Our results demonstrate that T-614 exerts an anticachectic effect in tumor-bearing mice through the inhibition of IL-6 gene expression.

No abstract

The first total synthesis of the 3,5‐disubstituted indolizidine toad alkaloid 239Q from the known pyrrolidine 1 has been achieved, in seven steps with a 35 % overall yield. The relative stereochemistry of natural 239Q was determined unambiguously by comparison of GC‐FTIR spectra of synthetic material with the skin extracts of the toad Melanophryniscus cupreuscapularis. The C7 congeners at the 5‐position (12 and 13) showed strong antagonist activities on the α4β2 nicotinic acetylcholine receptors.

Glomerulopathy with fibronectin deposits (GFND) is a rare hereditary kidney disease with autosomal dominant inheritance. A 21-year-old woman who had been diagnosed with GFND 10 years ago was admitted for investigation of a rapid decline in her renal function, hemolytic anemia, and cardiac dysfunction. A renal biopsy showed GFND accompanied by extraglomerular vascular lesions. Comprehensive treatments against hypertension and anemia improved the renal function. Although there have been few reports of vascular lesions in GFND, we suspect that endothelial hyperpermeability resulting from hypertension caused the fibronectin deposition and narrowing of the extraglomerular vascular lumens, thereby accelerating hypertension and inducing hemolytic anemia.

The relationship of endogenous nitric oxide (NO) to the gastric mucosal protective effect of the novel anti-ulcer agent T-593, (+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3-[2-[[[5-(methylamino) methyl-2-furyl]methyl]thio]ethyl]-2-(methylsulfonyl) guanidine, was investigated in rats. T-593 (3-30 mg/kg, p.o.) dose dependently prevented the formation of gastric mucosal lesions induced by oral administration of aspirin (200 mg/kg) in 0.15 N HCl (HCl-aspirin). Pretreatment with N(G)-nitro-L-arginine methylester (L-NAME), a selective inhibitor of NO synthase (NOS), attenuated the mucosal protective effect of T-593. This effect of L-NAME was antagonized by pretreatment with L-arginine, a substrate of NOS, but not with D-arginine. Activity of total NOS composed of inducible and constitutive NOS in the gastric mucosa was decreased by HCl-aspirin, and T-593 inhibited this decrease. On the other hand, HCl-aspirin and T-593 did not affect inducible NOS activity in the gastric mucosa. Furthermore, we confirmed that T-593 inhibits the decrease in gastric mucosal blood flow (GMBF) induced by HCl-aspirin, and this effect is completely inhibited by pretreatment with L-NAME. These results suggest that the mucosal protective effect of T-593 is partly mediated by endogenous NO via improvement of GMBF and that a possible mechanism for the effect of T-593 is the maintenance of constitutive NOS activity in gastric mucosa.