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Biomedical subjects

Y Motoyama

Publications and source records attributed to Y Motoyama.

At least 19 recordsLinked to original sources
PubMed1992

Pentamidine: a non-peptide GPIIb/IIIa antagonist--in vitro studies on platelets from humans and other species.

In this paper we show that the non-peptide anti-parasite agent pentamidine is a broad spectrum anti-platelet agent with an IC50 of 1.1 microM in ADP-induced platelet aggregation in human platelet rich plasma (PRP). It had similar activity when collagen, arachidonic acid, platelet activating factor, thrombin and epinephrine were used. It had no effect on platelet intracellular cAMP levels. It inhibited 125I-fibrinogen, 125I-fibronectin and 125I-von Willebrand factor binding to ADP-activated fixed platelets with IC50 values of 160, 160 and 60 nM respectively. Pentamidine showed a high degree of species selectivity with slightly less activity in monkey and dog PRP and little activity in guinea pig, rabbit, rat and mouse PRP compared with human. This was similar to the other RGD analogues tested. This species specificity was shown to be dependent on the species of platelets and independent of the species of fibrinogen. Thus, pentamidine is a potent non-peptide inhibitor of fibrinogen binding to GPIIb/IIIa.

Amino Acid Sequence↗
PubMed1992

TFC-612, a prostaglandin E1 derivative, enhances fibrinolytic activity in rats.

TFC-612 inhibited thrombus formation on wire coils inserted into the lumen of the inferior vena cava of rats after 5 oral doses of 1.0 and 3.2 mg/kg and subcutaneous doses of 1.0 and 3.2 micrograms/rat/hr. This compound showed slight inhibition of platelet aggregation induced by collagen at 1.0 and 3.2 mg/kg (po) and significant inhibition at 10 mg/kg. TFC-612 had no effect on the plasma coagulation system at 3.2 mg/kg. Conversely, oral doses of 0.32-3.2 mg/kg dose- dependently enhanced fibrinolytic activity as measured by euglobulin clot lysis time and lysis area on fibrin plates by euglobulin fraction. TFC-612 did not enhance fibrinolytic activity in vitro. These results suggest that the enhancement of fibrinolytic activity by TFC-612, which may be due to an increase in tissue plasminogen activator release or reduction of plasminogen activator inhibitors release, contributes to its inhibition of thrombus formation.

Alprostadil↗
PubMed1992

Studies on antiplatelet agents. I. Synthesis and platelet inhibitory activity of 5-alkyl-2-aryl-4-pyridylimidazoles.

5-Alkyl-2-aryl-4-pyridylimidazoles were synthesized and tested in rat ex vivo platelet aggregation studies. Among these compounds, 2-(2-fluorophenyl)-5-methyl-4-(3-pyridyl)imidazole (25) was most potent, and showed 98% inhibition at a dose of 10 mg/kg (p.o.). 25 had inhibitory activity on cyclooxygenase, thromboxane A2 (TXA2) synthetase, and phosphodiesterase, and also showed inhibited KCl-induced contraction of rat aorta. All compounds have little acute toxicity and appear to be free of adverse effects on the stomach.

Animals↗
PubMed1991

The effects of TFC-612, a 7-thia prostaglandin E1 derivative, on platelet function.

The anti-platelet activities of TFC-612, methyl 6-(((1R, 2S, 3R)-3-hydroxy-2-((1E, 3S, 5R)-3-hydroxy-5-methyl-1-nonenyl)-5- oxocyclopentyl) thio)hexanoate, were compared to prostaglandin E1 (PGE1). TFC-612 inhibited human, guinea-pig and rabbit platelet aggregation induced by ADP, collagen or epinephrine with potency 1-8 times that of PGE1. TFC-612 also inhibited thrombin induced (14C) serotonin release in rabbit platelets. Platelet aggregation was dose dependently inhibited 1 hr after oral administration of TFC-612 (0.32-1.0 mg/kg) and the inhibition lasted up to 6 and 24 hours at 0.32 and 1.0 mg/kg, respectively, in guinea-pigs. In contrast, PGE1 had no effect with oral administration at a dose of 3.2 mg/kg. TFC-612 (0.32-3.2 micrograms/kg, i.v.) induced platelet disaggregation of thrombi on Achilles tendon in the extracorporeal shunt model in cats. In addition, TFC-612 (1 mg/kg, po) inhibited the adhesiveness of guinea-pig platelets to a glass bead column ex vivo. TFC-612 increased cyclic AMP (cAMP) levels in rabbit platelets. Thus, the anti-platelet action of TFC-612 may be due to an increase in cAMP levels. These results indicate that TFC-612 might be an orally active anti-thrombotic drug.

Alprostadil↗
PubMed1991

The effects of TFC-612, a 7-THIA prostaglandin E1 derivative, on platelet function.

The anti-platelet activities of TFC-612, methyl 6-(( 1R,2S,3R)-3-hydroxy-2-((1E,3S,5R)-3-hydroxy-5-methyl-1-nonenyl)-5- oxocyclopentyl) thio)hexanoate, were compared to prostaglandin E1 (PGE1). TFC-612 inhibited human, guinea-pig and rabbit platelet aggregation induced by ADP, collagen or epinephrine with potency 1-8 times that of PGE1. TFC-612 also inhibited thrombin induced (14C) serotonin release in rabbit platelets. Platelet aggregation was dose dependently inhibited 1 hr after oral administration of TFC-612 (0.32-1.0 mg/kg) and the inhibition lasted up to 6 and 24 hours at 0.32 and 1.0 mg/kg, respectively, in guinea-pigs. In contrast, PGE1 had no effect with oral administration at a dose of 3.2 mg/kg. TFC-612 (0.32-3.2 micrograms/kg, iv) induced platelet disaggregation of thrombi on Achilles tendon in the extracorporeal shunt model in cats. In addition, TFC-612 (1 mg/kg, po) inhibited the adhesiveness of guinea-pig platelets to a glass bead column ex vivo. TFC-612 increased cyclic AMP (cAMP) levels in rabbit platelets. Thus, the anti-platelet action of TFC-612 may be due to an increase in cAMP levels. These results indicate that TFC-612 might be an orally active anti-thrombotic drug.

Administration, Oral↗
PubMed1989

[Physiopathology of kinin forming system in reproduction].

We studied contact factors and kinin-kallikrein in normal non-pregnant and pregnant women, FXII deficient toxemia and DIC. The results obtained are as follows: 1. The levels of plasma prekallikrein, high molecular weight kininogen, kallikrein inhibitor, and C-1 INA were gradually decreased at delivery, and the levels of kallikrein like activity and bradykinin were increased during pregnancy and at the time of parturition. These facts indicate that kinin kallikrein systems played important role in uterine contraction. 2. The levels of contact factors (FXII and FXI) were lower at delivery than those of term. 3. In rat uterus, specific binding of bradykinin was observed by the method of radio receptor assay in the pelet of 10,000 X g fetal membranes, and its activity was 38%. 4. A synthetic kallikrein inhibitor (OS-291, MS) and bradykinin antagonist inhibited completely spontaneous uterine contraction of Wistar rats during delivery. 5. In the case of FXII deficiency, the levels of plasma prekallikrein, high molecular weight kininogen were normal, but at delivery, these levels were lower than those of term. The levels of kallikrein like activity which was half of normal parturition level was increased at parturition. 6. In cases of DIC (17) and severe toxemia (22), plasma prekallikrein levels were lower than the normal controls. The decrease was due to consumption of plasma prekallikrein to kallikrein activation.

Animals↗
PubMed1988

A new prostaglandin E1 analogue (TFC-612) prevents a decrease in motor nerve conduction velocity in streptozocin-diabetic rats.

A new prostaglandin E1 analogue (TFC-612) was orally given to streptozocin-diabetic rats for 4 weeks after the induction of diabetes and its effects on motor nerve conduction velocity were studied. The compound significantly prevented a decrease of the velocity but did not reverse abnormal sorbitol and myo-inositol contents of the sciatic nerve. The results suggest that TFC-612 has a potent effect on diabetic nerve dysfunction via other mechanism than the correction of sorbitol and myo-inositol metabolisms and could be a potential compound for therapy of diabetic polyneuropathy.

Alprostadil↗
PubMed1988

Effects of FR50948, a new orally active antiallergic agent, in experimental allergic models.

The antiallergic activity of sodium 10-(2,3-dimethyl pentanamido)-4-oxo-4H-pyrimido [1,2-C] quinazoline-3-carboxylate-hydrate (FR50948) was studied and compared with the activities of sodium cromoglycate (SCG) and lodoxamide. FR50948 had inhibitory effects on type I and type III allergic reactions, but not on type II and IV allergic reactions. FR50948 also had weak inhibitory effects on inflammation (carrageenin paw edema and adjuvant arthritis) and SRS release from rat neutrophils, but no antagonistic effects to histamine and serotonin. The inhibitory effect of FR50948 on IgE-mediated type I allergic reactions was essentially the same as those of SCG and lodoxamide, because FR50948 inhibited the histamine release from rat peritoneal mast cells and had cross tachyphylaxis with SCG in the rat PCA test. However, FR50948, like lodoxamide, had a stronger activity than SCG and was effective by the oral route, unlike SCG which was effective only by the parenteral route. Furthermore, the inhibitory effects of FR50948 on type III reactions and inflammatory reactions were much more potent than those of SCG and equal to those of lodoxamide, and the effect on IgG-mediated PCA was stronger than that of either reference drug. These results suggest that FR50948 will be beneficial in clinical use.

Animals↗
PubMed1984

Protective effect of FR35447 on experimental cerebral infarction.

The protective effect of 2-(5-chloro-2-phenoxyanilino)-2-imidazoline [FR35447] on cerebral infarction was examined in animal models. FR35447 in p.o. doses of 1 mg/kg or more caused a marked reduction of arachidonate-induced cerebral infarction in rats. Since FR35447 (10(-6) M) inhibited platelet aggregation induced by adrenaline plus the divalent cation ionophore A23187, as did yohimbine (10(-6) M), the protective effect of FR35447 is presumed to be due to its blocking activity on the alpha 2 adrenoceptors of platelets. However, additional mechanisms appear to participate in the protective effect of FR35447 on cerebral infarction. A ten-day treatment with FR35447 in p.o. doses of 1 to 10 mg/kg/day decreased serum lipid peroxide levels in vitamin E deficient rats, suggesting that FR35447 may have free radical scavenging activity. Moreover, FR35447 (greater than or equal to 10(-5) M) increased red cell deformability. These effects of FR35447 suggest that it may be useful in preventing or treating cerebral infarction.

Animals↗
PubMed1982

The central anti-serotonin activity of zotepine, a new neuroleptic, in rats.

2-Chloro-11-(2-dimethyl-aminoethoxy) dibenzo [b, f] thiepin (zotepine) is a new neuroleptic drug which is structurally different from known neuroleptics. Zotepine, chlorpromazine, propericiazine, and cyproheptadine inhibited hyperthermia induced by dosing with fenfluramine in rats in a warm environment (26-28 degrees C). Fenfluramine is known to induce hyperthermia by mediation of central serotonin. Zotepine had a 10 times or greater potency than chlorpromazine, propericiazine and cyproheptadine in inhibiting the hyperthermia. Thioridazine did not inhibit the hyperthermia, whereas haloperidol accelerated the hyperthermia. Zotepine was also the most potent inhibitor of 3H-serotonin binding to rat cortical synaptosomes in vitro. However, cyproheptadine had the strongest anti-serotonin activity in rat fundus preparations, while zotepine and other neuroleptics showed the same order of potency. These results showed that zotepine is a unique neuroleptic with potent central anti-serotonin activity. The central anti-serotonin activity of zotepine is discussed in connection with its lesser extrapyramidal side effects in humans.

Animals↗
PubMed1979

Studies of human liver bilirubin-glycosyl transferase. Bilirubin UDP-xylosyl and UDP-glucuronyl transferase activities in diseased human livers.

The activity of bilirubin UDP-xylosyl transferase as well as UDP-glucuronyl transferase in liver biopsy specimens of 3 control subjects, 42 cases with liver disease and 5 cases with Gilbert's syndrome was measured. Normal values of these enzyme levels were determined to be 142--302 U/kg protein for the former and 260--400 U/kg protein for the latter. Both enzyme levels in acute hepatitis in convalescence and chronic hepatitis were nearly in the normal range. In the cirrhotic liver they tended to a small decrease and patients with Gilbert's syndrome demonstrated significantly decreased enzyme levels. These enzyme levels were only correlated with serum unconjugated bilirubin concentration, but not with the other liver function tests. Finally, both enzyme activities were exactly correlated with each other.

Bilirubin↗
PubMed1979

Interaction between aspirin and prostaglandins in the isolated guinea-pig tracheal muscle.

The effects of PGE2 and PGF2 alpha on the tonus of isolated guinea-pig tracheal chain were investigated and compared with those of histamine and acetylcholine. PGE2 reduced tonus in normal resting state, but elevated tracheal tonus reduced by aspirin. Such PGE2-induced contractions did not exceed the initial resting tonus, and the magnitude and duration of the contractions progressively diminished with increase of PGE2 concentrations. Aspirin produced neither relaxation nor contraction in the presence of a low dose of PGE2. Unlike PGE2, PGF2 alpha produced a dose-related contraction in the normal tracheal chain, and the contractile response to PGF2 alpha was markedly potentiated by aspirin. In the presence of PGF2 alpha, aspirin no longer produced tracheal relaxation but produced a dose-related contraction. The contractile effect of histamine but not of acetylcholine was also potentiated by aspirin, but there was a slight difference between PGF2 alpha and histamine in that the potentiation of action of PGF2 alpha by aspirin was more easily diminished by PGE2. These results suggest that PGE2 plays an important role in the maintenance of the resting tonus of the isolated guinea-pig tracheal chain, and in large doses it also acts as a tracheal relaxant and attenuates the tracheal responses to PGF2 alpha and histamine.

Acetylcholine↗
PubMed1978

Serum glycoproteins in the liver diseases. V. Desialylated glycoproteins in chronic hepatitis.

Serum desialylated glycoprotein level was tested for chronic hepatitic patients. The level was significantly elevated in patients with chronic aggressive hepatitis but not in chronic persistent hepatitis comparing to normal subjects. In chronic aggressive hepatitis, severe type (2B), serum desialylated glycoprotein levels were significantly enhanced but not in moderate type (2A) when compared to chronic persistent hepatitis. Sera taken serially from patients with chronic aggressive hepatitis, severe type (2B), demonstrated a slight correlation between circulating desialylated glycoprotein level and serum glutamic-pyruvic transaminase activity.

Adult↗
PubMed1978

Studies on human liver bilirubin-UDP-glycosyl transferase. I. Assay methods for bilirubin-UDP-glucuronyl and -xylosyl transferases of human liver specimen.

Micromethods for estimation of bilirubin uridine diphosphate-glucuronyl and -xylosyl transferases in liver are described. With these methods, a liver specimen as small as 10 mg is sufficient for assay of either enzyme activity and 15 mg is sufficient for assay of both enzymes. Normal values for livers with minimal elevation of SGOT and minimal histological change were 0.260-0.400 U/g protein for glucuronyl transferase and 0.142-0.302 U/g protein for xylosyl transferase.

Bilirubin↗
PubMed1977

Serum glycoproteins in the liver diseases. III. Desialylated glycoproteins in the acute hepatitis.

Circulating desialylated glycoprotein level in acute hepatitis was studied by using the competitive binding assay reported by us. Statistically significant differences of the level among acute hepatitis in the peak of illness, fulminating hepatitis and normal subjects were observed. The desialylated glycoprotein level in acute hepatitis was elevated associating with S-GPT and serum bilirubin levels, and it returned to the normal range before S-GPT and serum bilirubin were normalized. The desialylated glycoprotein in a fulminant hepatitis was increasing associated with bilirubin even when S-GPT was decreasing.

Acute Disease↗
PubMed1977

Serum glycoproteins in the liver diseases. IV. Alpha-1 acid glycoprotein level in liver cirrhosis.

Circulating alpha-1 acid glycoprotein level in cirrhotic patients was determined by radioimmunoassay, and was compared to the ones in normal subjects and chronic active hepatitis with sublobular necrosis. Serum alpha-1 acid glycoprotein levels in liver cirrhosis (p less than 0.001) and chronic active hepatitis with sublobular necrosis (p less than 0.02) were significantly reduced comparing to the normal subjects, although any statistically significant difference was not observed between the formers. In liver cirrhosis, thie serum alpha-1 acid glycoprotein level correlated negatively with serum albumin concentration but neither with serum alpha-1 globulin fraction nor with Indocyanine green clearance rate.

Chronic Disease↗