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Biomedical subjects

S Konno

Publications and source records attributed to S Konno.

At least 145 records · Page 8Linked to original sources

Effects of sumatriptan on the cerebral intraparenchymal microcirculation in the cat.

1. Sumatriptan, a 5-hydroxytryptamine (5-HT)1-like receptor agonist, is effective against the headache of migraine. The effects of sumatriptan injected via the carotid artery on the cerebral microcirculation were studied in 10 anaesthetized cats. 2. The local cerebral blood volume (CBV), mean transit time of blood (MTT) and cerebral blood flow (CBF) in the parieto-temporal cortex were measured by a photoelectric method. CBV represents the cumulative dimensions of the cerebral microvessels. 3. Sumatriptan at 5 and 50 micrograms kg-1 had no significant effects on the CBV, MTT, CBF, and mean arterial blood pressure (MABP); 500 micrograms kg-1 of sumatriptan reduced the CBV, prolonged the MTT, and decreased the CBF (approximately -20%) without affecting the MABP. Sumatriptan, 5 mg kg-1, elicited transient reductions in CBV and CBF, which were attributable to the rapid and marked falls of MABP seen with this dose. 4. Thus, while a high dose of sumatriptan (500 micrograms kg-1) exhibits direct vasoconstrictor actions on the cerebral vessels, low doses of sumatriptan, within the therapeutic range, elicit no vasoconstriction. The data do not support a vasoconstrictor action of sumatriptan playing a primary role in reversing the headache of migraine.

Animals↗

[Studies on as-triazine derivatives. XIX. Synthesis of 2,3-diarylpyrazine 2,3-diarylpyridine derivatives as blood platelet aggregation inhibitors].

4,5-Diphenyl-2-ethoxypyrimidine (1), 3,4-diphenyl-6-ethoxypyridazine (2) and 2,3-diphenyl-5-ethoxypyrazine (3) were evaluated for inhibitory activity towards arachidonic acid-induced aggregation of rabbit blood platelet in vitro. 2,3-Diphenyl-5-ethoxypyrazine (3) exhibited significant inhibitory activity. Thus, various 5-substituted 2,3-bis(4-methoxyphenyl)pyrazines were synthesized by the nucleophilic substitution reaction of 5-chloro-2,3-bis(4-methoxyphenyl)pyrazine (9). In a similar manner, substituted 2,3-bis(4-methoxyphenyl)pyridines were prepared from 2,3-bis(4-methoxyphenyl)-6-methylsulfonylpyridine (17), which was synthesized by the cycloaddition retro Diels-Alder reaction of 5,6-bis(4-methoxyphenyl)-3-methylsulfonyl-1,2,4-triazine (16) with norbornadiene. Among the compounds prepared, 6-isopropoxy-2,3-bis(4-methoxyphenyl)-pyrazine (10f) showed the most potent inhibitory activity, which was more than the activity of anitrazafen[5,6-bis(4-methoxyphenyl)-3-methyl-1,2,4-triazine.

Animals↗

[Studies on biphasic animal model of asthma--lymphocytes and eosinophils].

To clarify the role of lymphocytes and eosinophils in the late asthmatic response (LAR) observed several hours after OA challenge, and in airway inflammation observed 24 hrs after OA challenge in OA sensitized guinea pigs, we examined the infiltration and/or accumulation of lymphocytes and eosinophils in lung tissues by PKH2 labeling technique and Luna staining technique, respectively. The guinea pigs showed LAR 6 hrs after exposure to antigen, when moderate infiltration of lymphocytes and marked accumulation of eosinophils were observed in lung tissues. At 24 hrs after OA challenge, intensive infiltrations of both lymphocytes and eosinophils into the lung were observed. Pretreatment with MTX (methotrexate) suppressed LAR, inhibited infiltrations of lymphocytes and eosinophils into lung tissues at 6 hrs (LAR) and at 24 hrs after OA challenge, and prevented bronchial hyperresponsiveness to methacholine 48 hrs after antigen exposure in a dose-dependent manner. These findings suggest that lymphocytes and eosinophils are involved in LAR and also in the chronic airway inflammation which is believed to make the bronchial asthmatic condition more severe and more refractory. Also, our results showed that MTX, which has an inhibitory action on such inflammation, may be a useful bronchial asthma.

Animals↗

[Blunt trauma with combined femoral arterial and venous occlusion].

Blunt trauma to common femoral artery is rare, and it is frequently unrecognized. A 61-year-old man who fell while carrying a log and struck on his right groin, presented right leg edema and intermittent claudication one month later. Both right femoral arterial and venous occlusion was suspected by Doppler flowmeter, confirmed by venography and arteriography which showed concomitant external iliac arterial occlusion. He underwent prosthetic bypass grafting from common iliac artery to common femoral artery and embolectomy of femoral vein. Circulation to the right leg was restored, but postphlebitic syndrome had remained which was ameliorated by wearing the elastic stocking.

Femoral Artery↗

[A successful mitral valve replacement for infective endocarditis with mitral valve aneurysm].

We reported a rare case of mitral valve aneurysm. The patient was a 67-year-old woman with regurgitation of mitral and aortic valve due to infective endocarditis. Preoperative two-dimensional echocardiogram revealed a aneurysmal change and prolapsing on anterior mitral leaflet. Left ventriculogram showed mitral regurgitation of Sellers IV. She underwent mitral valve replacement with 27 mm Carbo Medicus prosthesis successfully. There was a perforated valvular aneurysm (21 x 15 x 11 mm) and inflammatory cleft on anterior mitral leaflet at histopathological findings. The pathogenesis of mitral valve aneurysm was generally infective endocarditis and rarely congenital anomaly, syphylis, Aortitis syndrome, or Marfan syndrome. Mitral valve replacement was a procedure of choice for mitral valve aneurysm, which is especially large, perforated and severely inflammatory one.

Aged↗

[Successful surgical repair for a patient with atrial septal defect and severe pulmonary hypertension--its surgical indication and prostaglandin E1 use for postoperative pulmonary hypertensive crisis].

A 45-year-old woman with atrial septal defect and pulmonary hypertension was admitted for surgical repair. Cardiac catheterization data revealed pulmonary to systemic flow ratio (Qp/Qs) of 1.81, pulmonary artery pressure (PAP) of 82/30 mmHg and pulmonary vascular resistance (PVR) of 10.8 unit. Open lung biopsy was added to evaluate pulmonary vascular obstructive disease (PVOD) which was shown Heath-Edwards grade 3 PVOD. Following closure of the defect, PAP (systolic) exceeded momentarily systemic level after cardiopulmonary bypass. Prostaglandin E1 drip was remarkably effective to bring down PAP during early postoperative period. Although PAP has not been shown significant decrease on catheterization of one year after surgery, great symptomatic improvement has been achieved.

Alprostadil↗

[A case report of central pontine myelinolysis associated with serum hyperosmolality after open heart surgery].

A 65-year-old man was admitted with a sudden onset of dyspnea. Severe mitral regurgitation due to torn chordae tendinae was revealed on UCG. Mitral valve replacement was undergone. The postoperative course was complicated with a low cardiac output syndrome which was successfully treated with IABP, catecholamines and vasodilators. However, stupor developed on the 4 th postoperative day, following by tetrapregia on the 8 th day, and deep coma on the 15 th day respectively. Laboratory studies of the 4 th day disclosed the following values, serum sodium 150 mEq/l, blood urea nitrogen 84.7 mg/dl, blood sugar 184 mg/dl and calculated serum osmolality 354 mOsm/l. Cranial CT of the 15 th day showed an obscure low density area in the central pons which was strongly suggestive of central pontine myelinolysis (CPM). His CNS symptoms improved dramatically after administration of thyrotropin-releasing hormone tartrate (TRH-T). A diagnosis of CPM was made on MRI of the 41 st day. He discharged without any neurological deficit on the 62 nd day.

Aged↗

[Bronchial reactivity to methacholine and serotonin in six inbred mouse strains].

We examined six mouse strains, A/J, DBA/2, WBB6F1-W/Wv, WBB6F1- +/+, C3H/HeN, C57BL/6, for their bronchial reactivity to methacholine and serotonin. The mice were anaesthetized with intraperitoneal sodium pentobarbital. The trachea was intubated and one jugular vein was cannulated. Then, the mice were ventilated on air, using a small animal ventilator at a rate of 60 strokes/min with a tidal volume of 0.5 ml. Methacholine and serotonin diluted to various concentrations were administered intravenously. Bronchoconstriction was assessed by the modified Konzett-Rossler method. According to their bronchial responsiveness to methacholine and serotonin, the strains were grouped into high- (A/J, DBA/2), middle- (WBB6F1-W/Wv, -+/+) or low- (C3H/HeN, C57BL/6) responder groups.

Animals↗

Inhibition of human T-lymphocyte activation by macrolide antibiotic, roxithromycin.

Effects of macrolide antibiotic, roxithromycin (RXM) on human lymphocytes in culture were studied. The drug showed a dose-dependent inhibition of 3H-thymidine and 35S-methionine uptake responding to T cell mitogens and purified protein derivative of tuberculin (PPD). Activation by PPD, as assessed by 3H-thymidine uptake, was more sensitive to inhibition than the response to T cell mitogens. The drug produced a loss of blasts when added soon after transformation commenced. Immunosuppressive effects of RXM were further characterized by using four different types of metabolized RXM, RU 28111, RU 39001, RU 44981 and RU 45179. The most potent inhibitor of lymphocyte transformation was RU 45179, followed by RU 44981, RU 39001 and RU 28111 have little activity.

Cells, Cultured↗

Influences of roxithromycin on cell-mediated immune responses.

We investigated the effects of roxithromycin (RXM), a synthesized macrolide antibiotic on murine cellular immune responses by examining the in vitro proliferative response of lymphocytes, interleukin 1 (IL-1) production and interleukin 2 (IL-2) production. RXM was orally administered to BALB/c mice at a dose of 5 mg/kg once a day for 42 days. Spontaneous blastic activity of lymphocytes prepared from mice administered with RXM for 7 days was higher than those from control mice. The activity peaked at the 14th day, and then decreased gradually to control levels by the 42nd day. Time kinetics of lymphocyte blastogenesis to concanavalin A showed a pattern similar to that observed in spontaneous blastic activity. Oral administration of RXM also influenced cytokine production; short-term (for 14 days) administration of RXM enhanced both IL-1 and IL-2 production but long-term (for 42 days) administration inhibited them.

Animals↗

Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin.

BACKGROUND AND PURPOSE: The purpose of this study was to compare the effects of low-to-high doses of aspirin on platelet aggregability determined by different methods and on the metabolism of thromboxane A2 and prostacyclin. METHODS: We administered increasing doses (40, 320, and 1,280 mg/day) of aspirin to 19 poststroke patients and studied the differences in 1) the changes in platelet aggregability depending on the methods of evaluation and 2) the concentrations of prostaglandin metabolites in the blood and urine. RESULTS: Aggregation of platelet-rich plasma induced by a strong stimulus (10 microM ADP) was significantly reduced after 40 mg/day aspirin (p less than 0.005), and this reduction was similar to that after higher aspirin doses. In contrast, aggregation of platelet-rich plasma induced by weaker stimuli (1 and 5 microM ADP) decreased less significantly after 40 mg/day aspirin compared with that after higher aspirin doses. The serum thromboxane B2 generated after ex vivo incubation was reduced significantly (by 85%) after 40 mg/day aspirin and decreased further after 320 mg/day (by 96%) and 1,280 mg/day (by greater than 99%) of aspirin. The urinary 11-dehydro-thromboxane B2 concentration decreased less significantly after 40 mg/day aspirin (by 42%) compared with that after 320 mg/day (by 78%) and 1,280 mg/day (by 91%) aspirin doses. The urinary concentration of 2,3-dinor-6-keto-prostaglandin F1 alpha did not decrease after 40 mg/day aspirin but decreased significantly after higher doses of aspirin. CONCLUSIONS: These findings suggest that different doses of aspirin may be necessary to prevent thrombogenesis induced by different triggers of different strengths and that 40 mg/day aspirin is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.

6-Ketoprostaglandin F1 alpha↗

[Studies on as-triazine derivatives. XVIII. Synthesis of 5,6-diaryl-1,2,4-triazine derivatives as blood platelet aggregation inhibitors].

5,6-Diphenyl-, 3,5-diphenyl-, and 3,6-diphenyl-1,2,4-triazine (as-triazine) derivatives were evaluated for inhibitory activity towards arachidonic acid-induced aggregation of rabbit blood platelet in vitro. Among the isomers, 5,6-diphenyl-as-triazine derivatives were active, therefore a phenyl substituent on the as-triazine ring at the 5- and 6-position was essential for the inhibitory activity. Thus, various 3-substituted 5,6-diaryl-as-triazines were synthesized by the nucleophilic substitution reaction of 5,6-diaryl-3-methylsulfonyl-as-triazines with O,N,C-nucleophiles. In the case of as-triazines having different aryl groups at the 5- and 6-positions, the compounds were prepared by the step-wise addition reaction of Grignard reagents with 3-methylthio-as-triazine. Among these compounds, ethyl 5-(4-methoxyphenyl)-6-phenyl-as-triazine-3-acetate (24a) and ethyl 5,6-bis(4-methoxyphenyl)-as-triazine-3-acetate (24f) showed the most potent inhibitory activity, which was almost equal to the activity of anitrazafen.

Animals↗

[Synthesis of 6-alkylaminopyridazine-3-carboxylic acid derivatives as dopamine beta-hydroxylase inhibitors].

A series of 6-alkylaminopyridazine-3-carboxylic acid derivatives was tested for dopamine beta-hydroxylase inhibitory activity in vitro according to the method of Kruse et al. Methyl 6-alkylaminopyridazine-3-carboxylates (4) were synthesized through the reaction of methyl 6-chloropyridazine-3-carboxylate (1) with ammonia followed by the condensation with primary amines, and by the methanolysis of the resulting 6-alkylaminopyridazine-3-carboxamides (3) in methanol in the presence of boron trifluoride etherate. Among tested compounds, 6-benzylaminopyridazine-3-carboxylic acid was found to have the most potent inhibitory activity, which was in the same level of the activity of fusaric acid.

Dopamine beta-Hydroxylase↗

Rates of detection of Salmonella and Campylobacter in meats in response to the sample size and the infection level of each species.

Pork, beef and chicken meat samples were collected from slaughter houses, poultry-processing plants and meat shops. Rates of incidence of Salmonella spp., Campylobacter jejuni and C. coli with respect to the sample size were compared and the most probable number for these species were determined. Salmonella spp. were detected in 69 (24.1%) of 286 chicken meat samples, in three (3.2%) of 94 pork samples, and in one (1.9%) of 52 beef samples. With chicken meat, the rates of detection were: 19.9% in 25-g, 15.7% in 10-g, and 12.2% in 1-g samples. The populations in most probable numbers, that gave positive results in 31 (20.8%) of 149 samples, ranged from 30 to 10(4) per 100 g, the majority (93.5%) being between 30 and 10(3) per 100 g. C. jejuni and C. coli were detected in 106 (67.9%) of 156 chicken meat samples, in two (2.1%) of 94 pork samples, and none of 52 beef samples. The results obtained with different sample sizes of chicken were compared. Positive rates were 55.8%, 39.7%, 27.6% in 10 g, 1 g, and 0.1 g, respectively. The most probable numbers in 107 (68.6%) positives out of 156 chicken samples examined ranged from 30 to 10(6) per 100 g: 46 (29.5%) contained between 10(2) and 10(3) per 100 g, 22 (14.1%) between 10(3) and 10(4) per 100 g, and the other 19 samples (12.2%) between 10(4) and 10(5) per 100 g.

Animals↗

Cerebellar hypoplasia associated with Arnold-Chiari malformation in a Japanese shorthorn calf.

A case of Arnold-Chiari malformation associated with severe cerebellar hypoplasia in a Japanese Shorthorn calf is reported. Histological examination revealed severe and extensive lesions in the cerebellar vermis. Hypoplasia of the cerebellum in Arnold-Chiari malformation appeared to indicate the abnormal embryonic development of the neural tissue, but the exact cause is not known.

Animals↗

[The mechanism of airway hyperresponsiveness following immediate bronchial response in ovalbumin (OA)-sensitized guinea pigs].

We have previously demonstrated that airway responsiveness was enhanced following a late bronchial response (LBR) after an allergen challenge in ovalbumin (OA)-sensitized guinea pigs. The purpose of the present studies was to evaluate whether airway responsiveness to methacholine increased after an immediate bronchial response (IBR) and the possible involvement of the beta-adrenoceptor dysfunction in OA-sensitized guinea pigs. Guinea pigs were actively sensitized by aerosolized OA. Following OA exposure, IBR appeared. After IBR when specific airway resistance returned to the base line value, airway responsiveness to methacholine increased significantly. Before OA exposure, propranolol induced bronchoconstriction (PIB) was not provoked, however, after IBR, PIB was provoked and the guinea pigs died because of severe bronchoconstriction. These results suggest that airway responsiveness to methacholine increases significantly after IBR. Furthermore, the dysfunction of the beta-adrenoceptor may be a mechanism of this hyperresponsiveness in OA-sensitized guinea pigs.

Animals↗