initially administered and was switched to thiabendazole because of the presence of hyperinfection. Although two cycles of thiabendazole treatment were given, the larvae were not eradicated. This case report suggests that long term corticosteroid therapy caused the hyperinfection syndrome of Strongyloides stercoralis in a patient who was auto-infected with this nematode.

Adrenal Cortex Hormones↗

PubMed1988

The relationship of hyperalgesia in SART (repeated cold)-stressed animals to the autonomic nervous system.

1. The mechanism of hyperalgesia observed in SART (repeated cold)-stressed animals (mice and rats) was studied in relation to the autonomic nervous system. 2. SART stress reduced the nociceptive threshold previously increased in vagotomized mice, but failed to change the threshold previously decreased in sympathectomized mice. 3. The nociceptive threshold previously decreased in SART-stressed mice was elevated by vagotomy, but decreased still more by sympathectomy. 4. Lesion of ventromedial (VMH), anterior (AH) or posterior hypothalamus (PH) prevented decrease in the nociceptive threshold of rats by SART stress, but lesion of the lateral hypothalamus (LH) had no such effect. 5. The nociceptive threshold previously decreased in stressed rats did not change by VMH, AH or PH lesion, but increased by LH lesion. 6. The above findings indicate that hyperalgesia in SART-stressed animals apparently bears little relation to the parasympathetic nervous system, but is associated relatively more with reduced tone in the sympathetic nervous system.

Animals↗

PubMed1988

Changes in platelet count and related parameters in SART-stressed mice and the action of administered neurotropin.

In order to hematologically characterize SART-stressed (repeated cold-stressed) animals, which are regarded as model animals of clinical dysautonomia, general hematological analyses were performed in mice subjected to various types of stress. SART-stressed mice showed significant increases in erythrocyte count, hemoglobin, hematocrit and specific gravity of whole blood, no change in leukocyte count and a marked decrease in platelet count. Among the above changes, the decreased platelet count was particularly characteristic of SART-stressed mice. Splenectomy failed to inhibit the SART stress-induced thrombocytopenia. Bone marrow megakaryocyte counts increased following the stress. The bleeding time of SART-stressed mice was more than double that of normal mice. Consecutive administrations of Neurotropin, a sedative analgesic, completely blocked the alterations in platelet count, megakaryocyte count and bleeding time in SART-stressed mice without producing any effect in unstressed mice. From the present results, it is suggested that SART-stressed mice may be characterized by thrombocytopenia, which is not attributable to enhanced function of the spleen or suppressed platelet production in the bone marrow. Moreover, Neurotropin appears to be effective for moderating SART stress.

Alprazolam↗