The combination of purified recombinant human platelet-derived growth factor-BB and equine particulate bone graft for periodontal regeneration

Background: The objective of this study is to evaluate the potential for periodontal regeneration of a critical‐sized defect with the application of recombinant human platelet‐derived growth factor (rhPDGF‐BB) combined with either a particulate equine or a β‐tricalcium phosphate (β‐TCP) matrix. Methods: Critical‐sized intrabony 2‐wall defects were created bilaterally on the distal surface of the second premolar and the mesial surface of the first molar in nine hounds. Twelve defects received rhPDGF‐BB/equine treatment, 12 defects received rhPDGF‐BB/β‐TCP treatment, and the remaining 12 sites served as sham‐surgery controls. The animals were sacrificed after a 10‐week healing period. Results: Clinical healing was uneventful without obvious signs of overt gingival inflammation. Histologic and histomorphometric analyses revealed statistically that there were differences among the three groups in terms of new bone formation (P <0.001). The amount of test material for both rhPDGF‐BB/equine and rhPDGF‐BB/β‐TCP groups was comparable, but the amount of newly formed bone was significantly higher (P <0.01) in favor of the rhPDGF‐BB/equine group. The amount of new cementum formed for the rhPDGF‐BB/equine group (4.8 ± 1.3 mm) was significantly higher (P =0.001) than the sham‐surgery control group (1.7 ± 1.9 mm). Conclusion: Both rhPDGF‐BB/equine and rhPDGF‐BB/β‐TCP have the potential to support the regeneration of the periodontal attachment apparatus.     

Vertical ridge augmentation using an equine bone and collagen block infused with recombinant human platelet-derived growth factor-BB: a randomized single-masked histologic study in non-human primates

Background: This study tests the effectiveness of hydroxyapatite and collagen bone blocks of equine origin (eHAC), infused with recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB), to augment localized posterior mandibular defects in non‐human primates (Papio hamadryas). Methods: Bilateral critical‐sized defects simulating severe atrophy were created at the time of the posterior teeth extraction. Test and control blocks (without growth factor) were randomly grafted into the respective sites in each non‐human primate. Results: All sites exhibited vertical ridge augmentation, with physiologic hard‐ and soft‐tissue integration of the blocks when clinical and histologic examinations were done at 4 months after the vertical ridge augmentation procedure. There was a clear, although non‐significant, tendency to increased regeneration in the test sites. As in the first two preclinical studies in this series using canines, experimental eHAC blocks infused with rhPDGF‐BB proved to be a predictable and technically viable method to predictably regenerate bone and soft tissue in critical‐sized defects. Conclusion: This investigation supplies additional evidence that eHAC blocks infused with rhPDGF‐BB growth factor is a predictable and technically feasible option for vertical augmentation of severely resorbed ridges.     

一测多评法测定香鳞毛蕨有效部位中10种间苯三酚类成分

目的建立香鳞毛蕨DryopterisFragrans有效部位中10种间苯三酚类成分的一测多评测定方法。方法采用高效液相色谱法,以绵马素BB为内参物,测定其与绵马素PB、绵马素AB、黄绵马酸BB、田基黄绵马酸A、黄绵马酸PB、异黄绵马酸PB、黄绵马酸AB、Compound VI和绵马酚B的相对校正因子,采用相对校正因子计算这9种间苯三酚成分的量,实现一测多评。同时采用外标法测定有效部位中该10种成分的量,并比较2种测定方法的差异,以验证一测多评法的可行性和准确性。结果各相对校正因子重复性良好,12批有效部位中10种间苯三酚成分量的计算值与实测值无显著性差异。结论在缺少对照品的情况下,以绵马素BB为内参物,建立的一测多评法可用于香鳞毛蕨有效部位的定量分析,为香鳞毛蕨多指标成分质量评价提供参考。     

Role of endogenous 4-1BB in the development of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterized by the production of autoantibodies directed against nuclear antigens including nucleosomes and DNA. To determine the role of T-cell costimulatory molecule 4-1BB in the regulation of SLE, MRL-Fas(lpr) (lpr) mice deficient in 4-1BB (lpr/4-1BB(-/-)) were generated and their disease phenotype was compared to that of control lpr mice. The main finding of this study is that the lpr/4-1BB(-/-) mice had more pronounced skin lesions which appeared earlier, increased lymphadenopathy, increased renal damage, and higher mortality than 4-1BB-intact control lpr mice. The increased severity of lesions in lpr/4-1BB(-/-) mice was closely associated with increases in CD4(+) T, CD3(+) B220(+) double-negative T cells, serum immunoglobulin, anti-dsDNA autoantibodies, and tissue immunoglobulin deposits. These data suggest that the 4-1BB-4-1BB ligand signalling pathway plays an important role in SLE and that deletion of 4-1BB confers susceptibility to lpr mice, leading to accelerated induction of disease and early mortality.     

Seguimiento clínico de una muestra contemporánea de pacientes con fibrilación auricular en tratamiento con digoxina: resultados del estudio AFBAR

Introduction and objectivesWe aimed to assess and compare the effect of digoxin on clinical outcomes in patients with atrial fibrillation vs those under beta-blockers or none of these drugs.MethodsAFBAR is a prospective registry study carried out by a team of primary care physicians (n = 777 patients). Primary endpoints were survival, survival free of admission due to any cause, and survival free of admission due to cardiovascular causes. The mean follow up was 2.9 years. Four groups were analyzed: patients receiving digoxin, beta-blockers, or digoxin plus beta-blockers, and patients receiving none of these drugs.ResultsOverall, 212 patients (27.28%) received digoxin as the only heart control strategy, 184 received beta-blockers (23.68%), 58 (7.46%) were administered both, and 323 (41.57%) received none of these drugs. Digoxin was not associated with all-cause mortality (estimated hazard ratio = 1.42; 95% confidence interval, 0.77-2.60; P = .2), admission due to any cause (estimated hazard ratio = 1.03; 95% confidence interval, 0.710-1.498; P = .8), or admission due to cardiovascular causes (estimated hazard ratio = 1.193; 95% confidence interval 0.725-1.965; P = .4). No association was found between digoxin use and all-cause mortality, admission due to any cause, or admission due to cardiovascular causes in patients without heart failure. There was no interaction between digoxin use and sex in all-cause mortality or in survival free of admission due to any cause. However, an association was found between sex and admission due to cardiovascular causes.ConclusionsDigoxin was not associated with increased all-cause mortality, survival free of admission due to any cause, or admission due to cardiovascular causes, regardless of underlying heart failure.Full English text available from: www.revespcardiol.org/en     

Improving the Th1 cellular efficacy of the lead Yersinia pestis rF1-V subunit vaccine using SA-4-1BBL as a novel adjuvant

The lead candidate plague subunit vaccine is the recombinant fusion protein rF1-V adjuvanted with alum. While alum generates Th₂ regulated robust humoral responses, immune protection against Yersinia pestis has been shown to also involve Th₁ driven cellular responses. Therefore, the rF1-V-based subunit vaccine may benefit from an adjuvant system that generates a mixed Th₁ and humoral immune response. We herein assessed the efficacy of a novel SA-4-1BBL costimulatory molecule as a Th₁ adjuvant to improve cellular responses generated by the rF1-V vaccine. SA-4-1BBL as a single adjuvant had better efficacy than alum in generating CD4⁺ and CD8⁺ T cells producing TNFα and IFNγ, signature cytokines for Th₁ responses. The combination of SA-4-1BBL with alum further increased this Th₁ response as compared with the individual adjuvants. Analysis of the humoral response revealed that SA-4-1BBL as a single adjuvant did not generate a significant Ab response against rF1-V, and SA-4-1BBL in combination with alum did not improve Ab titers. However, the combined adjuvants significantly increased the ratio of Th₁ regulated IgG_2c in C57BL/6 mice to the Th₂ regulated IgG₁. Finally, a single vaccination with rF1-V adjuvanted with SA-4-1BBL + alum had better protective efficacy than vaccines containing individual adjuvants. Taken together, these results demonstrate that SA-4-1BBL improves the protective efficacy of the alum adjuvanted lead rF1-V subunit vaccine by generating a more balanced Th₁ cellular and humoral immune response. As such, this adjuvant platform may prove efficacious not only for the rF1-V vaccine but also against other infections that require both cellular and humoral immune responses for protection.     

小组学习和SPOC混合教学在医学院校程序设计类课程中的实践研究

分析传统教学存在的问题,提出针对医学院校程序设计类课程实施小组合作学习和SPOC混合教学模式,详细阐述该模式学习内容、教学实践情况及教学效果,指出该模式有助于提高学生学习效果、成绩以及自主学习能力。