The long-term effects after hematopoietic stem cell transplant on leg muscle strength,physical inactivity and fatigue

PurposeThe purpose of this study was to analyze the effects of leg muscle strength and fatigue on step-count as a measure of physical activity for people staying at home after hematopoietic stem cell transplantation (HSCT).MethodNineteen persons receiving HSCT were assessed from hospitalization until about 2 months after discharge. Mean daily step-count was taken as a measure of physical activity. Leg muscle strength was measured in three ways (knee extension, ankle plantar flexion, and ankle dorsiflexion strength) at two points in time (time of hospital discharge and after 2 months). Fatigue and anxiety were assessed using the Japanese Cancer Fatigue Scale and State-Trait Anxiety Inventory. Correlations between the above and factors affecting physical activity were also investigated by multiple regression analysis.ResultsClinical follow-up measurements in subjects were made an average of 81.0 days after discharge. Subjects with higher mean step-count during hospitalization (β = 0.647, p = 0.000) and greater ankle plantar flexion strength/kg (β = 0.361, p = 0.021) reported higher mean step-count at home (adjusted R² = 0.701, p = 0.021). Subjects with body mass index <22.0 kg/m² also showed higher step-counts at home compared to other subjects. Mean fatigue score at home was 16.8 (SD = 8.75), a level not associated with clinical problems, and the proportion of physical fatigue was significantly lower than during hospitalization.ConclusionMean step-count at home was most strongly affected by ankle plantar flexion strength/kg, and increasing ankle plantar flexion strength/kg was shown to promote recovery of normal physical activities.     

Evaluation of in vivo genotoxicity induced by N‐ethyl‐N‐nitrosourea,benzo[a]pyrene,and 4‐nitroquinoline‐1‐oxide in the Pig‐a and gpt assays

The recently developed Pig‐a mutation assay is based on flow cytometric enumeration of glycosylphosphatidylinositol (GPI) anchor‐deficient red blood cells caused by a forward mutation in the Pig‐a gene. Because the assay can be conducted in nontransgenic animals and the mutations accumulate with repeat dosing, we believe that the Pig‐a assay could be integrated into repeat‐dose toxicology studies and provides an alternative to transgenic rodent (TGR) mutation assays. The capacity and characteristics of the Pig‐a assay relative to TGR mutation assays, however, are unclear. Here, using transgenic gpt delta mice, we compared the in vivo genotoxicity of single oral doses of N‐ethyl‐N‐nitrosourea (ENU, 40 mg/kg), benzo[a]pyrene (BP, 100 and 200 mg/kg), and 4‐nitroquinoline‐1‐oxide (4NQO, 50 mg/kg) in the Pig‐a (peripheral blood) and gpt (bone marrow and liver) gene mutation assays. Pig‐a assays were conducted at 2, 4, and 7 weeks after the treatment, while gpt assays were conducted on tissues collected at the 7‐week terminal sacrifice. ENU increased both Pig‐a and gpt mutant frequencies (MFs) at all sampling times, and BP increased MFs in both assays but the Pig‐a MFs peaked at 2 weeks and then decreased. Although 4NQO increased gpt MFs in the liver, only weak, nonsignificant increases (two‐ or threefold above control) were detected in the bone marrow in both the Pig‐a and the gpt assay. These findings suggest that further studies are needed to elucidate the kinetics of the Pig‐a mutation assay in order to use it as an alternative to the TGR mutation assay. Environ. Mol. Mutagen. 54:747–754, 2013. © 2013 Wiley Periodicals, Inc.     

Spirotoamides A and B, novel 6,6-spiroacetal polyketides isolated from a microbial metabolite fraction library

Two new 6,6-spiroacetal polyketides, spirotoamides A (1) and B (2), were isolated from a microbial metabolite fraction library of Streptomyces griseochromogenes JC82-1223 by screening of structurally unique compounds based on a search of spectral database. The fraction library was constructed using a systematic separation method to efficiently discover new metabolites from microbial sources such as actinomycetes and fungi. The structures of 1 and 2 were elucidated by 2D-NMR and mass spectrometric measurements. They belong to a class of polyketides, and contain a 6,6-spiroacetal core structure and a carboxamide group. The biosynthetic pathway of 1 and 2 is discussed in the text.     

Characterization of Aggregated Antibody-Silicone Oil Complexes: From Perspectives of Morphology, 3D Image,and Fcγ Receptor Activation

Pre-filled syringes (PFS) have been in widespread use as an administration device for therapeutic antibodies in recent decades. Generally, the inner barrel and syringe of PFS are coated with silicone oil (SO) for lubrication. Multiple studies have focused on the fact that the SO adsorbs denatured antibody molecules, and induces antibody aggregation. Aggregated antibodies are recognized as a potential risk for evoking immunogenic responses in patients. The characteristics of the aggregated antibody-SO complexes, including their concentration, population, shape, three-dimensional (3D) image, and Fcγ Receptors (FcγRs) activation have been obscurely acknowledged so far. In the present work, we prepared aggregated antibody-SO complexes by agitation and analyzed using multifaceted techniques such as flow imaging, confocal fluorescence microscopy, and cell-based assays for FcγRs activation. The results emphasized that the SO accelerates the increase in sub-visible particles and antibody aggregation. The confocal fluorescence microscopy analysis revealed the high-resolution 3D images of aggregated antibody-SO complexes. The FcγRs reporter cell assay clarified that the pre-mixed and agitated Ab + SO have higher FcγRs activation capability compared to the agitated Ab. Overall, this study advances the view that SO has an effect to increase the risk of agitation-induced aggregated antibody particles.