Effects of Different Absorption Enhancers on the Permeation of Ebiratide,an ACTH Analogue,across Intestinal Membranes

The permeation of ebiratide (H-Met(O₂)-Glu-His-Phe-d -Lys-Phe-NH(CH₂)₈NH₂), a novel ACTH analogue, across the intestinal mucosae has been examined by use of isolated intestinal membranes from rats in a modified Ussing chamber. Regional differences were observed in the permeation of ebiratide across intestinal membranes; the order of membrane permeability was jejunum > ileum > duodenum > colon. Overall, the permeation of ebiratide was relatively poor. The effects of various absorption enhancers were examined to increase the intestinal permeability to ebiratide. Sodium glycocholate and sodium caprate had no significant enhancing effect on the permeability of the jejunal membrane, but significantly enhanced the permeation of ebiratide through the colonic membrane. On the other hand, N-dodecyl-β-d -maltopyramoside (LM) significantly enhanced the permeation of ebiratide through both jejunal and colonic membranes. In general, the absorption-enhancing effects of these agents were more predominant in the colon than in the jejunum. Membrane damage by the absorption enhancers was evaluated by measuring the amount of protein released from the intestinal membrane. It was found that all the absorption enhancers slightly increased the amount of protein released, but that the amounts of protein released in the presence of these enhancers were much less than in the presence of ethylenediaminetetraacetic acid (EDTA), used as a positive control. These findings suggest that the absorption enhancers, especially LM might be useful adjuvants for improving the intestinal absorption of peptide and protein drugs, including ebiratide.     

A Case of Poorly Differentiated Early Adenocarcinoma of the Stomach Forming a Protruded Type Lesion

Abstract: A case of poorly differentiated adenocarcinoma (undifferentiated type by Nakamura, diffuse type by Lauren) of the stomach infiltrating the submucosa and forming a protruded type lesion is reported. A 60-year-old man underwent endoscopic examination, which revealed a protruded type lesion with a nodular configuration and shallow ulceration accompanied by slough along the greater curvature of the upper gastric body, which was proved to be poorly differentiated adenocarcinoma by endoscopic biopsy. The patient underwent radical surgery, consisting of total gastrectomy with pancreato-splenectomy. Macroscopic observation of the resected specimen revealed a protruded type lesion, measuring 30 mm in diameter, in the fundus along the greater curvature. The surface of the lesion had an irregular and nodular configuration with erythema and superficial erosions. Although, in the setting of early gastric cancer, poorly differentiated adenocarcinomas are usually macroscopically depressed or ulcerated type, this case presented a protruded type lesion (polypoid type). We report this unusual case because of its extremely important implications in the discussion of gastric cancer therapy.     

Mycophenolate mofetil therapy for children with intractable nephrotic syndrome

BACKGROUND: Cyclosporin A (CyA) can suppress relapses and reduce proteinuria in frequent-relapse nephrotic syndrome (FRNS) and steroid-resistant nephrotic syndrome (SRNS). However, some patients remain resistant to CyA therapy. The purpose of the present paper was to evaluate mycophenolate mofetil (MMF) treatment in pediatric patients with CyA-resistant intractable nephrotic syndrome. METHODS: MMF therapy was given to 11 patients with FRNS who had relapse despite CyA therapy, and one patient with SRNS who had been receiving combined therapy using steroid and CyA until immediately before the start of MMF. MMF was administered at a daily dose of 750-1000 mg/m(2) in two divided doses. RESULTS: Ten of the 11 patients with FRNS were able to maintain remission. Among them, seven patients remained relapse free for 1 year, and two patients had a decrease in the frequency of relapse after initiation of MMF therapy. One patient, however, had repeated cycles of remission and relapse, and was considered resistant to MMF therapy. The total prednisolone dose during the period from month 6 to month 12 after the start of MMF therapy was significantly lower than that during the 6 month period before the start of MMF therapy. The patient with SRNS, who had not achieved remission despite CyA administration, had complete remission on MMF. No serious adverse effects were seen in any of the present patients. CONCLUSION: MMF could be useful in CyA-treatment-refractory FRNS and CyA-resistant SRNS.