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During cancer chemotherapy, drugs such as 5-HT3 receptor antagonists have typically been used to control vomiting and anorexia. We examined the effects of oxytocin (OXT), which has been linked to appetite, on cisplatin-induced anorexia in rats. Fos-like immunoreactivity (Fos-LI) expressed in the supraoptic nucleus (SON), the paraventricular nucleus (PVN), the area postrema and the nucleus of the solitary tract (NTS) after intraperitoneal (ip) administration of cisplatin. We also examined the fluorescence intensity of OXT-mRFP1 after ip administration of cisplatin in OXT-mRFP1 transgenic rats. The mRFP1 fluorescence intensity was significantly increased in the SON, the PVN, and the NTS after administration of cisplatin. The cisplatin-induced anorexia was abolished by OXT receptor antagonist (OXTR-A) pretreatment. In the OXT-LI cells, cisplatin-induced Fos expression in the SON and the PVN was also suppressed by OXTR-A pretreatment. These results suggested that central OXT may be involved in cisplatin-induced anorexia in rats.

消化管の一部が右横隔膜下と肝臓の間に嵌入した病態をChilaiditi症候群と呼ぶ．今回われわれは絞扼性イレウスを合併し腸切除を要した，小腸型Chilaiditi症候群の1例を経験したので報告する．症例は52歳女性，腹痛・嘔吐にて当院受診．CTで絞扼性イレウスを合併した小腸型Chilaiditi症候群と診断し，同日緊急開腹術を施行した．開腹所見では肝右葉表面と右横隔膜下との間に小腸が嵌入し，絞扼していた．嵌入小腸を整復したが，壊死小腸の切除を要した．Chilaiditi症候群は大多数が結腸のみの嵌入で，無症状であれば経過観察される場合が多い．しかし小腸型Chilaiditi症候群の場合は，イレウスの合併による緊急手術の必要性を考慮に入れた慎重な経過観察が必要と考えられる．

症例は65歳，男性．腹痛・高度の貧血を主訴に当院入院．血液生化学検査で貧血・CRPの上昇を認め，腫瘍マーカー（CA19-9）の上昇を認めた．腹部CT・腹部MRIで小腸壁肥厚を伴う腫瘤像を認め，両側副腎に転移を疑う腫瘤性病変を認めた．小腸腫瘤性病変からの出血が貧血の原因と診断し，緊急手術を施行した．開腹所見ではTreitz靱帯から20cmの空腸に下行結腸浸潤を伴う腫瘤と腸間膜リンパ節転移を認めたため，小腸・下行結腸部分切除術を施行した．両側副腎腫瘍は遠隔転移と診断し，根治的切除は困難と考え切除しなかった．病理組織学的には異型性の強い細胞を認め，免疫染色では上皮系マーカーのCAM5.2・AE1/AE3，間葉系マーカーのvimentinのみが陽性で，原発性小腸未分化癌と診断した．原発性小腸未分化癌の報告は少なく極めて稀である．今回われわれは，両側副腎転移を伴った原発性小腸未分化癌の1例を経験したので文献的考察を加えて報告する．

A case of retroperitoneal fibrosis associated with scirrhous gastric cancer is reported. A sixty two-year-old Japanese female was admitted because of acute renal failure. The patient's serum creatinine level showed 3.2 mg/dl while the blood urea nitrogen level was 23 mg/dl. An ultrasound study of the upper abdomen revealed bilateral hydronephrosis. Drip infusion pyelography revealed a dilated right renal pelvis without ureteral obstruction. The left kidney was not opacified, suggesting a functional disorder. Gastrography and gastrofiberscopy revealed scirrhous gastric cancer. Signet ring cell carcinoma was later demonstrated histologically by biopsy specimens. CT demonstrated a prominent thickening of the gastric wall and hydronephrosis, although no prevertebral soft tissue masses were observed. A total gastrectomy was performed with failure to surgically decompress the ureters because fibrous plaque had firmly enveloped the retroperitoneal structures. Biopsy specimens of the retroperitoneum revealed an invasion of the tumor cells and prominent fibrosis. As an etiology of renal failure, ureteral stenosis resulting from secondary retroperitoneal fibrosis was also considered.

A 69-year-old Japanese female was admitted because of general fatigue. Laboratory data showed elevation of serum total bilirubin, transaminase, gamma-glutamyl transpeptidase, and creatinine levels. An immunological study revealed hypergammaglo-bulinemia, low titer of complement, and high titers of antinuclear antibody, anti-DNA antibody, and circulating immune complexes. Antibodies to parainfluenza virus 3 were positive. Histology of the liver disclosed numerous giant cell hepatocyte transformations with the lobular architecture being slightly distorted by portal inflammation and fibrosis. These findings led us to make a diagnosis of giant cell hepatitis associated with systemic lupus erythematosus. Prednisolone was effective in improving the anemia and the serum immunoglobulin, immune complex, and antinuclear antibody levels. The addition of cyclosporine to the initial corticosteroid therapy was also beneficial in decreasing the transaminase level and in improving liver histology. The patient died of acute pneumonitis and renal failure on the 166th day after admission. Parainfluenza virus 3 and autoimmune mechanisms were thus considered to be the causes of the giant cell hepatitis.

It has previously been established that norepinephrine (NE) in the central nervous system is involved in feeding and the development of obesity. The present experiments were carried out to investigate the relationship between the uptake of NE by a crude hypothalamic homogenate and NE-mediated sympathetic activity in interscapular brown adipose tissue (IBAT). Sympathetic nervous system activity was assessed by measuring the binding of the purine nucleotide guanosine-5′-diphosphate (GDP) to mitochondria isolated from IBAT. Four situations known to alter food intake and sympathetic activity, namely, corticotropin releasing factor infusion, adrenalectomy, fenfluramine treatment and obesity due to genetic transmission were studied. In each case, [ 3 H]NE uptake by the hypothalamic preparation and GDP binding to IBAT mitochondria were measured. A highly significant negative correlation between the uptake of NE by hypothalamic homogenates and the binding of GDP to IBAT mitochondria was obtained in both lean and obese animals. These findings are discussed with regard to the regulation of food intake and sympathetic nervous system mediated thermogenesis.

D-glucosamine, 2-amino-2-deoxy-D-glucose, is known to be an endogenous glucose analogue and to antagonize glucose uptake and metabolism. The present experiments were aimed to clarify effects of glucosamine and related chemical substances on ingestive behavior, as well as its direct effects on hypothalamic neurons. Infusion of 24 mumole glucosamine into the third cerebroventricle induced feeding within 30 min in 5 rats out of 7 tested, accompanied by increased ambulatory activity. No periprandial drinking was observed. Plasma glucose level increased, peaking at 30 min after the injection. Plasma insulin level tended to increase, but not significantly. Electrophoretic application of glucosamine activated glucose-sensitive neurons in the lateral hypothalamus and suppressed glucoreceptors in the ventromedial hypothalamus. These facts, together with other reported results, suggest that glucosamine can modulate physiological feeding and that carbon 2 of the glucose molecule is important in feeding modulation by glucose analogues.

1,5-Anhydroglucitol (1DG, minus an oxygen on carbon 1 of the glucose molecule), has been known physiologically to be present in human cerebrospinal fluid. In order to clarify direct evidence concerning 1DG-induced feeding, hyperglycemia and adrenomedullary mediation of hyperglycemia, 1DG was infused into rat lateral ventricle in doses of 11.8, 21.0, 33.7 and 50.0 μmoles/rat, and its effects compared to those of 2-deoxy-D-glucose (2DG). A dose-dependent increase in food intake after 1DG was 1/3.4 to 1/10.6 of that produced by equimolar 2DG. After 1DG serum glucose concentration gradually increased, peaked at 30 min, and subsequently decreased. Hyperglycemia induced by 1DG was 1/2.1 to 1/2.2 of that produced by 2 DG and was reduced 81% following adrenomedullectomy, which was close to the value for 2DG: 80%. Results were consistent with known differences in the biochemical actions of 1DG and 2DG at the level of substrate specificity of the hexokinase and the rate of glucose transport. These actions suggest that 1DG could provide physiological signals for food intake.

Two endogenous γ-lactones, 3-hydroxy-4-butanolide (1) and 2-hydroxy-4-hydroxymethyl-4-butanolide (2) have been identified as substances that enhance, respectively, satiety and hunger by their effects on the feeding behavior and the central neurons of rats. To determine the stereochemistry of the physiologically active isomers, all the stereoisomers of these two lactones were synthesized and their effects on the feeding behavior and humoral factors were assessed by infusion into the rat third cerebroventricle. Among four isomers, (2S,4S)-2-hydroxy-4-hydroxymethyl-4-butanolide (2a) was most effective in elicitating the feeding and caused potent hypoglycemia with hyperinsulinemia. (S)-3-Hydroxy-4-butanolide (1a) suppressed the food intake more potently than the antipode and caused humoral responses reciprocal to those of 2a. From these facts, it was concluded that 1a and 2a are physiologically active forms for conveying intrinsic signals of satiety and hunger to neurons in the hypothalamus.

1,5-Anhydroglucitol (1-DG) has been known as an antimetabolic glucose analogue. Using gas chromatography, 1-DG was found to be physiologically present in rat serum. In order to investigate its direct and long-term effects on feeding, 1-DG was infused during the light period into the rat third ventricle in doses of 3.0, 6.0 and 12.0 mumol/rat. Its effects were then compared to those of similarly applied 2-deoxy-D-glucose (2-DG). Following initial hyperphagia, both of these glucose-analogues produced suppressive effects on feeding during the subsequent day throughout the light and dark periods. On the third day after 2-DG injection reduction of feeding did not recover completely to the pretreatment baseline levels, but it did recover after 1-DG. Both 1-DG and 2-DG caused linear dose-related hypophagia, with the slope for 1-DG being about half of that for 2-DG. It is suggested that the delayed hypophagia which followed the initial hyperphagia produced by deoxyglucose was a result of sustained inactivation of the Na-pump due to intracellular ATP deficiency caused by accumulation of deoxy-glucose-6-phosphate.

Structural specificity among short-chain organic acids for effects on feeding behavior, blood glucose and insulin was investigated by infusion of 1 exogenous and 6 endogenous derivatives into the rat third cerebral ventricle. Glyceric acid (GEA) (1.0 mumol), 3,4-dihydroxybutanoic acid gamma-lactone (3,4-DB) and 3,4,5-trihydroxypentanoic acid gamma-lactone (3,4,5-TP) (2.50 mumol) decreased food intake for, at most, 24 h. These acids depressed the size of the first meal after infusion, but did not affect latency to the first meal, eating speed, drinking or ambulation. Infusion of 2,4-dihydroxybutanoic acid gamma-lactone (2,4-DB) (1.25 mumol), 2,4,5-trihydroxypentanoic acid gamma-lactone (2,4,5-TP), and an exogenous compound, 2,4,5,6-tetrahydroxyhexanoic acid gamma-lactone (2,4,5,6-TH) (2.50 mumol), induced transient initial feeding which was not necessarily accompanied by periprandial drinking. Ambulation was concomitantly increased. Of these organic acids, 3,4-DB and 2,4,5-TP were most potent in their effects on feeding. Hyperglycemia was induced by 2.50 mumol 3,4-DB leaving insulin unaffected; 2.50 mumol 2,4,5-TP caused hypoglycemia, with a persistent but not significant rise in insulin. The results suggest that slight structural differences of endogenous organic acids, in particular the positions of hydroxyl groups on the lactone ring of 4-butanolide, may be important in feeding modulation by conveying intrinsically reciprocal signals to neurons involved in feeding and satiety.

To test the possibility that theophylline induced circadian disappearance of food intake might depend upon rhythmic disruption of blood glucose, insulin and free fatty acids (FFA), theophylline was administered chronically. This markedly lengthened postprandial intermeal intervals during the dark, and induced approximately identical intermeal intervals and identical meal sizes in the light and dark periods. In contrast to the clear light-dark dependent oscillations of serum glucose, insulin and FFA in the controls, the theophyllinized rats lost circadian fluctuation of each of these three chemical substances. Further, theophyllinized rats, unlike controls, had no time-dependent fluctuation in the levels of these substances at -120, -60 or -15 min preceding the onset of the first meal before the dark. These findings, together with previous reports, explain the disappearance of nocturnal feeding rhythm in theophyllinized rats in terms of functional destruction of circadian regulation in the hypothalamus which modulate the production of chemical determinants of food intake.

Two endogenous γ-lactones, 3-hydroxy-4-butanolide (1) and 2-hydroxy-4-hydroxymethyl-4-butanolide (2) have been identified as substances that enhance, respectively, satiety and hunger by their effects on the feeding behavior and the central neurons of rats. To determine the stereochemistry of the physiologically active isomers, all the stereoisomers of these two lactones were synthesized and their effects on the feeding behavior and humoral factors were assessed by infusion into the rat third cerebroventricle. Among four isomers, (2S,4S)-2-hydroxy-4-hydroxymethyl-4-butanolide (2a) was most effective in elicitating the feeding and caused potent hypoglycemia with hyperinsulinemia. (S)-3-Hydroxy-4-butanolide (1a) suppressed the food intake more potently than the antipode and caused humoral responses reciprocal to those of 2a. From these facts, it was concluded that 1a and 2a are physiologically active forms for conveying intrinsic signals of satiety and hunger to neurons in the hypothalamus.

In order to clarify the effects of endogenous organic acids on short and long-term feeding behavior, ingestive behavior was monitored for 2 hr before and after intra-third ventricular infusions of 3,4-dihydroxybutyric acid (2-deoxytetronic acid, 2-DTA), 2,4,5-trihydroxypentanoic acid (3-deoxypentonic acid, 3-DPA), and 3-hydroxybutyric acid (3-HBA). In addition, meal patterns were recorded for 2 days before and after the ventricular infusions. 2-DTA suppressed both short and long-term feeding by decreasing meal size (MS). 3-DPA elicited transient feeding behavior, but caused no change in long-term feeding. 3-HBA initially stimulated feeding, but subsequently suppressed long-term feeding by decreasing MS and prolonging postprandial intermeal interval (IMI). The suppressive effects of 3-HBA on feeding behavior lasted about 24 hr longer than those of 2-DTA. Based upon these observations as well as our previous reports, it appears that some of the processes affecting hunger and satiation are mediated by changes in central and peripheral concentrations of these organic acids.

The deoxy analogues of D-glucose, 1-deoxy-D-glucosamine and D-glucosamine, are biochemically and structurally similar to 1-deoxy-D-glucose, so their direct effects on food intake were studied. Both 12 and 24 μmol 1-deoxy-glucosamine potently decreased feeding and body weight after an initial transient elicitation of food intake. The suppression included decreased meal size and prolonged postprandial intermeal interval which persisted for at least 3 days after injection. Ambulatory activity was unaffected. The initial elicitation of feeding was not accompanied by drinking episodes, and subsequent drinking suppression was persisted. These findings, plus other biochemical evidence, suggest that inversion with an amino group or removal of a hydroxyl group from C-2 and/or C-1 may effect feeding.

In previous studies, 1,5-anhydro-D-glucitol (1-DG), an endogenous glucose analog, was found to significantly influence physiological feeding behavior. The relationships between the hydroxyl group positions on the pyranose ring carbons and the anorectic action induced by 1-DG and its analogs are discussed. To investigate the effects of these glucose analogs on ingestive behavior, 24 mumole of test solution was injected into the rat third cerebral ventricle immediately before normal eating time, which starts at the beginning of the dark. After initial transient hyperphagia, 1-DG suppressed feeding during the first 12-hr dark period. It prolonged postprandial intermeal interval beginning shortly after injection, but eating rate was not affected and meal size did not decrease until near the end of the normal feeding period. The incidence of drinking episodes decreased concomitant with feeding suppression. Feeding and drinking suppression were also produced by 1,2-dideoxy-D-glucose, 1,3-dideoxy-D-glucose, and 1,4-dideoxy-D-glucose, although they were less potent than 1-DG. They suppressed feeding by prolonging the postprandial intermeal interval, but did not change meal size or eating rate. The anorectic effects of 1-DG were abolished by removal of the hydroxyl group at carbon 6 and by epimerization at carbons 2, 3, and 4. These findings indicate that feeding suppression induced by 1-DG and its analogs is induced mainly by prolongation of the postprandial intermeal interval, and the presence or absence of a hydroxyl group on each carbon of 1-DG is important for its feeding suppression.

1,5-Anhydroglucitol (1-DG) and 2-deoxy-D-glucose (2-DG) have been found to show delayed suppression of food intake succeeding to an initial hyperphagia. In addition, 1-DG which has been physiologically traced was suggested to provide physiological signals for control of food intake. In order to clarify the molecular structural mechanisms of feeding suppression induced by glucose analogues, feeding behavioral modes of action in 5 deoxy analogues of glucose were examined. The experiments were carried out in a sound proof room illuminated daily from 0800-2000 hr using adult male rats. Test solutions were infused around 1950 hr into the intra-ventricle III. Decrease of food intake and body weight was observed during the first day after 1-DG injection, while it reverted to their initial levels on the second day. 2-DG had the same suppressive effect on the first day. The magnitude of suppression elicited by 5-thioglucose was about ten times that produced by equimolar 1-DG. 1,2-Dideoxy-D-glucose, however, was less potent than 1-DG for producing anorexia. In contrast to these analogues, 1-deoxy-D-mannose did not produce any changes in food intake or body weight. Taken together with these results, it is highly probable that oxygens at the position of carbon 1,2 and 5 of glucose may play an important role on producing feeding suppression.