Inflammatory bowel disease (IBD) appears to be an inappropriate response to an antigen that leads to chronic inflammation rather than repair. This review looks at the role of endothelin-1 (ET-1) as a proinflammatory agent in IBD. ET-1 antagonists in animal models reduce the incidence and severity of IBD. These antagonists may be useful for treatment of IBD in humans.

These studies aimed to determine the effect of smooth muscle cells (SMCs) on angiogenic behavior of endothelial cells (ECs) within fibrin hydrogels, an extracellular matrix (ECM) commonly used in tissue engineering. We developed a 3-D, fibrin-based co-culture assay of angiogenesis consisting of aggregates of SMCs with ECs seeded onto the aggregates’ surface. Using digital fluorescence micrography, EC matrix invasion was quantified by average length of sprouts (ALS) and density of sprout formation (DSF). We demonstrated that ECs and SMCs co-invade into the ECM in close proximity to one another. ECs that were co-cultured with SMCs demonstrated increased invasion compared to ECs that were cultured alone at all time points. At Day 19, the ALS of ECs in co-culture was 327 +/− 58 µm versus 70 +/− 11 µm of ECs cultured alone (p=.01). The DSF of co-cultured ECs was also significantly greater than that of ECs cultured alone (p=.007 on Day 19). This appeared to be a function of both increased EC invasion and well as improved persistence of EC sprout networks. At 7 days, ECs in co-culture with proliferation-inhibited SMCs previously treated with Mitomycin-C (MMC) demonstrated significantly attenuated sprouting compared to ECs co-cultured with SMCs that were untreated with MMC (82 +/− 14 µm versus 205 +/− 32 µm; p < .05). In assays in which multiple co-culture aggregates were cultured within a single hydrogel, we observed directional invasion of sprouts preferentially towards the other aggregates within the hydrogel. In co-culture assays without early EC/SMC contact, the ALS of ECs cultured in the presence of SMCs was significantly greater than those cultured in the absence of SMCs by Day 3 (320 +/− 21 µm versus 187 +/− 16 µm; p < .005). We conclude that SMCs augment EC matrix invasion into 3-D fibrin hydrogels, at least in part resulting from SMC proliferative and invasive activity. Directed invasion between co-culture aggregates and augmented angiogenesis in the absence of early contact suggests a paracrine mechanism for the observed results.

No abstract

ADT is considered an effective first-line treatment for men with both advanced and non-metastatic prostate cancer. Despite the importance of ADT in prostate cancer treatment, ADT is associated with potential side effects, including BMD reduction, resulting in increased risk of osteoporosis and fractures. 1,2 The pathophysiologic reason is that when testosterone is reduced the usual balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption is disrupted, with bone resorption outstripping formation. Osteoclast activity is at least in part mediated by parathyroid hormone (PTH). Studies have shown that testosterone increases bone density by inhibiting PTHmediated osteoclast activity. 3-5 Testosterone also exerts a bone-protective effect via conversion to estrogen. In men who have low testosterone concentration due to ADT (or any cause), osteoclast activity is not appropriately inhibited, leading to increased bone resorption and therefore bone loss or osteoporosis. 6 It has been shown that during the first year of exposure to ADT, there is a five-to 10-fold increase in the rate of bone loss as well as fracture risk. This risk increases as the duration of ADT therapy increases. 7,8 In men with non-metastatic prostate cancer receiving ADT, BMD can be maintained or increased significantly by treatment with bisphosphonates, zoledronic acid, alendronate, or pamidronate. [9][10][11][12][13] At Loyola University Medical Center, 5222 men were diagnosed with prostate cancer between January 2006 and January 2014. Of 513 men who were treated with a gonadotropin-releasing-hormone (GnRH) agonist, 105 (20%) had a DXA scan. Of 487 men who were treated with antiandrogen therapy, 103 (21%) had a DXA. Out of 278 men who received both GnRH agonist and anti-androgen therapy, 64 (23%) received a DXA.These findings suggest that the deleterious effects of ADT on bone are not well recognized and that efforts should be made to raise the level of awareness of this important risk factor. Conflict of interestNone declared.

Introduction: Aortic pseudoaneurysm (AP) is a late complication of aortic repair. Without intervention, it carries a mortality rate up to 61%. Surgical repair has significant in-hospital mortality (6.9-12.6%) and high healthcare costs. Endovascular stent grafting has 15.2% all-cause mortality and 9.3% re-intervention rates. Percutaneous vascular plug/occluder technology emerged as a potentially safer and cheaper alternative to surgical AP closure. We will share our experience with this technology to enhance its success rate, safety, and cost-effectiveness. Methods: We retrospectively reviewed percutaneous AP closure cases with vascular plug/occluder technology published (2005 - 2016) and analyzed them alongside those performed at our institution (2017 - 2019). Results: We identified 40 cases of percutaneous AP closure with vascular plug/occluder technology in the literature and 10 performed at our institution. Our patients had a 1.9-day average length of stay with 100% successful targeted AP closure compared to 92% in the literature group. Over a 12-month median follow-up period (range 3-47 months), AP demonstrated stable or reduced sac size in 6 (60%) of our cases but increased in 4 (40%), necessitating surgical intervention. Literature cases had a 2-month median follow-up period with a 65% success rate. Death occurred in 40% of our patients from non-AP-related causes and in 8% of the literature group from AP closure-related complications. The cost per procedure was $49,580, which is hypothetically less than open surgical repair. Conclusion: Our experience shows a viable option for vascular plug/occluder technology in percutaneous AP repair, given its initial safety and cost-effectiveness. Our results highlight the critical role of follow-up imaging in identifying AP expansion and the need for further intervention. The high non-aorta-related mortality seen in follow-up emphasizes the high-risk nature of the population due to co-morbidities. .