Effects of Inositol 1,4,5-triphosphate on Osteoclast Differentiation in RANKL-induced Osteoclastogenesis

The receptor activator of NF-κB ligand (RANKL) signal is an activator of tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the activation of NF-κB and other signal transduction pathways essential for osteoclastogenesis, such as Ca(2+) signaling. However, the intracellular levels of inositol 1,4,5-trisphosphate (IP(3)) and IP(3)-mediated cellular function of RANKL during osteoclastogenesis are not known. In the present study, we determined the levels of IP(3) and evaluated IP(3)-mediated osteoclast differentiation and osteoclast activity by RANKL treatment of mouse leukemic macrophage cells (RAW 264.7) and mouse bone marrow-derived monocyte/macrophage precursor cells (BMMs). During osteoclastogenesis, the expression levels of Ca(2+) signaling proteins such as IP(3) receptors (IP(3)Rs), plasma membrane Ca(2+) ATPase, and sarco/endoplasmic reticulum Ca(2+) ATPase type2 did not change by RANKL treatment for up to 6 days in both cell types. At 24 h after RANKL treatment, a higher steady-state level of IP(3) was observed in RAW264.7 cells transfected with green fluorescent protein (GFP)-tagged pleckstrin homology (PH) domains of phospholipase C (PLC) δ, a probe specifically detecting intracellular IP(3) levels. In BMMs, the inhibition of PLC with U73122 [a specific inhibitor of phospholipase C (PLC)] and of IP(3)Rs with 2-aminoethoxydiphenyl borate (2APB; a non-specific inhibitor of IP(3)Rs) inhibited the generation of RANKL-induced multinucleated cells and decreased the bone-resorption rate in dentin slice, respectively. These results suggest that intracellular IP(3) levels and the IP(3)-mediated signaling pathway play an important role in RANKL-induced osteoclastogenesis.     

Severity assessment tools to guide ICU admission in community-acquired pneumonia: systematic review and meta-analysis

Background  

The aim of this meta-analysis was to determine if severity assessment tools can be used to guide decisions regarding intensive care unit (ICU) admission of patients with community-acquired pneumonia.     

Sustained seroconversion of chronic hepatitis B infection after stem cell transplantation

Serap A, Funda O, Bengu K, Mehmet K, Nazan C, Rasit Y, Savas K. Sustained seroconversion of chronic hepatitis B infection after stem cell transplantation.
Pediatr Transplantation 2011: 15: E92–E95. © 2010 John Wiley & Sons A/S. Abstract: We present an 18‐yr‐old adolescent with acute lymphocytic leukemia, who underwent peripheral blood SCT with serologically and histologically documented chronic hepatitis B infection. Prior and during the transplant process, lamivudine was administered orally and he underwent SCT with a twofold decrease in viral load at the time of transplant from his HLA full matched, HBV natural immune (anti‐HBs and anti‐HBc positive) donor. Successful engraftment was achieved and three months after SCT, HBV seroconversion was documented accompanied with an ALT flare. Chronic graft‐versus‐host disease coincided after the transplantation, and he has been on immunosuppressive treatment for 25 months with sustained HBV seroconversion. We assume that adoptive immunity transfer combined with antiviral treatment might also constitute sustained seroconversion in chronic HBV, besides the reported risk of reactivation.     

Dual-energy computed tomography (DECT) in emergency radiology: basic principles,techniques, and limitations

Recent advances in computed tomography (CT) technology allow for acquisition of two CT datasets with different X-ray spectra. There are different dual-energy computed tomography (DECT) technical approaches such as: the dual-source CT, the fast kilovoltage-switching method, and the sandwich detectors technique. There are various postprocessing algorithms that are available to provide clinically relevant spectral information. There are several clinical applications of DECT that are easily accessible in the emergency setting. In this review article, we aim to provide the emergency radiologist with a discussion on how this new technology works and how some of its applications can be useful in the emergency room setting.