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Biomedical subjects

K Kogi

Publications and source records attributed to K Kogi.

At least 37 records · Page 2Linked to original sources
PubMed1993

Syntheses and biological activities of chemically stable prostacyclin mimics with cis-bicyclo[4.3.0]nonene ring system: the novel homoisocarbacyclin analogues.

The synthetic studies concerning a series of homoisocarbacyclin analogues, which are homologous compounds of isocarbacyclin, with cis-bicyclo[4.3.0]non-2-ene or cis-bicyclo[4.3.0]non-3-ene as a nucleus have been carried out. The general synthetic methods of homoisocarbacyclin analogues have been accomplished starting with the versatile Corey lactone. Among the analogues synthesized in the present studies, a promising compound (TY-11223) exhibiting a good selectivity in biological actions was found to be studied further.

Animals↗
PubMed1993

Biochemical and pharmacological properties of a newly synthesized proton pump (H+/K(+)-ATPase) inhibitor, TY-11345 in experimental animals.

We investigated the effects of the newly synthesized proton pump inhibitor TY-11345, (+/-)-2-[(4-methoxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin- 9-yl)sulfinyl]-1H-benzimidazole sodium salt, on gastric mucosal proton pump (H+/K(+)-ATPase) activity, gastric acid secretion and gastro-duodenal lesions in experimental animals. TY-11345 potently inhibited H+/K(+)-ATPase activity in isolated rabbit gastric mucosal microsomes; and the inhibitory effect was enhanced under weak acid conditions, the IC50 (concentrations that inhibit the enzyme activity by 50%) being 5.8 microM and 9.9 microM at pH 6.0 and pH 7.4, respectively. In Ghosh & Schild rats, intravenous injection of TY-11345 significantly inhibited gastric acid secretion stimulated by tetragastrin; the effect of TY-11345 was twice as potent as that of omeprazole. In pylorus ligated rats, TY-11345 inhibited basal gastric acid secretion by both the intraduodenal and oral routes, with ED50 values of 1.2 and 4.0 mg/kg, respectively. These effects were 9 and 5 times more potent than those of omeprazole, respectively. Moreover, the antisecretory effect of TY-11345 persisted for more than 24 hr in pylorus ligated rats. In experimental ulcer models, TY-11345 prevented the formation of water-immersion stress, ethanol or indomethacin-induced gastric lesions and mepirizole-induced duodenal lesions in rats. The antiulcer effects of TY-11345 were 3 to 15 times more potent than those of omeprazole. These results suggest that TY-11345 has potent antisecretory and antiulcer effects which are exerted by suppression of H+/K(+)-ATPase activity in gastric parietal cells, so that TY-11345 should be useful for the clinical treatment of peptic ulcer diseases.

Acetates↗
PubMed1992

A novel homoisocarbacyclin analog with potent and long-lasting activity.

A synthesis of a novel and chemically stable homoisocarbacyclin analog, TY-11223 (3), has been accomplished. The analog (3), given intravenously or orally, showed potent and long-lasting activities in inhibiting platelet aggregation and, in addition, a good selectivity in biological activities.

Animals↗
PubMed1991

The antihypertensive effect of 2-alkynyladenosines and their selective affinity for adenosine A2 receptors.

We examined the affinity for adenosine receptors and the antihypertensive effects of 2-alkynyladenosines, especially 2-hexynyladenosine (2-H-Ado) and 2-octynyladenosine (2-O-Ado). The order of decreasing affinity of 2-H-Ado, 2-O-Ado, and other agonists tested for A1 receptors was N6-cyclopentyladenosine (CPA) greater than N6-cyclohexyladenosine (CHA) greater than N6-R-phenylisopropyladenosine (R-PIA) greater than 2-chloroadenosine (CADO) = 5'-N-ethylcarboxamideadenosine (NECA) greater than N6-S-phenylisopropyladenosine (S-PIA) greater than 2-H-Ado greater than 2-O-Ado greater than 2-phenylaminoadenosine (CV-1808), and that for A2 receptors was 2-H-Ado greater than 2-O-Ado = NECA greater than CADO greater than CV-1808 greater than R-PIA greater than CPA greater than CHA greater than S-PIA. The Ki values of 2-H-Ado and 2-O-Ado for [3H] NECA binding to A2 receptors were 4.1 and 12.1 nM, respectively, and those for [3H]CHA binding to A1 receptors were 146 and 211 nM, respectively: the affinity of 2-H-Ado and 2-O-Ado for A2 receptors was about 36- and 17-fold higher than their affinity for A1 receptors. Injection of 2-H-Ado and 2-O-Ado (0.03-100 micrograms/kg) decreased the blood pressure of anaesthetized spontaneously hypertensive rats (SHR). A slight decrease in heart rate was observed after i.v. injection of 100 micrograms/kg 2-H-Ado and 2-O-Ado. A potent and long-lasting antihypertensive effect was also observed after oral administration of 2-H-Ado and 2-O-Ado to conscious SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1991

Pharmacological profile of the 2-alkynyladenosine derivative 2-octynyladenosine (YT-146) in the cardiovascular system.

We investigated the cardiovascular effects of 2-octynyladenosine (YT-146), an adenosine A2 agonist, in various mammalian preparations in comparison with adenosine and 2-chloroadenosine. YT-146, when intravenously administered, caused a dose-dependent decrease of blood pressure in anesthetized normotensive rats (with ED30 values of 0.4 micrograms/kg), and YT-146 was 250 times more potent than adenosine. Whereas adenosine and 2-chloroadenosine decreased heart rate at approximately equihypotensive doses, YT-146 had no negative chronotropic effects at h hypotensive doses. Orally given YT-146 (0.1 - 1 mg/kg) produced a potent and long-lasting antihypertensive effect in spontaneously hypertensive rats. YT-146 was 15.9 and 12.5 times more potent than adenosine in producing relaxation of isolated porcine coronary arteries and in increasing dog coronary blood flow, respectively. Although YT-146 was equipotent to adenosine in causing a negative inotropic effect in isolated guinea pig atria, it was less potent than adenosine in producing atrioventricular conduction block in guinea pigs. On the other hand, 2-chloroadenosine was 9.1, 1.8 and 2.4 times more potent than adenosine in lowering blood pressure, relaxing isolated porcine coronary arteries and increasing dog coronary blood flow, respectively. 2-Chloroadenosine was the most potent in producing cardiodepression, i.e., negative inotropy and atrioventricular conduction block in guinea pigs. From these results, we concluded that YT-146 is a potent coronary vasodilator and also a potent, orally active and long-acting hypotensive agent having less cardiac depressant activity.

Adenosine↗
PubMed1989

Training in practical ergonomics improvements.

Recent ILO experiences show that concrete ergonomics improvements can result from learning-by-doing training in real settings. Particularly important is to build on local practice focusing on good examples already available. Checklist exercise, demonstrating low-cost solutions and group work are effective training tools. Opportunities can be widely created by such enabling training.

Developing Countries↗
PubMed1987

Contribution of isosorbide-5-mononitrate, a major metabolite of isosorbide dinitrate (ISDN), to the hemodynamic effect of ISDN administered orally in conscious dogs.

This study was designed to determine the extent, to which isosorbide-5-mononitrate (5-ISMN) contributes to the hemodynamic effect of isosorbide dinitrate (ISDN) in conscious dogs. Test drugs (ISDN or 5-ISMN) were given orally. Either ISDN or 5-ISMN produced a decrease in blood pressure dose-dependently, the decrease in pulse pressure being specific; the pattern of blood pressure change induced by ISDN or 5-ISMN was different from that induced by nifedipine or prazosin. The effect of ISDN (2 mg/kg) was almost equivalent to that of 5-ISMN (4 mg/kg) and the effect of ISDN (4 mg/kg) to that of 5-ISMN (8 mg/kg). After administration of ISDN, both ISDN and 5-ISMN appeared in the plasma, and the effect of ISDN well-correlated with the increase in the plasma concentration of 5-ISMN. Contribution of 5-ISMN to the effect of ISDN was estimated to be about 30% from the value of the plasma concentration of 5-ISMN at 3 to 4 hr after administration, when the maximal response to ISDN occurred. Based on the data of the area under the plasma concentration curve of 5-ISMN (from 0 to 10 hr after administration), the fraction of biotransformation to 5-ISMN from ISDN was calculated to be 73.6 to 76.6% (based on moles). Because the ability of 5-ISMN to decrease pulse pressure was about 1/2 (or 41% based on moles) of that of ISDN, the contribution of 5-ISMN to the effect of ISDN was estimated to be about 30% in total, the value being similar with that estimated at 3 to 4 hr after administration.

Administration, Oral↗
PubMed1986

Inhibitory effects of formaldehyde inhalation on the cardiovascular and respiratory systems in unanesthetized rabbits.

The mechanisms of the marked inhibitory effects of 10 ppm formaldehyde (HCHO) inhalation on heart rate and respiratory movement were investigated in unanesthetized rabbits. Inhibition of the heart rate and respiratory movement induced by HCHO inhalation was caused by a reflex reaction during sensory irritation of the upper respiratory tract, mainly the nasal mucosa, but not of the lower respiratory tract, mainly the lung. These reflex reactions, particularly decreases in the heart rate, were not blocked by vagotomy, atropine or prazosin, but were blocked by propranolol, phenoxybenzamine, phentolamine, yohimbine and guanethidine. These results suggest that these reflex reactions are derived from sympathetic nervous activity rather than parasympathetic nervous activity, and the reflex bradycardia is caused by inhibiting the transmitter release at the adrenergic nerve endings.

Animals↗
PubMed1985

[Effects of isosorbide 5-mononitrate on cardiovascular function. (I). Effects on the left ventricular system].

Effects of isosorbide 5-mononitrate (5-ISMN) on cardiovascular function were compared with those of isosorbide dinitrate (ISDN), verapamil and propranolol. In anesthetized open-chest dogs, intravenous injection of 5-ISMN (1 mg/kg, 3 mg/kg) scarcely decreased cardiac contractile force (CCF) and heart rate (HR). The systolic blood pressure (SBP) fell in a dose-dependent manner, and the degree of the change was greater than that in diastolic blood pressure (DBP). Especially, left ventricular pressure (LVP) and left ventricular dp/dt (LVdp/dt) were significantly decreased, and a considerable reduction in left ventricular end-diastolic pressure (LVEDP) was also observed. Intravenous injection of verapamil (0.3 mg/kg) considerably lowered DBP. While HR, CCF, LVP and LVdp/dt were markedly decreased, LVEDP showed a moderate increase. Propranolol (0.5 mg/kg, i.v.) greatly decreased LVdp/dt together with HR and CCF. Conversely, LVEDP showed a slight increase. There was no change in SBP, DBP and LVP. The vasodilating potency of 5-ISMN was 150 times smaller than that of ISDN on the contractile response in isolated rabbit thoracic aorta. On the other hand, in terms of decrease in pulse pressure, the potency exhibited by 5-ISMN was about 4 times (intravenous administration in anesthetized dogs) or 1.5 times (oral administration in conscious dogs) smaller than that of ISDN. The present results suggest that 5-ISMN shows a high bioavailability and a potency comparable to ISDN, especially in the case of peroral administration. Taking these results together with the fact that transient left ventricular failure occurs during myocardial ischemia into consideration, it is thought that peroral 5-ISMN preparation may be useful in the therapy of angina pectoris.

Animals↗
PubMed1985

[Effects of isosorbide 5-mononitrate on cardiovascular function. (II). Effects on pre-load and after-load].

Effects of isosorbide 5-mononitrate (5-ISMN) on cardiovascular function were compared with those of verapamil hydrochloride and propranolol hydrochloride in anesthetized open-chest dogs. Intravenous injection of 5-ISMN (3 mg/kg) considerably lowered systolic blood pressure (SBP). Especially, stroke volume (SV), cardiac output (CO), cardiac work (CW) and systolic right ventricular pressure (SRVP) were significantly decreased. 5-ISMN also produced a continuous reduction in mean pulmonary artery pressure (MPAP), mean pulmonary capillary wedge pressure (MPCWP) and mean right atrium pressure (MRAP), while heart rate (HR) and total peripheral resistance (TPR) were not altered significantly. Intravenous injection of verapamil (0.3 mg/kg) considerably lowered diastolic blood pressure (DBP). Verapamil also caused a significant decrease in HR, CW and TPR and a slight decrease in SRVP and MPCWP. However, SV was significantly increased, and slight increases in MPAP and MRAP were also observed. Propranolol (0.5 mg/kg, i.v.) greatly decreased HR together with CO, CW, SRVP and MPAP and slightly decreased MPCWP, while it caused a considerable increase in 3V and a slight increase in TPR. The finding that administration of 5-ISMN resulted in reduction of pre-load and after-load suggests the possibility that this drug might decrease venous return and thereby reduce myocardial oxygen requirements.

Animals↗
PubMed1984

A study of work injuries in eight Asian countries.

This study is based on a survey conducted in Hong Kong, Indonesia, Korea, Malaysia, the Philippines, Singapore, Sri Lanka and Thailand on occupational injuries during the years 1975-1980. The number of work accidents have risen rapidly during this period in all of the 8 countries studied. In the case of Thailand, the total number of work injuries increased four fold from 1975-1978, whereas, in Singapore it has almost doubled in 6 years. The number of permanent disablement nearly trebled in Korea, and the Philippines for the year 1967-1980. The largest percentage of accidents are lost-time injuries in all of the 8 countries. Thailand had a three fold increase in lost-time injuries whilst in Hong Kong the figure doubled. Six out of the 8 countries indicated that the building construction industry had the largest number of fatal accidents, followed by the manufacturing industry.

Accidents, Occupational↗
PubMed1983

Pharmacological and toxicological studies on domiodol, a new mucolytic agent and expectorant.

The efficacy and toxicity of a compound containing organically bound iodine, 4-hydroxymethyl-2-indomethyl-2,3-dioxolane (domiodol), were evaluated. After oral and intravenous administration domiodol increased respiratory tract excretion indirectly measured on the basis of bronchial secretion in rats. Based on Kasé's method for quantitatively collecting respiratory tract fluid from rabbits, oral domiodol at the dose of 50-200 mg/kg induced a dose-related increase in respiratory tract fluid. In addition, oral domiodol (50 and 100 mg/kg) significantly reduced the viscosity of sputum collected quantitatively from rabbits with subacute bronchitis induced by long-term exposure to SO2 gas; the percentage decrease in viscosity was statistically correlated with the content of dry matter, protein and polysaccharides in the sputum. Domiodol had a marked cilio-excitatory effect, but did not affect experimental asthma in guinea-pigs or the respiratory resistance of anesthetized dogs. Subacute toxicity of the substance was investigated in rats. In serum biochemistry tests mean triglycerides were reduced in both sexes at dose levels higher than 32 mg/kg. Changes of T3 levels and a slight increase in thyroid weight accompanied by minimal histological alterations were observed in rats given high doses of domiodol. The majority of the changes observed were reversible after withdrawal of domiodol.

Airway Resistance↗