Search PubMed⌕ Search

Biomedical subjects

N Fukuda

Publications and source records attributed to N Fukuda.

At least 163 records · Page 9Linked to original sources
PubMed1996

Synergistic effect of polyoxotungstates in combination with beta-lactam antibiotics on antibacterial activity against methicillin-resistant Staphylococcus aureus.

The in vitro antibacterial effect of the combination of various polyoxometalates with beta-lactam antibiotics on methicillin-resistant Staphylococcus aureus (MRSA) strains is investigated by the use of both the National Committee for Clinical Laboratory Standards (NCCLS) disk method and the agar dilution method. Keggin-structural polyoxotungstates such as K7[PTi2W10O40].6H2O (5) and K7[BVW11O40].7H2O (8) and their lacunary species formulated by [XW11O39]n- and[XW9O34]n- potentiated the antibacterial activity of beta-lactam antibiotics such as oxacillin, piperacillin and cefazolin on MRSA with high selectivity. The depression of bacterial growth with the coexistence of polyoxotungstates and oxacillin was confirmed by the measurement of the bacterial turbidity at 660nm. Polyoxomolybdates and polyoxovanadates, on the other hand, exhibited hardly any synergistic effect in combination with oxacillin. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the membrane proteins separated from MRSA revealed that polyoxotungstates depressed the formation of penicillin-binding protein 2'(PBP2'), an enzyme which is essential for cell wall construction in the MRSA growth. It is concluded that polyoxotungstates make the MRSA strains susceptible to beta-lactam antibiotics.

Anti-Bacterial Agents↗
PubMed1996

Antianginal effect of RS-5773, a diltiazem congener, in the methacholine-induced anginal model in rats.

The antianginal effect of RS-5773 ((2S,3S)-3-acetoxy-8-benzyl-2,3-dihydro-5-[2-(dimethylamino)- ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepine-4-(5H)-one hydrochloride), a newly developed benzothiazepine derivative, was evaluated in an angina model rat. Close-coronary artery injections of methacholine in anesthetized rats evoked ischemic electrocardiographic (ECG) changes (S wave elevation of about 0.6 mV). The ECG changes produced by methacholine were reproducible for as long as 6 hr. Intravenous and intraduodenal administration of RS-5773, diltiazem or clentiazem produced dose-dependent suppressions of the ischemic ECG changes. RS-5773 exceeded the other two agents both in the maximum suppressive effect on S wave elevation and in the duration of action after intravenous administration. The antianginal potency expressed as AUC (area under the curve), i.e., the percent suppression of S wave elevation integrated over time, revealed that RS-5773 was 16 times and 7 times more potent than diltiazem and clentiazem, respectively. A similar order of potency difference was observed after intraduodenal administration, and RS-5773 sustained its effect for about 6 hr at 3 mg/kg. In addition, RS-5773 did not cause excessive hypotension or depression of atrioventricular conduction. These results suggest that RS-5773 has a preferable profile as an antianginal agent.

Angina Pectoris, Variant↗
PubMed1996

Prevention of cardiac hypertrophy by a sub-antihypertensive dose of the alpha 1-adrenergic antagonist bunazosin in Dahl salt-sensitive rats.

To assess the protective effect of an alpha 1-blocker on the development of cardiac hypertrophy, the selective alpha 1-receptor antagonist bunazosin (2 mg/kg/d, by oral gavage and in drinking water) was given to male Dahl salt-sensitive rats fed a 4% NaCl diet for 7 weeks. Control animals received water only by the same method. Treatment with bunazosin was started when the animals were 7 weeks of age. Blood pressure, pulse rates, and body weight were measured every week during the experiment. Urine was collected for 24 h on the final day of the experiment. All animals were killed by decapitation, blood was collected, and the heart was removed. In both the treated and control groups, time-dependent increase in blood pressure and body weight were observed, and there were no significant differences between the groups in blood pressure or body weight during the experiment. Pulse rate remained unchanged in both groups throughout the experiment. The left ventricular weight/body weight ratio and the left ventricular tissue DNA content were significantly lower in the rats receiving bunazosin than in the control rats. Plasma renin activity, plasma aldosterone, and plasma atrial natriuretic peptide did not differ significantly between the two groups. No significant differences in glomerular filtration rate, urine volume, sodium excretion, urinary metanephrine excretion, and urinary normetanephrine excretion were noted between the two groups. The results indicate that a sub-antihypertensive dose of bunazosin can inhibit the development of cardiac hypertrophy without suppression of the pressure load, suggesting an important role of alpha 1-adrenergic receptors in the pathogenesis of cardiac hypertrophy following the development of hypertension.

Adrenergic alpha-Antagonists↗
PubMed1996

Assessment of left atrial pressure and volume changes during atrial systole with transesophageal pulsed Doppler echocardiography of transmitral and pulmonary venous flow velocities.

To determine whether transmitral and pulmonary venous flow velocity patterns can be used to evaluate left atrial pressure and volume changes during atrial systole, we performed transesophageal pulsed Doppler echocardiography and right heart catheterization in 85 patients (20 with hypertrophic cardiomyopathy, 20 with dilated cardiomyopathy, 30 with prior myocardial infarction, and 15 with mitral regurgitation), and 35 normal subjects. Pulsed Doppler variables from transmitral and pulmonary venous flow velocities during atrial systole were compared with mean pulmonary capillary wedge pressure (mean PCWP), pressure rise during atrial systole (PCWP-A), and left atrial volume change during atrial systole (delta LAV). The mean PCWP correlated significantly with the peak atrial systolic transmitral flow (r = -0.38, p < 0.05) and pulmonary venous flow (r = 0.40, p < 0.05) velocities in all patients. The PCWP-A correlated significantly with the peak atrial systolic transmitral flow (r = -0.39, p < 0.05) and pulmonary venous flow (r = 0.68, p < 0.0001) velocities in all patients. There was a particularly close correlation between the PCWP-A and the peak atrial systolic pulmonary venous flow velocities. The sum of the time-velocity integral of the atrial systolic transmitral and pulmonary venous flow velocities (TAI) correlated closely with the delta LAV (r = 0.70, p < 0.0001) in all patients. Thus, the peak atrial systolic pulmonary venous flow velocity correlated well with left atrial pressure changes during atrial systole. Furthermore, the sum of the time-velocity integral of the atrial systolic transmitral and pulmonary venous flow velocities correlated well with left atrial volume changes during atrial systole. Therefore, transesophageal echocardiographic measurements of atrial systolic transmitral and pulmonary venous flow velocities are reasonable indicators of left atrial pressure and volume changes during atrial systole.

Adult↗
PubMed1996

Hypertriglyceridemia and fatty liver of fasting rats after administration of emeriamine.

The effect of emeriamine, a potent inhibitor of the entry of fatty acids into mitochondria on lipid metabolism, was examined. Emeriamine (10 mg/kg body weight) was orally administered to rats under the two different physiological conditions of a 2-day fast or refeeding with a high-carbohydrate diet after a 2-day fast. When rats were refed with a high-carbohydrate diet, serum and hepatic ketone bodies and the levels of free fatty acids decreased, and triglycerides significantly increased compared with fasting rats. However, no significant effect of emeriamine on serum and hepatic lipids was observed between two refeeding groups with or without emeriamine. Conversely, when emeriamine was administered to fasting rats, the levels of serum and hepatic triglycerides increased about 11- and 5-fold, respectively. However, the increased level of hepatic triglycerides was not accompanied by the activities of fatty acid synthetase and NADPH-generating enzymes. The analysis of serum lipoprotein revealed that very low-density lipoprotein consisted of triglyceride-rich particles and there were less apolipoproteins in the fasting rat given emeriamine. We also determined the 120-kDA protein content, which was probably dependent on lipogenesis. The level of 120-kDa protein was greatly increased with or without the administration of emeriamine after refeeding with a high-carbohydrate diet, but the concentration of 120-kDa protein was slight in the fasting rat with emeriamine. These results suggest that specific inhibition of fatty acid oxidation by emeriamine diverted the exogenous fatty acid to the esterification pathway, and induced fatty liver and hypertriglyceridemia under fasting conditions.

Animals↗
PubMed1996

Effects of refeeding diets on emeriamine-induced fatty liver in fasting rats.

We recently reported that fatty liver and hypertriglyceridemia are easily induced by the administration of an inhibitor of fatty acid oxidation (emeriamine; (R)-3-amino-4-trimethylaminobutyric acid) to fasting rats, and that these conditions are not accompanied by the increased de novo synthesis of fatty acid [J. Nutr. Sci. Vitaminol., 42, 111-120, (1996)]. To study whether emeriamine-induced fatty liver is affected by nutrients during recovery from fatty acid oxidation inhibition, we fed rats with either a high-carbohydrate (HCHO) diet or a high-fat (HFAT) diet. Rats fed an HCHO diet following the administration of emeriamine showed a marked decrease in serum and hepatic triglycerides, and a marked increase in hepatic glycogen. The lower levels of serum and hepatic triglycerides were accompanied by decreased activities of the NADPH-generating enzymes such as malic enzyme and glucose-6-phosphate dehydrogenase. By contrast, rats fed an HFAT diet showed less significant changes in hepatic triglyceride and glycogen levels. These results suggest a reciprocal relationship between the triglyceride level and glycogen accumulation caused by HCHO diet during recovery from emeriamine.

Animals↗
PubMed1996

Systolic and diastolic mitral regurgitation in a patient with annulo-aortic ectasia demonstrated by color Doppler flow imaging.

A rare case of annulo-aortic ectasia is reported in a 65-year-old man who had aortic and mitral regurgitation during systole and diastole. He was hospitalized for further examination of the heart due to cardiomegaly and heart murmurs. Aortography revealed severe aortic regurgitation. On color Doppler flow imaging, we could detect red aortic regurgitant signals in the left ventricular cavity during diastole, and mosaic and blue mitral regurgitant signals in the left atrial cavity during systole and diastole associated with a relatively long R-R interval, respectively. The unique observation of diastolic mitral regurgitation is discussed.

Aged↗
PubMed1996

Peculiar patterns of aortic regurgitation and carotid pulse due to dysfunction of a Medtronic Hall prosthetic valve: a case report.

We describe a patient with dysfunction of a Medtronic Hall prosthetic valve showing peculiar patterns of aortic regurgitation and carotid pulse caused by valvular thrombosis. The aortic regurgitation was considered to be caused by a significant delay in prosthetic valve closure, manifested by a peculiar regurgitation pattern limited to early diastole, in association with widely split closing clicks and an abnormally low dicrotic notch in the carotid pulse. At surgery, fibrin thrombi were noted just below the prosthetic ring in the minor outflow region which restricted disc movement. The fibrin thrombi were removed and the valve was rotated 90 degrees. Following reoperation, all abnormalities disappeared.

Angiography↗
PubMed1996

[Non-surgical treatment of intrahepatic calculi].

It is obvious that the most favorable therapeutic results can be obtained by hepatic lobectomy in the patients with intrahepatic calculi. However the number of patients in which hepatic lobectomy can be indicated is limited because of localization of lesions and some others. Endoscopic stone-extraction technique is the only therapeutic tool available in those patients. In this paper, technical know-how of postoperative cholangioscopy (POCS) and percutaneous transhepatic cholangioscopy (PTCS) was introduced and their clinical significance for management of intrahepatic calculi were discussed. POC was safely carried out 3 weeks after surgery if the extra-ductal limb of T-tube, lager than 14 Fr size, in the common bile duct, was brought out through the abdominal wall as straight as possible to obviate a tortuous sinus tract. PTCS was carried out through the sinus tract dilated up to over 14 Fr size after percutaneous transhepatic biliary drainage. Advantages of these modalities are; 1) they can be safely and repeatedly carried out if the sinus tract is maintained open. 2) stones visible are readily removable with the use of basket forceps or stone-integrator under endoscopic guidance and 3) preoperative application of PTCS provides us the important informations necessary to decide an adequate surgical procedure by delineation of intrahepatic anatomy. For the period started from 1975 when we introduced the first model of cholangiofiberscope to the end of 1995, 134 cases with intrahepatic calculi have been encountered and stone extraction was successful in 119 cases, success rate being 88.8%. The prognosis of the patients in which stone-extraction was successful was generally good. Main causes of failure in 15 cases were attributable to difficult location of lesion to perform choplangioscopy and concomitant liver cirrhosis or pururent cholangitis. The 6 cases with concomitant liver cirrhosis and pururent cholangitis were passed away before stone-extraction was completed. Therefore it can be said that complete stone-extraction was POCS or PTCS is very important to obtain a better long term prognosis in the cases with intrahepatic calculi. The authors believe that therapeutic results of inrahepatic calculi will be improved with the use of POCS or PTCS.

Adult↗
PubMed1996

[Evaluation of myocardial sympathetic nerve function in patients with mitral valve prolapse using iodine-123-metaiodobenzylguanidine myocardial scintigraphy].

Mitral valve prolapse (MVP) is closely related to myocardial sympathetic nerve function. This study evaluated the presence of impaired myocardial sympathetic nerve function by Iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy in nine patients with MVP. For comparison, 15 healthy subjects without heart disease were investigated (control group). Single photon emission computed tomography (SPECT) and anterior planar myocardial scintigraphy were performed 15 min (initial images) and 3 hours (delayed images) after injection of MIBG (111 MBq). The location and degrees of reduced tracer uptake were evaluated. Myocardial MIBG uptake was quantified by uptake ratio of the heart (H) to upper mediastinum (M) on the anterior planar images (H/M). Percentage washout of MIBG in nine sectors of all oblique slices along the short-axis was calculated. The washout rates were higher at the inferoposterior and septal segments in patients with anterior leaflet prolapse, and at inferoposterior and lateral segments in patients with posterior leaflet prolapse. The bull's eye map showed increased washout rate in the apical and posteroseptal basal segments. There was no significant difference in the H/M ratio between MVP patients and the control group. These results indicate that MIBG can be used to evaluate localized myocardial sympathetic nerve function in MVP.

3-Iodobenzylguanidine↗
PubMed1995

Pharmacology of CS-866, a novel nonpeptide angiotensin II receptor antagonist.

CS-866, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy-4-(1-hydroxy-1- methylethyl)-2-propyl-1-(4-[2-(tetrazol-5-yl)-phenyl]phenyl)met hylimidazol- 5-carboxylate, a prodrug type angiotensin receptor antagonist, is deesterified to the active acid, RNH-6270. RNH-6270 inhibited [125I]angiotensin II binding to bovine adrenal cortical membranes (angiotensin AT1 receptors) with an IC50 value of 7.7 nM, but not [125I]angiotensin II binding to bovine cerebellar membranes (angiotensin AT2 receptors), indicating the selectivity of the compound for angiotensin AT1 receptors. In guinea pig aortas, RNH-6270 reduced the maximal response of the concentration-contractile curve for angiotensin II (pD'2 = 9.9), but had no effect on the contractile response induced by phenylephrine or KCl. In conscious rats, intravenously injected RNH-6270 inhibited angiotensin II-induced pressor responses in a dose-dependent manner, and orally administered CS-866 produced a long-lasting inhibition of angiotensin II pressor responses. SK&F-525A, a P-450 inhibitor, suppressed the angiotensin II inhibitory effect of losartan, but not that of CS-866. These results demonstrate that RNH-6270 is a potent and AT1-selective angiotensin receptor antagonist and that, after oral administration, CS-866 has a long-lasting angiotensin II inhibitory action which is not affected by drug metabolizing enzymes in the liver.

Adrenal Cortex↗
PubMed1995

Predisposing factors for severe mitral regurgitation in idiopathic mitral valve prolapse.

To elucidate predisposing factors for severe mitral regurgitation (MR) in idiopathic mitral valve prolapse (MVP), 124 MVP patients were classified into the following categories: 55 with isolated clicks (click group), 35 with a late-systolic murmur (late-SM group), and 34 with a holosystolic murmur (holo-SM group). Their clinical and echocardiographic findings were compared with those of 26 patients with spontaneous chordal rupture (rupture group). In 22 patients in the click group, 24 in the late-SM group, and 22 in the holo-SM group, follow-up studies were performed for a mean of 4.5 years (range 1 to 13.5). The mean age was youngest in the click group and oldest in the rupture group. The click and late-SM groups showed a female predominance, but the holo-SM and rupture groups showed a male predominance. There was no difference in the incidence of systemic hypertension among the 4 groups. Most patients in the click and late-SM groups had anterior leaflet prolapse. In the holo-SM and rupture groups, however, the incidence of posterior leaflet involvement was significantly increased. The incidence of thickened mitral valve increased in order of the click (8%), late-SM (21%), holo-SM (38%), and rupture (50%) groups. Six patients in the holo-SM group developed chordal rupture with severe MR during the follow-up period. In the click and late-SM groups, however, there were no complications and no development into a holo-SM. Thus, aging, male sex, posterior leaflet prolapse, thickened mitral valve, and holo-SM were found to be important predisposing factors for severe MR in idiopathic MVP.

Adult↗
PubMed1995

Enhancement effect of carteolol on the clonidine-induced vasodilation of rat mesenteric arteries.

It has demonstrated that carteolol can increase the endothelium-dependent vasodilation induced by alpha-2 adrenergic agonist. In order to evaluate the effect of carteolol, and to clarify the mechanism, we examined the effects of 10 microM carteolol on the vasodilation induced by increasing doses (10(-7)-10(-4) M) of clonidine in perfused rat mesenteric arteries preconstricted with 100 microM phenylephrine. Clonidine elicited a dose-dependent vasodilation of the mesenteric arteries preconstricted with phenylephrine. Carteolol enhanced the vasodilation induced by higher doses (10(-5) and 10(-4) M) of clonidine, although carteolol itself exerted no direct vasodilating effect. On the other hand, 10 microM propranolol or 10 microM metoprolol did not augment the clonidine-induced vasodilation. In the presence of 100 microM NG-monomethyl L-arginine (LNMMA), an analogue of L-arginine, the enhancement of the clonidine-induced vasodilation by carteolol was abolished. This inhibition by LNMMA was restored with 300 microM L-arginine, but not with 300 microM D-arginine. These results suggest that carteolol enhances the clonidine-induced vasodilation by an endothelial-related mechanism mediated by the release of endothelium-derived nitric oxide in resistance vessels.

Animals↗
PubMed1995

Effects of enalapril on left ventricular mass and diastolic function in essential hypertension: special reference to duration of hypertension.

Using M-mode and pulsed Doppler echocardiography, the effects of enalapril on left ventricular (LV) hypertrophy and diastolic dysfunction in essential hypertension and the relation between improvement in these two parameters and duration of hypertension were evaluated. The subjects, 30 previously untreated hypertensive patients, were divided into nonhypertrophy (18 patients) and hypertrophy (12 patients) groups. All patients received enalapril at a daily dose of 5 to 10 mg for 6 months. Left ventricular mass by M-mode echocardiography and LV inflow (LVIF) velocity by transthoracic pulsed Doppler echocardiography were measured before and after enalapril therapy. In the nonhypertrophy group, enalapril significantly increased peak early diastolic LVIF (E) velocity (P < .05), slightly lowered peak atrial systolic LVIF (A) velocity, significantly decreased their ratio (A/E) (P < .01), and significantly shortened both the deceleration time, from the peak of the early diastolic wave, and isovolumic relaxation time (P < .05 and P < .01, respectively). In the hypertrophy group, enalapril significantly increased E (P < .05), slightly lowered A, significantly decreased A/E (P < .05), slightly shortened the deceleration time and isovolumic relaxation time, and slightly decreased LV mass. The administration of enalapril correlated significantly and positively with the duration of hypertension and the rates of change in A/E and LV mass in all of the hypertensive patients (P < .01 and P < .05, respectively). These results suggest that long-term administration of enalapril to hypertensive patients improves LV diastolic hemodynamics regardless of the presence or absence of LV hypertrophy and that the effects are most remarkable in patients with the shortest duration of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Characteristics and expression of transforming growth factor-beta receptor subtypes on vascular smooth muscle cells from spontaneously hypertensive rats.

OBJECTIVE: To investigate the characteristics and expression of transforming growth factor (TGF)-beta receptor subtypes on vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. METHODS: The effects of TGF-beta 1 on DNA synthesis were evaluated by [3H]-thymidine incorporation into quiescent VSMC plated at high (5 x 10(4) cells/cm2) or low (5 x 10(3) cells/cm2) cell density. Specific binding of TGF-beta to VSMC was assessed by incubation of the cells with [125I]-TGF-beta 1. Affinity labelling of receptor subtypes was achieved by exposure of the cells to [125I]-TGF-beta 1 and cross-linking with disuccimidyl suberate. RESULTS: VSMC from SHR displayed a biphasic DNA synthesis response to TGF-beta 1 at high cell density, with DNA synthesis stimulated by low concentrations of TGF-beta 1 but not by high concentrations, whereas at low cell density there was a small increase in DNA synthesis in response to TGF-beta 1. TGF-beta 1 inhibited DNA synthesis in VSMC from WKY rats at both high and low cell densities. Binding assays revealed that VSMC from SHR had a larger number of TGF-beta receptors and a higher affinity for TGF-beta at high and at low cell densities. The affinity labelling with [125I]-TGF-beta 1 revealed the presence of receptor subtypes with relative molecular masses of 280-300, 85, 70, 60 and 50 x 10(3) on vascular smooth muscle cells from both rat strains at high cell density. The abundance of the 85 x 10(3) molecular mass receptor subtype was greater in VSMC from SHR. The 85 x 10(3) molecular mass receptor subtype was not detected on VSMC from either strain at low cell density. CONCLUSION: The present results suggest a different expression of TGF-beta receptor subtypes on VSMC from SHR and WKY rats. These differences may account for the exaggerated proliferative response of VSMC from SHR to TGF-beta.

Animals↗