Long-term outcomes of two rescue therapies in lamivudine-refractory patients with chronic hepatitis B: combined lamivudine and adefovir, and 1-mg entecavir

Background/AimsAdefovir (ADV) and lamivudine (LAM) combination therapy (ADV+LAM) has been a useful option for patients with LAM-resistant (LAM-r) chronic hepatitis B (CHB). However, the long-term outcomes of LAM+ADV and 1-mg entecavir (ETV) rescue therapies have still been limited. The aim of this study was to determine the long-term outcomes of these two rescue therapies.MethodsSixty patients with LAM-r CHB underwent rescue therapy with LAM+ADV (n=36) or 1-mg ETV (n=24). We determined the duration of rescue therapy, timing and type of mutation, undetectable serum hepatitis B virus (HBV) DNA by PCR (lower limitation of detection, < 140 copies/mL), biochemical response (alanine aminotransferase < 40 IU/mL), and the incidence of hepatitis B virus e antigen (HBeAg) seroconversion and virologic breakthrough.ResultsBaseline characteristics did not differ between the two therapy groups. The duration of rescue therapy was 56 months (range, 14-100 months) in the ADV+LAM group and 42 months (range, 12-73 months) in the ETV group (P=0.036). The cumulative rates of HBV DNA undetectability and HBeAg seroconversion up to 6 years were 88.6% and 43.0%, respectively, in the ADV+LAM group, and 45.8% and 31.8% in the ETV group. The rate of virologic breakthrough and resistance was 14.4% in the ADV+LAM group and 71.9% in the ETV group (P=0.001).ConclusionsCombination of LAM and ADV therapy for up to 6 years achieved modest rates of virological suppression and resistance. ETV is not an optimal therapy because the risk of viral breakthrough to ETV increases over time

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

Identification of novel peptides that stimulate human neutrophils

Neutrophils play a key role in innate immunity, and the identification of new stimuli that stimulate neutrophil activity is a very important issue. In this study, we identified three novel peptides by screening a synthetic hexapeptide combinatorial library. The identified peptides GMMWAI, MMHWAM, and MMHWFM caused an increase in intracellular Ca2+ in a concentration-dependent manner via phospholipase C activity in human neutrophils. The three peptides acted specifically on neutrophils and monocytes and not on other non-leukocytic cells. As a physiological characteristic of the peptides, we observed that the three peptides induced chemotactic migration of neutrophils as well as stimulated superoxide anion production. Studying receptor specificity, we observed that two of the peptides (GMMWAI and MMHWFM) acted on formyl peptide receptor (FPR)1 while the other peptide (MMHWAM) acted on FPR2. Since the three novel peptides were specific agonists for FPR1 or FPR2, they might be useful tools to study FPR1- or FPR2-mediated immune response and signaling

Pathogenesis of Korean SapelovirusA in piglets and chicks.

Sapelovirus A (SV-A), formerly known as porcine sapelovirus as a member of a new genus Sapelovirus, is known to cause enteritis, pneumonia, polioencephalomyelitis and reproductive disorders in pigs. We have recently identified α2,3-linked sialic acid on GD1a ganglioside as a functional SV-A receptor rich in the cells of pigs and chickens. However, the role of GD1a in viral pathogenesis remains elusive. Here, we demonstrated that a Korean SV-A strain could induce diarrhoea and intestinal pathology in piglets but not in chicks. Moreover, this Korean SV-A strain had mild extra-intestinal tropisms appearing as mild, non-suppurative myelitis, encephalitis and pneumonia in piglets, but not in chicks. By real-time reverse transcription (RT) PCR, higher viral RNA levels were detected in faecal samples than in sera or extra-intestinal organs from virus-inoculated piglets. Immunohistochemistry confirmed that high viral antigens were detected in the epithelial cells of intestines from virus-inoculated piglets but not from chicks. This Korean SV-A strain could bind the cultured cell lines originated from various species, but replication occurred only in cells of porcine origin. These data indicated that this Korean SV-A strain could replicate and induce pathology in piglets but not in chicks, suggesting that additional porcine-specific factors are required for virus entry and replication. In addition, this Korean SV-A strain is enteropathogenic, but could spread to the bloodstream from the gut and disseminate to extra-intestinal organs and tissues. These results will contribute to our understanding of SV-A pathogenesis so that efficient anti-sapelovirus drugs and vaccines could be developed in the future.This study was supported by a grant (2014R1A2A2A01004292) of the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning, Bio-industry Technology Development Program (315021-04) through the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (iPET) funded by the Ministry of Agriculture, Food and Rural Affairs, and Korea Basic Science Institute grant (C33730), Republic of Korea. IG is a Wellcome Senior Fellow supported by the Wellcome Trust (097997/Z/11/Z). Chonnam National University provided funding to Mun-Il Kang (2012). The Mab against SV-A capsid protein was received as a generous gift from Dr. M. Dauber (Friedrich-Loeffler Institute, Germany).This is the accepted version of the article. The final version is available from the Microbiology Society via http://dx.doi.org/10.1099/jgv.0.00057

Development of Dross Height Measurement System Using PMP Algorithm

This study attempted to develop a system which measures where dross (a thick film or mass of metal oxides floating on a molten metal) should be dumped by robots in large-iron plate coating sites in which robots are used to handle thermal and chemical materials

Effect of dual treatment with SDF-1 and BMP-2 on ectopic and orthotopic bone formation.

The potent stem cell homing factor stromal cell-derived factor-1 (SDF-1) actively recruits mesenchymal stem cells from circulation and from local bone marrow. It is well established that bone morphogenetic protein-2 (BMP-2) induces ectopic and orthotopic bone formation. However, the exact synergistic effects of BMP-2 and SDF-1 in ectopic and orthotopic bone regeneration models have not been fully investigated. The purpose of this study was to evaluate the potential effects of simultaneous SDF-1 and BMP-2 treatment on bone formation.Various doses of SDF-1 were loaded onto collagen sponges with or without BMP-2.These sponges were implanted into subcutaneous pockets and critical-size calvarial defects in C57BL/6 mice. The specimens were harvested 4 weeks post-surgery and the degree of bone formation in specimens was evaluated by histomorphometric and radiographic density analyses. Osteogenic potential and migration capacity of mesenchymal cells and capillary tube formation of endothelial cells following dual treatment with SDF-1 and BMP-2 were evaluated with in vitro assays.SDF-1-only-treated implants did not yield significant in vivo bone formation and SDF-1 treatment did not enhance BMP-2-induced ectopic and orthotopic bone regeneration. In vitro experiments showed that concomitant use of BMP-2 and SDF-1 had no additive effect on osteoblastic differentiation, cell migration or angiogenesis compared to BMP-2 or SDF-1 treatment alone.These findings imply that sequence-controlled application of SDF-1 and BMP-2 must be further investigated for the enhancement of robust osteogenesis in bone defects

Analysis of Factors Associated with the Postoperative Healing of Medication-Related Osteonecrosis of the Jaw in Patients with Osteoporosis

Background: Surgical treatment is considered the best approach by many researchers for medication-related osteonecrosis of the jaws (MRONJ). While postoperative outcomes are mainly favorable, wound healing still fails in some cases. This retrospective study aimed to evaluate the factors affecting the postoperative healing of MRONJ. Methods: This study involved 400 osteoporosis patients who received surgical treatment from January 2009 to January 2018 in Kyungpook National University Hospital. The patient, drug, and clinical factors were collected as investigation variables. The obtained data were statistically analyzed to identify relationships between the factors and healing aspect. Results: Univariate logistic regression analysis showed that the route of drug administration, bone exposure, types of surgical management, and wound management had a significant influence (p &lt; 0.05) on the healing outcome. Sequestrectomy with primary closure had a more positive effect on favorable healing. In the multivariate logistic regression test, the effect of wound management alone was not statistically significant (p &gt; 0.05). Conclusion: In patients with osteoporosis, the factors such as intravenously administered drugs, fistulas that were probed to the bone, and surgical management with curettage were associated with a lower rate of postoperative complete healing of MRONJ, whereas primary closure of wounds led, possibly, to good healing outcomes. The strengths of the study include its relatively large sample size and that its results can hopefully aid in the clinical decisions for practitioners and future research studies for researchers

Anti-Obesogenic Effects of Sulforaphane-Rich Broccoli (Brassica oleracea var. italica) Sprouts and Myrosinase-Rich Mustard (Sinapis alba L.) Seeds In Vitro and In Vivo

Glucoraphanin (GRA), a glucosinolate particularly abundant in broccoli (Brassica oleracea var. italica) sprouts, can be converted to sulforaphane (SFN) by the enzyme myrosinase. Herein, we investigated the anti-obesogenic effects of broccoli sprout powder (BSP), mustard (Sinapis alba L.) seed powder (MSP), and sulforaphane-rich MSP-BSP mixture powder (MBP) in bisphenol A (BPA)-induced 3T3-L1 cells and obese C57BL/6J mice. In vitro experiments showed that MBP, BSP, and MSP have no cytotoxic effects. Moreover, MBP and BSP inhibited the lipid accumulation in BPA-induced 3T3-L1 cells. In BPA-induced obese mice, BSP and MBP treatment inhibited body weight gain and ameliorated dyslipidemia. Furthermore, our results showed that BSP and MBP could activate AMPK, which increases ACC phosphorylation, accompanied by the upregulation of lipolysis-associated proteins (UCP-1 and CPT-1) and downregulation of adipogenesis-related proteins (C/EBP-&alpha;, FAS, aP2, PPAR-&gamma;, and SREBP-1c), both in vitro and in vivo. Interestingly, MBP exerted a greater anti-obesogenic effect than BSP. Taken together, these findings indicate that BSP and MBP could inhibit BPA-induced adipocyte differentiation and adipogenesis by increasing the expression of the proteins related to lipid metabolism and lipolysis, effectively treating BPA-induced obesity. Thus, BSP and MBP can be developed as effective anti-obesogenic drugs

The effect of simultaneous SDF-1 and BMP-2 treatment on ectopic bone formation.

<p>Faxitron soft X-ray images after subcutaneous implantation of collagen sponge with/without BMP-2 (2.5μg) and SDF-1 (0, 0.1, 0.5, or 1 μg/collagen sponge) in mice. (A) Radiographic image of the harvested collagen sponges 4 weeks after implantation. (B) Comparison of radiological density of collagen sponges from different treatment groups (*, <i>p</i> < 0.05).</p

The effect of simultaneous treatment with SDF-1 and BMP-2 on orthotopic bone formation.

<p>Soft X-ray examination was carried out after implantation of collagen sponges to critical-size calvarial defects with/without BMP-2 (2.5μg) and SDF-1 (0, 0.1, 0.5, or 1 μg/collagen sponge) in mice. (A) Representative radiographic images, (B) Quantification of bone regeneration by radiographic density at 4 weeks post-implantation (*, <i>p</i> < 0.05).</p