Breakthrough fungemia due to Candida fermentati with fks1p mutation under micafungin treatment in a cord blood transplant recipient.

The prophylactic use of antifungal drugs in allogeneic hematopoietic cell transplant recipients has revealed that the rate of non-albicans candidemia has increased. We herein report the case of a patient with adult T-cell leukemia who developed candidemia due to Candida fermentati during micafungin treatment after cord blood transplantation. The isolate was identified on day 47 by sequencing of the internal transcribed spacer region of the ribosomal RNA gene. The sequencing of the hot spot region of fks1p of isolate revealed naturally occurring amino acid substitutions, which conferred reduced echinocandin susceptibility. This case highlights that breakthrough candidemia due to C. fermentati occurred in a patient receiving micafungin treatment.

Effect of supplementation of soy sauce oil and Ca salts of fatty acids on rumen fermentation, milk production and conjugated linoleic acid in milk of dairy cows.

Eight cows were used to evaluate the effects of supplementation of soy sauce oil (SO) or Ca salts of fatty acids (FA) on rumen fermentation and milk production. The control diet (CO) consisted mainly of hay, corn silage and a concentrate. In the experimental diets, 400 g/day per cow of SO or FA (soybean oil and rapeseed oil) was supplemented to the CO diet. Experimental period for the three treatments was 14 days, and milk samples were taken during the last 2 days and rumen sample was taken on the last day. Dry matter intake was not affected by the treatments. The number of rumen protozoa at 0 h increased by SO and FA diets. Total volatile fatty acids at 2 h after feeding of SO diet was decreased compared to CO. The milk composition yield did not differ among treatments, although the percentages of fat and protein were decreased by SO and FA diets. The proportions of C8-C16 fatty acids in milk fat decreased, and those of C18 increased by SO and FA diets. The proportion of cis-9, trans-11 conjugated linoleic acid in milk fat by SO and FA diets increased by 120% and 135%, respectively. In spite of the slight suppression of rumen fermentation by SO diet, negative effects on feed intake and milk production were not detected.

Simple and highly sensitive assay system for TNFR2-mediated soluble- and transmembrane-TNF activity.

Drugs that target tumor necrosis factor-alpha (TNF) are particularly important in the treatment of severe inflammatory progression in rheumatoid arthritis, Crohn's disease and psoriasis. Despite the central role of the TNF/TNF receptor (TNFR) in various disease states, there is a paucity of information concerning TNFR2 signaling. In this study, we have developed a simple and highly sensitive cell-death based assay system for analyzing TNFR2-mediated bioactivity that can be used to screen for TNFR2-selective drugs. Using a lentiviral vector, a chimeric receptor was engineered from the extracellular and transmembrane domain of human TNFR2 and the intracellular domain of mouse Fas and the recombinant protein was then expressed in TNFR1(-/-)R2(-/-) mouse preadipocytes. Our results demonstrate that this chimeric receptor is capable of inducing apoptosis by transmembrane- as well as soluble-TNF stimuli. Moreover, we found that our bioassay based on cell death phenotype had an approximately 80-fold higher sensitivity over existing bioassays. We believe our assay system will be an invaluable research tool for studying TNFR2 and for screening TNFR2-targeted drugs.

Optimization of protein therapies by polymer-conjugation as an effective DDS.

Due to recent advances in disease proteomics, many disease-related proteins have been found. It is expected that there will be therapeutically useful proteins among them. However, it is clinically difficult to use most proteins as effective and safe drugs because of their very low stability and pleiotropic actions in vivo. To promote disease proteomic based drug development for protein therapies, we have attempted to develop an optimal polymer-conjugation system for improving the therapeutic potency of proteins. In this review, we introduce this innovative protein-drug system.

The targeting of anionized polyvinylpyrrolidone to the renal system.

We reported that the co-polymer composed of vinylpyrrolidone and maleic acid selectively distributed into the kidneys after i.v. injection. To further optimize the renal drug delivery system, we assessed the renal targeting capability of anionized polyvinylpyrrolidone (PVP) derivatives after intravenous administration in mice. The elimination of anionized PVP derivatives from the blood decreased with increasing anionic groups, and the clearance of carboxylated PVP and sulfonated PVP from the blood was almost similar. But carboxylated PVP efficiently accumulated in the kidney, whereas sulfonated PVP was rapidly excreted in the urine. The renal levels of carboxylated PVP were about five-fold higher than sulfonated PVP. Additionally, carboxylated PVP was effectively taken up by the renal proximal tubular epithelial cells in vivo after i.v. injection. These anionized PVP derivatives did not show any cytotoxicity against renal tubular cells and endothelial cells in vitro. Thus, these carboxylated and sulfonated PVPs may be useful polymeric carriers for drug delivery to the kidney and bladder, respectively.