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Biomedical subjects

N Fukuda

Publications and source records attributed to N Fukuda.

At least 271 records · Page 15Linked to original sources

Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia.

The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled [14C]glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-[1,2-14C]choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis.

Animals↗

Effect of prolonged ACTH stimulation on adrenal renin and aldosterone.

Changes in adrenal renin, which have been regarded as mediator of aldosterone secretion in the adrenal gland, following prolonged ACTH treatment were investigated in male Wistar rats. After 2 days of daily sc injection of ACTH (Cortrosyn-Zinc, 50 micrograms/day), parallel increases in adrenal renin and aldosterone, and plasma aldosterone (PA) were induced. The plasma renin activity (PRA) was slightly but not significantly decreased. Prolonged treatment with ACTH for 8 days increased the adrenal renin, causing a marked reduction in the adrenal aldosterone concentration. The degree of decrease in the PRA was again not significant and similar to that after 2 days of ACTH treatment. Contrary to previout reports which have indicated participation of adrenal renin in the regulation of aldosterone secretion in the adrenal gland, the present results showed reciprocal changes in adrenal renin and aldosterone after prolonged treatment with ACTH. The present findings suggest a complicated relation between adrenal renin and aldosterone secretion in the adrenal gland.

Adrenal Glands↗

Morphological evaluation of the atherogenicity of corn oil, hydrogenated corn oil, and butter fat in quail.

The atherogenicity of corn oil, hydrogenated corn oil, and butter fat was studied using 57 fourty-day-old male Japanese quails. The animals were fed one of the following diets: basal diet, basal diet with corn oil plus cholesterol, basal diet with hydrogenated corn oil plus cholesterol, or basal diet with butter fat plus cholesterol. Each atherogenic diet contained 15% fat and 2% cholesterol. Marked hypercholesterolemia developed in all fat-fed groups after 3 weeks or 3 months, but no significant difference was seen among the groups. The degree of the luminal narrowing of the ascending aorta and brachiocephalic arteries was highest in the corn oil group and lowest in the hydrogenated fat group. Ultrastructurally, all the fat-fed groups showed similar cellular changes in their aortic lesions. The major cell type of the thickened intima was fibroblast-like cells with or without lipid droplets. Immunohistochemical studies disclosed that alpha-1-antichymotrypsin was strongly positive for fibroblast-like cells in the thickened intima, whereas it was negative for those in the tunica media of the ascending aorta and its branches. These data suggest that hydrogenated corn oil has a less potent stimulating effect on the thickening of the arterial intima than corn oil and butter fat.

Animals↗

[Genesis and clinical significance of the "low-pitched" aortic ejection sound].

The genesis and clinical significance of the aortic ejection sound with a low-frequency predominance and delayed appearance were studied. This is recorded on the phonocardiogram in some patients with left ventricular dysfunction. Subjects studied consisted of 10 patients with a low-pitched ejection sound and seven patients with an ordinary high-pitched aortic ejection sound. No patients had echocardiographic findings suggestive of organic lesions of the aortic valve. Time relationships among the ejection sounds, aortic valve echograms and carotid artery pulses, and then movements of the aortic valve cusps and non-invasively estimated left ventricular systolic function were compared between the two groups. Results were as follows: 1. The low-pitched ejection sound: 1) The beginning of the sound was nearly coincident with the onset of the upstroke of the carotid artery pulse and the initial full opening of the aortic valve cusps. 2) The beginning of the ejection systolic murmur followed immediately after the ejection sound. 3) The amplitude of the sound was closely related to the height of the carotid artery pulse in a case of atrial fibrillation. 2. The low-pitched ejection sound vs the high-pitched ejection sound: 1) The onset of the low-pitched ejection sound was significantly delayed. 2) The amplitude and the velocity of the initial opening of the aortic valve cusps were significantly decreased. 3) The preejection period (PEP) was significantly prolonged; the ejection time (ET) was significantly shortened; and the PEP/ET ratio was significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗

[Systolic clicks in mitral valve prolapse: their pathophysiological relationship to the grade and causes of prolapse].

To re-evaluate the clinical significance of non-ejection systolic clicks in mitral valve prolapse (MVP), 154 patients with idiopathic MVP (idiopathic group) and 54 patients with secondary MVP associated with atrial septal defect (secondary group) were studied using phonocardiography and two-dimensional echocardiography. There was no significant difference in the incidence of systolic clicks between the idiopathic (30%) and secondary (24%) groups. The severer the degree of prolapse, the higher the incidence of systolic clicks in both the groups. A systolic click was observed independently of age in the idiopathic group. In the secondary group, however, a systolic click was not observed in patients under 30 years old and increased with advancing age in frequency. The intensity of systolic click tended to increase in proportion to the increase of severity of prolapse in both the groups. These results suggested that systolic clicks may appear irrespective of the causes of prolapse and that the production and the intensity of systolic clicks may be related to the degree of changes in the mitral valve-chordal system and the degree of prolapse.

Adolescent↗

[Diurnal variation of the QT intervals in idiopathic mitral valve prolapse].

Diurnal variation of QT intervals was analyzed using Holter monitoring for 44 patients with mitral valve prolapse (MVP), and the relationship between ECG changes and autonomic nervous dysfunction was assessed by measuring blood catecholamine during bicycle ergometer exercise and various autonomic functional tests. The following results were obtained. 1. The QT intervals in MVP patients had greater diurnal variations and the averaged QTc was in a high level all the time. 2. Positivity of the autonomic functional tests and the catecholamine level after exercise were significantly high in patients of MVP. 3. After catecholamine depletion by beta-blocking agent (carteolol: 15 mg a day, 5 to 12 months' duration), the variation of QTc became less marked. These data indicate the presence of autonomic dysfunction in patients of MVP.

Adolescent↗

[Diastolic right ventricular hemodynamics in right ventricular overloads assessed by pulsed Doppler echocardiography].

To assess right ventricular (RV) filling dynamics, RV inflow velocity patterns of pulsed Doppler echocardiograms and jugular pulse tracings were analyzed in 59 patients with various types of RV overloads and in 20 normal subjects. The patients were classified as (1) RV volume overload group (RVVO) consisting of 25 patients with atrial septal defect (ASD) without pulmonary hypertension (PH), (2) RV pressure overload group consisting of 26 patients including 12 with primary pulmonary hypertension (PPH), eight with mitral stenosis, three with pulmonary stenosis and three with cor pulmonale, and (3) RV volume and pressure overload group consisting of eight patients with ASD and PH. The acceleration time (AT), deceleration time (DT) and the A/D ratio were measured from the RV inflow velocity patterns, and v-y interval and the y/H ratio were measured from jugular pulse tracings. The results were as follows: 1. AT was significantly prolonged in groups with pressure overload as well as pressure and volume overload compared with that of the normal controls. 2. DT was significantly prolonged in all overload groups compared with that of the normal controls except for PPH, and was particularly prolonged in the group with pressure overload. 3. The A/D ratio was significantly increased in all overload groups, particularly in the groups with pressure overload. 4. In patients with volume overloads, the v-y interval was longer and the y/H ratio was higher than in the normal controls. RVVO shifted to the right and superiorly. The reverse was true in the pressure overload group, and the high ratios were observed in the remainder. 5. In 12 patients with ASD evaluated pre- and postoperatively, AT, DT and the A/D ratio were restored to normal after surgery. These findings suggest that RV volume overload was characterized not only by increased inflow velocity during the rapid filling period, but prolongation of this period and compensatory increase of atrial inflow velocity. However, the pressure overload group had disturbed rapid filling and a decrease in end-diastolic RV compliance. The group with both pressure and volume overloads was between the two. In conclusion, the mode of RV filling in patients with RV overload showed various patterns depending on the type of overload. The RV inflow velocity pattern recorded by pulsed Doppler echocardiography is of use in discriminating these varieties.

Adult↗

[Van der Hoeve's syndrome with Ebstein's anomaly, and prolapse of the mitral and aortic valves: a case report].

A hitherto unrecognized case of van der Hoeve's syndrome complicated by Ebstein's anomaly, and prolapse of the mitral and aortic valves was reported. A 46-year-old woman presented with blue sclera, osteogenesis imperfecta and a hearing loss, which are typical symptoms of this syndrome. The electrocardiogram showed a type B WPW syndrome. The phonocardiogram showed a loud and widely split first heart sound, an accentuated protodiastolic extrasound, a decrescendo regurgitant systolic murmur, and a presystolic murmur. The x descent of the jugular phlebogram was obliterated by a markedly increased c wave. Based on M-mode and two-dimensional echocardiograms, 1) the interventricular septal motion was paradoxical and the closure of the tricuspid valve was delayed, 2) the septal tricuspid leaflet was displaced toward the apex from its normal annular insertion on the apical four-chamber view, 3) the three leaflets of the tricuspid valve were abnormally elongated, 4) the anterior mitral leaflet and the non-coronary cusp of the aortic valve were elongated and prolapsed. Doppler echocardiography detected severe tricuspid and mild mitral regurgitations. We suggest that the development of Ebstein's anomaly is possibly related to that of osteogenesis imperfecta genetically and that not only Ebstein's anomaly but a connective tissue disorder contributes to the elongated and prolapsed leaflets.

Abnormalities, Multiple↗

Fundamental tumor perfusion analysis with nuclear magnetic resonance imaging using gadolinium-diethylene triamine pentaacetic acid.

The measurement of blood perfusion is an important factor for both the diagnosis and follow-up of tumor lesions. However, noninvasive detection of this local blood flow factor is very difficult. To accomplish this, we tried to calculate tissue blood perfusion indexes with nuclear magnetic resonance imaging using gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). We experimentally applied this method to C3H mouse's tumor NFSa (fibrosarcoma) and its recurrence tumor R1137, whose experimental hypoxic cell fraction is different; that is, R1137 is more oxic than NFSa. Imaging pulse sequence was T1 (TR = 1,000 ms, TI = 300 ms), and longitudinal relaxation rate (R1 = 1/T1) values were calculated. Injected dose of Gd-DTPA was 0.1 mmol/kg. The T1 images produced are from both the preinjection period from every 5 min postinjection for 30 min. Using two-exponential analysis and compartment analysis we calculated two fundamental parameters: uptake index and flow index as blood perfusion factors. We found that this method has the possibility of differentiating the tissue's hypoxic cell fraction and is effective both for follow-up study after radiation therapy and for tissue characterization.

Animals↗

Abnormal response of adrenocorticotropin to corticotropin releasing factor in spontaneously hypertensive rats.

The pituitary-adrenocortical response to ovine corticotropin-releasing factor (CRF) was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) anesthetized with pentobarbital. After intravenous administration of various doses of CRF (0.1, 1.0 and 10 micrograms), the plasma levels of ACTH were significantly increased in both groups. ACTH increments after various doses of CRF were dose-dependent in WKY. ACTH increments after injections of 0.1, 1.0, and 10 micrograms of CRF in SHR were 123.2 +/- 36.5 (SE), 123.0 +/- 52.2 and 60.3 +/- 48.5 pg/ml at 5 min, and 386.3 +/- 73.8, 243.4 +/- 86.6 and 220.0 +/- 31.4 pg/ml at 15 min, respectively. The ACTH increments in SHR at 15 min after administration of 0.1 microgram of CRF were higher (p less than 0.02) than those in WKY. However, ACTH increments in SHR after administration of 10 micrograms of CRF were lower than those in WKY at 5 min (p less than 0.05) and 15 min. These data suggest that the plasma ACTH responses to various doses of CRF represent a dose-unrelated plateau response in SHR. The plasma levels of corticosterone after administration of various doses of CRF did not change significantly and there were no significant differences between the two strains. The results of these experiments suggest that SHR have an abnormal response of the pituitary-adrenocortical axis to CRF, and the abnormal response may be attributable to desensitization of the pituitary to CRF.

Adrenocorticotropic Hormone↗

Suppression of plasma aldosterone by chronic ACTH administration is offset by converting enzyme inhibitor.

In order to elucidate the mechanism of suppression of plasma aldosterone by chronic ACTH administration, especially the role of the renin-angiotensin system and dopamine, we administered ACTH with or without MK422, a converting enzyme inhibitor, to reduce the endogenous angiotensin II in rats, and measured the plasma renin activity, plasma corticoid concentrations and urinary dopamine excretion. The plasma aldosterone concentration (PAC) was decreased after chronic ACTH administration. However, in the ACTH + MK422 administered group, aldosterone suppression was not observed. It appeared therefore that the aldosterone suppressing mechanism was independent of the weakened renin-angiotensin system following chronic ACTH administration, since PAC was not decreased in the ACTH + MK422 administered group when angiotensin II might be completely eliminated. The urinary excretion of dopamine was significantly increased in the chronic ACTH + MK422 administered group as well as in the chronic ACTH administered group. This suggested that the inhibitory effect of dopamine on aldosterone did not contribute significantly to the suppression of plasma aldosterone. The present results suggest therefore that the mechanism of suppression of plasma aldosterone following chronic ACTH administration was not dependent on the renin-angiotensin system and dopamine.

Adrenocorticotropic Hormone↗

[Correlations between the features of first heart sound and opening snap and the shape and motion of the anterior mitral leaflet in patients with mitral stenosis].

To evaluate the relationship between the motion pattern and degree of organic change of the anterior mitral leaflet (AML) and the features of the mitral component of the first heart sound (M1) or the opening snap (OS), 37 patients with mitral stenosis (MS) were studied by auscultation, phonocardiography and echocardiography. Based on the features of M1 and OS according to auscultation and phonocardiography, the patients were categorized as group I, 18 patients with loud and snappy M1 and OS; group II, 12 patients with snappy M1 but small and dull OS; and group III, seven patients with small and dull M1 and OS. Intensities of M1 and OS were calculated by the ratios of their amplitudes to the aortic component of the second heart sound on the high frequency phonocardiograms recorded at points of the maximum intensities, respectively. Echocardiographic parameters related to productions of M1 and OS were obtained from M-mode and two-dimensional echograms of the AML; they were amplitudes and velocities on closing and opening, M1 area defined as that between end-diastolic and systolic echoes, OS area between systolic and early diastolic echoes, the doming area between the trailing edge of an early diastolic echo and a line projected from the anterior annulus to the tip of the leaflet, and the degree of systolic ballooning. Results were as follows: 1. Significant differences in the area of the mitral valve orifice were found among three groups. The area was maximum in group II, minimum in group III and intermediate in group I. 2. In group I, the body of the AML was pliable, resulting in a ballooning into the left atrium in systole and a marked doming toward the left ventricle in early diastole. Various parameters related to the production of M1 and OS in group I were significantly increased as compared with those of the other two groups. 3. In group II, the body of the AML was not pliable in spite of mild organic changes in the valve. The degree of early diastolic doming was mild. Compared to group III, the intensity of M1 in group II was significantly larger, but no significant difference was observed in the parameters related to the production of M1 between the two groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗