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Biomedical subjects

T Kanayama

Publications and source records attributed to T Kanayama.

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

Antithrombotic effects of KP-10614, a novel and stable prostacyclin (PGI2) analog.

A chemically stable prostacyclin analog, KP-10614 [(4z,16s)-4,5,18,18,19,19-hexadehydro-16,20-dimethyl-delta 6(9;alpha)-9(o)- methano-PGI1], has been compared with two other prostacyclin derivatives (Iloprost and TEI-7165) and one prostaglandin E1 derivative (OP-1206) with respect to ADP-induced in vitro aggregation of human platelets and ex vivo platelet aggregation in rats and dogs, given by bolus injection and i.v. infusion. These compounds were also tested on the systemic arterial blood pressure of rats and dogs. KP-10614 was the most potent inhibitor of in vitro platelet aggregation induced by ADP with IC50 of 1 nM among the compounds studied in this report, and it also showed ex vivo effectiveness at doses much lower than the other three compounds. KP-10614 was also orally active. At oral doses of 25, 50 and 100 micrograms/kg, this new compound caused a dose-dependent inhibition of ex vivo platelet aggregation in rats, whereas the other three compounds were effective only at 500 micrograms/kg or more. In addition, KP-10614 showed definite antithrombotic effects at a dose range of 0.1 to 1 microgram/kg i.v. in various thrombosis models in which platelet aggregation was mainly involved. These results indicate that KP-10614 possesses therapeutic potential in thrombotic diseases.

Administration, Oral↗
PubMed1989

Biphasic accumulation of leukocytes in rat cardiac infarct tissue caused by leukotriene B4 and complement.

An initial increase (3-12 hr) in the polymorphonuclear leukocytes (PMN) counts after ligation of the rat left main coronary artery was reduced by 49.4% (at 12 hr) by a 5-lipoxygenase inhibitor, AA-861 (80 mg/kg, p.o., 1 hr before ligation). Depletion of the complement components induced by cobra venoma factor (CVF) (i.v.), given one day before, resulted in significant reduction in the PMN accumulation after 12 hr (by 63.6% at 24 hr). The combined treatment (CVF+AA-861) suppressed the PMN accumulation by 69.7% (24 hr). The infarct size at 48 hr was also reduced by approximately 36% by either AA-861, CVF or combined treatments.

Animals↗
PubMed1987

Detection of the cross-linking amino acid, histidinoalanine, in human brown cataractous lens protein.

In human nuclear cataract, with its progression, high polymers protein mass, which is aggregated and strengthened by disulfide cross-links and other covalent cross-links, accumulates in the nuclear region to cause hardening of the lens nucleus. However, the structure of non-disulfide covalent cross-links has not been clearly confirmed yet. Recently a cross-linking amino acid, histidinoalanine, was discovered in connective tissue and is thought to cause hardening of the tissue with aging. The content of this amino acid in the lens nucleus was studied. Nuclear cataract was classified on the basis of nuclear color as described by Pirie (1986). The content of histidinoalanine was found to be 0.05 +/- 0.03 nmol mg-1 in normal nucleus; 0.06 +/- 0.03 nmol mg-1 in grade I (uniform pale yellow); 0.05 +/- 0.03 nmol mg-1 in grade II (deep yellow nucleus); 0.38 +/- 0.07 nmol mg-1 (P less than 0.01) in grade III (hazel-brown nucleus) and 3.35 +/- 2.76 nmol mg-1 (P less than 0.01) in grade IV (deep brown nucleus). The result suggests that histidinoalanine is one of the non-disulfide cross-links of lens proteins in nuclear cataract and is closely related to the grade of cataract.

Adult↗
PubMed1984

Effect of 1-(3-chloroanilino)-4-phenylphthalazine (MY-5445), a specific inhibitor of cyclic GMP phosphodiesterase, on human platelet aggregation.

The effects of a novel compound, 1-(3-chloroanilino)-4-phenylphthalazine (MY-5445), on cyclic nucleotide metabolism and in vitro aggregation of human platelets were investigated. The concentrations of MY-5445 producing 50% inhibition of human platelet aggregation induced by 3 microM ADP, 3 micrograms/ml of collagen and 100 micrograms/ml of arachidonic acid were 0.07, 0.02 and 0.17 microM, respectively. Addition of MY-5445 significantly elevated cyclic GMP content in human platelets but had no effect on cyclic AMP content, suggesting that the drug affects principally the cyclic GMP metabolism in the platelet. Although MY-5445 had no effect on either adenylate cyclase or guanylate cyclase activity, it inhibited specifically human platelet cyclic GMP phosphodiesterase which was separated from cyclic AMP phosphodiesterase by diethylaminoethyl-cellulose column chromatography. The inhibitory effect of MY-5445 on cyclic GMP phosphodiesterase was also demonstrated by direct binding of the enzyme to MY-5445 coupled Sepharose, which was a useful tool for purifying the cyclic GMP phosphodiesterase from human platelet. These results would suggest that MY-5445 inhibits human platelet aggregation by increasing cyclic GMP content and that it provides a useful probe for elucidating the role of cyclic GMP in platelet aggregation.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1978

Vasodilation produced by prostacyclin (PGI2) and 9(O)-thiaprostacyclin (PGI2-S) in the canine femoral circulation.

The action of 9(0)-thiaprostacyclin (PGI2-S) was compared with that of prostacyclin (PGI2) and papaverine in the femoral circulation of dogs. PGI2-S, injected into the dog femoral artery in a dose of 0.1 microgram or higher, produced marked vasodilation in the femoral artery without any change in blood pressure. The potentcy of PGI2-S was one tenth that of PGI2, and was a hundred times that of papaverine. The stability of PGI2-S in neutral solution was forty times that of PGI2.

Animals↗
PubMed1977

Neuromuscular effects of i.a. infusion of lignocaine in man.

Neuromuscular effects of lignocaine during and after i.a. infusion were studied in healthy adult patients, using evoked electromyography. Supramaximal, paired stimuli were applied to the ulnar nerve with variable intervals between the two stimuli. The amplitude of the hypothenar muscle action potential to the second component of the paired stimulus (test response) was compared with that evoked by the first component (conditioning response). During and after i.a. infusion of lignocaine, there were marked decreases of the test response at intervals from 7 to 100 ms after the conditioning stimulus, although the decreases of the conditioning response were slight or negligible. The finding of decreased test responses coincided with the results obtained with tetanic stimulation such as pronounced fade and only slight post-tetanic potentiation. Differences between these findings and those found with muscle relaxants were compared, and it was concluded that the mechanism responsible for these results might be attributed to an effect of lignocaine on the motor nerve terminal.

Action Potentials↗
PubMed1975

Relationship between hepatic hemodynamics and biliary pressure in dogs: its significance in clinical shock following biliary decompression.

The changes in the hepatic hemodynamics were promptly reflected in the biliary pressure in dogs. Both wedged hepatic venous pressure and portal venous pressure increased in response to the elevated biliary pressure, and conversely decreased following rapid biliary decompression, suggesting that the changes in the biliary pressure might affect the hepatic hemodynamics post-sinusoidally. It was supposed that too rapid biliary decompression might trigger the following consequences; 1) decrease in sinusoidal pressure, 2) increase in sinusoidal inflow, and 3) extravasation of intravascular fluid in the perivascular space. When these were not sufficiently compensated, they could trigger shock in the jaundiced patients.

Adult↗
PubMed1975

An electromyographic study of muscle relaxants in man.

Supramaximal paired stimuli were applied to the ulnar nerve, and the amplitude of the muscle action potential evoked in the abductor digiti minimi by the second member of the stimulus pair (test response) was compared with that evoked by the first component (conditioning response). The interval between the two components of the stimulus pair (the pair interval) was increased stepwise from 7 to 100 msec and a curve (recovery curve) was obtained by relating the changes in pair interval to the difference in amplitude of the test and conditioning responses. Alterations of the recovery curve (RC) during partial paralysis by muscle relaxants were investigated in healthy adult patients under the lightest plane of general anaesthesia. The control curve obtained in 32 subjects before the administration of a muscle relaxant drug was characterized by slight depressions at very short intervals of paired stimuli, followed by a slight potentiation at 20-100 msec. With non-depolarizing relaxants, RC altered to the characteristic pattern of potentiation at very short intervals of stimuli, followed by a notable depression at longer intervals. In depolarizing blocks with small doses of suxamethonium, the depression of RC at short intervals in the control was enhanced and the pattern of RC was different from that of non-depolarizing agents. When desensitization blocks were instigated by the i.v. administration of suxamethonium, the RC patterns were similar to those of competitive agents.

Action Potentials↗