Compositional dependence of the apatite formation ability of Ti–Zr alloys designed for hard tissue reconstruction

Ti–Zr alloys are expected to be novel biomaterials with low stress shielding owing to their lower Young’s moduli than pure Ti. The drawback of metallic biomaterials is that their bone-bonding abilities are relatively low. NaOH and heat treatments have been performed to provide Ti–50Zr with apatite-forming ability in the body environment, which is essential for bone bonding. However, the systematic compositional dependence of apatite formation has not been revealed. In the present study, NaOH treatment of Ti–Zr alloys with various compositions and bone-bonding abilities was assessed in vitro by apatite formation in simulated body fluid (SBF). The corrosion current density in NaOH aqueous solution and the amount of Na incorporated into the surface tended to decrease with increasing Zr content. The apatite-forming ability of the treated alloy significantly decreased when the Zr content was ≥60 atom%. This phenomenon is attributed to the (1) low OH content on the surface, (2) low Na incorporation into the treated alloy surface, which enhances apatite formation, and (3) low ability of P adsorption to the Ti–Zr alloy in SBF following Ca adsorption to trigger apatite nucleation. Although the adhesion of the titanate/zirconate layer formed on the surfaces to the substrates increased as Zr content increased, the adhesion between the apatite and the substrate was still low

Inner membrane YfgM–PpiD heterodimer acts as a functional unit that associates with the SecY/E/G translocon and promotes protein translocation

PpiD and YfgM are inner membrane proteins that are both composed of an N-terminal transmembrane segment and a C-terminal periplasmic domain. Escherichia coli YfgM and PpiD form a stable complex that interacts with the SecY/E/G (Sec) translocon, a channel that allows protein translocation across the cytoplasmic membrane. Although PpiD is known to function in protein translocation, the functional significance of PpiD-YfgM complex formation as well as the molecular mechanisms of PpiD-YfgM and PpiD/YfgM- Sec translocon interactions remain unclear. Here, we conducted genetic and biochemical studies using yfgM and ppiD mutants and demonstrated that a lack of YfgM caused partial PpiD degradation at its C-terminal region and hindered the membrane translocation of VemP, a Vibrio secretory protein in both Escherichia coli and Vibrio alginolyticus. While ppiD disruption also impaired VemP translocation, we found that the yfgM and ppiD double deletion exhibited no additive or synergistic effects. Together, these results strongly suggest that both PpiD and YfgM are required for efficient VemP translocation. Furthermore, our site-directed in vivo photo-crosslinking analysis revealed that the tetratricopeptide repeat domain of YfgM and a conserved structural domain (NC domain) in PpiD interact with each other and that YfgM, like PpiD, directly interacts with the SecG translocon subunit. Crosslinking analysis also suggested that PpiD/YfgM complex formation is required for these proteins to interact with SecG. In summary, we propose that PpiD and YfgM form a functional unit that stimulates protein translocation by facilitating proper interactions with the Sec translocon

Thin observation module by bound optics (TOMBO) : concept and experimental verification

This paper was published in Optics Express and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://dx.doi.org/10.1364/AO.40.001806 Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law

Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization

Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization.BackgroundAnaphylatoxin C5a mediates inflammatory responses through interaction with a specific C5a receptor (C5aR), the expression of which is thought to be restricted to peripheral blood leukocytes. Although the presence of C5aR on cultured mesangial cells and tubular epithelial cells has recently been documented, the tissue distribution of C5aR in diseased kidney has not yet been determined.MethodsImmunohistochemistry and nonradioactive in situ hybridization for C5aR were performed in 34 tissue samples of kidneys from patients with various renal diseases, including 4 with minimal change nephrotic syndrome (MCNS), 5 with membranous nephropathy (MN), and 25 with mesangial proliferative glomerulonephritis (mesGN; 15 patients with IgA nephropathy, 5 with non-IgA mesGN, and 5 with lupus nephritis). Normal portions of surgically resected kidney served as the control.ResultsIn normal kidneys, C5aR protein was detected in tubular epithelial cells, while C5aR mRNA was detected in a few glomerular cells, tubular epithelial cells, and vascular endothelial and smooth muscle cells. In MCNS, the distribution of C5aR protein and mRNA was similar to that in normal kidneys. In MN and mesGN, C5aR protein and mRNA were detected in mesangial cells, glomerular epithelial and endothelial cells, Bowman's capsule cells, tubular cells, infiltrating cells, and vascular endothelial and smooth muscle cells. The glomerular expression of C5aR mRNA and protein correlated positively with the degree of mesangial hypercellularity and mesangial matrix expansion in mesGN. In the tubulointerstitium, interstitial expression of C5aR mRNA correlated positively with the degree of tubular atrophy and interstitial broadening in mesGN. Furthermore, the interstitial expression of C5aR mRNA correlated positively with the level of serum creatinine.ConclusionsOur results indicate that renal cells produce C5aR and that activation of C5a/C5aR pathway on renal cells may be involved in tissue injury in mesGN

Involvement of Leptin in the Progression of Experimentally Induced Peritoneal Fibrosis in Mice

013LeptinThe isJapana hormoneSociety mainlyof Histochemistryproduced byandwhite adipose cells, and regulates body fat and food intake by acting on hypothalamus. Leptin receptor is expressed not only in the hypothalamus but in a variety of peripheral tissues, suggesting that leptin has pleiotropic functions. In this study, we investigated the effect of leptin on the progression of peritoneal fibrosis induced by intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 2 or 3 weeks in mice. This study was conducted in male C57BL/6 mice and leptin-deficient ob/ob mice. Peritoneal fluid, blood, and peritoneal tissues were collected 15 or 22 days after CG injection. CG injection increased the level of leptin in serum and peritoneal fluid with thickening of submesothelial compact zone in wild type mice, but CG-injected ob/ob mice attenuate peritoneal fibrosis, and markedly reduced the number of myofibroblasts, infiltrating macrophages, and blood vessels in the thickened submesothelial area. The 2-week leptin administration induced a more thickened peritoneum in the CG-injected C57BL/6 mice than in the PBS group. Our results indicate that an upregulation of leptin appears to play a role in fibrosis and inflammation during peritoneal injury, and reducing leptin may be a therapeutically potential for peritoneal fibrosis

Association between potassium supplementation and the occurrence of acute kidney injury in patients with hypokalemia administered liposomal amphotericin B: a nationwide observational study

Background: Hypokalemia and acute kidney injury (AKI) occur in patients administered liposomal amphotericin B (L-AMB), a wide-spectrum anti-fungicidal drug. However, the association between potassium supplementation and the occurrence of AKI in patients with hypokalemia who were administered L-AMB is not well understood.Methods: Using nationwide claims data and laboratory data, the occurrence of AKI during L-AMB treatment was retrospectively compared between patients with hypokalemia who were or were not supplemented with potassium and between those adequately or inadequately supplemented with potassium (serum potassium levels corrected to ≥3.5 mEq/L or remained < 3.5 mEq/L, respectively) before or after L-AMB treatment initiation.Results: We identified 118 patients who developed hypokalemia before L-AMB treatment initiation (43 received potassium supplementation [25 adequate and 18 inadequate supplementation] and 75 did not receive potassium supplementation), and 117 patients who developed hypokalemia after L-AMB initiation (79 received potassium supplementation [including 23 adequate and 15 inadequate supplementation] and 38 did not receive potassium supplementation). The occurrence of any stage of AKI was similar between patients with hypokalemia, regardless of potassium supplementation (i.e., before L-AMB treatment initiation [supplementation, 51%; non-supplementation, 45%; P = 0.570] or after L-AMB initiation [supplementation, 28%; non-supplementation, 32%; P = 0.671]). After adjusting for confounding factors, we found that the occurrence of any stage of AKI was not associated with potassium supplementation before L-AMB initiation (odds ratio [OR]: 1.291, 95% confidence interval [CI]: 0.584–2.852, P = 0.528) or after L-AMB initiation (OR: 0.954, 95% CI: 0.400–2.275, P = 0.915). The occurrence of any stage of AKI tended to decline in patients with hypokalemia who were adequately supplemented with potassium (44%) before, but not after, L-AMB initiation relative to that in patients inadequately supplemented with potassium (61%), however this result was not significant (P = 0.358).Conclusion: Potassium supplementation was not associated with any stage of AKI in patients with hypokalemia who were administered L-AMB

Efficacy of early administration of liposomal amphotericin B in patients with septic shock: A nationwide observational study

Introduction: Liposomal amphotericin B (L-AMB), a broad spectrum anti-fungicidal drug, is often administered to treat invasive fungal infections (IFIs). However, the most suitable time to initiate treatment in septic shock patients with IFI is unknown.Methods: Patients with septic shock treated with L-AMB were identified from the Japanese Diagnosis Procedure Combination national database and were stratified according to L-AMB treatment initiation either at septic shock onset (early L-AMB group) or after the onset (delayed L-AMB group) to determine their survival rates following septic shock onset and the shock cessation period.Results: We identified 141 patients administered L-AMB on the day of or after septic shock onset: 60 patients received early treatment, whereas 81 patients received delayed treatment. Survival rates after septic shock onset were higher in the early L-AMB group than in the delayed L-AMB group (4 weeks: 68.4% vs 57.9%, P = 0.197; 6 weeks: 62.2% vs 44.5%, P = 0.061; 12 weeks: 43.4% vs 35.0%, P = 0.168, respectively). The septic shock cessation period was shorter in the early L-AMB group than in the delayed L-AMB group (7.0 ± 7.0 days vs 16.5 ± 15.4 days, P < 0.001), with a significant difference confirmed after adjusting for confounding factors with propensity score matching (7.1 ± 7.2 days vs 16.7 ± 14.0 days, P = 0.001).Conclusion: Early L-AMB administration at septic shock onset may be associated with early shock cessation

The First Very Long Baseline Interferometry Image of 44 GHz Methanol Maser with the KVN and VERA Array (KaVA)

We have carried out the first very long baseline interferometry (VLBI) imaging of 44 GHz class I methanol maser (7_{0}-6_{1}A^{+}) associated with a millimeter core MM2 in a massive star-forming region IRAS 18151-1208 with KaVA (KVN and VERA Array), which is a newly combined array of KVN (Korean VLBI Network) and VERA (VLBI Exploration of Radio Astrometry). We have succeeded in imaging compact maser features with a synthesized beam size of 2.7 milliarcseconds x 1.5 milliarcseconds (mas). These features are detected at a limited number of baselines within the length of shorter than approximately 650 km corresponding to 100 Mlambda in the uv-coverage. The central velocity and the velocity width of the 44 GHz methanol maser are consistent with those of the quiescent gas rather than the outflow traced by the SiO thermal line. The minimum component size among the maser features is ~ 5 mas x 2 mas, which corresponds to the linear size of ~ 15 AU x 6 AU assuming a distance of 3 kpc. The brightness temperatures of these features range from ~ 3.5 x 10^{8} to 1.0 x 10^{10} K, which are higher than estimated lower limit from a previous Very Large Array observation with the highest spatial resolution of ~ 50 mas. The 44 GHz class I methanol maser in IRAS 18151-1208 is found to be associated with the MM2 core, which is thought to be less evolved than another millimeter core MM1 associated with the 6.7 GHz class II methanol maser.Comment: 19 pages, 3 figure

Evaluation of Candida peritonitis with underlying peritoneal fibrosis and efficacy of micafungin in murine models of intra-abdominal candidiasis

Candida peritonitis is a crucial disease, however the optimal antifungal therapy regimen has not been clearly defined. Peritoneal fibrosis (PF)can be caused by abdominal surgery, intra-abdominal infection, and malignant diseases, and is also widely recognized as a crucial complication of long-term peritoneal dialysis. However, the influence of PF on Candida peritonitis prognosis remains unknown. Here, we evaluated the severity of Candida peritonitis within the context of PF and the efficacy of micafungin using mice. A PF mouse model was generated by intraperitoneally administering chlorhexidine gluconate. Candida peritonitis, induced by intraperitoneal inoculation of Candida albicans, was treated with a 7-day consecutive subcutaneous administration of micafungin. Candida infection caused a higher mortality rate in the PF mice compared with the control mice on day 7. Proliferative Candida invasion into the peritoneum and intra-abdominal organs was confirmed pathologically only in the PF mice. However, all mice in both groups treated with micafungin survived until day 20. Micafungin treatment tends to suppress inflammatory cytokines in the plasma 12 h after infection in both groups. Our results suggest that PF enhances early mortality in Candida peritonitis. Prompt initiation and sufficient doses of micafungin had good efficacy for Candida peritonitis, irrespective of the underlying PF