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A 75-year-old man with fever was diagnosed with alveolar hemorrhage. Antineutrophil cytoplasmic antibodies for myeloperoxidase and proteinase 3 were absent. He received corticosteroid therapy, which immediately improved his symptoms and chest radiological findings. After the discontinuation of corticosteroids, fever and general fatigue relapsed, and renal function deteriorated with hematuria and proteinuria. A nerve conduction study revealed mononeuritis multiplex. Renal biopsy demonstrated focal necrotizing crescentic glomerulonephritis with endocapillary proliferative lesions, immunofluorescence C3 deposits, and electron-microscopic subepithelial hump-like deposits. Nephritis-associated plasmin receptor (NAPlr) and plasmin activity, biomarkers of infection-related glomerulonephritis, were positive in glomeruli. Although pathological findings suggested infection-related glomerulonephritis (IRGN), clinical manifestations, such as alveolar hemorrhage and mononeuritis multiplex, suggested systemic small vessel vasculitis. After corticosteroid therapy, systemic symptoms disappeared, and the gradual amelioration of hematuria and proteinuria was observed. Based on the clinical symptoms for which steroid therapy was effective, the patient was considered to have systemic small vessel vasculitis, the etiology of which may have been associated with infection.

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 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.

The effect of T-593, a novel anti-ulcer agent, on the healing of cryocautery-induced rat gastric ulcer was investigated histologically in comparison with that of famotidine. Seven days after ulceration, T-593 (30 mg/kg) or famotidine (30 mg/kg) was orally administered twice daily for 8 weeks. Two, 4 and 8 weeks after the start of administration, the ulcer size was measured by a stereoscopic microscope, and the gastric mucosa was observed histologically. The thickness of the regenerated mucosa, the density and the arrangement of gastric glands, the degree of inflammatory-cell infiltration in the submucosal tissue and the number of microvessels in the submucosal tissue were quantified. In macroscopical evaluation, T-593 and famotidine significantly accelerated ulcer healing, and the time courses of the ulcer index were similar in both cases. In histological evaluation of healed ulcers, T-593 normalized the thickness of regenerated mucosa and reduced the degree of inflammatory-cell infiltration and the number of microvessels in the submucosal tissue, while famotidine had no effect. In conclusion, T-593 possesses accelerating effects not only on the restoration of regenerated mucosa but also on the maturation of submucosal tissue. Therefore, T-593 improves the quality of ulcer healing.

T-593 consists of two optical isomers, (-)-S and (+)-R. Our previous report showed that T-593 has biphasic effects, that is a long-lasting antisecretory action and an improving effect on gastric mucosal blood flow (GMBF). In this study, we compared the sole potency of each isomer on these bi-phasic effects. On the anti-secretory action investigated by the pylorus-ligation method, the (-)-S-isomer showed strong inhibition, while the (+)-R-isomer showed no effect, whereas the GMBF improvement was provided by the (+)-R-isomer. These results show the bi-phasic effects of racemic T-593 are separately derived from each isomer. The (-)-S-isomer strongly inhibited acute gastric mucosal lesion formation, with a potency comparable to T-593 itself, while the (+)-R-isomer showed less effect. Chronic gastric ulcer induced by acetic acid was, however, not healed by the sole treatment of each optical isomer, while racemic T-593 showed a significant effect. This result shows not only anti-secretion but also GMBF improvement is necessary to heal the chronic ulcer. This interesting property of T-593 is expected to raise the quality of ulcer healing (QOUH) and also may prevent ulcer recurrence.