HCMV-infection in a human arterial organ culture model: effects on cell proliferation and neointimal hyperplasia

<p>Abstract</p> <p>Background</p> <p>The impact of infections with the human cytomegalovirus (HCMV) for the development of atherosclerosis and restenosis is still unclear. Both a clear correlation and no correlation at all have been reported in clinical, mostly serological studies. In our study we employed a human non-injury ex vivo organ culture model to investigate the effect of an in vitro permissive HCMV-infection on cell proliferation and neointimal hyperplasia for a period of 56 days.</p> <p>Results</p> <p>During routine-nephrectomies parts of renal arteries from 71 patients were obtained and prepared as human organ cultures. Cell free HCMV infection was performed with the fibroblast adapted HCMV strain AD169, the endotheliotropic strain TB40E, and a clinical isolate (AN 365). After 3, 7, 14, 21, 28, 35, and 56 days in culture staining of HCMV-antigens was carried out and reactive cell proliferation and neointimal thickening were analysed. Successful HCMV-infection was accomplished with all three virus strains studied. During the first 21 days in organ culture no cell proliferation or neointimal hyperplasia was detected. At day 35 and day 56 moderate cell proliferation and neointimal hyperplasia was found both in HCMV-infected segments and mock infected controls. Neointimal hyperplasia in productively HCMV-infected segments was lower than in non infected at day 35 and day 56, but relatively higher after infection with the endotheliotropic TB40E in comparison with the two other strains.</p> <p>Conclusion</p> <p>The data do not support the hypothesis that HCMV-infection triggers restenosis via a stimulatory effect on cell proliferation and neointimal hyperplasia in comparison to non infected controls. Interestingly however, even after lytic infection, a virus strain specific difference was observed.</p

Human organ cultures with double stainings against HCMV-antigens and von Willebrand factor (identification of endothelial cells) or smooth muscle α-actin (identification of smooth muscle cells)

<p><b>Copyright information:</b></p><p>Taken from "HCMV-infection in a human arterial organ culture model: effects on cell proliferation and neointimal hyperplasia"</p><p>http://www.biomedcentral.com/1471-2180/7/68</p><p>BMC Microbiology 2007;7():68-68.</p><p>Published online 20 Jul 2007</p><p>PMCID:PMC1950876.</p><p></p> The endotheliotropic character of TB40E is demonstrated by the presence of HCMV early antigen after 3, 14, and 21 days (big arrow; A, B, C) within von Willebrand positive cells (small arrow); no smooth muscle α-actin positive cells are found in the area of the TB40E-virus (day 14; B). The tropism of AD169 as fibroblast adapted strain to smooth muscle cells is demonstrated by the presence of HCMV early antigen (big arrow; D, E, F) within α-actin positive cells (small arrow); no positive stainings against von Willebrand factor are found in the area of the AD169-virus (day 7; D)

[Secondary malignancies in urinary diversions]

In contrast to ureterosigmoidostomy no reliable clinical data exist for tumor risk in different forms of urinary diversion using isolated intestinal segments.In 44 German urological departments, operation frequencies, indications, patient age, and operation dates of the different forms of urinary diversion, operated between 1970 and 2007, could be registered. The secondary tumors up to 2009 were registered as well and related to the numbers of the different forms of urinary diversions resulting in tumor prevalences.In 17,758 urinary diversions 32 secondary tumors occurred. The tumor risk in ureterosigmoidostomy (22-fold) and cystoplasty (13-fold) is significantly higher than in other continent forms of urinary diversion such as neobladders or pouches (p<0.0001). The difference between ureterosigmoidostomy and cystoplasty is not significant, nor is the difference between ileocecal pouches (0.14%) and ileal neobladders (0.05%) (p=0.46). The tumor risk in ileocecal (1.26%) and colonic neobladders (1.43%) is significantly higher (p=0.0001) than in ileal neobladders (0.5%). Of the 16 tumors that occurred following ureterosigmoidostomy, 16 (94%) developed directly at the ureterocolonic borderline in contrast to only 50% following urinary diversions via isolated intestinal segments.From postoperative year 5 regular endoscopic controls of ureterosigmoidostomies, cystoplasties, and orthotopic (ileo-)colonic neobladders are necessary. In ileocecal pouches, regular endoscopy is necessary at least in the presence of symptoms or should be performed routinely at greater intervals. Following neobladders or conduits, only urethroscopies for urethral recurrence are necessary