Abstract Islet transplantation (ITx) has potential as a therapy for patients with type 1 diabetes. For successful engraftment and insulin independence, the transplanted islets must establish an ...adequate, stable blood supply. Angiopoientin-1 (Ang1) is a specific growth factor that induces vascularization via the Tie2 or Tie1 receptor. In this study, we used an in vitro angiogenesis assay to evaluate islet function following transplantation and the effect of the Ang1 variant cartilage oligomeric matrix protein (COMP) Ang1 on isolated islets. The enhanced function of islets transduced with COMP-Ang1 was also confirmed in a streptozotocin (STZ)-induced diabetic mice model. In a three-dimensional collagen-based culture system, the transduction of COMP-Ang1 into islets significantly increased angiogenesis compared with the bacterial-β-galactosidase (LacZ)-transduced controls and an intact, nontransduced islet negative control group. COMP-Ang1 transduced islets also attenuated hyperglycemia in syngeneic diabetic C57BL/6 mice and enhanced glucose tolerance by areas under the curves of intraperitoneal glucose tolerance tests. These findings demonstrated the capacity of COMP-Ang1 to promote revascularization in cultured islets, which may contribute to successful transplantation in vivo.
Using a 4,4′,4′′-tris(
N-carbazolyl)-triphenylamine (TCTA) small molecule interlayer, we have fabricated efficient green phosphorescent organic light emitting devices by solution process. ...Significantly a low driving voltage of 3.0
V to reach a luminance of 1000
cd/m
2 is reported in this device. The maximum current and power efficiency values of 27.2
cd/A and 17.8
lm/W with TCTA interlayer (thickness 30
nm) and 33.7
cd/A and 19.6
lm/W with 40
nm thick interlayer are demonstrated, respectively. Results reveal a way to fabricate the phosphorescent organic light emitting device using TCTA small molecule interlayer by solution process, promising for efficient and simple manufacturing.
Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster, associated with poor quality of life and increased patient and healthcare resource expenditure. This randomized ...controlled trial aims to evaluate the efficacy and safety of SIKD1977 (Sogeonjungtang) in combination with standard treatment and estimate an effective dose for treating PHN.
This is a protocol for a randomized, placebo-controlled, double-blind, multicenter trial. A total of 90 eligible participants with PHN will be recruited from three hospitals and randomly allocated to high-dose group, low-dose group, or placebo group in a 1:1:1 ratio. The trial will involve a 6-week oral administration of SIKD1977/placebo, and a 1-week follow-up period. The primary outcome will be the weekly average change in average daily pain score (ADPS) from baseline to the end of treatment. The secondary outcomes will include the weekly average changes in ADPS from baseline to week 2, 4, and 7, differences in Short-Form McGill Pain Questionnaire, Visual analogue scale, 5-level EuroQol-5 dimensions, Patient Global Impression of Change, and consumption of rescue drugs. All adverse events will be assessed during the trial.
This study will provide evidence for the efficacy and safety of SIKD1977, and an effective dose for PHN.
This protocol has been registered in the Clinical Research Information Service with the identification code KCT0007939.
Abstract There is some controversy regarding the exact cytomegalovirus (CMV) antigenemia titer that should be used as a guideline for preemptive anti-CMV therapy. We performed 634 consecutive kidney ...transplantations between January 2000 and June 2007. Preemptive therapy employed intravenous gancyclovir treatment when the CMV antigenemia titer was ≥50/4 × 105 leukocytes after kidney transplantation. The 634 recipients were allocated into 2 groups according to the peak CMV antegenemia: group A, CMV antigenemia titer <50/4 × 105 ( n = 550); and group B, ≥50/40 × 105 ( n = 84). Among the 634 recipients, 264 were positive for CMV antigenemia, and 61 developed symptomatic CMV infections. The incidence of symptomatic CMV infections in group B was significantly higher than in group A. Two cases in both groups developed tissue-proven CMV disease: group A CMV colitis and CMV nephritis, and group B, 2 cases of CMV colitis. Graft and patient survival rates in groups A and B at 5 years posttransplantation were not different. The authors concluded that a CMV antigenemia titer of ≥50/4 × 105 leukocytes can be considered an appropriate guideline for preemptive anti-CMV therapy.
4-1BB (CDw 137), a member of the tumor necrosis factor receptor (TNFR) superfamily, is a costimulatory receptor primarily expressed on activated T cells. It has been shown that the administration of ...agonistic anti-4-1BB monoclonal antibody (mAb) enhances tumor immunity and allogenic immune responses. Paradoxically, we found that the administration of anti-4-1BB mAb reduced the incidence and severity of inflammatory bowel disease. In this study, we investigated the effects of anti-4-1BB mAb in a murine intestinal inflammation model, which induced by the hapten reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS) and mimics immunologic characteristics of human Crohn's disease (CD). Colitis was induced by rectal administration of 2
mg of TNBS in 35% ethanol using a vinyl catheter positioned 4
cm from the anus. All mice were sacrificed 3 and 10 days after the TNBS administration. The disease activity index (DAI), histological changes of the colon and production of cytokines (IL-2, IL-4, IL-10 and IFN-γ) were evaluated. The surface molecules of T cells in peripheral blood, spleen and mesenteric lymph nodes were analyzed by flow cytometry. When mice were treated with anti-4-1BB mAb, improvement in both wasting and histopathologic signs of colonic inflammation was observed. The increase a number of splenic CD4
+CD25
+ T cells and decreased synthesis of the Th1 cytokine IL-2 also occurred. Interestingly, increased production of Th1 cytokine IFN-γ and proportion of CD8
+ T cells were observed in mice treated with anti-4-1BB mAb in comparison to the colitic mice. These studies show, for the first time, that agonistic anti-4-1BB mAb can improve experimental colitis by reduction of IL-2 and augmentation of CD4
+CD25
+ regulatory T cells. TNBS colitis is Th1-mediated and has similar histologic features and distribution of inflammation to CD. This study suggests that anti-4-1BB mAb therapy could be effective in the treatment of patients with CD.
BACKGROUND: Influenza vaccines are prepared annually based on global epidemiological surveillance data. However, since there is no method by which to predict the influenza strain that will cause the ...next pandemic, the demand to develop new vaccination strategies with broad cross-reactivity against influenza viruses are clearly important. The ectodomain of the influenza M2 protein (M2e) is an attractive target for developing a vaccine with broad cross-reactivity. For these reasons, we investigated the efficacy of an inactivated H9N2 virus vaccine (a-H9N2) mixed with M2e (1xM2e or 4xM2e) proteins expressed in Escherichia coli, which contains the consensus of sequence the extracellular domain of matrix 2 (M2e) of A/chicken/Vietnam/27262/09 (H5N1) avian influenza virus, and investigated its humoral immune response and cross-protection against influenza A viruses. RESULTS: Mice were intramuscularly immunized with a-H9N2, 1xM2e alone, 4xM2e alone, a-H9N2/1xM2e, or a-H9N2/4xM2e. Three weeks post-vaccination, mice were challenged with lethal homologous (A/ chicken /Korea/ma163/04, H9N2) or heterosubtypic virus (A/Philippines/2/82, H3N2 and A/aquatic bird/Korea/maW81/05, H5N2). Our studies demonstrate that the survival of mice immunized with a-H9N2/1xM2e or with a-H9N2/4xM2e (100% survival) was significantly higher than that of mouse-adapted H9N2 virus-infected mice vaccinated with 1xM2e alone or with 4xM2e alone (0% survival). We also evaluated the protective efficacy of the M2e + vaccine against infection with mouse-adapted H5N2 influenza virus. Protection from death in the control group (0% survival) was similar to that of the 1×M2e alone and 4xM2e alone-vaccinated groups (0% survival). Only 40% of mice vaccinated with vaccine alone survived challenge with H5N2, while the a-H9N2/1×M2e and a-H9N2/4×M2e groups showed 80% and 100% survival following mouse-adapted H5N2 challenge, respectively. We also examined cross-protection against human H3N2 virus and found that the a-H9N2/1×M2e group displayed partial cross-protection against H3N2 (40% survival), whereas vaccine alone, 1×M2e alone, 4×M2e alone, or H9N2/1×M2e groups showed incomplete protection (0% survival) in response to challenge with a lethal dose of human H3N2 virus. CONCLUSIONS: Taken together, these results suggest that prokaryote-expressed M2e protein improved inactivated H9N2 virus vaccine efficacy and achieved cross-protection against lethal influenza A virus infection in mice.
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