Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling

Priapism, abnormally prolonged penile erection in the absence of sexual excitation, is associated with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. It is common among males with sickle cell disease (SCD), and SCD transgenic mice are an accepted model of the disorder. Current strategies to manage priapism suffer from a poor fundamental understanding of the molecular mechanisms underlying the disorder. Here we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected priapic activity. ADA enzyme therapy successfully corrected the priapic activity both in vivo and in vitro, suggesting that it was dependent on elevated adenosine levels. Further genetic and pharmacologic evidence demonstrated that A2B adenosine receptor-mediated (A2BR-mediated) cAMP and cGMP induction was required for elevated adenosine-induced prolonged penile erection. Finally, priapic activity in SCD transgenic mice was also caused by elevated adenosine levels and A2BR activation. Thus, we have shown that excessive adenosine accumulation in the penis contributes to priapism through increased A2BR signaling in both Ada -/- and SCD transgenic mice. These findings provide insight regarding the molecular basis of priapism and suggest that strategies to either reduce adenosine or block A2BR activation may prove beneficial in the treatment of this disorder.     

Anti‐inflammatory effect of platelet‐rich plasma on nucleus pulposus cells with response of TNF‐α and IL‐1

The purpose of this study was to investigate the anti‐inflammatory effect of platelet‐rich plasma (PRP) with collagen matrix on human nucleus pulposus (NP) cell in response to pro‐inflammatory cytokines such as tumor necrosis factor‐alpha (TNF‐α) and interleukin‐1 (IL‐1). NP cells from human disks were cultured in a monolayer and maintained in the collagen matrix prior to the addition of recombinant human IL‐1 and TNF‐α. After applying IL‐1 and TNF‐α, PRP prepared by using a commercially available platelet concentration system was added. The response was investigated using real‐time PCR for mRNA expression of type II collagen, aggrecan, matrix metalloproteinase‐3 (MMP‐3), and cyclooxygenase‐2 (COX‐2). The combination of IL‐1β and TNF‐α led to decrease of matrix synthesis gene expression such as collagen type II and aggrecan and increase of the degradation gene expression of COX‐2 and MMP‐3, compared to the control. Consecutive PRP exposure significantly recovered the down‐regulated gene expression of collagen type II and aggrecan and significantly reduced the increased MMP‐3 and COX‐2 gene expression, compared to that of control groups with pro‐inflammatory cytokines. The administration of PRP with collagen matrix markedly suppressed cytokine‐induced pro‐inflammatory degrading enzymes and mediators in the NP cell. It also rescued gene expression concerning matrix synthesis, thereby stabilizing NP cell differentiation. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:551–556, 2014.     

Clinical outcomes of second-look endoscopy after gastric endoscopic submucosal dissection: predictive factors with high risks of bleeding

Background

A second-look endoscopy is routinely performed after endoscopic submucosal dissection (ESD) in many institutions, although the need is questionable. Additional hemostatic procedures might be necessary for the post-ESD ulcer with a high risk of bleeding. We investigated the predictive factors for post-ESD ulcers with a high risk of bleeding.

Methods

Second-look endoscopy was performed on the day following ESD. The post-ESD ulcers were categorized into two risk groups according to the Forrest classification: high-risk ulcer stigma (type I and IIa) and low-risk ulcer stigma. We analyzed the risk factors associated with high-risk ulcer stigma and late delayed bleeding.

Results

During the study period, 616 ESD procedures were performed. Second-look endoscopy revealed that the incidence of high-risk ulcer stigma post-ESD was 15.1 %. Early and late delayed bleeding rates were 3.7 and 1.9 %, respectively. Multivariate analysis revealed that submucosal fibrosis and nausea were significantly related to high-risk ulcer stigma after ESD. Multivariate analysis revealed that surface erosion, location of the lesion, and high-risk ulcer stigma identified by second-look endoscopy were significantly associated with late delayed bleeding.

Conclusions

The effective use of selective second-look endoscopy will help limit unnecessary procedures. Submucosal fibrosis and nausea were risk factors associated with high-risk ulcer stigma after ESD.     

一次性使用卫生用品生产环境与产品的细菌污染调查

对上海5种卫生用品生产企业进行了细菌污染调查。产品细菌数低于允许标准的合格率为71.43％,车间空气的合格率为82.96％,工作台表面合格率为90.12％,工人手表面细菌数合格率为81.48％。原料、生产环节与工人手污染程度对细菌污染量有明显影响。