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Biomedical subjects

A Akashi

Publications and source records attributed to A Akashi.

At least 55 records · Page 3Linked to original sources
PubMed1990

Protective effect of DM-9384, a novel pyrrolidone derivative, against experimental cerebral anoxia.

The protective effects of DM-9384 [N-(2,6-dimethylphenyl)-2-(2-oxo- 1-pyrrolidinyl) acetamide] against cerebral anoxia were investigated using various animal models. Oral administration of DM-9384 resulted in a significant prolongation of survival time in mice and rats subjected to the normobaric hypoxia; its minimal effective doses were 30 and 10 mg/kg, respectively. A significant protection by this drug against hypobaric hypoxia, histotoxic anoxia and cerebral ischemia also occurred in mice at a dose of 100 mg/kg, p.o. Bifemelane (100-300 mg/kg, p.o.) was protective against these models except for hypobaric hypoxia, and the effects of piracetam, aniracetam and pramiracetam (1000 mg/kg, p.o.) were variable depending on the type of anoxia model used. DM-9384 (100 mg/kg and lower) attenuated the hypolocomotion and the disturbance of cerebral energy metabolism such as a decrease in ATP, an increase in lactate and lactate/pyruvate ratio induced by hypoxia in rats. The spontaneous motor activity, uptake and utilization of brain glucose in normal animals, however, were not influenced by this drug. Based on these results, DM-9384 is characterized as a broad spectrum anti-anoxic drug with negligible CNS depression, and the cerebral protective effect of this drug may be, at least in part, attributable to its ability to improve the cerebral energy metabolic disturbance.

Animals↗
PubMed1990

Antiulcer effects of 3-[[[2-(3,4-dimethoxyphenyl)ethyl] carbamoyl]methyl]-amino-N-methylbenzamide in experimental gastric and duodenal ulcers.

Effects of 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl] methyl]-amino-N-methylbenzamide (DQ-2511), a newly synthesized compound, were evaluated using various types of experimental gastric and duodenal ulcers in rats. Pretreatment with DQ-2511, over the dose range 30-300 mg/kg p.o., resulted in a dose-related inhibition of water-immersion stress-, serotonin-, acetylsalicylic acid (ASA)-, indometacin-, ethanol-, and 2-deoxy-D-glucose(2DG) plus indometacin-induced gastric ulcers as well as cysteamine-induced duodenal ulcers. The antiulcer potencies of DQ-2511 were equal to or greater than those of H2-receptor antagonist cimetidine in these ulcer models except for ASA- and 2DG plus indometacin-induced ulcers. The rate of healing of chronic gastric ulcers induced by acetic acid was significantly accelerated by DQ-2511 (100 and 300 mg/kg p.o.) but not by the same doses of cimetidine. DQ-2511, at doses of 30 mg/kg p.o. and above, produced a significant decrease in gastric acid and pepsin output in pylorus-ligated rats. In anesthetized rats with acute gastric fistulae, 30 mg/kg i.v. of DQ-2511 significantly inhibited gastric acid secretion stimulated by 2DG, whereas it did not affect gastric hyperacidity evoked by either carbachol, histamine or pentagastrin. At effective antiulcer doses, this compound produced a sustained increase in gastric mucosal blood flow in conscious, restrained rats. Based on these observations, DQ-2511 is characterized as a new antiulcer compound with beneficial effects on both gastric aggressive and defensive factors. Furthermore, these results indicate a possible superiority of DQ2511 over cimetidine in regard to its antiulcer potency and spectrum.

Animals↗
PubMed1989

Influence of antihypertensive treatment with budralazine on autoregulation of cerebral blood flow in spontaneously hypertensive rats.

We studied the effect of chronic antihypertensive treatment with budralazine on the lower blood pressure limit of cerebral blood flow autoregulation using spontaneously hypertensive rats. Cerebral blood flow in the parietal cortex and caudate nucleus was measured to determine the lower limit using the hydrogen clearance method. The lower limit in both cerebral regions was significantly higher in 10 untreated spontaneously hypertensive rats than in 10 Wistar-Kyoto rats. The upward-shifted lower limit was restored to close to normal in the caudate nucleus and was partially restored in the parietal cortex of nine rats by 9 weeks of treatment with the high dose (50-68 mg/kg/day) of budralazine, which kept blood pressure constant at approximately normotension during the treatment period; the lower limit was slightly restored in both cerebral regions of seven rats by 4 weeks of treatment with the high dose. However, 9 weeks of treatment with the low dose (19-27 mg/kg/day) of budralazine, which produced moderate continuous hypotension in nine rats, did not apparently influence the lower limit. Our results suggest that long-term antihypertensive therapy with budralazine reduces the upward-shifted lower blood pressure limit of cerebral blood flow autoregulation toward normal and that the restoration induced by budralazine depends on the degree of blood pressure reduction as well as on the duration of the therapeutic period.

Animals↗
PubMed1989

[The effect of an antihypertensive drug budralazine on cerebrovascular lesions in salt-loaded SHR].

Budralazine was evaluated for its protective effect on the onset of cerebrovascular lesions in SHR given 1.5% NaCl as drinking water. The salt-loading for 67 days rapidly accelerated the development of hypertension in SHR (from 180 to over 250 mmHg, 40 days after the loading). The acceleration of hypertension was accompanied by an increase in the incidence of brain softening, cerebral infarct, angionecrosis and hemorrhage by 30-60% following the thrombosis and necrosis of cerebral arterioles. Renal angionecrosis associated with the interstitial nephrosis was also observed by 90% in the animals. Throughout the salt-loading period, oral administration of budralazine (1, 4 and 15 mg/kg/day) resulted in a dose-dependent inhibition of the accelerated hypertension. At larger doses (4 and 15 mg/kg/day), budralazine almost completely ameliorated the cerebral and renal lesions and significantly attenuated the rise of weight in the brain and heart observed in the salt-loaded control rats. Changes in the serum biochemical findings were also inhibited by this drug. In some of the parameters measured, budralazine appeared to be more efficacious than hydralazine (1, 4 and 15 mg/kg/day, p.o.). These results suggest that budralazine attenuates the serious development of hypertension and reduces the incidence and severity of stroke in salt-loaded SHR.

Animals↗
PubMed1989

Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384) on learning and memory in rats.

Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide (DM-9384) on learning and memory were studied using four different experimental rat models. In electroconvulsive shock- or scopolamine-induced amnesia in the step-through passive avoidance task, DM-9384 improved both types of amnesia when administered before the training trial. Aniracetam also showed similar but somewhat weaker effects. Furthermore, in the scopolamine amnesia model, an improvement was confirmed with arecoline. The dose-response curves for these compounds were bell-shaped. In the shuttle box active avoidance task, DM-9384 administered daily 1 hr before each training session facilitated the acquisition process of the avoidance response. In addition, the experiment of light-dark discrimination task with positive reinforcement showed that this compound administered daily after each session slightly accelerated the acquisition process of the correct response. These results suggest an ability of DM-9384 to enhance cognitive functions.

Animals↗
PubMed1989

[Serum and tissue concentration of tegafur and 5-FU after administration of tegafur suppository in patients with lung cancer--correcting the influence of residual blood in the tissue].

Tissue concentration of tegafur and 5-FU was studied in 25 patients with of primary lung cancer, given 2 x 750 mg of tegafur suppository daily preoperatively (total doses 3.75-9.75 g, mean 5.16 g). Furthermore, the influence of blood remaining in the tissue was corrected in the determination of tegafur and 5-FU concentration. The tegafur level in tumor tissue (9.614 +/- 5.739 micrograms/g) was significantly (p less than 0.01) low compared with those in serum and normal lung tissue (13.185 +/- 8.198 micrograms/ml, 12.954 +/- 10.048 micrograms/g). On the other hand, the 5-FU level in tumor tissue (0.124 +/- 0.208) was significantly (p less than 0.01, p less than 0.05) high compared with those in serum and normal lung tissue (0.019 +/- 0.013 micrograms/ml, 0.035 +/- 0.031 micrograms/g) and showed approximately 2.5 times more minimum effective concentration against tumor cells (0.05 micrograms/g). The results show that preoperative administration of 2 x 750 mg of tegafur suppository daily is effective for the transfer of tegafur and 5-FU to lung cancer tissue.

Adult↗
PubMed1989

[Complication related to operative procedure in lung cancer and mediastinal malignancy--report of 6 cases].

Of the patients who underwent surgical treatment for the respiratory system at our hospital over the past 9 years, 6 were postoperatively complicated with chylothorax, 1 with liquorrhea and the other one with paraplegia. Chylothorax occurred after mediastinal lymph node dissection which was carried out for the treatment of malignant tumors. In five cases, it occurred on the left side, and in the sixth case, it occurred on the right side. In 2 patients who received conservative treatment, there was no reduction in chyle outflow, and they died of cerebral infarction and sepsis. The other 4 cases were surgically treated. In 3 of them, the impaired site of the thoracic duct was confirmed by administration of Sudan III before surgery. We confirmed that early reoperation for the chylothorax after lung resection should be performed. Liquorrhea occurred from the 5th costvertebral joint which had been directly infiltrated by lung carcinoma. Fortunately, the postoperative course was uneventful, though the patient complained of dizziness and headache until 14 postoperative days. The case of paraplegia was caused by oxydized cellulose cotton that entered the epidural space via the intervertebral foramen. It was used for hemostasis in the 5th costvertebral joint. This case indicates that oxydized cellulose cotton, which swells when it absorbs water, should be carefully used for hemostasis around the nerves.

Adolescent↗
PubMed1989

[The result of extended thymectomy in patients with myasthenia gravis of pure ocular type].

We studied postoperative status of 14 patients with myasthenia gravis of ocular type who underwent extended thymectomy. Nine patients were in remission, three improved, and two unchanged. No patient became worse and died. The remission rates at one, three, five, and ten years after operation were 50.0%, 58.3%, 60.0%, and 80.0%. The palliation rates at one, three, five, and ten years after operation were 64.3%, 75.0%, 80.0%, and 100%. The remission rate at one year after operation in patients of ocular type was significantly (p less than 0.05) higher than that in generalized type (191 patients). The mean preoperative duration of symptoms in patients who obtained remission after surgery was 7.2 +/- 6.5 months, while mean duration was 85.6 +/- 45.8 months in those patients who could not obtain remission, indicating a significant difference (p less than 0.05) of duration of symptoms between two groups. Among 89 patients with generalized as well as ocular symptoms before extended thymectomy, 62 patients (69.7%) still complained of ocular symptoms and 48 patients (53.9%) had generalized symptoms with or without ocular symptoms in 1 to 12 years after operation. This result shows that ocular symptoms do not disappear more easily than generalized ones. We conclude that extended thymectomy should be performed even in patients with myasthenia gravis of pure ocular type.

Adult↗
PubMed1989

[Study on indication of unilateral pulmonary artery occlusion test in patients undergoing pneumonectomy].

We tried to establish an indication of unilateral pulmonary artery occlusion test (UPAO), by analyzing the preoperative data of UPAO, overall and regional pulmonary function tests, and arterial blood gas in 55 patients who were intended for pneumonectomy. Our limits of functional indication for pneumonectomy were PPA less than or equal to 25 mmHg or TPVRI less than or equal to 700 dyne.cm-5.m2. PPA correlated with the inverse of contralateral FEV1.0/BSA (FEV section 1.0) and DLCO/BSA (section DLCO), which were calculated by multiplying preoperative values by contralateral ventilation fraction. TPVRI correlated with age, the inverse of PaO2, the inverse of FEV section 1.0, and the inverse of section DLCO. Multiple regression analysis yielded the equation, TPVRI approximately p = 1120/section DLCO + 24800/PaO2 + 6.40 X Age -506. In order to make false negative zero, the values of each parameter were as follows: age greater than or equal to 55, PaO2 less than or equal to 85 mmHg, FEV section 1.0 less than or equal to 0.8 L/m2, section DLCO less than or equal to 6.0 ml/min/mmHg/m2 and TPVRI approximately p greater than or equal to 450 dyne.sec.cm-5.m2. The specificities of each parameter were 18.6%, 20.9%, 39.2%, 40.4% and 59.0%. Therefore, in order to make false positive patients least, the criteria of TPVRI approximately p greater than or equal to 450 dyne.sec.cm-5.m2 should be used.

Adult↗
PubMed1988

Cholinergic innervation of the main and the accessory olfactory bulbs of the rat as revealed by a monoclonal antibody against choline acetyltransferase.

The main and accessory olfactory bulbs (MOB and AOB) of the rat were immunohistochemically stained with a monoclonal antibody against choline acetyltransferase (ChAT) in order to know the difference in the distribution patterns of cholinergic fibers between these two structures. A few ChAT-immunoreactive cell bodies were found in the superficial and middle parts of the external plexiform layer (EPL) of the MOB, in the granule cell layer (GCL) of the MOB, and in the GCL of the AOB. The frequency in appearance of these cells was 0.9 cells/section in the MOB and 0.3 cells/section in the AOB. While the glomerular layer (GL) and the superficial part of the EPL were most densely innervated in the MOB, the internal plexiform layer received the richest innervation in the AOB. There were no immunoreactive structures in the olfactory nerve layer of the MOB and in the vomeronasal nerve layer and glomerular layer of the AOB. In addition to a relatively homogenous distribution of cholinergic fibers in the MOB and AOB, there were several foci of very dense network of immunoreactive fibers at the posterior level of the OB. These foci formed a part of the modified glomerular complex that was recently identified using 2-deoxyglucose method and was presumed to be related to suckling behaviour in the neonatal rat.

Animals↗
PubMed1988

Prediction of postoperative respiratory failure in patients undergoing lung resection for lung cancer.

To evaluate the correlation between predicted postoperative lung function and postoperative respiratory morbidity, 156 patients with lung cancer who underwent resection were classified into four groups based on the degree of postoperative problems: Group 1--no problems (116 patients); Group 2--retention of sputum or atelectasis requiring bronchofiberscopy two or more times (17 patients); Group 3--tracheostomy or mechanical ventilation for more than 2 days or both (14 patients); and Group 4--postoperative death (9 patients). The mean ages of Groups 2, 3, and 4 were significantly (p less than 0.05) higher than the mean age of Group 1. The predicted postoperative lung function (F) was assessed by the formula F = [1-(b-n)/(42-n)] x f, where f is the preoperative vital capacity or forced expiratory volume in one second, b is the number of subsegments of the resected lung lobe, and n is the number of subsegments obstructed by the tumor, which was assessed by the findings on the chest tomogram, on the bronchogram, at bronchofiberscopy, or a combination of these. The total number of subsegments was assumed to be 42. The predicted postoperative % FEV1 was 65.1 +/- 19.3% in Group 1,55.3 +/- 10.6% in Group 2,37.6 +/- 12.1% in Group 3, and 42.3 +/- 18.4% in Group 4. It was significantly (p less than 0.05) different between all the groups except between Groups 3 and 4. All 10 patients with a predicted postoperative % FEV1 of less than 30% were in Groups 3 and 4. We conclude that special attention to postoperative management is needed for patients whose predicted postoperative %FEV1 is lower than 30%.

Aged↗
PubMed1988

Molecular cloning and expression of a gene for a factor which stabilizes formation of inhibitor-mitochondrial ATPase complex from Saccharomyces cerevisiae.

Stabilizing factor, a 9 kDa protein, stabilizes and facilitates formation of the complex between mitochondrial ATP synthase and its intrinsic inhibitor protein. A clone containing the gene encoding the 9 kDa protein was selected from a yeast genomic library to determine the structure of its precursor protein. As deduced from the nucleotide sequence, the precursor of the yeast 9 kDa stabilizing factor contains 86 amino acid residues and has a molecular weight of 10,062. From the predicted sequence we infer that the stabilizing factor precursor contains a presequence of 23 amino acid residues at its amino terminus. We also used S1 mapping to determine the initiation site of transcription under glucose-repressed or derepressed conditions. These experiments suggest that transcription of this gene starts at three different sites and that only one of them is not affected by the presence of glucose.

Adaptor Proteins, Signal Transducing↗
PubMed1988

Analysis of the mechanism underlying the vasodilator action of carvedilol in pithed spontaneously hypertensive rats.

The present experiments were carried out to examine the vasodilator mechanism(s) of carvedilol by use of pithed spontaneously hypertensive rats (SHR). Animals were pithed and the dose-pressor response curves to various agonists were obtained 0.5 or 1 hour after oral administration of either carvedilol (30 mg/kg), labetalol (60 mg/kg), prazosin (0.1 mg/kg) or hydralazine (3 mg/kg). These doses of drugs caused approximately equihypotensive responses in the conscious state. Carvedilol significantly shifted the dose-pressor response curve to the right for phenylephrine but not for B-HT 920, angiotensin II and vasopressin. Labetalol and prazosin also significantly shifted the dose-response curve to the right for phenylephrine but not for angiotensin II. The rank order of inhibitory action on the phenylephrine response was prazosin greater than labetalol greater than carvedilol. In addition, carvedilol produced a slight but significant inhibition of the pressor responses to serotonin (5-hydroxytryptamine), which was nearly identical in magnitude to that seen with hydralazine. These results suggest that the vasodilator action of carvedilol is mainly attributed to alpha 1-adrenoceptor blockade, although additional non-adrenergic mechanism(s) of action cannot be excluded.

Adrenergic beta-Antagonists↗
PubMed1988

Immunohistochemical conditions for staining choline acetyltransferase-containing axon terminals in the rat.

Immunohistochemical conditions for staining cholinergic axon terminals using a commercially available anticholine acetyltransferase (anti-ChAT) monoclonal antibody were determined in the rat. A number of variations of procedures including fixative composition, fixation time, and incubation time and temperature in the anti-ChAT antibody solution were tested. Optimal procedures for minimizing the chance of negative staining of ChAT-containing axon terminals consisted of perfusion with a mixture of 4% paraformaldehyde and 0.2% glutaraldehyde for 3 min followed by a fixative containing only 4% paraformaldehyde for 10 min, and reaction with the anti-ChAT antibody for 2 days at 37 C. The distribution patterns of axon terminals stained in the cerebral cortex and the hippocampal formation were comparable to those reported by other investigators using different monoclonal antibodies.

Animals↗
PubMed1988

General pharmacological properties of muroctasin.

General pharmacological effects of N2-[(N-acetyl-muramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-ly sine MDP-Lys(L18), muroctasin) were examined and the following results were obtained. 1. Central nervous system: MDP-Lys(L18) had no effect on behavior, spontaneous motor activity, electroshock- and chemoshock-induced convulsions, hexobarbital sleeping time, pain threshold (mice), conditioned avoidance response (rats) at a dose of 0.4 mg/kg, s.c. and EEG as well as spinal reflex (cats) at a dose of 0.4 mg/kg, i.v. It produced a significant elevation in body temperature (rabbits) at doses of 13 micrograms/kg, s.c. and greater. 2. Respiratory and cardiovascular system (dogs): MDP-Lys(L18) did not show any significant effect on respiratory and cardiovascular functions at a dose of 0.4 mg/kg i.v. 3. Autonomic nervous system: MDP-Lys(L18) induced a miosis (rabbits) at doses of 13 micrograms/kg s.c. and greater. It did not affect norepinephrine-induced pressor and acetylcholine-induced depressor responses (dogs) and contraction of the nictitating membrane induced by electrical stimulation (cats) at a dose of 0.4 mg/kg i.v. 4. Smooth muscles: In the experiments using the isolated ileum, vas deferens, trachea (guinea pigs) and uterus (rats), MDP-Lys(L18) showed neither spasmogenic nor spasmolytic activity at a concentration of 4 x 10(-6) g/ml. Gastrointestinal propulsion (mice), gastric mucosa, gastric emptying rate and gastric secretion (rats) were not affected by this drug at a dose of 0.4 mg/kg s.c. MDP-Lys(L18) did not influence gastrointestinal motility (dogs) at a dose of 0.4 mg/kg, i.v. 5. Miscellaneous: MDP(L-18) suppressed carrageenan-induced edema (rats) at doses of 0.13 mg/kg s.c. and greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Non-Hodgkin's lymphoma of the pleural cavity developing from long-standing pyothorax.

Malignant lymphomas developing in tissue affected by a long-standing severe inflammatory process of nonautoimmune nature are presented. Two men and a woman aged 50, 58, and 73 years, were admitted after 22 to 30 year histories of pyothorax resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. The diagnoses at admission were chronic pyothorax associated with a lung mass. Microscopically, tumors diffusely or locally proliferated with thickened pleura were present. A histologic examination showed that all the tumors were diffuse non-Hodgkin's lymphomas (NHL) of immunoblastic type with (one case) or without (two cases) plasmacytoid differentiation. Immunohistochemistry on paraffin sections revealed restricted expression of immunoglobulin light chains in one case showing plasmacytoid differentiation. A review of the literature showed that malignant lymphomas of this type have been reported exclusively from Japan but never from Western countries.

Aged↗