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Biomedical subjects

K Obara

Publications and source records attributed to K Obara.

At least 145 records · Page 8Linked to original sources

Effects of a selective inhibitor of cyclic AMP phosphodiesterase on the pial microcirculation in feline cerebral ischemia.

We evaluated the effects of cilostazol, a selective inhibitor of cyclic adenosine monophosphate phosphodiesterase, on the pial vessels of adult cats subjected to endothelial damage followed by middle cerebral artery occlusion. Six cats were treated with cilostazol and four with 30% N,N-dimethylformamide in 70% saline (solvent). The brain surface was irradiated with ultraviolet rays through a cranial window for 3 minutes to selectively damage the endothelium of the pial vessels in both groups. Beginning 32 minutes after termination of the irradiation, the middle cerebral artery was occluded for 30 minutes. Thirty minutes before occlusion, intravenous infusion of 30 micrograms/kg/min cilostazol or 0.1 ml/kg/min solvent was begun and continued until the end of the study. Before occlusion, the infusion of cilostazol induced a significant (p less than 0.05) dilatation while the infusion of solvent produced no significant changes in the diameter of the pial arteries. The pial veins of solvent-treated cats showed significant (p less than 0.05) constriction during occlusion, whereas cilostazol-treated cats exhibited only mild constriction of the pial veins. The formation of platelet thrombi after occlusion was significantly (p less than 0.05) inhibited in the pial veins of cilostazol-treated compared with solvent-treated cats. Similarly, the microcirculation of the pial veins was effectively restored after reopening of the middle cerebral artery in cilostazol-treated compared with solvent-treated cats. Our data suggest that cilostazol is an effective antithrombotic agent as well as a potent vasodilator acting on vascular smooth muscle.

Animals↗

Effects of nicorandil on isolated smooth muscle cells from guinea-pig taenia caeci.

1. The effects of nicorandil on guinea-pig taenia caeci were investigated with the use of isolated smooth muscle cells and glycerin-treated muscle fiber bundles. 2. Nicorandil inhibited high K-, Ca2+- and carbachol-induced contractions in a dose-dependent manner without affecting 45Ca fluxes in isolated cells. 3. Nicorandil had no effect on ATP-induced contraction of glycerin-treated muscle fiber bundles. 4. The present results suggest that nicorandil may inhibit the contraction by action on the contractile proteins in an indirect manner in guinea-pig taenia caeci.

Animals↗

Stable prostacyclin analogue preventing microcirculatory derangement in experimental cerebral ischemia in cats.

We evaluated the effect of a stable synthetic prostacyclin analogue, TRK-100, on the microcirculatory derangement occurring in feline pial vessels with endothelial damage after middle cerebral artery occlusion. Fifteen adult cats were divided into an untreated group (Group 1, n = 8) and a treated group (Group 2, n = 7). Thirty minutes after 10 minutes of ultraviolet irradiation, which selectively damaged endothelium in the pial vessels, the middle cerebral artery was occluded in both groups and maintained for 30 minutes. In Group 2, 50 ng/kg/min TRK-100 was continuously infused intravenously following ultraviolet irradiation. In both the pial arteries and veins, platelet aggregate adhesion to the endothelium with subsequent thrombus formation was significantly (p less than 0.01 and p less than 0.05, respectively) inhibited during middle cerebral artery occlusion in Group 2 compared with Group 1. Similarly, blood flow stasis in the pial veins was effectively prevented in Group 2 during occlusion. Furthermore, the pial artery diameter returned to the control level during the late period of occlusion, whereas in Group 1 the pial artery remained constricted. Our data suggest that TRK-100 can prevent microcirculatory derangement in the acute stage of ischemic stroke.

Animals↗

Effects of the new calcium antagonist 2-nitratopropyl 3-nitratopropyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate on cerebral circulation in cats.

Effects of CD-349 (2-nitratopropyl 3-nitratopropyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate) on cerebral circulation were studied in 10 cats. The cats were fixed in a stereotactic head-holder, and two burr holes were made at 3-mm intervals over the left parietal cortex. Through one cranial window, the pial artery and vein diameters were measured continuously by a newly developed videocamera system in conjunction with a width analyzer, and the other one was used for measurement of cerebral blood volume (CBV). The pial artery (141 +/- 14 micron) was dilated by 16.6 +/- 4.9% (p less than 0.01) 1 min and 24.8 +/- 5.1% (p less than 0.01) 5 min after the CD-349 injection. The pial vein (101 +/- 20 micron) was also dilated with the percent increase of the diameter being 11.4 +/- 4.0% (p less than 0.01) 1 min and 11.3 +/- 4.9% (p less than 0.05) 5 min after the CD-349 administration. The CBV was also increased. The mean arterial blood pressure was decreased by 39.8 +/- 7.3 mmHg (p less than 0.01) 1 min and 34.4 +/- 5.5 mmHg (p less than 0.01) 5 min after drug injection. Thereafter, the blood pressure gradually returned to the pre-drug level. Form these results it is suggested that CD-349 exerts direct vasodilatory action via inhibition of calcium influx across vascular cell membranes into cerebral vessels.

Animals↗

Relationship between length-tension relation and 20,000 dalton myosin light chain phosphorylation in guinea-pig taenia caeci.

1. Relationship between length-tension relation and phosphorylation of 20,000 dalton myosin light chain (LC20) in guinea-pig taenia caeci was investigated. 2. At in situ length (Lb), a good linear correlation was obtained between isometric tension and LC20 phosphorylation in high-K+-stimulated muscle. 3. In 100 mM K+-stimulated muscle, the active tension decreased at muscle lengths other than Lb, but no significant decrease in degree of LC20 phosphorylation was observed. 4. These results suggest that in guinea-pig taenia caeci, the major portion of the decrease in active tension at muscle lengths other than Lb is not due to a decrease in degree of activation.

Animals↗

Ca2+-induced Ca2+ release in skinned single smooth muscle cells isolated from guinea-pig taenia caeci.

The Ca2+ release from intracellular Ca2+ storage sites of skinned single smooth muscle cells isolated from guinea-pig taenia caeci was studied. The Ca2+ release from intracellular Ca2+ storage sites of the skinned single cells was enhanced by the presence of submicromolar concentrations of Ca2+ in the solution. The Ca2+ release was enhanced by caffeine and adenine, and suppressed by Mg2+ and procaine. These results suggest that the Ca2+-induced Ca2+ release mechanism may play an important role in the release of Ca2+ from intracellular storage sites of guinea-pig taenia caeci smooth muscle cells.

Adenine↗

[Clinical evaluation on the usefulness and safety of norfloxacin in a twice-a-day regimen against upper respiratory tract infections].

Sixty-six patients with tonsillitis or pharyngolaryngitis received oral norfloxacin (NFLX) 200 mg b.i.d. or 300 mg b.i.d. for not less than 3 days in general at School of Medicine, Yokohama City University, and 6 related hospitals. The results are summarized as follows: 1. Ten patients were excluded from the study because 4 patients did not present at the follow-up visits, 4 patients did not follow the protocol and 2 patients had unclear infections. Thus, 56 patients were evaluated. 2. The fifty-six evaluable patients were classified as follows: Twenty patients were with tonsillitis and 36 were with pharyngolaryngitis. Thirty-eight patients were treated with 200 mg b.i.d. while 18 patients received 300 mg b.i.d. Thirty-two patients were male and 24 patients were female. Three patients were inpatients and 53 patients were outpatients. Most of patients were light or moderate cases, and the 26 patients had mild underlying disorders. 3. Clinical improvements were observed in 11 of 15 patients (73.3%) with tonsillitis and 25 of 30 patients (83.3%) with pharyngolaryngitis (80.0% overall) within 7 days administration. 4. Clinical improvements were observed in 15 of all 20 patients (75.0%) with tonsillitis and 30 of all 36 patients (83.3%) with pharyngolaryngitis (80.4% overall). 5. Bacteriologically, "eradication", "decrease" and "replacement" were observed in 6, 2 and 1 patients, respectively. 6. As for adverse effects, nausea and headache were observed in 1 patient and abnormal changes in laboratory findings were noted in 1 patient (slight elevations of GOT and GPT). 7. Oral NFLX 200 mg b.i.d. or 300 mg b.i.d. was as almost equally effective as 200 mg t.i.d. in tonsillitis or pharyngolaryngitis. Thus NFLX 200 mg b.i.d. or 300 mg b.i.d. appears to give sufficient clinical efficiency. 8. When antibacterial activity and serum half-life of NFLX are considered, twice daily administration was confirmed to be sufficiently effective in the clinical application.

Adolescent↗

Efflux of 45Ca from isolated smooth muscle cells of guinea-pig taenia caeci.

Single smooth muscle cells were isolated from guinea-pig taenia caeci by digestion with collagenase. The 45Ca desaturation curve from isolated cells, which were previously washed with Ca2+-free solution containing EGTA in Ca2+-free modified Locke solution, consisted of three components (half-time: 1.0, 3.8 and 12.4 min). The 45Ca efflux from isolated cells in the third component was significantly increased by caffeine. This increase was suppressed by procaine, but was not affected by La3+. These results suggest that, in guinea-pig taenia caeci, there are at least four Ca2+ compartments: superficial low and high affinity bound Ca2+ and cellular low and high affinity bound Ca2+. Caffeine releases Ca2+ from the cellular high affinity binding sites.

Animals↗

Comparison between pial and intraparenchymal vascular responses to cervical sympathetic stimulation in cats. Part 1. Under normal resting conditions.

To investigate the role of sympathetic regulation in both resistance and capacitance vessels in cerebral circulation, the response of pial and intraparenchymal vessels to sympathetic nerve stimulation were simultaneously examined in 14 cats by means of a newly developed video camera photoelectric system. The system consisted of a video camera system for measurement of pial vascular diameters and a photoelectric apparatus for estimating regional cerebral blood volume in the intraparenchymal vessels. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min. Initially, both the pial and intraparenchymal vessels constricted. The large pial arteries (173 +/- 25 micron, mean +/- SEM) remained constricted throughout the stimulation, whereas the intraparenchymal vessels began to dilate after the initial constriction and exceeded the control level at 175 +/- 25 s despite continued stimulation. In conclusion, such sympathetic nerve stimulation is considered to exert a constrictive effect on the intraparenchymal as well as the pial vessels at the early stage. The compensatory dilation of the intraparenchymal vessels was delayed 3 min after initiation of the stimulation.

Animals↗

Effects of (D-Met2,Pro5)-enkephalinamide and naloxone on pial vessels in cats.

To elucidate the fundamental actions of endogenous opioids and naloxone on the cerebral circulation, the effects of (D-Met2,Pro5)-enkephalinamide and naloxone on pial vessels were investigated in cats. Pial arteries (165.7 +/- 24.9 microns) were found to dilate after the intravenous administration of 1 mg/kg of (D-Met2,Pro5)-enkephalinamide, and a definite dilatation of 7.1-7.6% persisted for 15 min. Pial veins (100.6 +/- 20.2 microns) also dilated but to a lesser degree. The MABP (118.7 +/- 10.5 mm Hg) decreased by 20 mm Hg immediately after the injection, but gradually returned to the initial value 15 min later. The observed cerebral vasodilatation may be attributable to sympathetic inhibition mediated either by the presynaptic opiate receptors of the cerebral vessels or by the opiate receptors in the brainstem. After the intravenous administration of 1 mg/kg of naloxone, pial arteries (122.0 +/- 17.2 microns) showed a slight but significant dilatation of 2.3-5.3%. There were no significant changes in pial veins (87.0 +/- 12.4 microns). MABP (130.4 +/- 12.3 mm Hg) was slightly increased after the injection. Although the mechanism involved was unclear, the cerebral vasodilatation occurring after the administration of naloxone may contribute to its ameliorating effect on the neurological symptoms following cerebral ischemia.

Animals↗

Changes in cyclic AMP and cyclic GMP levels in the contraction-relaxation cycle of isolated smooth muscle cells from guinea-pig taenia caeci.

The present study was undertaken to investigate the role of cyclic AMP and cyclic GMP in the regulation of the contraction-relaxation cycle in isolated smooth muscle cells from guinea pig taenia caeci. The contraction of isolated smooth muscle cells induced by both caffeine (4 X 10(-3) M) and carbachol (10(-4) M) consisted of an initial activation phase and a following spontaneous relaxation phase. Isoproterenol (10(-4) M) inhibited the carbachol-induced contraction and raised intracellular cyclic AMP level of isolated smooth muscle cells. Both the inhibition of the carbachol-induced contraction and the rise in cyclic AMP level elicited by isoproterenol were blocked by propranolol (10(-4) M). Caffeine increased intracellular cyclic AMP level significantly and contracted isolated smooth muscle cells. Caffeine and carbachol contracted isolated smooth muscle cells and increased intracellular cyclic GMP level. Cyclic GMP was significantly increased in spontaneous relaxation phase. The data suggest that beta-adrenergic inhibitory effect on cholinergic excitation in the mammalian isolated smooth muscle cells is mediated by the change in intracellular cyclic AMP level and that cyclic GMP related to the relaxation in these single cells. Thus, it appears that caffeine-induced contraction might be due to the stimulation of Ca2+-induced Ca2+ release by cyclic AMP.

Animals↗