Acute pulmonary and splenic response in an in vivo model of whole-body low-dose X-radiation exposure.

Purpose: Diagnostic radiation is an important part of patient care in the Intensive Care Unit; however, there is little data on the acute effects of exposure to these doses. We investigated pulmonary and splenic response 30 minutes, 4 hours or 24 hours after exposure to 2 mGy, 20 mGy, 200 mGy or 4 Gy whole-body X-radiation in a Sprague Dawley rat model. Materials and methods: Lung injury was assessed via respiratory mechanics, pulmonary edema, cellular, and proteinaceous fluid infiltrate and protein expression of oxidative stress markers. The radiation effect on the spleen was determined via proliferation, apoptosis and protein expression of oxidative stress markers. Results: All measurements of the lung did not differ from sham animals except for an increase in catalase after high dose exposure. Stimulated splenocyte proliferation increased after sham and low dose exposure, did not change after 200 mGy exposure and was significantly lower after 4 Gy exposure. The number of apoptotic cells increased 4 hours after 4 Gy exposure. There were fewer apoptotic cells after low dose exposure compared to sham. Both catalase and MnSOD were increased after 4 Gy exposure. Conclusion: There was no measured effect on pulmonary function while there was an impact to the spleen after low and high dose exposure.

Giardia duodenalis induces pathogenic dysbiosis of human intestinal microbiota biofilms.

Giardia duodenalis is a prevalent cause of acute diarrheal disease worldwide. However, recent outbreaks in Italy and Norway have revealed a link between giardiasis and the subsequent development of chronic post-infectious irritable bowel syndrome. While the mechanisms underlying the causation of post-infectious irritable bowel syndrome remain obscure, recent findings suggest that alterations in gut microbiota communities are linked to the pathophysiology of irritable bowel syndrome. In the present study, we use a laboratory biofilm system to culture and enrich mucosal microbiota from human intestinal biopsies. Subsequently, we show that co-culture with Giardia induces disturbances in biofilm species composition and biofilm structure resulting in microbiota communities that are intrinsically dysbiotic - even after the clearance of Giardia. These microbiota abnormalities were mediated in part by secretory-excretory Giardia cysteine proteases. Using in vitro cell culture and germ-free murine infection models, we show that Giardia-induced disruptions of microbiota promote bacterial invasion, resulting in epithelial apoptosis, tight junctional disruption, and bacterial translocation across an intestinal epithelial barrier. Additionally, these dysbiotic microbiota communities resulted in increased activation of the Toll-like receptor 4 signalling pathway, and overproduction of the pro-inflammatory cytokine IL-1beta in humanized germ-free mice. Previous studies that have sought explanations and risk factors for the development of post-infectious irritable bowel syndrome have focused on features of enteropathogens and attributes of the infected host. We propose that polymicrobial interactions involving Giardia and gut microbiota may cause persistent dysbiosis, offering a new interpretation of the reasons why those afflicted with giardiasis are predisposed to gastrointestinal disorders post-infection.