Does time of CCI measurement affect the evaluation of platelet transfusion effectiveness?

The measurement of corrected count increment at 1-h post-transfusion (CCI-1 h) of platelet concentrate (PC) transfusion is recommended, but in the revised Japanese Guideline (2017) it was changed to “after 10-min to 1-h”, following the revision of the guidelines from Western countries. Here, we aimed to investigate on the feasibility to apply the CCI measured at 10-min or 30-min post-transfusion as the surrogate of CCI-1 h. Peripheral blood was collected at 10-min, 30-min and 1-h post-transfusion of PC and the effectiveness of the transfusion was analyzed based on the CCI. In the period from December 2017 to February 2020, 8 patients, who received multiple PC transfusion (total 208) at our institution, were analyzed. We performed the univariate analyses to examine the relationship between CCI value and the categorical variables, p-value <0.1 was obtained for gender (p = 2.91 × 10^?19), fever after transfusion (p = 0.0163). The qualitative variables, namely measurement time (p = 0.0553), also showed p-value <0.1. Using these factors as covariates in the mixed effect model, we found that the measurement time (p = 0.0007) had a significant effect on the CCI value when looking at fixed effects. Although there is a tendency for decreased CCI values with time progression, the slope of the change in the mixed model was -0.00307, indicating that the CCI difference among the 3 measurements was small. Here we provide evidence that CCI measured at 10-min and 30-min post-transfusion give results comparable to those measured at 1-h post-transfusion, under the Japanese practice of platelet transfusion, which relies on 100 % single-donor apheresis PC, and ABO-identical whenever possible.     

Critical role of monocyte chemoattractant protein-1 receptor CCR2 on monocytes in hypertension-induced vascular inflammation and remodeling

Activated monocytes are present in the arterial walls of hypertensive patients and animals. Monocyte chemoattractant protein-1 (MCP-1), which controls monocyte function through its receptor (CCR2), is implicated in hypertensive inflammatory changes in the arterial wall. The role of CCR2 expression on monocytes in hypertension-induced vascular remodeling, however, has not been addressed. We hypothesized that CCR2 on monocytes is critical in hypertension-induced vascular inflammation and remodeling. Hypertension was induced by infusion of angiotensin II (Ang II) into wild-type mice, CCR2-deficient (CCR2-/-) mice, and bone marrow-transferred mice with a leukocyte-selective CCR2 deficiency (BMT-CCR2-/-). In wild-type mice, Ang II increased CCR2 intensity in circulating monocytes, which was prevented by an Ang II type-1 (AT1) receptor blocker or blunted in AT1 receptor-deficient mice. Enhanced CCR2 intensity on monocytes was observed in hypertensive patients and rats, and was reduced by treatment with the Ang II receptor blocker, supporting the clinical relevance of the observation in mice. In CCR2-/- and BMT-CCR2-/- mice, Ang II-induced vascular inflammation and vascular remodeling (aortic wall thickening and fibrosis) were blunted as compared with control mice. In contrast, Ang II-induced left ventricular hypertrophy developed in CCR2-/- and BMT-CCR2-/- mice. The present study suggests that CCR2 expression in monocytes has a critical role in vascular inflammation and remodeling in Ang II-induced hypertension, and possibly in other forms of hypertension.     

A case of tooth autotransplantation after long-term cryopreservation using a programmed freezer with a magnetic field

This case report describes the treatment of a skeletal Class III malocclusion with autotransplantation of a cryopreserved tooth. To gain an esthetic facial profile and good occlusion, extraction of bimaxillary premolars and surgical therapy were chosen. The patient had chronic apical periodontitis on the lower left first molar. Although she did not feel any pain in that region, the tooth was considered to have a poor prognosis. Therefore, we cryopreserved the extracted premolars to prepare for autotransplantation in the lower first molar area because the tooth would probably need to be removed in the future. The teeth were frozen by a programmed freezer with a magnetic field (CAS freezer) that was developed for tissue cryopreservation and were cryopreserved in −150°C deep freezer. After 1.5 years of presurgical orthodontic treatment, bilateral sagittal split ramus osteotomy was performed for mandible setback. Improvement of the facial profile and the occlusion were achieved in the retention phase. Six years after the initial visit, the patient had pain on the lower left first molar, and discharge of pus was observed, so we extracted the lower left first molar and autotransplanted the cryopreserved premolar. Three years later, healthy periodontium was observed at the autotransplanted tooth. This case report suggests that long-term cryopreservation of teeth by a CAS freezer is useful for later autotransplantation, and this can be a viable technique to replace missing teeth.     

The RNA-binding protein xCIRP2 is involved in apoptotic tail regression during metamorphosis in Xenopus laevis tadpoles

Frog metamorphosis induced by thyroid hormone (TH) involves not only cell proliferation and differentiation in reconstituted organs such as limbs, but also apoptotic cell death in degenerated organs such as tails. However, the molecular mechanisms directing the TH-dependent cell fate determination remain unclear. We have previously identified from newts an RNA-binding protein (nRBP) acting as the regulator governing survival and death in germ cells during spermatogenesis. To investigate the molecular events leading the tail resorption during metamorphosis, we analyzed the expression, the functional role in apoptosis, and the regulation of xCIRP2, a frog homolog of nRBP, in tails of Xenopus laevis tadpoles. At the prometamorphic stage, xCIRP2 protein is expressed in fibroblast, epidermal, nerve, and muscular cells and localized in their cytoplasm. When spontaneous metamorphosis progressed, the level of xCIRP2 mRNA remained unchanged but the amount of the protein decreased. In organ cultures of tails at the prometamorphic stage, xCIRP2 protein decreased before their lengths shortened during TH-dependent metamorphosis. The inhibition of calpain or proteasome attenuated the TH-induced decrease of xCIRP2 protein in tails, impairing their regression. These results suggest that xCIRP2 protein is downregulated through calpain- and proteasome-mediated proteolysis in response to TH at the onset of metamorphosis, inducing apoptosis in tails and thereby degenerating them.     

Effects of vascular endothelial growth factor-C and -D on osteoclast differentiation and function in human peripheral blood mononuclear cells

ObjectiveThe purpose of this study was to clarify the interaction of vascular endothelial growth factors (VEGFs)-C and -D with cell surface foetal liver kinase-1 (Flk-1) and fms-like tyrosine kinase-4 (Flt-4) receptors in the induction and activity of osteoclasts in cultured human peripheral blood mononuclear cells (PBMCs).DesignPBMCs were cultured on chamber slides or on ivory discs for 2 or 3 weeks in the presence of macrophage-colony stimulating factor (M-CSF), VEGF-A, -C or -D, or placental growth factor (PlGF) with or without receptor activator of nuclear factor kappa-B ligand (RANKL). The number of osteoclasts in each group was counted and the area of ivory resorption was measured. In addition, osteoclast differentiation was further analysed under the same conditions, but with the addition of specific neutralizing antibodies against Flk-1 and Flt-4.ResultsRANKL was essential for the induction of osteoclasts in PBMCs. However, significant differences were found in the number of osteoclasts induced by VEGF-A, -C, -D or M-CSF with RANKL compared with control groups lacking or containing RANKL. Blocking of either Flk-1 or Flt-4 resulted in a reduction in the enhancement of osteoclast differentiation in PBMCs by VEGF-C or -D with RANKL. The osteoclasts induced by VEGF-A, -C, -D or M-CSF with RANKL formed significantly larger resorption lacunae than those formed by osteoclasts induced by RANKL alone.ConclusionsThis study showed that VEGF-C and -D play a role in the induction of osteoclast differentiation through both Flk-1 and Flt-4 receptors and influence the area of the ivory resorption in PBMCs.     

Elucidation of the electron energy structure of TiO2(B) and anatase photocatalysts through analysis of electron trap density

A clear understanding of the electron energy structure of TiO₂(B)/anatase is needed to study the related catalytic reactions and design new composite photocatalysts. In this study, the electron energy structures of TiO₂(B) and anatase were estimated by analyzing the energy-resolved distribution of electron traps measured by reversed double-beam photoacoustic spectroscopy. In the mixture of TiO₂(B) and anatase, interfacial charge-transfer excitation from anatase to electron traps of TiO₂(B) was suggested. By analyzing this for TiO₂(B), the electron level with a relatively high density of states was found to be located ∼0.07 eV deeper than that for anatase. Furthermore, a similar electron energy structure was suggested for a composite photocatalyst having a mixed phase of TiO₂(B) and anatase.

The electron energy structures of TiO₂(B) and anatase were estimated by analyzing the energy-resolved distribution of electron traps.