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Biomedical subjects

M Kojima

Publications and source records attributed to M Kojima.

At least 667 records · Page 37Linked to original sources
PubMed1988

[Pharmacological studies of eicosapentaenoic acid ethylester (EPA-E) on high cholesterol diet-fed rabbits].

The effects of eicosapentaenoic acid ethylester (EPA-E) at daily doses of 3 and 30 mg/kg (p.o.) on vascular lesions and changes in blood components were investigated in rabbits fed with a 1% cholesterol diet for 12 weeks and partly compared with those given 30 mg/kg/day (p.o.) of ticlopidine. EPA-E at 30 mg/kg significantly improved the reduction in distensibility of isolated thoracic aorta caused by cholesterol diet feeding. Ticlopidine at 30 mg/kg also showed significant but milder improvement. EPA-E at 30 mg/kg, unlike ticlopidine, tended to lower cholesterol content in the thoracic wall and elastin fraction. Although EPA-E did not act on plasma total cholesterol, HDL-cholesterol and triglyceride contents, it tended to mildly reduce platelet aggregability in response to sodium arachidonate and the increased production of TXA2-like activity by platelets. In addition, daily doses of 30 mg/kg EPA-E caused a significant increase in plasma and platelet EPA-E contents without any change in docosahexaenoic acid and arachidonic acid contents. From these results, daily administration of EPA-E to cholesterol diet-fed rabbits caused a remarkable improvement of the reduction in distensibility of isolated thoracic aorta. The mechanism of this improvement by EPA-E appears to depend on the protection of elastic fibers from lipid deposition on the vascular wall.

Animals↗
PubMed1988

[The effects of eicosapentaenoic acid ethyl ester (EPA-E) on arterial thrombosis in rabbits and vascular lesions in rats].

The effects of highly purified ethyl ester of eicosapentaenoic acid (EPA-E) on ellagic acid-induced thrombus formation in the stenosed femoral artery in rabbits and on the progression of laurate-induced vascular lesions in rats were examined. (1) EPA-E in single administration significantly prevented the thrombus formation induced by ellagic acid in the stenosed femoral artery of rabbits. (2) EPA-E restored the hypercoagulation activity at 5 min and 3 hr after the ellagic acid injection. Platelet aggregability induced by arachidonic acid decreased at 5 min and 3 hr after the ellagic acid injection; EPA-E had little effect on this change. EPA-E showed almost no effect on fibrinolytic activity, blood viscosity and filterability of washed red blood cells after the ellagic acid injection. (3) Moreover, EPA-E in daily administrations showed a significant preventative effect against the laurate-induced vascular lesions in rats. The efficacy of EPA-E on arterial thrombosis and vascular lesions observed in this study suggests that EPA-E is a candidate for the treatment of peripheral circulatory disturbance.

Animals↗
PubMed1988

Study of the mechanism of inhibitory action of tranilast on chemical mediator release.

We investigated the mechanism of inhibitory action of tranilast on chemical mediator release by antigen-antibody reactions. Tranilast (10(-5)-10(-3) M) inhibited antigen (DNP-Ascaris)-induced histamine release from sensitized purified rat mast cells (PMC), but did not show an obvious influence on intracellular cyclic AMP. 45Ca uptake into PMC induced by antigen (300 micrograms/ml) was obviously suppressed by tranilast (10(-6)-10(-3) M). Tranilast (10(-4) M) inhibited antigen-induced histamine release from and 45Ca uptake into PMC independently of the presence or absence of glucose in the medium. On the other hand, 2-deoxyglucose (10(-2) M) markedly inhibited both responses in the absence but not in the presence of glucose. Tranilast slightly inhibited Ca-induced contraction of guinea pig taenia coli, but had no influence on aggregation of rabbit platelets. Verapamil (10(-6)-10(-4) M) had no effect on antigen-induced histamine release, but it markedly suppressed Ca-induced contraction and platelet aggregation. From these results, we suggest that the mechanism of inhibitory action of tranilast on the release of antigen-induced chemical mediator from mast cells involves the suppression of Ca uptake, but that its mode of action is apparently different from those of 2-deoxyglucose and verapamil.

Animals↗
PubMed1988

Mechanism of inhibitory action of tranilast on the release of slow reacting substance of anaphylaxis (SRS-A) in vitro: effect of tranilast on the release of arachidonic acid and its metabolites.

We investigated the mechanism of inhibitory action of tranilast, one of the anti-allergic drugs, on the release of slow reacting substance of anaphylaxis (SRS-A). Ionophore A23187 (0.5 or 0.2 micrograms/ml)-induced SRS-A release from rat peritoneal exudate cells (PEC) or human leucocytes was inhibited by tranilast (10(-5)-10(-3) M). The IC50 (the concentration which gives 50% inhibition) of tranilast on these reactions was approx. 10(-4) M. Prostaglandin (PG)E2 release from sensitized purified rat mast cells (PMC) by a specific antigen (DNP-Ascaris) was markedly suppressed by tranilast (10(-3) M). Similarly, ionophore A23187-induced PGE2 and 6-keto-PGF1 alpha releases from rat PEC were inhibited by tranilast (10(-5)-10(-3) M). DNP-Ascaris antigen-induced 3H-arachidonic acid (AA), 3H-PGE2, 3H-PGF2 alpha and 3H-PGD2 releases from rat PMC were markedly suppressed by tranilast (10(-5)-10(-3) M), DSCG (10(-5)-10(-4) M) and mepacrine (10(-3) M). The activity of AA-converting enzymes such as 5-lipoxygenase, cyclooxygenase, PGI2 synthetase, and glutathione-S-transferase was hardly influenced by tranilast (10(-5)-10(-3) M). From these results, we suggest that the mechanism of the inhibitory action of tranilast on the release of SRS-A is related to the processes prior to dissociation of AA from the membrane phospholipids.

Animals↗
PubMed1988

Developmental changes in the levels of substrates for cholera toxin-catalyzed and pertussis toxin-catalyzed ADP-ribosylation in rat cardiac cell membranes.

Developmental changes in the substrates for cholera toxin (CTX)- and pertussis toxin (PTX)-catalyzed ADP-ribosylation in cardiac (ventricular) cell membranes were studied in fetal (16- to 20-day), neonatal (0- to 20-day) and adult (2- to 3-month) rats. The CTX and PTX substrates were determined by the method of CTX-catalyzed and PTX-catalyzed ADP-ribosylation of the alpha-subunit of GTP-binding (G) proteins, respectively. As early as fetal day 16, three substrates (45-, 47- and 52-kDa proteins) were identified for CTX-catalyzed ADP-ribosylation and one substrate (41-kDa protein) for PTX-catalyzed ADP-ribosylation. The levels of the three CTX substrates (fmol/mg tissue) increased with development between fetal day 16 and neonatal day 16, and then they decreased to their adult levels. The level of the one PTX substrate (fmol/mg tissue) changed as follows: the substrate decreased between fetal day 16 and the day of birth, increased abruptly for 4 days neonatal and increased slowly thereafter until neonatal day 16, and then decreased to the final adult level. The PTX substrate seems to reach a nearly maximum level earlier than the CTX substrates. This information is essential for understanding the developmental changes in the transmembrane signaling system between membrane receptors and their effectors which are coupled with the stimulatory and inhibitory G proteins.

Adenosine Diphosphate Ribose↗
PubMed1988

Comparison of inhibitory effects of calcium channel blockers and that of a calmodulin antagonist in strips of mesenteric arteries from spontaneously hypertensive and normotensive rats.

Effects of calcium channel blockers and of calmodulin antagonist on the contractile responses to norepinephrine (NE) were compared between strips of mesenteric arteries from 6- and 14-week-old spontaneously hypertensive rats (SHR) and age-matched, normotensive Wistar-Kyoto rats (WKY). The ratio of the maximum contraction developed by NE to that by 60 mM KCl was significantly increased in strips from 14-week-old SHR. Niludipine, verapamil and diltiazem antagonized the maximum NE contraction to a greater extent in strips from 14-week-old SHR than in those from the WKY. However, the antagonism by niludipine of the KCl- or caffeine-induced contraction was not significantly different between the strips from 14-week-old SHR and those from WKY. In strips from 6-week-old rats, there was no difference in the antagonism by niludipine of the maximum NE contraction. On the other hand, the effect of W-7 on the maximum NE contraction was not significantly different between the strips from 14-week-old SHR and those from WKY. Schild plot analyses demonstrated that alpha 1-adrenoceptors were the same for the strips from SHR and WKY. These results suggest that the enhanced maximum NE contraction in the mesenteric artery from 14-week-old SHR reflects the increased transmembrane influx of calcium, and the activity of calmodulin seems to be the same for the two strains.

Adrenergic alpha-Antagonists↗
PubMed1988

[Establishment of a new hereditary-cataract mouse (CSM) strain derived from SENCAR mouse].

A mouse representing a new hereditary cataract strain was found in a mouse colony and a new line was established strain CSM. These mice were investigated genetically, histologically and biochemically. The results suggested that this cataract was apparently inherited through two recessive autosomal genes. Histologically the denucleation process of lens fibers was abnormal and small vacuoles appeared in the equatorial region of the lens cortex at 12 days. Biochemically, insoluble protein and sodium increased in the lens with age.

Animals↗