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Biomedical subjects

S Asai

Publications and source records attributed to S Asai.

At least 91 records · Page 5Linked to original sources

[Short-course chemotherapy of tuberculosis with pyrazinamide].

A 6-month regimen consisting of isoniazid (INH. 0.3-0.5 g).rifampicin (RFP. 0.3-0.45 g).pyrazinamide (PZA. 1.2-2.0 g) and streptomycin (SM. 0.75 g) or ethambutol (EB. 0.75-1.0 g) given for 2 month followed by isoniazid and rifampicin for 4 month is the preferred treatment for patients with fully susceptible organism, who adhere to treatment. Consideration should be given to treating all patients with directly observed treatment.

Antibiotics, Antitubercular↗

Central effect of melatonin against stress-induced gastric ulcers in rats.

We investigated the role of melatonin in the induction of gastric lesions induced by water immersion restraint stress or centrally administered thyrotropin-releasing hormone (TRH). Melatonin (0.1-1 ng) injected intracisternally (i.c) 30 min prior to stress dose-dependently inhibited the induction of gastric lesions by water immersion restraint stress, while 100 micrograms/kg, i.p. failed to protect the gastric mucosa. Preadministration of melatonin (1 ng, i.c.) significantly reduced (83%) the severity of gastric lesions induced by a TRH analogue (500 ng, i.c.). Serum melatonin concentrations 30 min after administration of 1 ng melatonin i.c. did not differ from those of rats receiving i.c. vehicle. These results suggest that melatonin plays a protective, anti-stress, role in the gastric mucosa via a mechanism involving the central nervous system.

Animals↗

Real-time monitoring of the effects of normothermia and hypothermia on extracellular glutamate re-uptake in the rat following global brain ischemia.

Brain hypothermia during ischemia may have a neuroprotective effect on pathological and functional outcomes in vivo. Although a microdialysis study demonstrated that hypothermia decreases glutamate release into the extracellular space, the issue of whether this suppression of the glutamate elevation normally accompanying ischemia is attributable to inhibition of intra-ischemic release or acceleration of post-ischemic re-uptake was not addressed. Recently, we established a real-time method for monitoring glutamate levels in extracellular space, utilizing a dialysis electrode. This method allows detailed analysis of the in vivo dynamics of biphasic glutamate elevation in the extracellular space during the intra-ischemic period and post-ischemic re-uptake. The present results show that post-ischemic hypothermia has little effect on the initial glutamate release, but remarkably enhances post-ischemic glutamate re-uptake.

Animals↗

Effects of lecithinized SOD on contusion injury in rats.

To analyze the effect of lecithinized superoxide dismutase (SOD) on superoxide accumulation after traumatic injury, the expression of Cu,Zn-SOD mRNA was examined after contusion in rat using Northern blotting. As determined by specific gravity, lecithinized SOD decreased brain edema. The expression of Cu,Zn-SOD mRNA increased at the core, peripheral and contralateral hemisphere of injury. These increases were then suppressed by lecithinized SOD. Our results support the hypothesis that superoxide may play an important role in edema formation after contusion, and that lecithinized SOD appears to prevent brain edema through a protective effect against superoxide injury.

Animals↗

Effect of deadtime loss on quantitative measurement of cerebral blood flow with technetium-99m hexamethylpropylene amine oxime.

Deadtime count loss may cause error in quantitative measurements with a gamma camera. We evaluated the effect of deadtime loss on the measurement of cerebral blood flow (CBF). Radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) was performed in 20 patients. A reference source was placed on the periphery of the detector to monitor deadtime loss, and CBF was calculated based on the data of radionuclide angiography with and without deadtime correction. In ten patients injected with 1110 MBq of the tracer, the CBF value without correction was 9.9%+/-1.8% higher than that with correction. This shows that deadtime loss may cause significant overestimation. The difference between CBF values obtained with and without correction was smaller in ten patients with an injected dose of 370 MBq (3.0%+/-1.2%). These results suggest a substantial effect of deadtime loss on CBF as measured by radionuclide angiography and 99mTc-HMPAO.

Adolescent↗

Hippocampal degeneration inducing impairment of learning in rats: model of dementia?

In the pharmacological field, the development of drugs effective for dementia is now widely anticipated because of the increase in the elderly population. Dementia has some histological degeneration in the brain, including the hippocampus. Preclinical evaluations of such drugs use animal models with memory impairment, since memory impairment is a major criterion of dementia. We therefore investigated two animal models with hippocampal degeneration. Neonatal administration of monosodium glutamate (MSG) induced specific degeneration of hippocampal pyramidal cells in the CA1 region of Wistar rats in adulthood. In these animals, the correct response rate during the acquisition period of light-dark discrimination learning was significantly lower than that in the control group. No significant changes were noted in the hippocampal concentrations of neurotransmitter substances, including acetylcholine and glutamate. In the second model, similar histological changes were observed at 3 weeks after oral administration of trimethyltin (TMT). These histological changes were accompanied by a reduction in the intrahippocampal concentrations of acetylcholine and glutamate. In the case of light-dark discrimination learning, neither pre- nor post-training administration of TMT affected the correct response rate during both the acquisition and retention test periods. In the case of 8-arm radial maze learning, the increase in correct response rate was significantly suppressed in comparison with that of the control group when TMT was administered at 4 weeks before starting the acquisition trial. This suppression was followed by a lower response rate in the retention test. On the other hand, the correct response rates in retention tests were not affected when TMT was administered after completion of the acquisition trial. These findings indicate that sole degeneration of the hippocampus was able to induce different types of memory impairment, and single evaluation of a drug with one learning paradigm was difficult to justify that a drug is effective for dementia.

Animals↗

Topical administration of prostaglandin E1 with iontophoresis for skin flap viability.

This study was performed to investigate the capability of iontophoretic delivery of prostaglandin E1 (PGE1) and the effect of this treatment on the viability of skin flaps on the rat dorsum model as described by Hammond and Ronald in 1993. The PGE1 level in the tissue sample under the electrode was assessed with radioimmunoassay. The iontophoretic treatment (for 20 minutes at 4 mA) with PGE1 solution (20 micrograms PGE1 in 2 ml saline) showed a significant increase of PGE1 in the flap tissue under the negative electrode (p < 0.05). Very little increase was observed after the iontophoresis of saline alone. This was not statistically significant. Iontophoretic treatment was given for 5 consecutive days following flap elevation. The survival area on the seventh postoperative day was significantly greater in the PGE1-treated flaps than that of either the control or saline-treated flaps. These results confirm the beneficial effect of iontophoretic treatment with PGE1 on the augmentation of skin flap viability.

Administration, Topical↗

Experimental investigation of battery-induced esophageal burn injury in rabbits.

OBJECTIVE: In recent years, small high-performance batteries have become very popular. With this increasing miniaturization of batteries, clinicians have noted an increasing frequency rate of esophageal injury due to battery ingestion by infants. The situation is associated with severe injury to the esophagus due to the electrical current produced, particularly in the case of high-performance batteries producing high currents. The pathophysiologic features and complications of esophageal battery burns have not been thoroughly investigated. Our study intended to investigate the pathophysiologic features and complications of esophageal battery burn. DESIGN: Open, randomized, controlled study. SETTING: Experimental animal laboratory in a university hospital. SUBJECTS: Male adult mixed-breed rabbits, 22 wks old and weighing 3 to 3.5 kg. INTERVENTIONS: The experimental rabbit model of esophageal injury due to battery ingestion described herein was designed to study not only the direct influence of contact with the battery but also damage to neighboring tissues and the biochemical and pathologic mechanisms of injury. We investigated the relationship between the direction of the inserted battery and the mechanism underlying these complications. Esophageal burn injury was created by placing a 3-V battery into the esophagus for 9 hrs. MEASUREMENTS AND MAIN RESULTS: The cathode side of the esophagus became increasingly alkaline, while the anode side was acidic. Low-voltage battery burns are likely to be due to secondary chemical reactions caused by the electric current because of acid generated at the anode and alkali at the cathode using a micro pH meter. Injury was significantly more severe on the alkaline side when a battery was placed with its cathode directed toward the trachea. Alkaline complications affecting neighboring tissues were more severe than acid complications. These results indicate that as well as the esophageal mucosa itself being injured, deleterious effects are exerted on surrounding tissues, the severity of which vary depending on the orientation and duration of the battery being lodged in the esophagus. CONCLUSIONS: The direction of the battery cathode, which produces alkali, is important in determining the severity of complications. Based on our investigation of the underlying mechanisms of these complications, we advocate the establishment of treatment guidelines for battery swallowing accidents.

Animals↗

Aspirin-induced asthma as a risk factor for asthma mortality.

We have recently reported severe airway obstruction and bronchial hyperresponsiveness (BHR) in fatal asthma compared with patients without a history of near-fatal asthma. Based on these findings, we evaluated whether aspirin-induced asthma (AIA) is a risk factor for asthma mortality by analyzing pulmonary function and BHR. FEV1.0% and methacholine inhalation threshold were significantly lower in the fatal asthma group compared with the AIA and non-AIA groups. However, there were no significant differences between the AIA and non-AIA groups. Our results suggested that AIA is not a risk factor for asthma mortality if avoidance of aspirin and aspirin-like drugs is assured.

Adult↗

A newly developed procedure for monitoring of extracellular proteins using a push-pull microdialysis.

A microdialysis technique combined with a push-pull pump was applied for monitoring protein dynamics in the liver. A newly developed probe has a 0.34 x 10-mm (membrane thickness, 0.05 mm) dialysis membrane of polysulfon and can allow the passage of molecules of up to approximately a few hundred kilodaltons in molecular weight. The probe was inserted in the liver of a rat under pentobarbital anesthesia. Perfusion medium (phosphate-buffered saline) was pumped through the microdialysis probe and collected every 15 min. Effect of ischemic treatment of the protein constitution and the activity of lactate dehydrogenase (LDH) in dialysate were determined to confirm the accuracy of the present technique. The protein constitute in preischemic dialysate differed from those obtained in the serum and hepatic homogenate, showing that the dialysate reflected extracellular protein. LDH activity was high immediately after insertion of the probe, decreased constantly, and then reached a plateau of a relatively low level. When transit ischemic treatment (for 15 min) was performed by ligation of both hepatic artery and portal vein, LDH activity increased significantly, which continued for over 5 h. The concentration of albumin in the dialysate increased immediately after the ischemia. Such changes in LDH activity and albumin concentration reflected ischemic change, and the newly developed technique may be useful for the monitoring of extracellular dynamics of proteins with molecular weight less than 200 kDa.

Albumins↗

Real time monitoring of biphasic glutamate release using dialysis electrode in rat acute brain ischemia.

Glutamate has been proposed to play a critical role in acute ischemic pathophysiology in the brain. In this study, glutamate was monitored by the dialysis electrode technique, in which glutamate is oxidized by glutamate oxidase producing hydrogen peroxide which is then amperometrically detected on a platinum electrode set at +650 mV vs Ag/AgCl. A dialysis electrode, which consists of a microdialysis probe with a built-in platinum electrode, provides a continuous glutamate oxidase perfusion inside of the probe. Perfusion with this solution allows real-time monitoring of glutamate dynamics in the extracellular space during ischemia. This study was designed to collect detailed information on rapid changes in the extracellular glutamate concentration of the rat striatum and demonstrated two distinct phases of glutamate release during early severe brain ischemia.

Amino Acid Oxidoreductases↗

Investigation of the mechanism of alcohol-induced bronchial asthma.

BACKGROUND: Many Japanese patients with asthma experience episodes or exacerbation of asthma after alcohol consumption. This phenomenon is not seen in Caucasians and is specific to Asians. This has been thought to be attributable to a difference in alcohol metabolism, in particular the metabolism of acetaldehyde, between Asians and Caucasians. METHODS: An oral ethanol challenge test, a leukocyte histamine release test, and an ELISA for detection of IgE specific to acetaldehyde-human serum albumin conjugate were carried out in 42 adults with bronchial asthma and nine healthy adults. RESULTS: Fifty-five percent of the patients with asthma responded to the ethanol challenge and showed a 20% or greater reduction in forced expiratory volume in 1 second. Blood acetaldehyde and plasma histamine levels were significantly higher in responders than in nonresponders. The leukocyte histamine release test revealed no ethanol-induced histamine release. Acetaldehyde, on the other hand, was found to induce histamine release in a volume-dependent manner. The histamine release was significantly higher in the asthma group (both responders and nonresponders) than in the healthy control group. ELISA did not detect any IgE specific to acetaldehyde-human serum albumin conjugate. CONCLUSION: Alcohol-induced bronchial asthma seems to develop as follows. Alcohol elevates blood acetaldehyde levels, which leads to degranulation of mast cells (or basophils). The resultant release of chemical mediators, such as histamine, induces asthma.

Acetaldehyde↗

Inhibitory effect of thromboxane A2 synthetase inhibitor, DP-1904, on antigen-induced contraction of human lung parenchyma.

BACKGROUND: Several mediators are released from mast cells during allergic reactions. These substances cause contraction of airway smooth muscles, increase the permeability of blood vessels, and enhance mucous secretion. Among these mediators, thromboxane A2 (TXA2) has a particularly strong bronchoconstrictive effect. OBJECTIVES: We examined antigen-induced contraction of excised human lungs and the suppressive effects of TXA2 synthetase inhibitor on TXA2 release. METHODS: Human lung parenchymal strips were subjected to passive sensitization with sera of 5+ RAST titer to the mite. They were suspended in magnus baths, to which buffer and 10(-4) to 10(-8) M of DP-1904, an inhibitor of TXA2 synthetase, were added. Following the measurement of TXB2 and leukotriene (LT) concentrations in each bath, parenchymal contraction was induced by the addition of a mite antigen. The concentration of TXB2 and LT was measured after contraction. RESULTS: Antigen-induced release of TXB2 was significantly suppressed by DP-1904 in a concentration-dependent manner. DP-1904 did not inhibit parenchymal contraction and the release of LT. CONCLUSIONS: Antigen-induced parenchymal contraction was not suppressed by inhibition of TXA2 release, suggesting that DP-1904 may not be effective in asthma.

Aged↗

[Invasive pulmonary aspergillosis caused by aspiration of polluted water after nearly drowning].

A 21-year-old male nearly drowned in a reservoir by a traffic accident and he aspirated a large mount of polluted water containing Aspergillus fumigatus. On admission to our hospital, he was alert but cyanotic. Chest rentogenograms showed scatter infiltrative shadows in bilateral lung fields. We administered methylpredonizolon and antimicrobial agents immediately because of respiratory failure which was rapidly progressing. During the following six days, infiltrative shadows diminished but multiple nodular shadows in both lung fields appeared. The diagnosis of pulmonary aspergillosis was confirmed by serological and microbiological studies. Intravenous amphotericin B and oral itraconazol were administrated, and clinical improvement was observed.

Adult↗

[Two cases of pulmonary dirofilariasis in Nagasaki Prefecture].

We reported two cases of pulmonary dirofilariasis in Nagasaki Prefecture. Each case was admitted to our hospitals for evaluation of an abnormal shadow on chest X-ray film taken for examination. We strongly suspected lung cancer before operation. It was resected in order to confirm the pathological diagnosis. There was a Dirofilaria immitis in the vessels surrounded by the necrotic tissues. The case of pulmonary dirofilariasis tends to increase in Japan, but the positive rate of dogs with Dirofilaria immitis tends to decrease, because of decreasing breeding places of mosquitoes by the spread of the public sewage system in Nagasaki City.

Adult↗

Csk enhances insulin-stimulated dephosphorylation of focal adhesion proteins.

Insulin has pleiotropic effects on the regulation of cell physiology through binding to its receptor. The wide variety of tyrosine phosphorylation motifs of insulin receptor substrate 1 (IRS-1), a substrate for the activated insulin receptor tyrosine kinase, may account for the multiple functions of insulin. Recent studies have shown that activation of the insulin receptor leads to the regulation of focal adhesion proteins, such as a dephosphorylation of focal adhesion kinase (pp125FAK). We show here that C-terminal Src kinase (Csk), which phosphorylates C-terminal tyrosine residues of Src family protein tyrosine kinases and suppresses their kinase activities, is involved in this insulin-stimulated dephosphorylation of focal adhesion proteins. We demonstrated that the overexpression of Csk enhanced and prolonged the insulin-induced dephosphorylation of pp125FAK. Another focal adhesion protein, paxillin, was also dephosphorylated upon insulin stimulation, and a kinase-negative mutant of Csk was able to inhibit the insulin-induced dephosphorylation of pp125FAK and paxillin. Although we have shown that the Csk Src homology 2 domain can bind to several tyrosine-phosphorylated proteins, including pp125FAK and paxillin, a majority of protein which bound to Csk was IRS-1 when cells were stimulated by insulin. Our data also indicated that tyrosine phosphorylation levels of IRS-1 appear to be paralleled by the dephosphorylation of the focal adhesion proteins. We therefore propose that the kinase activity of Csk, through the insulin-induced complex formation of Csk with IRS-1, is involved in insulin's regulation of the phosphorylation levels of the focal adhesion proteins, possibly through inactivation of the kinase activity of c-Src family kinases.

Amino Acid Sequence↗