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Biomedical subjects

N Fukuda

Publications and source records attributed to N Fukuda.

At least 19 recordsLinked to original sources

Effects of vitamin B12 on plasma melatonin rhythm in humans: increased light sensitivity phase-advances the circadian clock?

Vitamin B12 (methylcobalamin) was administered orally (3 mg/day) to 9 healthy subjects for 4 weeks. Nocturnal melatonin levels after exposure to bright light (ca. 2500 lx) were determined, as well as the levels of plasma melatonin over 24 h. The timing of sleep was also recorded. Vitamin B12 was given blind to the subjects and crossed over with placebo. We found that the 24-h melatonin rhythm was significantly phase-advanced (1.1 h) in the vitamin B12 trial as compared with that in the placebo trial. In addition, the 24-h mean of plasma melatonin level was much lower in the vitamin B12 trial than with the placebo. Furthermore, the nocturnal melatonin levels during bright light exposure were significantly lower in the vitamin B12 trial than with the placebo. On the other hand, vitamin B12 did not affect the timing of sleep. These findings raise the possibility that vitamin B12 phase-advances the human circadian rhythm by increasing the light sensitivity of the circadian clock.

Circadian Rhythm

[Development of a gel phantom for dose distributions by MR imager].

We reported a method of determining spatial dose distributions in tissue-equivalent phantoms using nuclear magnetic resonance imaging. To make a gel phantom, a cross-linked dextran gel (Sephadex G-200) was used as fixation agent of a ferrous sulphate solution. Although high quality images are obtained, the cost is very expensive to make the gel. We developed a new gel which is combined with an extra water absorbent polymer (Sumikagel N-100) and Sephadex G-200. The gel permits the determination of dose distributions for three dimensional treatment planning.

Ferrous Compounds

Seasonality in human sleep.

The timing of sleep and sleep EEG parameters in 10 healthy male subjects were investigated in four seasons under controlled conditions. The phase of nocturnal sleep was delayed about one and a half hours in winter as compared to that in summer. The duration of stage 4 sleep decreased and REM sleep increased significantly in winter compared with summer. The seasonality in the timing of sleep can be explained by photoperiodic time cues, but the changes in sleep EEG parameters are difficult to explain in terms of photoperiod.

Adult

Effect of a new anxiolytic, DN-2327, on learning and memory in rats.

The effects of a new anxiolytic, (2-(7-chloro-1,8-naphthyridin-2-yl)-3- [(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-carbonylmethyl] isoindolin-1-one (DN-2327), on the execution of step-through passive avoidance and delayed spontaneous alternation tasks were assessed and compared with those of diazepam (DZP) and buspirone. DN-2327 and buspirone (both 10 and 20 mg/kg, PO) impaired performance in the 48-h passive avoidance recall test when given prior to the test session, but not when given before the training trial. DZP impaired the performance at doses of more than 5 and more than 10 mg/kg PO when given prior to the test session and when given before the training trial, respectively. The action of DZP (10 mg/kg PO) when given before the training trial was antagonized by flumazenil (20 mg/kg, IP) and tended to be antagonized by DN-2327 (10 and 30 mg/kg, PO), but was not affected by buspirone. No evidence for possible amnesic effects of DN-2327 or buspirone on working memory was found in the delayed spontaneous alternation task, but DZP (3 and 10 mg/kg, PO) caused significant impairment of working memory. Electroshock sensitivities detected by flinch, jump, and vocalization thresholds were not influenced significantly by DN-2327 (30 and 100 mg/kg, PO), DZP (10 and 30 mg/kg, PO) or buspirone (30 and 100 mg/kg, PO).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Fistuloscopy for the management of postoperative intra-abdominal abscesses.

A new technique of fistuloscopy for evaluation and treatment of postoperative intra-abdominal abscesses is described which was used in 8 patients in whom drainage of abscesses following surgery was insufficient. A cholangiofiberscope was introduced into the fistula canal produced by the postoperative drainage. Fistuloscopy was combined with fistulography in all cases to delineate the extent of the inflammatory process. The guidewire was then placed under visual control through the endoscope followed by re-introduction of the drainage tube until a position most effective for pus drainage was achieved. Following this procedure, fever resolved in all 8 patients. Fistuloscopy is recommended to achieve sufficient drainage of intra-abdominal abscesses in those cases where percutaneous ultrasound- or CT-guided drainage fails to lead to significant clinical improvement.

Abscess

Seasonal variation in the human circadian rhythm: dissociation between sleep and temperature rhythm.

The circadian rhythms of sleep-wakefulness, rectal temperature, and plasma melatonin were measured in 10 healthy male subjects for five consecutive seasons. To minimize direct effects of seasonally changing environmental factors, the subjects stayed in a living facility for 4 days in each season, where ambient temperature, humidity, and social contacts were controlled, while the light intensity of the living room was substantially influenced by natural daylight. Seasonal variations were found in the timing of sleep, the mean body temperature, the phases of circadian temperature and melatonin rhythms, and the phase relation between sleep and the rectal temperature rhythm. The subjects went to bed earliest in summer, intermediate in spring and autumn, and latest in winter. A similar but more pronounced seasonality was observed in the wake-up time, which was earlier in summer than in winter. The acrophases of the rectal temperature and plasma melatonin rhythms, which were calculated by fitting a cosine curve, were located in an earlier time of day in summer than in winter. The phase-angle difference of the rectal temperature rhythm to sleep varied seasonally and was more positive in summer than in winter. These findings indicate that not only the external (to the local time) but also the internal (between circadian rhythms) phase relations of the human circadian rhythms depend on season.

Adult

Comparative study on the behavioral and EEG changes induced by diazepam, buspirone and a novel anxioselective anxiolytic, DN-2327, in the cat.

Behavioral and EEG effects of 2-(7-chloro-1,8-naphthyridin-2-yl)-3-[(1,4)-dioxa-8-(azas piro-[4.5]dec-8- yl)carbonylmethyl]isoindolin-1-one (DN-2327; 1, 5 and 20 mg/kg p.o.) were compared to those of diazepam (0.2 and 1 mg/kg p.o.) and buspirone (1 and 5 mg/kg p.o.) in freely moving cats. DN-2327 did not affect motor coordination or the relative percentages of the three sleep-wakefulness stages. Diazepam (1 mg/kg) increased wakefulness and non-REM sleep, and buspirone (5 mg/kg) also increased wakefulness and decreased REM sleep. In addition, diazepam (1 mg/kg) caused severe motor disturbance, but buspirone did not. The cortical EEG power density spectra during wakefulness were changed almost dose-dependently by DN-2327 (decreased: 2-7.75 Hz; increased: 20-49.75 Hz), and dose-dependently by diazepam (decreased: 2-7.75 Hz; increased 13-49.75 Hz) and buspirone (decreased: 4-9.75 and 13-19.75 Hz). The effect of DN-2327 on the cortical EEG varied with the sleep-wakefulness stage. The power of the 4- to 7.75-Hz frequency (theta) band of the hippocampal EEG during wakefulness was decreased by diazepam and buspirone but not by DN-2327, while the peak frequency of its spectra was decreased only by diazepam. On the other hand, during non-REM sleep, DN-2327 decreased the power of the theta band as did diazepam. These results indicate that the behavioral and EEG effects of DN-2327 differ completely from those of buspirone and considerably from those of diazepam and that the EEG effect of DN-2327 varies with the sleep-wakefulness stage.

Animals

Effects of L-NG-monomethyl arginine on the cyclic GMP formations in rat mesenteric arteries.

To evaluate the contribution of L-arginine as a precursor of the endothelium-derived relaxing factor (EDRF) on vascular cyclic GMP formation, we examined the effects of L-NG-monomethyl arginine (L-NMMA), and analog of L-arginine, on basal and acetylcholine (ACh)-, sodium nitroprusside (SNP)- and atrial natriuretic peptide (ANP)-induced cyclic GMP formations in rat mesenteric arteries. The mesenteric arteries were perfused with Krebs-Henseleit solution containing 0.2 mM isobutyl methyl xanthine. The effluents from the arteries were collected before and after infusions of graded doses of ACh, SNP or ANP in the absence or presence of 100 microM L-NMMA, and the levels of cyclic GMP were measured. Basal and ACh-induced cyclic GMP formations in the mesenteric arteries were significantly inhibited in the presence of L-NMMA, whereas a concomitant infusion of 300 microM L-arginine restored the inhibition of basal as well as ACh-induced cyclic GMP formations. L-NMMA did not affect SNP- and ANP-stimulated cyclic GMP formations, respectively. These results suggest that L-arginine is necessary for not only the stimulated cyclic GMP formation but also the basal cyclic GMP formation in the mesenteric arteries, whereas the SNP- and ANP-stimulated cyclic GMP formations in the arteries are independent of L-arginine.

Animals

[Characteristics of jugular venous pulse and its genesis in Ebstein's anomaly].

To clarify the characteristics of the jugular venous pulse and its genesis in Ebstein's anomaly, 6 patients with Ebstein's anomaly whose mean age was 45 +/- 9 years, and 10 normal subjects with a mean age of 27 +/- 6 years were studied by phono-mechanocardiography and echocardiography. The parameters included the relative height of the jugular "c" wave, the relative timing of the upstroke (Q-Cu interval) and the peak of the jugular "c" wave (Q-Cpeak interval), the relative timing of the upstroke of the carotid artery pulse, the relative timing of tricuspid valve closure (Q-Tc interval), the excursion of the closing motion of the anterior tricuspid leaflet (TV excursion), the distance between the anterior mitral annulus and the septal tricuspid annulus (M-T distance), the area of atrialized right ventricle (ARV area) and the maximum area of the tricuspid regurgitant signal. Among 6 patients with Ebstein's anomaly, tricuspid regurgitation was predominant in 4 and mild in the remaining 2. The results were as follows: 1. A large jugular "c" wave was observed in 4 of the 6 patients. Two patients with large ARV area had giant "c" wave. 2. The interval of the upstroke of the carotid artery pulse and that of the jugular "c" wave was about 39.2 msec. 3. The Q-Tc interval was significantly longer and the TV excursion was significantly greater in the patients than in the normal controls. 4. There was only a weak positive correlation between the Q-Cpeak interval and the Q-Tc interval. No significant correlation was observed between the relative height of the jugular "c" wave and the TV excursion. 5. There was a positive correlation between the relative height of the jugular "c" wave, the ARV area and M-T distance. 6. No obvious correlation was observed between the grade of tricuspid regurgitation and the relative height of the jugular "c" wave. These results suggest that augmentation of the "c" wave of the jugular venous pulse is characteristic of Ebstein's anomaly and that it correlates closely with the severity of displacement of the tricuspid valve and the size of the atrialized right ventricle.

Adult

[Clinical significance of the click intervals for the diagnosis of dysfunction of the Medtronic-Hall prosthetic valve].

To investigate the clinical significance of click interval for evaluation of prosthetic valve dysfunction, 20 patients underwent Medtronic-Hall (MH) valve replacement (14 in the mitral position and 6 in the aortic position) were studied by simultaneous high-speed recordings of phonocardiogram, echocardiogram and/or Doppler echocardiogram. Two of the 20 patients, one in the mitral and the other in the aortic position, showed MH valve dysfunction. Eleven patients with normally functioning Björk-Shiley (BS) valve in the mitral position served as controls. Results were as follows: 1. There were usually 3 opening clicks (OC1, OC2, OC3) in patients with normally functioning MH valve in the mitral position. These 3 clicks coincided in timing with the beginning of opening, maximum opening and the end of sliding motion, respectively. Both OC1 and OC2 of the MH valve occurred in similar timing with those of the BS valve (A2-OC1 interval: MH = 65.4 +/- 11.8 msec vs BS = 72.3 +/- 17.2 msec; OC1-OC2 interval: MH = 31.2 +/- 7.7 msec vs BS = 27.3 +/- 6.1 msec). However, OC3 occurred significantly later in MH valve than in the BS valve (OC2-OC3 interval: MH = 32.3 +/- 7.5 msec vs BS = 16.4 +/- 3.8 msec, p < 0.01). 2. There were 2 closing clicks (CC1, CC2) in normally functioning the MH valve in the aortic position. These 2 clicks coincided in timing with the beginning and the end of the closing motion, respectively. Mean value of CC1-CC2 interval in 5 prosthetic patients with normal function was 31.0 +/- 9.6 msec. 3. A patient with malfunctioning MH valve in the mitral position showed a markedly prolonged OC1-OC2 interval, ranging from 66 to 140 msec, and she had multiple diastolic clicks after the OC2 phase. Prolonged OC1-OC2 interval was mainly caused by the delay of appearance of OC2, and it was thought to be due to temporary limitation of opening motion of the valve by valve thrombosis. 4. A patient with malfunctioning MH valve in the aortic position showed a markedly prolonged CC1-CC2 interval (100 msec), and he had a significant severe aortic regurgitation during this phase. At operation, fibrinoid thrombus was attached to the aortic annulus at the side of minor orifice of the valve. Closing motion of the valve was disturbed by this thrombus, and the completion of valve closure was markedly delayed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

[Mitral valve prolapse associated with partial absence of commissural chordal insertion: report of two cases].

We reported 2 cases of mitral valve prolapse (MVP) associated with partial absence of the chordae tendineae. Case 1 was a 25-year-old man who was admitted to our hospital for further examinations of an apical pansystolic murmur (Levine 4/6) and the abnormal shadow on his chest radiograph. He was diagnosed as having grade 3 + mitral regurgitation (MR) by the Sellers classification and pulmonary varix by cardiac catheterization. Transesophageal echocardiography revealed MVP of the rough zone of the anterior mitral leaflet and MR blowing into the pulmonary varix. Case 2 was a 60-year-old man who was admitted to our hospital because of congestive heart failure and apical pansystolic murmur (Levine 4/6). Parasternal echocardiography revealed prolapse of both the anterior and posterior mitral leaflets and moderate MR. In both cases, absence of insertion of anterolateral commissural chordae was confirmed after surgery, and the abnormalities of chordal arrangement and insertion were considered as causes of MVP in these cases.

Adult

Effect of thyrotropin-releasing hormone on the neurologic impairment in rats with spinal cord injury: treatment starting 24 h and 7 days after injury.

The effect of treatment with thyrotropin-releasing hormone (TRH) or naloxone on the neurologic impairment after spinal cord injury was studied in rats with the severest neurologic impairment (complete paraplegia, no withdrawal response upon tail pinching, and urinary incontinence) 24 h and 7 days after injury. Subcutaneous treatment with TRH (2.5, 10 and 40 mg/kg per day) once daily for 7 consecutive days starting 24 h or 7 days after injury improved the neurologic function in the rats with cord injury in a dose-related manner, with a minimum effective dose of less than 2.5 mg/kg per day in both cases. However, subcutaneous treatment with naloxone (40 mg/kg per day) once daily for 7 consecutive days starting 24 h after injury did not exert any beneficial effects on neurologic function. These results indicate that TRH but not naloxone treatment starting 24 h and as late as 7 days after injury is effective in rats with the severest neurologic impairment following spinal cord injury. Thus, it is suggested that the duration of the effectiveness of late treatment with TRH on the neurologic impairment in rats with spinal cord injury is more than 1 week, while the duration with naloxone is less than 24 h.

Animals

Contribution of serotonin neurons to the functional recovery after spinal cord injury in rats.

The contribution of serotonin neurons to the functional recovery after spinal cord injury was studied pharmacologically in rats with moderately severe neurologic impairment (complete paraplegia but responsive to tail pinching) 24 h after thoracic spinal cord (T11) compression-induced injury. Fourteen days after cord injury the levels of endogenous norepinephrine (NE, -33%), dopamine (DA, -50%) and serotonin (5-HT, -55%) in the lumbar cord in the injury control rats were decreased and there were significant correlations between the neurologic score and the NE level (rs = 0.562, P less than 0.01) and the 5-HT level (rs = 0.745, P less than 0.001) but not the DA level. Bilateral i.c.v. injection of 5,7-dihydroxytryptamine (200 micrograms/rat) 24 h after cord injury significantly retarded the neurologic recovery during the 14 days after injury, accompanied by a further reduction in the 5-HT level (-86%) but not in the NE or DA level. On the other hand, neither p-chlorophenylalanine (PCPA) (300 mg/kg, i.p., once daily starting 24 h after injury for 13 consecutive days) nor reserpine (1 mg/kg, i.p., 4 times, once 24 h after injury and then every fourth day) had any influence on the time course of the neurologic recovery during the 14 days after injury, although PCPA treatment further reduced the levels of NE (-50%) and 5-HT (-91%), and reserpine treatment further reduced the levels of NE (-95%), DA (-73%) and 5-HT (-85%).(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine

Pharmacologic profile of a new anxiolytic, DN-2327: effect of Ro15-1788 and interaction with diazepam in rodents.

In order to characterize the pharmacologic profile of DN-2327, an isoindoline benzodiazepine (BZD) receptor ligand, its interactions with Ro15-1788 and diazepam were analyzed in rodents. The anti-conflict action of DN-2327 in two conflict tests using rats, the punished water-lick conflict (Vogel conflict) and the punished bar-pressing conflict test, was completely attenuated by treatment with Ro15-1788. The anti-convulsive (pentylenetetrazol [PTZ] induced convulsion) effect of DN-2327 was also reduced by Ro15-1788. These results suggest that the anti-conflict and anti-convulsive actions of DN-2327 may be mediated via BZD receptors. On the other hand, DN-2327 only slightly affected the motor coordination in mice and rats, as estimated by the inclined screen test and the climbing test, respectively; however, the compound attenuated the motor incoordination produced by diazepam. Furthermore, the pentobarbital potentiating effect of diazepam was reduced by pretreatment with DN-2327 in mice. In the Vogel conflict test, additive effects were observed upon the conflict test, additive effects were observed upon the concomitant administration of subeffective doses (5 mg/kg, PO) of DN-2327 and diazepam. DN-2327 at 20 mg/kg, PO, did not reduce but slightly potentiated the anti-conflict effect of the maximum effective dose of diazepam. For PTZ-induced convulsions, DN-2327, 0.5 and 20 mg/kg, PO, doses which produced partial and complete anti-convulsive effects, respectively, in rats did not reduce but increased additively the effects of diazepam. DN-2327 at 10 and 20 mg/kg, PO, doses which both produced partial anti-convulsive effects in mice, showed an additive effect with the partial effects of diazepam.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of DN-2327, a new anxiolytic, diazepam and buspirone on exploratory activity of the rat in an elevated plus-maze.

In the present study, the effects of a new anxiolytic, DN-2327, were compared to those of diazepam and buspirone in rats in the elevated plus-maze test. Two indices of anxiety were obtained in this test: the number of entries into the open arms expressed as a percentage of the total number of arm entries and the percentage of time spent on the open arms. Both a typical anxiolytic, diazepam, at 2.5, 5 and 10 mg/kg, PO and a new anxiolytic, DN-2327, at 2.5 and 5 mg/kg, PO dose-dependently increased the two indices: the percentage of time spent on the open arms and the percentage of open-arm entries. On the other hand, pentylenetetrazol (PTZ) at 10 and 20 mg/kg, IP decreased the two indices dose dependently as did yohimbine at 1.5 and 3 mg/kg, IP. DN-2327 at 2.5 and 5 mg/kg, PO and diazepam at 5 and 10 mg/kg, PO dose dependently and significantly increased the two indices that were suppressed following administration of PTZ at 10 mg/kg, IP. The effects of both DN-2327, 5 mg/kg, PO, and diazepam, 10 mg/kg, PO, on the two indices were significantly antagonized by the benzodiazepine (BZD) receptor antagonist flumazenil, 20 mg/kg, IP. Buspirone (2.5-20 mg/kg, PO) did not affect either of the two responses but dose dependently decreased the number of rearings, although in the Vogel conflict test, the anti-conflict activity of buspirone was equipotent to that of diazepam and DN-2327 at the minimum effective dose (10 mg/kg, PO) of each drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Hepatocytes enhance neurite regeneration and survival from transected nerve terminals.

The culture of hepatocytes dissociated from adult mice by the collagenase perfusion method enables neurons or neuronal tissues to be cultured with hepatocytes or in hepatocyte-conditioned media. Co-culture with hepatocytes or hepatocyte-conditioned media enhances neurite regeneration and their survival from nerve-transected terminals of dorsal root ganglia with nerve fibers dissected from adult and aged mice. Hepatocytes secrete a factor which enhances not only neurite regeneration but also neurite survival. Activities of other known neurotrophic factors were not as crucial as those of the hepatocyte-conditioned medium, suggesting that this factor may differ from other trophic ones.

Age Factors

Reciprocal responses to exercise in hepatic ketogenesis and lipid secretion in the rat.

The effects of 4 weeks of voluntary exercise (rotating wheel) on serum and liver lipid levels were studied in 6-week-old male Wistar rats. The hypotriglyceridemic effect of exercise was not influenced by the dietary fat levels (4.5 and 14.5%), whereas the hypocholesterolemic effect was higher in a low-fat diet than in a high-fat diet. Although the serum cholesterol-lowering effect of exercise was marginal, the beneficial effect on hepatic lipids was observed only in rats fed a high-cholesterol diet. The hepatic contribution to the serum lipid-lowering action of exercise was examined in the isolated perfused livers of rats fed a low fat diet. The reduction (34%) of serum triglyceride by exercise corresponded to the decrease (32%) in the hepatic triglyceride secretion rate, indicating a significant role of the liver in the hypotriglyceridemic effect of exercise. In contrast, the decrease (31%) in serum total cholesterol was considerably greater than that (23%) in the hepatic secretion, suggesting an extra-hepatic contribution. On the other hand, the hepatic production of ketone body was increased by exercise. These results indicate that the altered hepatic partition of long-chain free fatty acids between esterification and oxidation is one of the causative factors for the serum lipid-lowering effect of exercise.

Animals