Safety and efficacy of intravenous ferric carboxymaltose in Japanese patients with iron-deficiency anemia caused by digestive diseases: an open-label, single-arm study.

Iron-deficiency anemia (IDA) accounts for majority of anemia. Although iron replacement therapy is effective, in Japan, conventional iron formulations have disadvantages such as gastrointestinal side effects for oral formulations and issues of frequent administration for intravenous (IV) formulations. Ferric carboxymaltose (FCM), which overcomes these limitations, is widely used as an IV iron source overseas. In this multi-center, open-label, single-arm study, we investigated the safety and efficacy of FCM up to 12 weeks after the start of administration in patients with IDA caused by digestive diseases. Thirty-nine patients diagnosed with IDA based on hemoglobin and serum ferritin levels were included. Eligible subjects were administered FCM until the total calculated iron dose (1000 or 1500 mg) was achieved over intervals of at least 1 week. A single iron dose was 500 mg. In the full analysis set (n = 39), the incidence of adverse events and adverse drug reactions was 71.8 and 48.7%, respectively. All events were as expected from the safety profile of IV iron. The mean change from baseline (10.39 g/dL) to the highest observed hemoglobin level was 3.31 g/dL. These results indicate the safety and efficacy of FCM for treating IDA caused by digestive diseases in Japanese patients.

DT40 knock-out and knock-in studies determine the regions necessary and sufficient for transcription and epigenetic conversion of the chicken Ig-ß gene.

The chicken Ig-ß locus is organized by three cell-type-specific genes and two ubiquitously expressed genes. B-cell-specific DNase I hypersensitive sites (DHS) in that locus, including three present inside the flanking gene, were grouped into six regions and deleted. The deletions decreased Ig-ß mRNA content to <0.1% of that of normal DT40 cells and converted epigenetic parameters such as histone modifications, CG methylation and DNase I hypersensitivity into inactive states. Knocked-in DHS regions into knock-out cells reactivated both transcription of the Ig-ß gene and epigenetic parameters. Thus, the collaboration of the scattered regulatory regions was essential and sufficient not only for B-cell-specific transcription of the Ig-ß gene, but also for the conversion of epigenetic parameters. On the basis of the knock-in studies, we determined the regions involved in the conversion and maintenance of the epigenetic parameters. These scattered regulatory regions were limited in vicinity such as in an intron of the gene, in the intergenic regions and in the introns of a flanking gene.