Evaluating glycogen signal contamination in muscle by (13)C MRS of the liver.

To evaluate the contamination of glycogen signal synthesized in skeletal muscle by that in the liver, long-term monitoring of over 7 h of in vivo [1-(13)C] glycogen synthesis/degradation at the right abdomen and left shoulder was achieved using a 3.0-T clinical MR system. (13)C MR spectra without localization were obtained from five healthy volunteers before and after oral administration of 85 g of d-glucose, including 10 g of 99% [1-(13)C] glucose. In all volunteers, the relative signal intensities at the abdomen to those at shoulder were about two- to fivefold, and those of time-course changes at the abdomen and shoulder were dissimilar. It is considered that the quantity of muscle-synthesized glycogen signal at the abdomen is less than that at the shoulder because of the lesser muscle volume at the abdomen, and it may be less affected for evaluating glycogen synthesis/degradation in the liver even without localization pulses.

Pharmacological profiles of a novel opioid receptor-like1 (ORL(1)) receptor antagonist, JTC-801.

Pharmacological effects of a novel opioid receptor-like1 (ORL(1)) receptor antagonist, [N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride] (JTC-801), were examined in in vitro and in vivo. JTC-801 inhibited the binding of [(3)H]-nociceptin to human ORL(1) receptors expressed in HeLa cells with a K(i) value of 44.5 nM. JTC-801 completely antagonized the suppression of nociceptin on forskolin-induced accumulation of cyclic AMP (IC(50) : 2.58 microM) using ORL(1) receptor expressing HeLa cells in vitro. In in vivo, when given intravenously at dosages of 0.01 mg kg(-1) and above, or orally at dosages 1 mg kg(-1) and above, JTC-801 antagonized the nociceptin-induced allodynia in mice. Effects of JTC-801 on various nociceptive models were examined. In mouse hot-plate test, JTC-801 prolonged escape response latency (ERL) to exposed heat stimulus with minimum effective doses (MED) of 0.01 mg kg(-1) by i.v. or 1 mg kg(-1) by p.o. In the rat formalin test, JTC-801 reduced both the first and second phases of the nociceptive response with MED of 0.01 mg kg(-1) by i.v. administration or 1 mg kg(-1) by p.o. administration. This anti-nociceptive action of JTC-801 was not inhibited by naloxone (10 mg kg(-1), s.c.). We have demonstrated that JTC-801 antagonizes the ORL(1) receptor response, and that JTC-801 has efficacious and potent anti-nociceptive effects in acute pain animal models not only by intravenous injection but also oral administration. These results suggest that JTC-801 may represent a new class of analgesics.

Monitoring of liver glycogen synthesis in diabetic patients using carbon-13 MR spectroscopy.

To investigate the relationship between liver glucose, glycogen, and plasma glucose in diabetic patients, in vivo liver carbon-13 magnetic resonance spectroscopy ((13)C MRS) with a clinical 3.0T MR system was performed. Subjects were healthy male volunteers (n=5) and male type-2 diabetic patients (n=5). Pre- and during oral glucose tolerance tests (OGTT), (13)C MR spectra without proton decoupling were acquired in a monitoring period of over 6h, and in total seven spectra were obtained from each subject. For OGTT, 75g of glucose, including 5g of [1-(13)C]glucose, was administered. The MR signals of liver [1-(13)C]glucose and glycogen were detected and their time-course changes were assessed in comparison with the plasma data obtained at screening. The correlations between the fasting plasma glucose level and liver glycogen/glucose rate (Spearman: rho=-0.68, p<0.05, n=10) and the fasting plasma glucose level and liver glycogen peak/fasting rate (Spearman: rho=-0.67, p<0.05, n=10) indicated that (13)C MRS can perform noninvasive measurement of glycogen storage/degradation ability in the liver individually and can assist in tailor-made therapy for diabetes. In conclusion, (13)C MRS has a potential to become a powerful tool in diagnosing diabetes multilaterally.