Susumu Miyabo

Effects of neonatal treatment with monosodium glutamate on circadian locomotor rhythm in the rat

In order to study the effects of treatment with monosodium glutamate (MSG) during the neonatal period on the intrinsic circadian timekeeping system in rats, the locomotor activity of blinded MSG-treated and control (saline-treated) rats was analyzed with power spectral analysis and cross-correlation. In contrast to a robust free-running circadian rhythm in the control rats, a significant shortening of the circadian period and rapid decomposition into ultradian components were noted in the MSG-treated rats. Computer-assisted stereometry of the hypothalamic nuclei revealed that, in addition to the well-known severe damage in the arcuate nuclei (ARC), the volumes of the suprachiasmatic nuclei (SCN) and ventromedial hypothalamic nuclei (VMH) were also reduced significantly in the MSG-treated rats. Although no gross histological damage was apparent in either the SCN and VMH, neonatal MSG treatment appears to impair the function of SCN to integrate many minor oscillations in the brain into a single, definite and precise circadian period.

Psychological correlates of stress-induced cortisol and growth hormone releases in neurotic patients.

&NA; The mirror drawing test was performed in 23 neurotic patients and plasma cortisol (Fk) and growth hormone (GH) were measured serially throughout the test. The patients personality was assessed by the Minnesota Multiphastic Personality Inventory and related to the endocrine findings. The results indicated that 1) Fk and GH have different personality correlates; 2) the Fk responders tend to be more “defensive” trying to maintain good “self‐control” over inner mental processes; 3) high GH level seems to be associated with personality features such as exaggeration, hostility, and a distorted thinking process; 4) psychoendocrine control mechanisms for Fk and GH tend to offset, rather than enhance, each other.

Ontogeny of circadian corticosterone rhythm in rats treated with monosodium glutamate neonatally

Abstract A lesion of the arcuate nucleus (ARC) was produced by subcutaneous administration of monosodium glutamate (MSG) to neonatal female rats. The onset and the amplitude of the circadian corticosterone rhythm in the MSG-treated rats were the same as those in the saline-injected controls. When rats were blinded at 35 days of age, the corticosterone rhythm free-runned in both groups. The results indicate that the neurons in the ARC do not play an essential role in the mediation circadian signals from the suprachiasmatic nucleus to the pituitary-adrenocortical system. MSG-treatment, however, seems to delay the phase shift of free-running corticosterone rhythm through yet unknown mechanisms.

Gastric Cancer Containing Insulin and Associated with Hypoglycemia

A patient with gastric cancer associated with hypoglycemia is described. Immunoassay of acid alcohol tissue extract revealed the presence of 7.6 mU. insulin per gram wet tissue weight in the primary tumor which weighed 10 gm. No insulin was detected in the hepatic metastasis. The concentration of pancreatic insulin was decreased and the serum insulin level was not elevated. Tissue insulinase activity was virtually absent in the primary tumor, whereas the hepatic metastasis showed activity comparable to that of normal liver. It is difficult to assume, however, that the release of insulin from the primary tumor, which contained such small quantities of the hormone, could be the Bole cause of hypoglycemia. An additional mechanism(s) must have been involved in the causation of hypoglycemia in this patient.

Effect of Intrahypothalamic Implantation of Cortisone Acetate on the Onset of Circadian Corticosterone Rhythm in Neonatal Female Rats

Subcutaneous administration of corticosteroids to neonatal rats has been reported to delay the onset of the circadian corticosterone rhythm. Micropellets of a cortisone acetate(CA)-paraffin mixture or paraffin alone were implanted intrahypothalamically or subcutaneously in 2-day-old female rats. 24- or 48-hour patterns of blood corticosterone were obtained serially in individual rats at 21, 28, 35, 56 and 120 days of age. Sham(paraffin)-implanted rats and those bearing CA pellets subcutaneously showed a well-defined circadian corticosterone rhythm at day 28. CA implantation into the anterior hypothalamus, however, caused a delay in the onset of the circadian corticosterone rhythm by 1 week together with a diminished amplitude. In rats with CA pellets in the medial basal hypothalamus, the corticosterone rhythm was not fully established even on day 56, but was evident in most animals on day 120. It is suggested that neonatal CA treatment exerts its effect by inhibiting the maturation of the efferent neural pathways carrying circadian signals from the suprachiasmatic nuclei.

Behavioral and other systemic effects of cortisol-21 sulfate.

Abstract Three milligrams of cortisol-21 -sulfate or cortisol free alcohol in oil suspension was administered intramuscularly to male rats on alternate days for 2–7 weeks. Open-field tests repeated at 2- or 3-day intervals revealed that both steroids had significant stimulatory effects on the animals exploratory behaviors (ambulation and rearing), when the treatments were started soon after weaning (postnatal day 21–24). The same treatments to adult rats (46 days old), however, did not cause any change in the activity levels. It was also shown that cortisol sulfate, in contrast to free cortisol, was inert as a glucocorticoid; it had no catabolic, gluconeogenic, lympholytic, or ACTH-suppressive effects. The results suggest that cortisol sulfate, and probably free cortisol as well, affects behavior through its direct action on the central nervous system rather than via its effects on intermediary metabolism or negative feedback on pituitary ACTH release.

A CASE OF CHRONIC INSULIN RESISTANCE

31才,男.やせ型.糖尿病の遺伝なし. 25才糖尿発見以来斷続的にインスリン治療を受けた.初め12単位でコントロールできたが,次第に必要量が増加した.インスリンアレルギーの既往なし.理学的所見正常.空腹時血糖174～328mg/d1,尿糖1日約400g.正規インスリン100単位静注で血糖降下ほとんどなし. NPHインスリン300単位で治療効果なく,ステロイドを追加した所,インスリンに反応するようになり,現在レンテ・インスリン80単位とn-butyl biguanide 150mgで尿糖1日5g位に抑えられている. agar gel electrophoresis等で著明なインスリン結合抗体が証明されたこと,患者血清がマウスでインスリンの血糖降下作用を抑制したこと,感染,酸性症,他の内分泌疾患がなくて300単位・インスリンでコントロールできず,ステロイドによりインスリン抗体価の減少とともにインスリンに反応するようになつたこと等から,慢性インスリン抵抗性の糖尿病と考えられる.