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Biomedical subjects

K Nonaka

Publications and source records attributed to K Nonaka.

At least 271 records · Page 15Linked to original sources

Preventive and therapeutic effects of large-dose nicotinamide injections on diabetes associated with insulitis. An observation in nonobese diabetic (NOD) mice.

This experiment was undertaken to explore a novel method of therapy for insulin-dependent diabetes mellitus (IDDM), using nonobese diabetic (NOD) mice that had symptoms and histologic changes similar to those of human IDDM patients. We examined preventive and therapeutic effects of large-dose nicotinamide administration on diabetes in NOD mice. Eighteen young female NOD mice without glycosuria were randomly divided into two groups; nine received subcutaneous nicotinamide (0.5 mg/g body wt) injections every day and the other nine were maintained as a control group and not injected. After 40 days, all of the mice given nicotinamide showed almost normal glucose tolerance and only mild insulitis on histologic study. On the other hand, marked glycosuria and severe insulitis were observed in six of the nine mice not injected. Four of six NOD mice given nicotinamide from the day of the first occurrence of marked glycosuria displayed a disappearance of glycosuria and an improvement in glucose tolerance during the therapy; however, urine sugar became negative in only one of six mice that received nicotinamide from 1 to 2 wk after the onset of marked glycosuria. These results indicate that nicotinamide has preventive and therapeutic effects on diabetes in NOD mice, and suggest the reversibility of B-cell damage, at least at a very early stage of IDDM.

Animals↗

Polysomnographic study of terminal sleep following delirium tremens.

Polysomnographic recording was performed during terminal sleep following delirium tremens (DT) in nine chronic alcoholics. After terminal sleep all the alcoholics fully recovered from DT. The duration of terminal sleep and DT differed among patients, but no significant correlation was found between the two. The most prominent feature in teh different stages of terminal sleep was a considerable decrease in slow wave sleep, especially stage 4 sleep. A slight decrease was observed in REM sleep, while stages 1 and 2 increased. A small amount of stages 1-REM and 2-REM was observed and a statistically significant correlation was noted between the appearance of these sleep stages. Intermittent wakefulness occurred in many patients. The disappearance of sleep cycles was observed in some patients. Therefore, terminal sleep following DT probably consists of recovery sleep from sleep deprivation caused by DT and disturbances of consciousness. Sleep cycles regularly occur in the former, but not in the latter.

Adult↗

Hypotensive and cardiovascular action of budralazine in unanesthetized and unrestrained dogs.

In renal hypertensive dogs, 1-[2-(1,3-dimethyl-2-butenylidene)hydrazino]phthalazine (budralazine) at doses of 1 and 2.5 mg/kg p.o. produced a gradual, progressive and significant fall in blood pressure which reached a maximum 3--4 h after dosing and persisted for 6--10 h. The hypotensive response to 1 mg/kg p.o. of budralazine was almost comparable to that to 2.5 mg/kg p.o. of reference drug hydralazine, but the duration of action of the former was much longer than that of the latter. At equihypotensive doses, budralazine was found to be approximately 3 times less potent than hydralazine in producing tachycardia. In normotensive dogs, budralazine at a dose of 1 mg/kg p.o. produced a significant increase in renal blood flow and a tendency for the increase in coronary blood flow associated with a significant and non-significant decrease in the peripheral vascular resistance. At this dose level, blood pressure remained almost unchanged.

Animals↗

The effects of parabiosis on serum and kidney glycosidase activities in spontaneously diabetic mice.

Spontaneously diabetic non-obese mice of the ICR strain were newly inbred in Shionogi laboratory, Japan. Animals became diabetic suddenly, more frequently and severely in females. Blood glucose levels were 452 +/- 73 mg/100 ml with serum insulin levels of less than 1.0 microU/ml in the fed state. Parabiosis with normal control ICR mice for 2 weeks decreased the blood glucose level to 260 +/- 51 mg/100 ml (P less than 0.01) and resulted in serum insulin levels of 46.0 +/- 18.0 microU/ml (P less than 0.01). Kidney homogenate beta-N-acetylglucosaminidase and beta-galactosidase activities were reduced in diabetic mice (42% and 44% decreases respectively) (P less than 0.025 and P less than 0.001), and restored almost to normal after 2 weeks of parabiosis. Renal alpha-mannosidase activity was decreased 43% (P less than 0.001) in the diabetic mice but unaffected by parabiosis. Serum beta-N-acetylglucosaminidase, beta-galactosidase and alpha-glucosidase activities were significantly increased in diabetic mice (179%; 233% and 58% increase respectively) (P less than 0.005, P less than 0.001 and P less than 0.001), and returned to normal with parabiosis.

Animals↗

Study on the effects of L-5HTP on the stages of sleep in man as evaluated by using sleep deprivation.

The effects of L-5HTP 200 mg on the EEG sleep pattern were investigated in normal subjects. When L-5HTP 200 mg was orally administered, only % S1 significantly decreased in comparison with the baseline. There was no change in any sleep stage on the first recovery night. On the second recovery night, % S1 significantly decreased, while % SR increased significantly. SWS did not show any change. The effects of L-5HTP 200 mg were investigated on the first recovery night after one night of sleep deprivation. SWS significantly increased on the first recovery night when a placebo was given, while this rebound increase of SWS disappeared and % S2 significantly increased on the first recovery night when L-5HTP was given. % SR significantly increased on the next night after the L-5HTP night.

5-Hydroxytryptophan↗

The sleep pattern of chronic alcoholics during the alcohol withdrawal period.

The sleep pattern of 13 alcoholics was recorded for five consecutive nights after the cessation of alcohol intake. In six of the 13 patients, delirium tremens occurred after hospitalization. A decrease of total sleep time and slow wave sleep was more pronounced in the patients with delirium tremens than in those without. REM sleep had slightly decreased in both groups. Rebound increase in REM sleep had not been observed in all the patients with delirium tremens. Stage 1-REM with tonic EMG was observed in these two groups. From these results we are inclined to hypothesize that a deficiency of cerebral 5-HT in alcoholics may lead to a pronounced decrease in slow wave sleep, with rapid eye movements appearing in stage 1 sleep.

Adult↗

Decrease in blood glucose and release of gut glucagon-like immunoreactive materials by bombesin infusion in the dog.

Synthetic bombesin (100 ng/min) was infused under pentobarbital anesthesia in normal dogs and in insulin deprived depancreatized dogs 4 days after surgery. The release of gut glucagon-like immunoreactive materials (gut GLI) calculated as the difference between the values measured using cross-reacting antiserum and a so-called pancreatic glucagon specific antiserum was markedly stimulated by bombesin infusion. Plasma glucagon immunoreactivity (GI) measured by pancreatic glucagon specific antiserum also showed a small increase, whereas plasma glucose decreased significantly with a transient rise in insulin. The plasma glucose level did not decrease in depancreatized dogs. Gut GLI response in the regional mesenteric vein to 5% glucose administered into the loop of the ileum was strongly augmented by bombesin infusion. It is concluded that (1) bombesin infusion decreased blood glucose level in normal dogs but not in depancreatized dogs. (2) Bombesin infusion markedly augmented the release of GLI from the intestine. (3) Bombesin also stimulated the release of glucagon which was probably of gastrointestinal origin. (4) Insulin release was stimulated transiently by bombesin infusion. Thus, a competition of gut GLI with glucagon at the glucagon receptor site may be an explanation of the reduction in blood glucose.

Animals↗

Parallel dysfunctions of pancreatic A, B and PP cells in insulin dependent diabetes.

To test the possibility that insulitis might play an etiological role in the pathogenesis of insulin dependent diabetes, functions of 3 kinds of islet constituting cells (A, B and PP cells) were estimated by quantifying secretory responses of glucagon-, C-peptide-and pancreatic polypeptide-producing cells to hyperglycemia and hypoglycemia. In insulin dependent diabetes, all 3 hormonal responses were severely impaired to the same extent. On the other hand, 3 islet cell functions were uniformly but less severely impaired in insulin independent diabetics without a diabetic family history. These results suggest that A, B, and PP cells of islet of Langerhans are evenly destroyed in parallel fashion at least in insulin dependent diabetes and in some insulin independent diabetes, suggesting insulitis as a possible cause of these types of diabetes.

Blood Glucose↗

[A system for biological pressure telemetry in conscious animals (author's transl)].

Cardiovascular studies on conscious laboratory animals are required for an accurate assessment in drug evaluations. However, attempts to define pharmacological significance of an agent in conscious and unrestrained animals have been limited by the techniques available for recording the cardiovascular parameters. We designed a system which can be applied to record biological pressure, such as the blood pressure, using a miniature FM-FM radio-transmitter and a receiver demodulator. The transmitter consists of a differential amplifier capable of an input signal up to 3 X 10(6) times, voltage controlled oscillator which triggers a 2-5 volts range and 76-90 MHz transmitting oscillator. The transmitter requires a 5.6 V mercury battery. Earphone output of a commercial FM radio-receiver serves for signals to the demodulator. The demodulator is based on the phase locked loop principle and is equipped with an independent output for instantaneous wave recording and the mean of this recording. Transmitting distance of the system may depend on the receiver, however, in most instances, the distance is over 39 meters, in an open field. Accuracy of the telemetering data is dependent on discharge characteristics of the mercury battery. After discharging 5%, the full capacity of the cell gives a sufficient zero stability and accurate pressure measurements.

Animals↗

A case of mesenteric cyst diagnosed by ultrasound examination and a review of Japanese literatures.

Mesenteric cyst is relatively rare, and its diagnosis is difficult. We carried out an ultrasound examination on a 6-year-old boy who showed intestinal obstruction. This examination revealed an abdominal mass, and he was diagnosed as mesenteric cyst. Later it was confirmed by operation. The histopathological examination revealed that it was a lymphangioma. A review was also carried out on 288 cases of mesenteric cyst in Japan.

Child↗