Reports of cytomegalovirus (CMV) colitis mainly concern patients with immunocompromisation resulting from, among others, HIV infection, allogeneic bone marrow transplantation and solid organ transplantation. CMV colit...Reports of cytomegalovirus (CMV) colitis mainly concern patients with immunocompromisation resulting from, among others, HIV infection, allogeneic bone marrow transplantation and solid organ transplantation. CMV colitis rarely occurs during standard chemotherapy for non-Hodgkin’s lymphoma (NHL). An unusual case of CMV enterocolitis in a 62-year-old patient is reported. After a first course of salvage chemotherapy for NHL, diffuse erosions and sloughing mucosa were seen throughout the large bowel. The final diagnosis was based on histological findings. Although ganciclovir and foscarnet are effective for CMV viremia, their use in the treatment of severe diarrhea in our patient did not result in improvement for one week, whereas concomitant use of octreotide led to rapid improvement. Octreotide may therefore be an effective agent for severe colitis.展开更多
AIM: To evaluate the natural history of human cytomegalovirus (HCMV) infection in a series of 28 ulcerative colitis patients in whom the search for HCMV was positive. METHODS: A series of 85 patients with moderate...AIM: To evaluate the natural history of human cytomegalovirus (HCMV) infection in a series of 28 ulcerative colitis patients in whom the search for HCMV was positive. METHODS: A series of 85 patients with moderate-se- vere ulcerative colitis flare-up were evaluated for a HCMV search by performing a haematoxylin and eosin stain, immunohistochemical assay and nested polymerase chain reaction on rectal biopsies. Among 85 screened patients (19 of whom were steroid resistant/dependant), 28 were positive for HCMV; after remission the patients were followed up clinically and histologically. RESULTS: Among the 22 patients with complete follow- up, in 8 (36%) patients HCMV-DNA persisted in the in- testinal specimens. Among the HCMV positive patients, 4 (50%) experienced at least one moderate-severeflare-up of colitis without evidence of peripheral HCMV. Among the 14 HCHV negative patients, 3 with pouches developed pouchiUs and 5 out of 11 (45%) experienced a colitis flare-up. CONCLUSION: Our preliminary results suggest that HCHV may remain in the colon afber an acute coltis flare- up despite remission; it seems that the virus is not responsible for the disease relapse.展开更多
AIM:To explore the anti-inflammatory potential of adeno-associated virus-mediated delivery of Tregitope 167 in an experimental colitis model.METHODS:The trinitrobenzene sulfonate(TNBS) model of induced colitis was use...AIM:To explore the anti-inflammatory potential of adeno-associated virus-mediated delivery of Tregitope 167 in an experimental colitis model.METHODS:The trinitrobenzene sulfonate(TNBS) model of induced colitis was used in Balb/c mice.Subsequently after intravenous adeno-associated virusmediated regulatory T-cell epitopes(Tregitope) delivery,acute colitis was initiated by intra-rectal administration of 1.5 mg TNBS in 40% ethanol followed by a second treatment with TNBS(0.75 mg in 20% ethanol) 8 d later.Control groups included mice not treated with TNBS(healthy control group) and mice treated by TNBS only(diseased group).At the time of sacrifice colon weight,the disease activity index and histology damage score were determined.Immunohistochemical staining of the colonic tissues was performed to asses the cellular infiltrate and the presence of transcription factor forkhead Box-P3(Foxp3).Thymus,mesenteric lymph nodes,liver and spleen tissue were collected and the corresponding lymphocyte populations were further assessed by flow cytometry analysis for the expression of CD4+ T cell and regulatory T cell associated markers.RESULTS:The Tregitope 167 treated mice gained an average of 4% over their initial body weight at the time of sacrifice.In contrast,the mice treated with TNBS alone(no Tregitope) developed colitis,and lost 4% of their initial body weight at the time of sacrifice(P < 0.01).The body weight increase that had been observed in the mice pre-treated with Tregitope 167 was substantiated by a lower disease activity index and a decreased colon weight as compared to the diseased control group(P < 0.01 and P < 0.001,respectively).Immunohistochemical staining of the colonic tissues for CD4+ showed that inflammatory cell infiltrates were present in TNBS treated mice with or without administration with tregitope 167 and that these cellular infiltrates consisted mainly of CD4+ cells.For both TNBS treated groups CD4+ T cell infiltrates were observed in the sub-epithelial layer and the lamina propria.CD4+ T cell infiltrates were also present in the muscularis mucosa layer of the diseased control mice,but were absent in the Tregitope 167 treated group.Numerous Foxp3 positive cells were detected in the lamina propria and sub-epithelium of the colon sections from mice treated with Tregitope 167.Furthermore,the Foxp3 and glycoprotein A repetitions predominant markers were significantly increased in the CD4+ T lymphocyte population in the thymus of the mice pre-treated with adeno-associated virus serotype 5(cytomegalovirus promoter-Tregitope 167),as cytomegalovirus promoter compared to lymphocyte populations in the thymus of diseased and the healthy control mice(P < 0.05 and P < 0.001,respectively).CONCLUSION:This study identifies adeno-associated virus-mediated delivery of regulatory T-cell epitope 167 as a novel anti-inflammatory approach with the capacity to decrease intestinal inflammation and induce longterm remission in inflammatory bowel disease.展开更多
文摘Reports of cytomegalovirus (CMV) colitis mainly concern patients with immunocompromisation resulting from, among others, HIV infection, allogeneic bone marrow transplantation and solid organ transplantation. CMV colitis rarely occurs during standard chemotherapy for non-Hodgkin’s lymphoma (NHL). An unusual case of CMV enterocolitis in a 62-year-old patient is reported. After a first course of salvage chemotherapy for NHL, diffuse erosions and sloughing mucosa were seen throughout the large bowel. The final diagnosis was based on histological findings. Although ganciclovir and foscarnet are effective for CMV viremia, their use in the treatment of severe diarrhea in our patient did not result in improvement for one week, whereas concomitant use of octreotide led to rapid improvement. Octreotide may therefore be an effective agent for severe colitis.
文摘AIM: To evaluate the natural history of human cytomegalovirus (HCMV) infection in a series of 28 ulcerative colitis patients in whom the search for HCMV was positive. METHODS: A series of 85 patients with moderate-se- vere ulcerative colitis flare-up were evaluated for a HCMV search by performing a haematoxylin and eosin stain, immunohistochemical assay and nested polymerase chain reaction on rectal biopsies. Among 85 screened patients (19 of whom were steroid resistant/dependant), 28 were positive for HCMV; after remission the patients were followed up clinically and histologically. RESULTS: Among the 22 patients with complete follow- up, in 8 (36%) patients HCMV-DNA persisted in the in- testinal specimens. Among the HCMV positive patients, 4 (50%) experienced at least one moderate-severeflare-up of colitis without evidence of peripheral HCMV. Among the 14 HCHV negative patients, 3 with pouches developed pouchiUs and 5 out of 11 (45%) experienced a colitis flare-up. CONCLUSION: Our preliminary results suggest that HCHV may remain in the colon afber an acute coltis flare- up despite remission; it seems that the virus is not responsible for the disease relapse.
基金Supported by Grant from the Broad Medical Research Program of The Broad Foundation,No. IBD-029 5R
文摘AIM:To explore the anti-inflammatory potential of adeno-associated virus-mediated delivery of Tregitope 167 in an experimental colitis model.METHODS:The trinitrobenzene sulfonate(TNBS) model of induced colitis was used in Balb/c mice.Subsequently after intravenous adeno-associated virusmediated regulatory T-cell epitopes(Tregitope) delivery,acute colitis was initiated by intra-rectal administration of 1.5 mg TNBS in 40% ethanol followed by a second treatment with TNBS(0.75 mg in 20% ethanol) 8 d later.Control groups included mice not treated with TNBS(healthy control group) and mice treated by TNBS only(diseased group).At the time of sacrifice colon weight,the disease activity index and histology damage score were determined.Immunohistochemical staining of the colonic tissues was performed to asses the cellular infiltrate and the presence of transcription factor forkhead Box-P3(Foxp3).Thymus,mesenteric lymph nodes,liver and spleen tissue were collected and the corresponding lymphocyte populations were further assessed by flow cytometry analysis for the expression of CD4+ T cell and regulatory T cell associated markers.RESULTS:The Tregitope 167 treated mice gained an average of 4% over their initial body weight at the time of sacrifice.In contrast,the mice treated with TNBS alone(no Tregitope) developed colitis,and lost 4% of their initial body weight at the time of sacrifice(P < 0.01).The body weight increase that had been observed in the mice pre-treated with Tregitope 167 was substantiated by a lower disease activity index and a decreased colon weight as compared to the diseased control group(P < 0.01 and P < 0.001,respectively).Immunohistochemical staining of the colonic tissues for CD4+ showed that inflammatory cell infiltrates were present in TNBS treated mice with or without administration with tregitope 167 and that these cellular infiltrates consisted mainly of CD4+ cells.For both TNBS treated groups CD4+ T cell infiltrates were observed in the sub-epithelial layer and the lamina propria.CD4+ T cell infiltrates were also present in the muscularis mucosa layer of the diseased control mice,but were absent in the Tregitope 167 treated group.Numerous Foxp3 positive cells were detected in the lamina propria and sub-epithelium of the colon sections from mice treated with Tregitope 167.Furthermore,the Foxp3 and glycoprotein A repetitions predominant markers were significantly increased in the CD4+ T lymphocyte population in the thymus of the mice pre-treated with adeno-associated virus serotype 5(cytomegalovirus promoter-Tregitope 167),as cytomegalovirus promoter compared to lymphocyte populations in the thymus of diseased and the healthy control mice(P < 0.05 and P < 0.001,respectively).CONCLUSION:This study identifies adeno-associated virus-mediated delivery of regulatory T-cell epitope 167 as a novel anti-inflammatory approach with the capacity to decrease intestinal inflammation and induce longterm remission in inflammatory bowel disease.