Effect of rhBMP-2 applied with a 3D-printed titanium implant on new bone formation in rabbit calvarium

Objective: This study sought to compare the biocompatibility of a three-dimensional (3D)-printed titanium implant with a conventional machined titanium product, as well as the effect of such implant applied with recombinant human Bone Morphogenetic Protein Type 2 (rhBMP-2) for guided bone regeneration. Methodology: Disk-shaped titanium specimens fabricated either by the conventional machining technique or by the 3D-printing technique were compared by MC3T3-E1 cells cytotoxicity assay. New bone formation was evaluated using a rapid prototype titanium cap applied to the calvaria of 10 rabbits, which were divided into two groups: one including an atelopeptide collagen plug on one side of the cap (group I) and the other including a plug with rhBMP-2 on the other side (group II). At six and 12 weeks after euthanasia, rabbits calvaria underwent morphometric analysis through radiological and histological examination. Results: Through the cytotoxicity assay, we identified a significantly higher number of MC3T3-E1 cells in the 3D-printed specimen when compared to the machined specimen after 48 hours of culture. Moreover, morphometric analysis indicated significantly greater bone formation at week 12 on the side where rhBMP-2 was applied when evaluating the upper portion immediately below the ca p. Conclusion: The results suggest that 3D-printed titanium implant applied with rhBMP-2 enables new bone formation

Nature-derived epigallocatechin gallate/duck’s feet collagen/hydroxyapatite composite sponges for enhanced bone tissue regeneration

Scaffolds mimicking structural and chemical characteristics of the native bone tissues are critical for bone tissue engineering. Herein, we have developed and characterized epigallocatechin gallate/duck's feet collagen/hydroxyapatite (EGCG/DC/HAp) composite sponges that enhanced the bone tissue regeneration. The three-dimensional composite sponges were synthesized by loading various amounts (i.e. 1, 5 and 10 μM) of EGCG to duck feet derived collagen followed by freeze-drying and then coating with hydroxyapatite. Several measuremental techniques were employed to examine the properties of the as-fabricated composite sponges including morphology and structure, porosity, compressive strength, etc. and as well compared with pristine duck feet derived collagen. SEM observations of EGCG/DC/HAp sponges showed the formation of a highly porous collagen matrix with EGCG embodiment. The porosity and pore size of sponges were found to increase by high EGCG content. The compressive strength was calculated as 3.54 ± 0.04, 3.63 ± 0.03, 3.89 ± 0.05, 4.047 ± 0.05 MPa for 1, 5 and 10 μM EGCG/DC/HAp sponges, respectively. Osteoblast-like cell (BMSCs isolated from rabbit) culture and in vivo experiments with EGCG/DC/HAp sponges implanted in nude mouse followed by histological staining showed enhanced cell internalization and attachment, cell proliferation, alkaline phosphatase expressions, indicating that EGCG/DC/HAp sponges have ahigh biocompatibility. Moreover, highEGCG content in the EGCG/DC/HAp sponges have led to increased cellular behavior. Collectively, the 5 μM of EGCG/DC/HAp sponges were suggested as the potential candidates for bone tissue regeneration.This research was supported by Technology Commercialization Support Program [grant number 814005-03-3-HD020], MIFAFF; and Basic Science Research Program [grant number NRF2017R1A2B3010270] through the National Research Foundation of Korea, Ministry of Science, ICT and Future Planning, Republic of Korea.info:eu-repo/semantics/publishedVersio

Does Diabetes Mellitus Influence Standardized Uptake Values of Fluorodeoxyglucose Positron Emission Tomography in Colorectal Cancer?

Background/AimsHyperglycemia is associated with decreased 2-18[F]fluoro-2-deoxy-D-glucose (FDG) uptake by tumors assessed by positron emission tomography (PET). In this retrospective study we investigated a comparison of standardized uptake values (SUVs) in patients with primary colorectal cancers who either had diabetes mellitus (DM) or were otherwise healthy.MethodsThe medical records of 397 patients who were diagnosed with colorectal cancer and underwent PET-CT between January 2006 and December 2012 were analyzed. Eighty patients with DM and 317 patients without DM were included. Clinical characteristics were reviewed and maximal standardized uptake values (SUVmax) were calculated in the primary colorectal lesions.ResultsThere was no significant difference between tumor SUVmax in DM patients (10.60±5.78) and those without DM (10.92±5.44). In addition, no significant difference was detected between tumor SUVmax in DM patients with glycated hemoglobin (HbA1c) levels <8% (10.34±5.17) and those with HbA1c levels ≥8% (10.61±7.27). The maximum size of the primary colorectal tumor was associated with SUVmax in a linear regression analysis.ConclusionThe results of this study showed that DM did not influence FDG uptake values in colorectal cancer patients regardless of glucose levels

Polymorphisms in Genes That Regulate Cyclosporine Metabolism Affect Cyclosporine Blood Levels and Clinical Outcomes in Patients Who Receive Allogeneic Hematopoietic Stem Cell Transplantation

In patients who received allogeneic hematopoietic stem cell transplantation (HSCT), we investigated the correlations between single nucleotide polymorphisms (SNPs) in genes that regulate cyclosporine metabolism and clinical outcomes. All patients received sibling-matched HSCT. DNA samples of patients and donors were analyzed for 4 SNPs: MDR1 +1236C>T (rs1128503), +2677G>T>A (rs2032582), +3435C>T (rs1045642), and CYP3A5 +6986G>A (rs776746). A total of 156 patients (median age 40 years) were analyzed. Nineteen patients received HSCT for nonmalignant disease. The CYP3A5 +6986AA genotype was associated with a high cyclosporine blood level after transplantation. However, this genotype was not related to any particular clinical outcome. In contrast, the MDR1 +1236C>T SNP was correlated with specific clinical outcomes. When neither the donor nor the recipient had the CC genotype of MDR1 +1236, patients had lower creatinine levels (P < .001) and less transplantation-related mortality (TRM) (P = .012). These patients also showed longer overall survival (OS) in both univariate (P = .003) and multivariate (P = .003) analyses. Although the CYP3A5 +6986AA genotype was correlated with a high blood cyclosporine concentration, lack of the MDR1 +1236CC genotype in both the donor and recipient was correlated with less TRM and a longer OS in patients who received allogeneic HSCT

Central Pontine Myelinolysis in a Patient with Acute Lymphoblastic Leukemia after Hematopoietic Stem Cell Transplantation: A Case Report

We describe a 37-yr-old man who developed central pontine myelinolysis (CPM) after allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After HSCT, desquamation developed on the whole body accompanied by hyperbilirubinemia. The liver biopsy of the patient indicated graft-versus-host disease-related liver disease, and the dose of methylprednisolone was increased. Then, the patient developed altered mentality with eye ball deviation to the left, for which electroencephalogram and magnetic resonance imaging (MRI) scans were done. Brain MRI scan demonstrated the imaging findings consistent with central pontine myelinolysis and extrapontine myelinolysis. He did not have any hyponatremia episode during hospitalization prior to the MRI scan. To the best of our knowledge, presentation of CPM after allogeneic HSCT is extremely rare in cases where patients have not exhibited any episodes of significant hyponatremia. We report a rare case in which hepatic dysfunction due to graft-versus-host disease has a strong association with CPM after HSCT

Analysis of Hemodialysis-Associated Hypoglycemia in Patients with Type 2 Diabetes Using a Continuous Glucose Monitoring System

Background: Adequate glycemic control is important for patients with end-stage renal disease on maintenance hemodialysis (HD). Continuous glucose monitoring (CGM) systems are reported as a useful method for glucose monitoring in patients under maintenance HD. The object of this study was to describe glucose profiles and hypoglycemia associated with HD in diabetes patients using a CGM system. Methods: We recruited nine medically stable patients with type 2 diabetes under maintenance HD. CGMS (R) System Gold (R) (Medtronic MiniMed, Northridge, CA) was applied to the subjects for 144 h. During the period, HD using glucose-containing dialysate was performed every other day. Various glucose profiles were calculated from the CGM readings and compared between the day on and the day off dialysis. Results: Mean +/- SD for age, duration of diabetes, and hemoglobin A1c were 67 +/- 9 years, 24 +/- 9 years, and 8.6 +/- 1.2%, respectively. Hemoglobin A1c was correlated with mean glucose (rho = 0.780, P < 0.05) and with area under the curve for glucose above 180 mg/ dL (rho = 0.797, P < 0.05). Although there was no difference for mean amplitude of glycemic excursion between the day on and off HD, hypoglycemia occurred predominantly with day on HD. In the subjects who maintained antidiabetes agents with day on HD, glucose levels decreased with initiation of HD, causing significantly lower glucose levels compared to those during the equivalent time of the following day without HD. Conclusions: According to the CGM system, glucose variability was not affected by HD. However, in spite of glucose-containing dialysate, HD seemed to increase the risk of hypoglycemia.This study was supported by a grant from the Korea Science and Engineering Foundation (KOSEF) (0521-20080010) by the Ministry of Education, Science and Technology (MEST), by a grant from the Innovative Research Institute for Cell Therapy (A062260) by the Ministry of Health and Welfare, Republic of Korea, and by WCU project (R31-2008-000- 10103-0) of the MEST and the KOSEF.*INT DIAB FED, 2010, DIAB ATL*AM DIAB ASS, 2010, DIABETES CARE S1, V33, pS4Drechsler C, 2009, CIRCULATION, V120, P2421, DOI 10.1161/CIRCULATIONAHA.109.857268Riveline JP, 2009, NEPHROL DIAL TRANSPL, V24, P2866, DOI 10.1093/ndt/gfp181Kazempour-Ardebili S, 2009, DIABETES CARE, V32, P1137, DOI 10.2337/dc08-1688Kohnert KD, 2009, DIABETES CARE, V32, P1058, DOI 10.2337/dc08-1956SHIM Y, 2009, KOREAN J NUTR, V42, P577Tamborlane WV, 2008, NEW ENGL J MED, V359, P1464Wentholt IME, 2008, DIABETOLOGIA, V51, P183, DOI 10.1007/s00125-007-0842-6*US REN DAT SYST, 2008, USRSD 2008 ANN DAT RKohnert KD, 2007, DIABETES RES CLIN PR, V77, P420, DOI 10.1016/j.diabres.2007.01.021Burmeister JE, 2007, NEPHROL DIAL TRANSPL, V22, P1184, DOI 10.1093/ndt/gfl710Williams ME, 2006, KIDNEY INT, V70, P1503, DOI 10.1038/sj.ki.5001789Monnier L, 2006, JAMA-J AM MED ASSOC, V295, P1681Sangill M, 2006, AM J KIDNEY DIS, V47, P636, DOI 10.1053/j.ajkd.2006.01.007Rigalleau V, 2005, CURR OPIN CLIN NUTR, V8, P463Childs BP, 2005, DIABETES CARE, V28, P1245TANSEY MJ, 2005, DIABETES TECHNOL THE, V7, P109Loipl J, 2005, RENAL FAILURE, V27, P305, DOI 10.1081/JDI-200056608Cryer PE, 2003, DIABETES CARE, V26, P1902Djakoure-Platonoff C, 2003, DIABETES METAB, V29, P159Guerci B, 2003, DIABETES CARE, V26, P582*DIRECNET STUD GRO, 2003, DIABETES TECHNOL THE, V5, P781Boland E, 2001, DIABETES CARE, V24, P1858Morioka T, 2001, DIABETES CARE, V24, P909Kovatchev BP, 2000, J CLIN ENDOCR METAB, V85, P4287Jackson MA, 2000, CLIN NEPHROL, V54, P30Haviv YS, 2000, RENAL FAILURE, V22, P219Mastrototaro J, 1999, J PEDIATR ENDOCR MET, V12, P751Nakao T, 1998, INTERNAL MED, V37, P8261998, LANCET, V352, P837Davis SN, 1997, DIABETES, V46, P1328Morgan L, 1996, DIABETIC MED, V13, P5141993, N ENGL J MED, V329, P977MITRAKOU A, 1991, AM J PHYSIOL, V260, pE67DEFEO P, 1988, J CLIN INVEST, V82, P436SCHWARTZ NS, 1987, J CLIN INVEST, V79, P777SERVICE FJ, 1970, DIABETES, V19, P644

Effect of optimal sodium stearoyl-2-lactylate supplementation on growth performance and blood and carcass characteristics in Hanwoo steers during the early fattening period

Objective This study was conducted to evaluate the effect of different levels of total digestible nutrients (TDN) and sodium stearoyl-2-lactylate (SSL) supplementation on growth performance and blood and carcass characteristics in Hanwoo steers during the early fattening period. Methods Sixty Hanwoo steers (average body weight, 333±36.4 kg) were randomly allotted to 3 treatments, with twenty steers per treatment, and ten steers per pen with a size of 80 m2. Dietary treatments were as follows: CON, basal diet; treatment (TRT) 0.5, 0.5% down-spec of TDN with 0.1% SSL; TRT 1.0, 1.0% down-spec of TDN with 0.1% SSL. Results The results demonstrated that average daily gain and feed efficiency increased with TRT 0.5 (0.85 kg and 11.68) vs CON (0.82 kg and 11.27) or TRT 1.0 (0.78 kg and 10.74), indicating that 0.1% SSL supplementation in the feed of early fattening steers may result in a saving of 0.5% TDN. No significant differences were observed amongst all treatments (p> 0.05) for blood metabolite concentration and blood corpuscle values, which were all within the normally accepted range for healthy steers. Conclusion Our study suggests that a TDN 0.5% down spec with 0.1% SSL supplemented feed may be effective and profitable for the early fattening period of Hanwoo steers without causing adverse effects

Identification of Human B-1 Helper T Cells With a Th1-Like Memory Phenotype and High Integrin CD49d Expression

Human B-1 cells have been proposed to be CD20+CD27+CD43+CD1c− B cells found in the umbilical cord and adult peripheral blood, but their regulatory mechanisms have not been well elucidated. Previously, we reported that mouse CD49dhigh CD4+ T cells could enhance the secretion of natural antibodies by B-1 cells. In this study, we aimed to investigate the presence and helper functions of the human equivalents of murine CD49dhigh CD4+ T cells. Here, we showed that human CD49dhigh CD4+ T cells found in the peritoneal cavity (PEC), spleen, and peripheral blood can enhance the production of IgM antibodies by B-1 cells. As revealed in mouse, CD49dhigh CD4+ T cells were more abundant in the PEC and showed a higher tendency to form conjugates with B cells than CD49dlow CD4+ T cells. Moreover, CD49dhigh CD4+ T cells showed a Th1-like memory phenotype, characterized by high expression of CD44 and CXCR3; low expression of CD62L and CCR7; rapid production of IFN-γ, tumor necrosis factor-α, and IL-2 upon stimulation with phorbol myristate acetate and ionomycin; and rapid proliferation upon stimulation with anti-CD3 and anti-CD28 antibodies. These cells also expressed high levels of PD-1, ICOS, and CD5, suggesting that they are undergoing chronic stimulation. Remarkably, CD49dhigh CD4+ T cells specifically helped B-1 cells, but not follicular memory B cells (CD27+ CD43−CD1c−) or marginal zone B cells (CD27+CD43−CD1c+), produce IgM and IgG antibodies. In parallel, the titer of human anti-blood group A IgM was positively correlated with the frequency of CD49dhigh CD4+ T cells. In conclusion, we identified human CD49dhigh CD4+ T cells with a Th1-like memory phenotype that secrete Th1 proinflammatory cytokines and help B-1 cells secrete antibodies, thereby aiding in primary defense. We suggest that these CD49dhigh CD4+ T cells are a unique type of B-cell helper T cells distinct from follicular helper T cells