Erectile dysfunction precedes other systemic vascular diseases due to incompetent cavernous endothelial cell-cell junctions.

PURPOSE: Erectile dysfunction is often a harbinger of cardiovascular disease. We sought to gain mechanistic insight at the cellular and molecular levels into why erectile dysfunction precedes the clinical consequences of cardiovascular disease. MATERIALS AND METHODS: Diabetes was induced by intraperitoneal streptozotocin injection in 8-week-old C57BL/6J mice. At 8 weeks after diabetes induction, we determined the expression of endothelial cell-cell junction proteins and vascular endothelial permeability in the penis, heart and hind limb by systemic injection of various vascular space markers (350 Da to 2,000 kDa) or by immunohistochemical staining with antibody to oxidized low density lipoprotein. We also investigated the effect of recombinant Ang1 protein on cavernous endothelial permeability. RESULTS: Alterations in the integrity of the endothelial cell-cell junction, including a decrease in endothelial cell-cell junction proteins and an increase in vascular permeability to fluorescent tracers or oxidized low density lipoprotein, were prominent in the cavernous tissue of diabetic mice. In contrast, no significant changes in endothelial cell-cell junction proteins or vascular permeability were noted in heart or hind limb tissue according to the diabetic condition. Intracavernous injection of Ang1 protein, an anti-permeability factor, significantly decreased cavernous endothelial permeability to oxidized low density lipoprotein by restoring endothelial cell-cell junction proteins in diabetic mice. CONCLUSIONS: The incompetent cavernous endothelial cell-cell junction in the diabetic condition provides an important clue to why erectile dysfunction is highly prevalent and often precedes other systemic vascular diseases.

Peripheral T-cell lymphoma: the role of hematopoietic stem cell transplantation.

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphomas (NHLs). Whereas the incidence of the disease appears to increase during last decades and the prognosis remains dramatically poor, so far no standard treatment has been established. High-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT) has been proven effective in relapsed PTCL, while retrospective studies have shown a survival benefit as first-line treatment in some subsets of PTCL patients. However, given disease rarity, there is a paucity of randomized trials in both upfront and relapse setting. Here, we critically evaluated eligible prospective and retrospective studies that address the role of ASCT in treatment of PTCL, with respect to quality of design and performance. Additionally, the role of allogeneic transplantation has been reviewed. The comparison of ASCT with novel agents that emerge or the combination of both, are to be ascertained via prospective randomized trials in this field.

Brain-derived neurotrophic factor is up-regulated in severe acute cauda equina syndrome dog model.

To determine the level of brain-derived neurotrophic factor (BDNF) in experimental dog model of severe acute cauda equina syndrome, which was induced by multiple cauda equina constrictions throughout the entire lumbar (L), sacral (S) and coccygeal (Co) spinal cord and their central processes of the dorsal root ganglia neurons. Adult male mongrel dogs were randomly divided into 2 groups. The experiment group (n=4) was subjected to multiple cauda equina constrictions. The control group (n=4) was subjected to cauda equina exposure without constrictions. Level of BDNF in the spinal cord and the dorsal root ganglion cells (L7, S1-S3) was assessed 48 hours after multiple constrictions by immunohistochemical and histopathological analyses. 48 hours after multiple constrictions of cauda equina, up-regulation of BDNF within lumbosacral (L7-S3) spinal cord and dorsal root ganglion was observed in experimental group as compared to control group. Our result suggests that BDNF might play a role in the inflammatory and neuropathic pain as a result of multiple cauda equina constrictions. Regulation of BDNF level could potentially provide a therapy for treating cauda equina syndrome.

Ability of plasmid DNA complexed with histidinylated lPEI and lPEI to cross in vitro lung and muscle vascular endothelial barriers.

DNA complexes made with cationic polymers (polyplexes) developed as nonviral vectors for gene therapy must be enabled to cross through vascular endothelium to transfect underlying tissues upon their administration in the blood circulation. Here, we evaluated the transendothelial passage (TEP) of DNA complexes made with histidinylated linear polyethylenimine (His-lPEI) or linear polyethylenimine (lPEI). In vitro studies were performed by using established transwell lung and skeletal muscle vascular endothelial barriers. The models were composed of a monolayer of human lung microvascular endothelial (HMVEC-L) cells and mouse cardiac endothelial (MCEC) cells formed on a PET insert and immortalized human tracheal epithelial (ΣCFTE29o-) cells and mouse myoblasts (C2C12) as target cells cultured in the lower chamber, respectively. When the vascular endothelium monolayer was established and characterized, the transfection efficiency of target (ΣCFTE29o- and C2C12) cells with plasmid DNA encoding luciferase was used to evaluate TEP of polyplexes. The luciferase activities with His-lPEI and lPEI polyplexes compared to those obtained in the absence of endothelial cell monolayer were 6.5% and 4.3% into ΣCFTE29o- cells, and 18.5% and 0.23% into C2C12 cells, respectively. The estimated rate for His-lPEI polyplexes was 0.135 µg/cm(2).h and 0.385 µg/cm(2).h through the HMVEC-L and MCEC monolayers, respectively. These results indicate that His-lPEI polyplexes can pass through the lung and skeletal muscle vascular endothelium and can transfect underlying cells.