No abstract

There is increasing evidence that parasitic helminth infection has the ability to ameliorate other disease conditions. In this study the ability of the rat tapeworm, Hymenolepis diminuta, to modulate dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice is assessed. Mice receiving DNBS (3 mg intrarectally) developed colitis by 72 h after treatment. Mice infected 8 days before DNBS with five H. diminuta larvae were significantly protected from the colitis, as gauged by reduced clinical disease, histological damage scores, and myeloperoxidase levels. This anticolitic effect was dependent on a viable infection and helminth rejection, because no benefit was observed in mice given killed larvae or in infected STAT6 knockout mice or rats, neither of which eliminate H. diminuta. The anticolitic effect of H. diminuta was associated with increased colonic IL-10 mRNA and stimulated splenocytes from H. diminuta- plus DNBS-treated mice produced more IL-10 than splenocytes from DNBS-only treated mice. Coadministration of an anti-IL-10 Ab blocked the anticolitic effect of prophylactic H. diminuta infection. Also, mice infected 48 h after DNBS treatment showed an enhanced recovery response. Finally, using a model of OVA hypersensitivity, we found no evidence of concomitant H. diminuta infection enhancing enteric responsiveness to subsequent ex vivo OVA challenge. The data show that a viable infection of H. diminuta in a nonpermissive system exerts a profound anticolitic effect (both prophylactically and as a treatment) that is mediated at least in part via IL-10 and does not predispose to enhanced sensitivity to bystander proteins.

Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is an enteric pathogen that causes potentially fatal symptoms after intimate adhesion, modulation of intestinal epithelial signal transduction, and alteration of epithelial function (eg, barrier disruption). Although the epithelial barrier is critical to gut homeostasis, only a few agents, such as transforming growth factor (TGF)-beta, can enhance or protect epithelial barrier function. Our aims were to delineate the mechanism(s) behind TGF-beta-induced barrier enhancement and to determine whether TGF-beta could prevent EHEC-induced barrier disruption. Using monolayers of the human T84 colonic epithelial cell line, we found that TGF-beta induced a significant increase in transepithelial electrical resistance (a measure of paracellular permeability) through activation of ERK MAPK and SMAD signaling pathways and up-regulation of the tight junction protein claudin-1. Additionally, TGF-beta pretreatment of epithelia blocked the decrease in transepithelial electrical resistance and the increase in transepithelial passage of [(3)H]-mannitol caused by EHEC infection. EHEC infection was associated with reduced expression of zonula occludens-1, occludin, and claudin-2 (but not claudin-1 or claudin-4); TGF-beta pretreatment prevented these changes. These studies provide insight into EHEC pathogenesis by illustrating the mechanisms underlying TGF-beta-induced epithelial barrier enhancement and identifying TGF-beta as an agent capable of blocking EHEC-induced increases in epithelial permeability via maintenance of claudin-2, occludin, and zonula occludens-1 levels.

BackgroundCOVID-19 infections have been shown to be associated with a range of thromboembolic disease.ObjectiveTo describe our endovascular experience in a consecutive series of patients with COVID-19 who presented with large vessel occlusions, and to describe unique findings in this population.MethodsMechanical thrombectomy was performed on five consecutive patients with COVID-19 with large vessel occlusions. A retrospective study of these patients was performed. Patient demographics, laboratory values, mechanical thrombectomy technique, and clinical and angiographic outcomes were reviewed.ResultsFour patients with COVID-19 presented with anterior circulation occlusions and one patient with COVID-19 presented with both anterior and posterior circulation occlusions. All patients had coagulation abnormalities. Mean patient age was 52.8 years. Three patients presented with an intracranial internal carotid artery occlusion. Two patients presented with an intracranial occlusion and a tandem thrombus in the carotid bulb. One patient presented with an occlusion in both the internal carotid and basilar arteries. Clot fragmentation and distal emboli to a new vascular territory were seen in two of five (40%) patients, and downstream emboli were seen in all five (100%) patients. Patient clinical outcome was generally poor in this series of patients with COVID-19 large vessel occlusion.ConclusionOur series of patients with COVID-19 demonstrated coagulation abnormalities, and compared with our previous experience with mechanical thrombectomy in large vessel occlusion, this group of patients were younger, had tandem or multiple territory occlusions, a large clot burden, and a propensity for clot fragmentation. These patients present unique challenges that make successful revascularization difficult.