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Biomedical subjects

K Munakata

Publications and source records attributed to K Munakata.

At least 19 recordsLinked to original sources

Evaluation of the usefulness of a novel injectable cephalosporin, E1040, and ceftazidime for management of complicated urinary tract infections caused by Pseudomonas aeruginosa and Proteus mirabilis by using the rat urolithiasis model.

A novel injectable cephalosporin, E1040, significantly eradicated Pseudomonas aeruginosa from the urine, in contrast to ceftazidime, in rats with complicated P. aeruginosa urinary tract infections associated with urinary stones, suggesting that E1040 is a prospective therapeutic agent in the management of refractory Pseudomonas urinary tract infections.

Animals

Two cases of variant form angina pectoris associated with myocardial bridge--a possible relationship among coronary vasospasm, atherosclerosis and myocardial bridge.

Myocardial bridge (MB) is a congenital anomaly of the coronary artery and may occur in 5 to 12% of the human population. However, the mechanism of MB-induced myocardial ischemia is still speculative. We report 2 cases of variant form angina pectoris associated with MB in which myocardial ischemia seemed to be related to the interaction between coronary perfusion and MB. In case 1, electrocardiography during anginal attack at rest showed ST elevation in the inferior leads and MB was observed after percutaneous transluminal coronary angioplasty at the site of the right coronary artery lesion following successful dilatation. In case 2, MB of the left anterior descending coronary was located in the identical portion where coronary vasospasm was induced by intracoronary acetylcholine injection, although ischemia during the spontaneous anginal attack was limited to the inferior area of myocardium. These 2 cases suggest that MB can be, at least in some patients, one of the possible causes of the endothelial damage which seems to be related to coronary vasospasm; this was documented in both cases.

Angina Pectoris, Variant

Evaluation of effects of novel urease inhibitor, N-(pivaloyl)glycinohydroxamic acid on the formation of an infection bladder stone using a newly designed urolithiasis model in rats.

By using our new infection stone model of a rat, we evaluated the effect of a novel urease inhibitor, N-(pivaloyl)glycinohydroxamic acid (P-GHA), on the formation of an infection bladder stone. The oral dosing of P-GHA significantly inhibited the elevation of the urinary ammonia level of rats having the urinary tract infection with Proteus mirabilis. A short term regimen (7 d, 730 +/- 38 mg/kg) with P-GHA significantly inhibited the development of the infection bladder stone. Furthermore, a long term combination regimen (11 d) of P-GHA and aminobenzylpenicillin markedly inhibited the development of the infection bladder stone, and also caused a very slight renal impairment to the rats tested in contrast with the method of Vermeulen et al. Our infection stone model in rats, therefore, seems to be useful for the evaluation of therapeutic agents in long term examinations.

Ampicillin

Effects of a novel urease inhibitor, N-(diaminophosphinyl)isopentenoylamide on the infection stone in rats.

We evaluated the effect of a novel potent urease inhibitor, N-(diaminophosphinyl)isopentenoylamide (IPA), on the development of an infection bladder stone using our urolithiasis model in rats. IPA was excreted into urine after oral administration to rats, and the cumulative urinary recovery rate of unchanged IPA reached about 29.6% within 24 h (50 mg/kg). The oral administration of IPA (6.25 mg/kg, b.i.d., 5 d) significantly inhibited the development of the infection bladder stone. The present result suggests that IPA is a very promising compound in the prevention of formation and recurrence of an infection stone owing to a high efficacy and a low toxicity of IPA in animals.

Animals

Effect of pericardium on regional myocardial systolic function in acute ischemia.

To know whether or not the pericardium affects regional myocardial systolic function in acute ischemia, we measured ischemic and non-ischemic segment lengths of the left ventricle using ultrasonic crystals in 10 open-chest dogs with the pericardium preserved. When the left ventricular pressure and segment lengths were stable after left circumflex coronary occlusion, we opened the pericardium widely. After coronary occlusion, end-diastolic length (EDL) in ischemic and non-ischemic segments increased, and the ischemic segment showed paradoxical systolic expansion while the non-ischemic segment increased its active shortening. After pericardiectomy, heart rate, left ventricular systolic pressure, and peak positive and negative dP/dt did not change. EDL in ischemic and non-ischemic segments further increased from 12.02 +/- 0.18 to 12.50 +/- 0.16 mm (mean +/- S.E., p less than 0.01) and from 11.12 +/- 0.20 to 11.45 +/- 0.18 mm (p less than 0.05), respectively, despite the concomitant fall in left ventricular end-diastolic pressure (LVEDP) from 12.4 +/- 0.6 to 10.6 +/- 0.8 mmHg (p less than 0.01). End-systolic length in ischemic and non-ischemic segments also increased from 12.37 +/- 0.25 to 12.70 +/- 0.20 mm (p less than 0.05) and from 8.50 +/- 0.13 to 8.74 +/- 0.13 mm (p less than 0.01), respectively, although the left ventricular end-systolic pressure did not change. Maximum expanded systolic length of the ischemic segment also increased from 12.99 +/- 0.20 to 13.42 +/- 0.16 mm (p less than 0.01). These results indicate that, in acute ischemia, the pericardium inhibits paradoxical systolic expansion of the ischemic region and increase in end-systolic length of non-ischemic segment. Thus, it is concluded that the pericardium modifies the regional myocardial systolic function in acute ischemia, perhaps through the mechanical restraint of the pericardium.

Animals

Angiographic response to a vasodilating drug, nicorandil, in patients with coronary artery disease.

To investigate the usefulness of nicorandil as an antianginal drug, we compared the coronary vasodilatory response in nonstenotic coronary artery segments and the hemodynamic response in 26 coronary artery disease patients. Both responses were studied prior to sublingual administration of 10 mg of this drug and 10, 30 and 60 min afterward. The plasma nicorandil concentration was determined up to 120 min after administration. The mean coronary dilating ratio of nicorandil was 117% 30 min after administration (p less than 0.01) and showed a good correlation to the plasma nicorandil concentration. The mean maximum dilating ratio of each patient was 125%. There was no difference between individual coronary arteries or between proximal and distal segments in terms of the coronary artery dilating ratio. The plasma nicorandil concentration required for 120% dilation of the coronary arteries was 26 ng/ml, 89 ng/ml and 142 ng/ml for those cases with variant angina, exertional angina and postinfarction angina, respectively. Hemodynamic changes due to administration of this drug included a decrease in blood pressure, and a reduction in total peripheral resistance, rate-pressure product, pulmonary capillary pressure and stroke-work index. These results indicate that the antianginal effects of nicorandil are derived from its coronary vasodilatory action and an inhibitory effect on myocardial oxygen consumption.

Administration, Sublingual

[Role of the peptidergic nerves in Hirschsprung's disease and hypoganglionosis].

The purpose of this study is to examine the role of peptidergic nerves (VIP, Substance P, Neurotensin) in Hirschsprung's disease (aganglionosis) and hypoganglionosis in relation to the normoganlionic state of the colon using a mechanographic technique in vitro. The following results were obtained. 1) Normoganglionic muscle strips demonstrated the presence of intact non-adrenergic inhibitory nerve. The activities of such nerves, however, were reduced in hypoganglionic muscle strips, and were absent in aganglionic muscle strips. 2) Peptidergic nerve activities by VIP, substance P, and Neurotensin were present in normoganglionic muscle strips, while they were reduced in hypoganglionic muscle strips, and absent in aganglionic muscle strips. 3) VIP may act as a neurotransmitter-neuromodulator of non-adrenergic inhibitory nerve, while SP and Neurotensin may act as that of non-cholinergic excitatory nerve with some direct effect on the intestinal muscle.

Hirschsprung Disease

A case of progressive muscular dystrophy with numerous arterioluminal vessels.

A 48-year-old man had histologically demonstrated cardiac involvement associated with progressive muscular dystrophy. On coronary arteriography, numerous vascular communications between the coronary arteries and the left ventricular chamber were found. These vascular communications are considered to be the arterioluminal vessels. This is the first report of a case of progressive muscular dystrophy with numerous arterioluminal vessels.

Coronary Angiography

The degree of increment in plasma catecholamines in patients with mitral stenosis by mild exercise.

Although sympathetic excitation during mild exercise may readily occur in patients with mitral stenosis (MS), the degree of increment in plasma catecholamines has not been fully investigated. We imposed mild ergometric exercise (50 watts, 300 kg/min for 5 minutes) on five patients with mild MS (mitral valve area greater than or equal to 1.0 cm2) and eight with severe MS (mitral valve area less than 1.0 cm2) while they were undergoing cardiac catheterization. In patients with severe MS, total plasma catecholamine levels during exercise were remarkably higher (2821 +/- 783 [SEM] pg/ml) than in those with mild MS (957 +/- 113 pg/ml, p less than 0.05) and in seven control subjects (612 +/- 75 pg/ml, p less than 0.05). This marked increment could not be predicted by heart rate response, which did not differ between severe and mild MS (166 +/- 5 vs 153 +/- 10 bpm). In contrast with catecholamine change, the cardiac index in severe MS showed a very small increment. Results suggest that mild daily exercise can remarkably increase plasma catecholamine levels in severe MS, and this may accelerate various complications of this disorder.

Adult

Electrophysiological effects of flecainide on guinea pig ventricular muscle in high [K+]o, acidosis and hypoxia.

The electrophysiological effects of flecainide on the action potential were examined in guinea pig ventricular muscles using microelectrode recording methods. Under the control conditions, flecainide (0.5-1 microgram/ml) did not alter the resting potential, action potential duration (APD) or effective refractory period (ERP). The major effect of flecainide was on maximum upstroke velocity (Vmax), which was depressed in a dose-dependent manner. In high [K+] medium (potassium concentration = 10 mM), Vmax was depressed by 16.8% at a concentration of 1.0 microgram/ml (8.8% in normal [K+]o). In metabolic acidosis (pH = 6.89), it was depressed by 15.7% at the same concentration of the drug (8.3% in normal condition). The changes in ERP and ERP/APD90% in high [K+]o and metabolic acidosis were not significantly different from the normal condition. After hypoxic perfusion for 15 min, Vmax depression by flecainide was 16.3% (7.4% in control medium). The increase of ERP/APD90% was also greater in hypoxia. These data indicate that the most prominent effect of flecainide is Vmax depression which is enhanced under the high K+, acidic and hypoxic conditions. Therefore, it is suggested that flecainide may be most effective for ventricular arrhythmias occurring in myocardial ischemia.

Acidosis

Cholera toxin, a potent inducer of epidermal hyperplasia but with no tumor promoting activity in mouse skin carcinogenesis.

Intracutaneous injection of cholera toxin into mice induced epidermal hyperplasia to a greater extent than 12-O-tetradecanoylphorbol-13-acetate. It also induced adenylate cyclase and though weakly, ornithine decarboxylase of the epidermis. Cholera toxin, however, showed no tumor promoting activity in mouse skin carcinogenesis. In the single stage promotion, cholera toxin (50 ng) was injected once a week for 10 weeks into the skin of SENCAR mice initiated with 25 micrograms 7,12-dimethylbenz[a]anthracene, but no tumors developed. In the two-stage promotion test, cholera toxin (10-100 ng) was injected for one or two weeks into the initiated skin and then mezerein (4 micrograms) was applied twice a week for 18 weeks, but the toxin did not increase incidence or numbers of papillomas.

9,10-Dimethyl-1,2-benzanthracene

[Clinical and histologic studies of abnormal intramural plexus with special reference to hypoganglionosis].

Since April 1973, 230 patients, who were suspected of Hirschsprung's disease, have been examined by rectal mucosal biopsy, barium enema and ano-rectal manometry. Their rectal mucosal specimens have been taken both from the regions 2cm upwards and just above the dentate line, and have been studied by means of acetylcholinesterase (AChE)-staining and hematoxylin-eosin (H-E)-staining. Specimens obtained by rectal full-thickness biopsies or operations were examined by means of AChE-staining, H-E-staining and silver-impregnation. Eleven out of the 230 patients were histologically diagnosed as hypoganglionosis. All rectal mucosas of hypoganglionosis showed a few small submucous plexus. According to the findings of nerve fibers, however, cases of hypoganglionosis were divided into three groups. The recognition of nerve fibers partially proliferated in rectal mucosa at the newborn age leads the diagnosis to type A. The type B is diagnosed as Hirschsprung's disease only through the recognition of proliferations of nerve fibers in rectal mucosa after the suckling age. In type C, no proliferation of nerve fibers can be recognized even after the suckling age. An accurate diagnosis of type C can be, therefore, made only through the examinations of myenteric plexus in full-thickness rectal specimen. On barium enema, a narrow segment was definite in 7 cases of hypoganglionosis, but was indefinite in the remaining 4 cases. The diseased segments of intestines were limited to the rectum or the rectosigmoid colon in 10 cases. Recto-anal sphincteric reflex showed an atypical reflex in 6 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Child