Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity.

Orexins (hypocretins) are a pair of neuropeptides implicated in energy homeostasis and arousal. Recent reports suggest that loss of orexin-containing neurons occurs in human patients with narcolepsy. We generated transgenic mice in which orexin-containing neurons are ablated by orexinergic-specific expression of a truncated Machado-Joseph disease gene product (ataxin-3) with an expanded polyglutamine stretch. These mice showed a phenotype strikingly similar to human narcolepsy, including behavioral arrests, premature entry into rapid eye movement (REM) sleep, poorly consolidated sleep patterns, and a late-onset obesity, despite eating less than nontransgenic littermates. These results provide evidence that orexin-containing neurons play important roles in regulating vigilance states and energy homeostasis. Orexin/ataxin-3 mice provide a valuable model for studying the pathophysiology and treatment of narcolepsy.

Orexin-induced food intake involves neuropeptide Y pathway.

Orexins (orexin-A and -B) are recently identified neuropeptides, which are thought to be implicated in the regulation of feeding behavior. We used a NPY-Y1 receptor specific antagonist, BIBO3304, to examine whether NPY is involved in orexin-induced feeding behavior. Intracerebroventricular administration of orexin-A (10 nmol) induced food intake in rats (food intake for 3 h; vehicle 0.3+/-0.2 g vs. orexin-A 10 nmol, 4.0+/-0.5 g, n=4). Orexin-induced feeding behavior was partially inhibited by prior administration of BIBO3304 (3 h food intake: orexin-A 10 nmol, 4.0+/-0.5 g vs. BIBO3304 (60 microgram) + orexin-A 10 nmol, 2.2+/-0.2 g, n=4). A low dose of BIBO3304 (30 microgram) did not show a significant inhibitory effect. BIBO3457, an inactive enantiomer, used as a negative control, did not show any inhibitory effect on orexin-A-induced feeding behavior. Fos expression was observed in NPY-containing neurons in the arcuate nucleus 1 h after orexin-A (10 nmol) was administered intracerebroventricularly (control 0.3+/-0.08%, orexin-A 10.2+/-0.8%, n=5 rats/group). These observations suggest that NPY is involved in orexin-induced feeding behavior. However, BIBO3304 did not completely abolish the effect of orexin-A. These results suggest that orexin-A elicits feeding behavior partially via the NPY pathway. The NPY system could be the one of downstream pathways by which orexin-A induces feeding behavior. Another pathway may also be involved in orexin-A-induced feeding behavior, because BIBO3304 did not completely abolish orexin-A-induced feeding behavior.

[Intrahepatic bilomas after hepatic arterial embolization of malignant hepatic neoplasms].

Reviewed and discussed are six cases of intrahepatic biloma that developed after hepatic arterial embolization therapy for malignant hepatic tumors. All six cases were administered emulsion of adriamycin and lipiodol and/or sponge gel particles, as the etiology of their disease was considered to be bile duct necrosis due to obstructions of peripheral supplying arterial branches. From the 23rd to the 76 days after embolization therapy, each lesion was detected by CT scan, and every case showed an elevation of serum alkaline phoshatase. Further, in 4 cases, hepatobiliary scintigraphy revealed a delayed bile clearance in the hepatic lobe. In one case followed up for 2 months, only one of two lesions disappeared. And in 5 cases that were followed up for more than 4 months, recovery occurred in 4 cases without any further treatment, but another case required percutaneous drainage for 3.5 months to be cured. An intrahepatic biloma, or bile duct necrosis, is a complication that can arise from hepatic arterial embolization therapy, so that careful follow-up must be given.

Chronotropic effect of the methanolic extracts of the plants of the Paris species and steroidal glycosides isolated from P. vietnamensis on spontaneous beating of myocardial cells.

Rhizomes of five identified plants of the Paris species, Liliaceae, and Rhizoma Paridis which are sold as a crude drug named "Zao Xiu," "Qiyeyizhihua" or other names in nine different markets in China were tested for their effects on cultured cardiomyocytes. In the standard medium, eight methanol extracts out of sixteen at a concentration of 0.2 mg/ml stopped the spontaneous beating of myocardial cell sheets, but these extracts significantly increased the beating rate when the concentration was reduced to one half. In the culture medium with a low calcium concentration, 0.5 mM, the beating rate of the cells decreased to about 60% of that of the control in the standard medium. The addition of five of the extracts to the low calcium medium at a concentration of 0.1 mg/ml caused a stop of cell beating, but the other extracts increased beating rate at least by 10%. These steroidal glycosides isolated from the rhyzomes of P. vietnamensis (Takht.) H. Li also stimulated cell beating. Among them, diosgenin-3)-alpha-L-rhamno-pyranosyl-(1---2)-(alpha-L-arabinofura nosyl-(1---4))-D-glucopranoside (compound 1) was the most effective stimulant for cell beating as well as calcium uptake by the myocardial cells.