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Biomedical subjects

M Ozeki

Publications and source records attributed to M Ozeki.

At least 73 records · Page 4Linked to original sources

Effects of catecholamines on myocardial viability in early reperfusion following hypothermic global ischemia in dogs--comparison between epinephrine and dobutamine.

Attempts were made to define the effects of epinephrine and dobutamine on the myocardium during early reperfusion for 60 minutes following hypothermic global ischemia at a myocardial temperature of 28 degrees C for 60 minutes under cardiopulmonary bypass. Ischemia was induced by cross-clamping the dog aorta. Epinephrine (0.1 microgram/kg/min) and dobutamine (5 micrograms/kg/min) were given throughout the reperfusion period by intravenous drip infusion, a control group was treated with saline infusion. Comparison of hemodynamic parameters was made before cardiopulmonary bypass, and at 30 and 60 minutes of reperfusion. Epinephrine and dobutamine significantly increased stroke volume index, left ventricular stroke work index and tissue calcium content compared with saline, however, myocardial water content was only slightly higher in the group given saline, compared with the other two groups. Myocardial mitochondrial membranes and cristae were slightly damaged and creatine phosphate content was reduced. Ultrastructural integrity was related to myocardial tissue calcium content, with a significant negative correlation. These results suggest that epinephrine (0.1 microgram/kg/min) will improve stroke volume index and left ventricular stroke work index, as does dobutamine (5 micrograms/kg/min), however, both agents had a minimal effect on reducing myocardial morphological and biochemical integrity, although catecholamines have detrimental effects on the myocardium in early reperfusion following ischemia.

Animals↗

[Pharmacokinetic study of cefsulodin in children].

Cefsulodin (CFS), a cephem antibiotic, was administered to 26 children aged from 11 months to 11 years by intravenous injection or intravenous 1-hour drip infusion in doses of 15 and 50 mg/kg body weight to investigate serum and urinary concentrations. The following results were obtained. Serum concentration The serum concentrations of CFS at 5 minutes after intravenous injection of 15 and 50 mg/kg were 57.1 and 224.2 micrograms/ml, respectively. The biological half-lives (T 1/2 beta) were 1.28 and 1.12 hours. The serum concentration of CFS after intravenous 1-hour drip infusion reached a peak at the end of infusion, i.e. 29.9 micrograms/ml for 15 mg/kg and 121.9 micrograms/ml for 50 mg/kg, and T 1/2 beta were 1.22 hours for 15 mg/kg and 1.27 hours for 50 mg/kg. The AUC was proportional to the doses for both intravenous injection and intravenous drip infusion. The serum clearance was about twice the value in adults and the distribution volume was about 1.5 times as large. Urinary excretion The urinary excretion up to 6 hours after administration was: 69.0% for 15 mg/kg and 61.9% for 50 mg/kg in cases of intravenous injection, and 62.4% for 15 mg/kg and 71.1% for 50 mg/kg in cases of intravenous 1-hour drip infusion. The percent urinary excretion was similar to that in adults.

Cefsulodin↗

Acute and subacute toxicity of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1 ,4-dihydropyridine (PP-1466).

The acute and subacute oral toxicity of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1,4 -dihydropyridine (PP-1466) was investigated in several animal species in comparison with nifedipine and nicardipine. A clear species difference in LD50 values was found in acute toxicity of PP-1466, and rabbits were the most sensitive between animal species used, then dogs, mice and rats in order. Prominent acute circulatory failure and associated secondary changes were noticed in toxic signs and autopsy findings. PP-1466 as well as nifedipine was apparently less toxic than nicardipine. In the subacute toxicity studies in rats, deaths occurred only in the 2000 mg/kg/d treated groups of both sexes of PP-1466 and nifedipine. Major changes in various observations and examinations were focussed on the cardiovascular system and liver. On the cardiovascular system, it was revealed as congestion and hemorrhage in the various organs and tissues on autopsy finding in dead rats during the test period. A dose-dependent increase in heart weight was observed in rats sacrificed at the termination of the test period. On the liver, it was revealed as a dose-dependent increase in liver weight, changes in liver lipid levels, changes in several serum biochemistry parameters, such as GOT, GPT and ALP (alkaline phosphatase) activities and lipid levels measured at the termination of the test period. These changes were toxicologically mild and functional except the autopsy findings in dead rats. Female rats were slightly more sensitive than males, and PP-1466 was slightly less toxic than nifedipine on subacute oral toxicity in rats.

Administration, Oral↗

[Traumatic mitral insufficiency: a case report].

A 25-year-old man was admitted to Juntendo University Hospital with chief complaints of nocturnal dyspnea and shortness of breath on Sept. 22, 1983. He had no history of rheumatic fever or bacterial endocarditis. He was violently kicked in the chest while practicing Shorinji-Kempo (Karate) in July 1977. His heart murmur was first noticed in April 1978, but he was asymptomatic for six years after the accident until transient nocturnal dyspnea developed January 1983. Physical examination on admission revealed a grade 4/6 apical holosystolic murmur, a markedly accentuated third sound, and hepatomegaly of two finger breadth in the right midclavicular line. An electrocardiogram revealed sinus tachycardia (100/min), left atrial overload and left ventricular hypertrophy. Chest radiography showed slight cardiac enlargement with a cardiothoracic ratio of 55%, and slightly increased pulmonary vascular markings. Two-dimensional echocardiography showed a markedly prolapsed posterior mitral leaflet and fluttering in diastole. Cardiac catheterization showed elevated pressure of pulmonary capillaries (a: 16, v: 30, mean: 19 mmHg), the pulmonary artery and the right ventricle. Left ventriculography revealed grade four (Sellers) mitral regurgitation. Mitral valve replacement was performed on October 13, 1983. A chorda tendinae supporting the posterior leaflet of the mitral valve was found to be ruptured just above its origin from the posterior papillary muscle. Histological examination of the resected valve showed increased spongiosa tissue which mimicked so-called myxomatous changes, but it seemed preferable to interpret this as a "secondary change due to increased hemodynamic stress" rather than the "primary change".

Adult↗

Combined treatment of coenzyme Q10 and aprotinin with intraaortic balloon pumping following aorto-coronary bypass surgery.

The effect of combined treatment of coenzyme Q10 (CoQ10) and aprotinin with intra-aortic balloon pumping (IABP) was evaluated in patients who underwent aorto-coronary bypass surgery. Forty-one patients were divided into two groups. Group A (27) were treated by IABP only and Group B (14) were treated by the concomitant use of CoQ10 and aprotinin with IABP. Both groups were subdivided into two groups with regard to the ability to be weaned from IABP (Group A-I, Group B-I) or the inability (Group A-II, Group B-II). CoQ10 was administrated intravenously at doses of 5-10 mg/kg/day and aprotinin was infused at doses 5,000-10,000 KU/kg/day. The percentile incidence of ability to be weaned from IABP was 93 per cent (13/14) in Group B was higher than that of 74 per cent (20/27) in Group A. There were no significant differences among Group A-I, Group A-II, and Group B-I with regard to preoperative and intraoperative factors. Serum GOT and CPK levels on the first postoperative day were significantly higher in Group A-II and Group B-I than those in Group A-I but there was no significant difference between GOT or CPK levels in Group A-II and Group B-I. These results suggest that concomitant treatment of CoQ10 and aprotinin with IABP leads to an improvement in postoperative low cardiac output syndrome.

Aprotinin↗

Pharmacological studies of FUT-175, nafamstat mesilate. I. Inhibition of protease activity in in vitro and in vivo experiments.

FUT-175, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate (nafamstat mesilate), a novel synthetic protease-inhibiting agent, was studied to determine its in vitro effects against various proteases and other enzymes, as well as to determine its in vivo protease inhibitory effects. FUT-175 was found to inhibit, in an intense, specific and reversible way, the enzyme activities of trypsin, C1r, C1s, thrombin, kallikrein and plasmin with IC50 values of the order of 10(-6)-10(-8) M. FUT-175 also inhibited complement-mediated hemolysis, including both classical and alternative pathways, sites of inhibition being on C1r and C1s as evidenced by the intermediate-cell technique. In animal model reactions in which the complement system is known to be involved as pathogenetic factors, e.g., Forssman shock, Forssman cutaneous vasculitis, zymosan-induced paw edema, endotoxin shock and local Shwartzman reaction, FUT-175 was highly effective in that, for example, intravenous dosing at 3 mg/kg could completely protect guinea pigs from the lethal Forssman shock. FUT-175 was also found to be effective in trypsin-induced shock in mice, in lethality due to thrombin-thrombosis in mice and in kinin formation in the inflammatory process in rats.

Animals↗

[Pharmacological studies of FUT-175, nafamstat mesilate. II. Effects on experimental acute pancreatitis].

Effects of FUT-175, a novel synthetic protease-inhibiting agent, on various models of experimental acute pancreatitis were examined. FUT-175 infused i.v. at a dose range of 5-50 micrograms/kg/min inhibited the increase in plasma trypsin activity and reduced the mortality of rabbits in trypsin-induced acute pancreatitis in a dose-dependent manner. Increase in serum amylase activity and pancreatic tissue lesion were attenuated in rabbits. In addition, FUT-175 infused i.v. at a dose range of 1-50 micrograms/kg/min reduced the mortality of rats in experimental acute pancreatitis produced by trypsin and endotoxin. FUT-175 infused i.v. at a dose range of 1-100 micrograms/kg/min protected the dogs from the increase in plasma trypsin activity and hypotension and shock induced by trypsin, well-known characteristics of acute pancreatitis. These results suggest that FUT-175 is beneficial as a therapeutic agent of acute pancreatitis.

Acute Disease↗

[Pharmacological studies of FUT-175, nafamstat mesilate. III. Anti-inflammatory activities of FUT-175].

Anti-inflammatory effects of FUT-175 (nafamstat mesilate), a new synthetic serine protease inhibitor, on various types of experimental inflammation were investigated in vivo and in vitro, in comparison with non-steroidal anti-inflammatory drugs (NSAID). The in vivo studies showed that FUT-175 has the abilities to inhibit almost all types of inflammatory reactions employed in the present study. In particular, being evaluated on the basis of the effect of indomethacin, FUT-175 exhibited relatively higher potencies against some reactions such as zymosan-induced increase of vascular permeability, scald paw edema, zymosan-induced granuloma-pouch, the Arthus reaction and acetic acid-induced writhing in which the complement system or the kallikrein-kinin system are considered to play an important role. The in vitro studies showed that FUT-175 is quite different from NSAID, that is, FUT-175 had no effects on heat-induced erythrocyte-lysis and heat-induced denaturation of bovine serum albumin. FUT-175 also had no effect on chemotaxis of polymorphonuclear leucocytes, but inhibited the production of chemotactic factor by antigen-antibody reaction. These above results suggested that FUT-175 has a different mode of action from NSAID and that serine protease inhibiting activities of this compound might play an important role in its anti-inflammatory effect.

Animals↗