Effects of central and peripheral injection of leptin on food intake and on brain Fos expression in the Otsuka Long-Evans Tokushima Fatty rat with hyperleptinaemia.

Hyperleptinaemia is observed in obese animals and humans, suggesting that leptin resistance rather than leptin deficiency is a characteristic feature of obesity. This study was designed to determine whether peripherally or centrally administered leptin is effective on the short-term food intake and expression of Fos protein in the hypothalamus in the Otsuka Long-Evans Tokushima Fatty (OLETF) or Long-Evans Tokushima Otsuka (LETO) rat, as a control. The OLETF rat exhibits a polygenic syndrome of hyperphagia, obesity, hyperinsulinaemia, and hyperglycaemia. Male OLETF rats of 5, 8, and 14 weeks of age became heavier than LETO rats. Serum leptin concentrations were not significantly different between LETO and OLETF rats at the age of 5 weeks, but in 8- and 14-week-old OLETF rats were increased to 3.4 and 2.9 times those of LETO rats, respectively. The 8-week-old OLETF and LETO rats were given intraperitoneal (i.p.) injections with recombinant mouse leptin to measure the kinetics. There was a dramatic increase in plasma leptin concentration at 1 h, a decline by 3 h, and the concentrations 6 h after injection were similar to the basal levels. There were no significant difference between OLETF and LETO rats. In LETO rats at 5, 8 and 14 weeks of age, i.p. injection of leptin significantly decreased food intake. Whereas 5-week-old OLETF rats responded to leptin with a decrease in food intake, 8- and 14-week-old OLETF rats became resistant to peripherally administered leptin. In contrast, intracerebroventricular (i.c.v.) injections of leptin were very effective in inhibiting food intake in both OLETF and LETO rats at 14 weeks of age. Intraperitoneal injection of leptin in the LETO rats at each age increased the number of Fos-positive nuclei detected in the ventromedial hypothalamic (VMH), the dorsomedial hypothalamic (DMH) and arcuate nuclei, whereas there was no significant increase in the number of cells expressing c-fos protein in the hypothalamus of the 8- and 14 week-old OLETF rats with hyperleptinaemia. On the other hand, increased expression of c-fos protein in the VMH, DMH and arcuate nuclei following i.c.v. injection of leptin was observed in both OLETF and LETO rats at 5, 8 and 14 weeks of age. These data demonstrated that obese OLETF rats are peripherally leptin resistant, while they retain sensitivity to centrally administered leptin.

[Psychological investigation on spa therapy in patients with bronchial asthma].

To evaluate the effects of complex spa therapy (swimming training in a hot spring pool + fango therapy + inhalation of iodine salt solution) on psychological factors, three psychological examinations; CMI (Cornell Medical Index), SDS (Self-Rating Depression Scale) and CAI (Comprehensive Asthma Inventory); were given 25 patients with bronchial asthma (10 male, 15 female, mean age 60 years), and the results of these examinations were compared before and after spa therapy. 1. Physical symptoms, respiratory system and CIJ symptoms by CMI were significantly improved after spa therapy, however the improvement of psychical symptoms was not significant. 2. In SDS, 11 of 25 patients showed more than 40 points, indicating depressive state. The number of such patients decreased from 11 to 2 and the mean SDS score significantly improved from 38.7 to 34.2 after spa therapy. 3. Conditioning, suggestion, fear of expectation, frustration, flight into illness, negative attitudes towards prognosis, and decreased motivation towards therapy by CAI were significantly reduced after spa therapy, with the reduction in negative attitudes towards prognosis and decreased motivation towards therapy being relatively large. Furthermore, CAI score, which is the average of the categories in CAI, was also significantly decreased from 37.9 to 28.4 after spa therapy. These results suggested that complex spa therapy improves psychological factors in patients with bronchial asthma.

Minute nonpolypoid adenomas of the colon depicted with barium enema examination.

To evaluate the usefulness of barium enema examination for detection of small nonpolypoid adenomas, the barium enema study findings were reviewed in patients with flat or depressed adenomas of the colon 3-5 mm in diameter that had been initially found during colonoscopy and that had been diagnosed as adenomas at histologic analysis. Eleven of the 21 nonpolypoid adenomas were depicted on radiographs; they tended to be located on the left side of the colon. The 10 other lesions were not detected retrospectively on barium enema radiographs. The radiographic findings in the depicted lesions included smooth, round, radiolucent areas; in seven of these lesions, round or irregular barium flecks were also seen. The radiolucent areas were attributed either to slightly elevated growth of adenomas or to surrounding hyperplasia of nonneoplastic glands; the central barium fleck seemed to conform to depressed areas within adenomas. Barium enema examination can demonstrate nonpolypoid adenomas of the colon, even though colonoscopy seems superior to barium enema examination for detection of these lesions.

[A case of pulmonary infiltration with eosinophilia (PIE) syndrome induced by Saiboku-To (TJ96). Detection of ECF activity in lymphocytes stimulated with TJ96].

A case of PIE syndrome induced by Saiboku-To (TJ96) is reported. A 56-year-old woman had been treated for intractable bronchial asthma since the age of 42 years. She had a history of PIE syndrome induced by disodium cromoglycate 4 years previously (Jpn. J. Thoracic Disease, 27.1.1989). To reduce the dose of prednisolone for her asthma, administration of TJ96 was started in Dec. 1989. After 5 months of TJ96 treatment, she developed dry cough, fever, and chest pain. Physical findings and laboratory examinations revealed pulmonary infiltrations in the right lung field and severe eosinophilia. Because of suspected drug-induced PIE, TJ96 was stopped and 30 mg/day prednisolone was administered. Her symptoms and laboratory abnormalities subsequently resolved. To confirm the diagnosis of drug-induced PIE syndrome, drug-induced lymphocyte stimulation tests with TJ96 and other drugs were performed. TJ96 significantly induced lymphocyte blastogenesis with a stimulation index of 6.1. Moreover, the supernatant of the incubation mixture of TJ96 and peripheral lymphocytes from the patient showed marked eosinophil chemotactic activity. To our knowledge, there has been no previous report of PIE syndrome induced by TJ96. In addition, this is the first report of the detection of ECF activity in lymphocytes induced by an offending drug in vitro.

The value of double-contrast barium enema in amebic colitis.

We report here our findings on the double-contrast barium enema given to 8 patients with amebic colitis and a comparison is made with endoscopic features. A definite diagnosis of amebic colitis was made by fecal examination or by endoscopic biopsy. Radiologic findings included fine marginal serration, aphthoid ulcers, minute barium flecks, marginal defects, loss of haustration, and deformities of the bowel. Aphthoid ulcers and marginal defects are both characteristic of amebic colitis. The double-contrast barium enema is most useful for differentiating amebiasis from other forms of colitis.

Nonsteroidal antiinflammatory agents. 3. Synthesis of the positional isomers of 4'-chloro-5-methoxy-3-biphenylylacetic acid and their antiinflammatory and analgesic activities.

The positional isomers 3a-i of 4'-chloro-5-methoxy-3-biphenylylacetic acid [1 (DKA-9), R = 4-ClPh; R' = MeO] which is a newly developed nonsteroidal antiinflammatory agent, have been prepared and evaluated for antiinflammatory and analgesic activities using both the carrageenan-induced rat paw edema and AcOH writhing assays. The 3- and 4-biphenylylacetic acids 3a,d, which closely resemble 1 (R = 4-ClPh, R' = MeO) structurally, showed, by far, excellent activities compared with the other isomers in these assays. However, none of the compounds tested was more active than 1 (R = 4-ClPh; R' = MeO). In this series of compounds, structural requirements for good antiinflammatory activity seemed to be parallel to those for analgesic activity.