Evaluation of apoptotic cells and immunohistochemical detection of FAS, FAS-L, Bcl-2, Bax, p53 and c-Myc in the skin of patients with chronic venous leg ulcers

Section: Immunohistochemistrymentioning

confidence: 99%

Changes in levels of apoptosis in the walls of different segments of great saphenous varicose veins

Han

Wang

et al. 2016

“…The immunohistochemical techniques and the TUNEL assay which were used have been described elsewhere. 13,18 For the histologic analysis, five fields per section were examined for staining at Â400 magnification. The immunohistochemical expression of apoptotic cells was determined according to the intensity of nuclear staining and the density and morphology of chromatin.…”

Section: Immunohistochemistry and Tunel Stainingmentioning

confidence: 99%

Dysregulated apoptosis of the venous wall in chronic venous disease and portal hypertension

Wang

et al. 2016

Introduction The etiology of varicose veins remains elusive. We hypothesized that abnormal cell cycle events in the vein wall may contribute to changes in the structural integrity, thus predisposing to the development of varicosities. The present study was designed to determine whether or not the same molecular apoptotic pathway exists between great saphenous and splenic veins. Methods Thirty-six samples of diseased splenic veins and varicose great saphenous veins were collected. Twenty-five samples of control splenic and great saphenous veins were also collected. The apoptotic cell proteins expression was immunohistochemically stained with antibodies (anti-Bax and anti-Bcl-xl). Apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay and immunofluorescence staining. The morphology of apoptotic cells was observed with an electron microscope. Results The apoptotic ratio in walls (intima and media) of diseased splenic vein and varicose great saphenous vein groups were significantly lower than the corresponding regions in the splenic vein and great saphenous vein groups ( p < 0.01), respectively. A significant difference was not noted in the ratio change of apoptotic cells between the diseased splenic vein and varicose great saphenous vein groups ( p > 0.05). The high positive expression of Bcl-xl proteins was detected in the diseased splenic vein and varicose great saphenous vein groups, respectively. While the high positive expression of Bax proteins was also observed in the splenic vein and great saphenous vein groups, respectively. Electron microscopic observations confirmed that endothelial and smooth muscle cells in diseased splenic vein, varicose great saphenous vein, splenic vein, and great saphenous vein walls exhibited apoptotic morphologic features, such as fuzzy mitochondrial cristae, medullary changes, and margination of the nuclear chromatin. Conclusions Our results showed the same dysregulation of apoptosis via the intrinsic pathway in diseased splenic veins and varicose great saphenous veins. This observational study suggests that apoptotic down-regulation in the veins wall is a cause of diseased splenic veins and varicose great saphenous veins, but does not exclude the possibility that other mechanisms are involved.

“…42 As with fibroblasts, the molecular mechanisms underlying keratinocyte failure remain unclear and are the subject of ongoing investigations. 43,44…”

Section: Aetiologymentioning

confidence: 99%

“…42 As with fibroblasts, the molecular mechanisms underlying keratinocyte failure remain unclear and are the subject of ongoing investigations. 43,44 Thrombophilia Some of the most severe and intractable CVU occur as part of the postphlebitic syndrome, especially when it develops following proximal and recurrent DVT. In a recent study of CVU patients screened for the factor V Leiden and prothrombin 20210A mutations; antithrombin, protein C and S deficiencies; antiphospholipid antibodies; hyperhomocysteinaemia (HHcy) and factor VIII, IX and XI levels, the overall prevalence of single and multiple thrombophilias were found to be significantly higher than in age-and sex-matched controls without venous disease.…”

Section: Failure Of Epithelializationmentioning

confidence: 99%

Epidemiology and aetiology of C4–6 disease

Bradbury

2010

Although our understanding of chronic venous insufficiency (CVI) has improved, many important questions remain unanswered. Ensuring that patients are appropriately referred for specialist assessment and then receive evidence-based, cost-effective treatment continues to be challenging. The lifetime of risk of chronic venous ulceration (CVU) is around 1% with approximately 10% ulcers being open at any one time. The incidence skin changes disease is about 10 times greater (10%). However, many of the studies upon which these estimates are based are old and/or methodologically flawed. There is reason to believe that the incidence, prevalence and characteristics of CVI/CVU may have changed considerably over the last 10-20 years and that future change is likely. Further cross-sectional and longitudinal epidemiological studies are required to establish the size and nature of the health-care need going forward in developed and increasingly developing countries. CVI culminating CVU is primarily the result of sustained ambulatory venous hypertension, which in turn arises from superficial and/or deep venous reflux with or without deep vein obstruction. However, there are many other elements to this complex condition, for example, microvascular dysfunction; calf muscle pump efficiency; dermal inflammation; disordered fibroblast function and matrix production; failure of epithelialization; congenital and acquired thrombophilia; malnutrition, obesity and diet; and bacterial colonization. None of the currently available treatment modalities is entirely satisfactory and novel therapies based upon a clearer understanding of the disease at the psychological, genetic, mechanical, microvascular and microscopic level are required.