ABSTRACT
Previously, the presence of a blood-myenteric plexus barrier and its disruption was reported in experimentally induced colitis via a macrophage-dependent process. The aim of this study is to reveal how myenteric barrier disruption and subsequent neuronal injury affects gut motility in vivo in a murine colitis model. We induced colitis with dextran sulfate sodium (DSS), with the co-administration of liposome-encapsulated clodronate (L-clodronate) to simultaneously deplete blood monocytes contributing to macrophage infiltration in the inflamed muscularis of experimental mice. DSS-treated animals receiving concurrent L-clodronate injection showed significantly decreased blood monocyte numbers and colon muscularis macrophage (MM) density compared to DSS-treated control (DSS-vehicle). DSS-clodronate-treated mice exhibited significantly slower whole gut transit time than DSS-vehicle-treated animals and comparable to that of controls. Experiments with oral gavage-fed Evans-blue dye showed similar whole gut transit times in DSS-clodronate-treated mice as in control animals. Furthermore, qPCR-analysis and immunofluorescence on colon muscularis samples revealed that factors associated with neuroinflammation and neurodegeneration, including Bax1, Hdac4, IL-18, Casp8 and Hif1a are overexpressed after DSS-treatment, but not in the case of concurrent L-clodronate administration. Our findings highlight that MM-infiltration in the muscularis layer is responsible for colitis-associated dysmotility and enteric neuronal dysfunction along with the release of mediators associated with neurodegeneration in a murine experimental model.
Subject(s)
Clodronic Acid , Colitis , Mice , Animals , Clodronic Acid/pharmacology , Colitis/chemically induced , Inflammation , Macrophages , Colon , Dextran Sulfate/toxicity , Mice, Inbred C57BL , Disease Models, AnimalABSTRACT
Ectopic pregnancy is a major gynecologic emergency, and remains a life-threatening syndrome. Hepatic pregnancy is an exceptionally rare form of ectopic pregnancy. The authors present a case of a 28 year old woman, who was admitted to hospital with epigastric pain. Diagnostic investigations showed a rare, 16-week-old ectopic pregnancy in the liver. The authors emphasise the importance of early diagnosis and management of ectopic pregnancy in order to reduce maternal mortality.
