Cutaneous leishmaniasis (CL) is caused by Leishmania infection of dermal macrophages and is associated with chronic inflammation of the skin. L. aethiopica infection displays two clinical manifestations, firstly ulcerative disease, correlated to a relatively low parasite load in the skin, and secondly non-ulcerative disease in which massive parasite infiltration of the dermis occurs in the absence of ulceration of epidermis. Skin ulceration is linked to a vigorous local inflammatory response within the skin towards infected macrophages. Fas ligand (FasL) and Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expressing cells are present in dermis in ulcerative CL and both death ligands cause apoptosis of keratinocytes in the context of Leishmania infection. In the present report we show a differential expression of FasL and TRAIL in ulcerative and non-ulcerative disease caused by L. aethiopica. In vitro experiments confirmed direct FasL- and TRAIL-induced killing of human keratinocytes in the context of Leishmania-induced inflammatory microenvironment. Systemic neutralisation of FasL and TRAIL reduced ulceration in a model of murine Leishmania infection with no effect on parasitic loads or dissemination. Interestingly, FasL neutralisation reduced neutrophil infiltration into the skin during established infection, suggesting an additional proinflammatory role of FasL in addition to direct keratinocyte killing in the context of parasite-induced skin inflammation. FasL signalling resulting in recruitment of activated neutrophils into dermis may lead to destruction of the basal membrane and thus allow direct FasL mediated killing of exposed keratinocytes in vivo. Based on our results we suggest that therapeutic inhibition of FasL and TRAIL could limit skin pathology during CL.
Though appendicitis is the most common cause of acute abdomen, the vermiform appendix as a cause of small bowel obstruction is a rarity. The inflamed appendix can cause obstruction by making a knot around the small bowel. There are only few case reports on Appendico-ileal knotting (AIK). We have not found any report on AIK causing small bowel obstruction during pregnancy. The diagnosis of acute abdomen in pregnancy is difficult due to the accompanying anatomic and physiologic changes. Because obstruction due to AIK present like any other cause of obstruction diagnosing the condition pre-operatively is uncommon. Here, we report 30 years old Gravida 9, Para 8 women who presented with cardinal symptoms of small bowel obstruction at term and found to have AIK intra-operatively. The challenge of difficulty in making the diagnosis and management options are discussed
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