[Guideline for evaluating drugs in chronic venous insufficiency. 10 May 2000 edition].
Explore the source record for details and available documents.
Chronic Disease↗
Biomedical subjects
W Vanscheidt
Publications and source records attributed to W Vanscheidt.
The role of the urokinase-type plasminogen activator (uPA) and its receptor (CD87) in lipodermatosclerosis.
BACKGROUND: Lipodermatosclerosis refers to a sclerosing panniculitis and dermopathy of the lower extremities sometimes seen in association with venous ulceration. Matrix metalloproteinases are implicated in the pathogenesis of venous leg ulcers and the in vitro activation of recombinant MMP-2 is controlled by the plasminogen activation system. To better understand the role of plasminogen activation in the pathogenesis of venous leg ulcers we investigated fibrinolytic factors and their inhibitors in tissue samples of lipodermatolsclerosis. METHODS: The expression and the functional state of the urokinase-type plasminogen activator (uPA), the tissue-type plasminogen activator (tPA), the urokinase receptor (CD87), the plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) were assayed using reverse transcription polymerase chain reaction, Western blot, fibrin zymography and immunohistochemistry analyses in tissue samples of lipodermatosclerosis. RESULTS: Our results provide direct evidence of elevated expression of uPA (p<0.01) and CD87 (p<0.01) mRNA and protein level in lipodermatosclerosis in comparison with healthy skin. By immunohistochemistry, elevated expression of uPA and CD87 could be detected. Fibrin zymography showed significantly elevated endogenous uPA activity (p<0.01) in liposclerotic lesions compared to healthy controls. CONCLUSION: Our findings indicate that elevated plasminogen activation in lipodermatosclerotic tissue may play a crucial role in the pathogenesis of venous leg ulceration.
Blotting, Western↗
Factor XIII-mediated inhibition of fibrinolysis and venous leg ulcers.
Densitometric analysis shows an accelerated healing rate and a significantly diminished lesional fibrinolytic activity in patients with venous leg ulcers treated topically with the fibrin-stabilising factor XIII compared with controls.
Administration, Topical↗
[Ulcus cruris. 1: Etiology, prevalence and diagnosis].
Explore the source record for details and available documents.
Diagnosis, Differential↗
[Therapy of lichen sclerosus et atrophicus vulvae with the CO2 silk touch laser].
A 50 year old woman with distinct lichen sclerosus et atrophicus was suffering from severe genital itching, dyspareunia and increasing urinary burning. Therapy attempts with topical glucosteroids and estrogens had been without effort. Treatment with CO2 laser in silk touch mode under insufflation anesthesia to an improvement of her skin lesions and a nearly complete remission of her symptoms.
Female↗
Guidelines for testing drugs for chronic venous insufficiency.
Explore the source record for details and available documents.
Bandages↗
Plasminogen activation in venous leg ulcers.
BACKGROUND: Venous leg ulceration results from chronic venous insufficiency of the lower extremities. We recently showed that matrix metalloproteinase (MMP) -2 plays a major part in the pathogenesis of venous leg ulcers. In vitro activation of recombinant MMP-2 is controlled by the activity of the urokinase-type plasminogen activator (uPA), which acts as a fibrin-independent plasminogen activator. The activity of MMP-2 is potentiated by binding of uPA to the uPA receptor (uPAR). OBJECTIVES: We aimed to clarify the role of plasminogen activation in venous leg ulcers. METHODS: The expression of uPA, uPAR, the tissue-type plasminogen activator, and plasminogen activator inhibitor (PAI) -1 and PAI-2 was investigated using reverse transcription followed by polymerase chain reaction and Western blotting. RESULTS: These provided direct evidence of elevated expression of uPA and uPAR at the mRNA and protein levels in venous leg ulcers, in comparison with healthy skin. By immunohistochemistry, elevated expression of uPA and uPAR was detected. Fibrin zymography showed significantly elevated endogenous uPA activity in venous leg ulcers in comparison with healthy controls. CONCLUSIONS: Our findings indicate venous leg ulcers to be characterized by elevated plasminogen activation, suggesting that this enzyme cascade plays a crucial part in maintaining proteolytic activity in venous leg ulcers.
Aged↗
Modulation of urokinase-type and tissue-type plasminogen activator occurs at an early stage of progressing stages of chronic venous insufficiency.
Chronic venous insufficiency (CVI) progresses through a series of clinical stages, from healthy skin to poorly healing leg ulcers. The aim of this study was to analyse the distribution pattern and activity level of urokinase-type (uPA) and tissue-type plasminogen activators (tPA) in normal skin and in tissue biopsies of progressing stages of CVI, prior to and including venous ulceration. Biopsies 6 mm thick were taken from 14 healthy volunteers and 37 patients with 5 different stages of CVI: telangiectases; stasis dermatitis; hyperpigmentation; lipodermatosclerosis; and leg ulcer. Changes in the enzymatic activity and spatial localization of uPA and tPA during the progression of CVI were examined using in situ histological zymography. Normal skin and skin with telangiectases showed a punctate PA activity, consisting of both uPA and tPA activity. As CVI progressed, an increase in the distribution of uPA and a decrease in tPA activity was observed. The spatial localization of uPA was widespread within the dermis of biopsies from stasis dermatitis and lipodermatosclerosis and was associated in particular with the dermoepidermal junction. Hyperpigmented skin revealed a pattern of PA expression similar to that of healthy skin. However, leg ulcer specimens exhibited peak levels of uPA with little tPA. Furthermore, a plasminogen-independent protease activity that was not present in any of the earlier stages of CVI appeared. Our results indicate that there are profound changes in PA activity during the progression of CVI and that these changes begin early in CVI, for example, in stasis dermatitis. We hypothesize that the balance or imbalance of the PA activity in the later stages of CVI is an important pathogenic factor for the development of venous leg ulcer.
Adult↗
Autologous platelet-derived wound healing factor promotes angiogenesis via alphavbeta3-integrin expression in chronic wounds.
Healing of venous leg ulcers depends on the adhesive interaction and formation of new vascular cells. Angiogenesis on the surface of angiogenic blood vessels requires the vascular integrin alphavbeta3 also known as the vitronectin receptor. Autologous platelet-derived wound healing factor (autologous PDWHF) has been described to regulate the wound healing process by forming granulation tissue in the early healing phase. Here we analysed the influence of autologous PDWHF on the expression of the alphavbeta3 integrin in tissue specimen of venous leg ulcers in comparison with placebo treated controls by using reverse transcriptase-polymerase chain reaction and immunohistochemistry. Our investigations provide evidence that mRNA and protein expression of alphavbeta3 were significantly increased in healing venous leg ulcers after 96 h treatment (p<0.05), whereas the total amount of alphavbeta3 mRNA and protein was not altered in placebo treated patients. In healing leg ulcers the alphavbeta3 integrin was predominantly localized around capillary vessels preferentially at sites of newly formed granulation tissue. Placebo controlled patients displayed no altered expression of the alphavbeta3 integrin in biopsy specimen. These findings suggest that topical autologous platelet-derived wound healing factor influences the process of angiogenesis/revascularization via alphavbeta3 integrin-expression hereby promoting granulation tissue formation in healing leg ulcers.
Aged↗
[Hyperbaric oxygenation therapy in wound healing disorders?].
Explore the source record for details and available documents.
Anti-Bacterial Agents↗
[Tumescent technique for local anesthesia. Use and prospectives of aa new anesthetic method].
The tumescent technique for local anesthesia (TLA) involves the infiltration of the subcutaneous fatty tissue with a large volume of a diluted local anesthetic. This large added volume increases the tension in the tissue, creating more favorable conditions for the action of the analgesic and for dermatological operative measures. Originally developed for use in the area of liposuction, TLA has since proved to have advantages over other forms of analgesia in numerous other dermatological indications. Overall, TLA is an effective and practical analgesic technique associated with comparatively few side effects that has been shown to be very useful in surgery of the skin.
Adipose Tissue↗
[Gene and protein family of matrix metalloproteinases. Structure, function and expression in the skin].
Explore the source record for details and available documents.
Gene Expression Regulation, Enzymologic↗
Treatment of hyperkeratosis areolae mammae naeviformis with the carbon dioxide laser.
Hyperkeratosis of the nipple and areola is a rare mamma condition. Typical lesions are characterized by persistent verrucous thickening and dark pigmentation of the nipple or areola (or both) and may occur unilaterally or bilaterally in both sexes. We report what we believe to be the first therapeutic trial with carbon dioxide laser in a patient with hyperkeratosis areolae mammae naeviformis.
Adult↗
Expression of the adhesion molecules ICAM-1, VCAM-1, LFA-1 and VLA-4 in the skin is modulated in progressing stages of chronic venous insufficiency.
In inflammation and wound healing, dynamic changes in cell adhesion and migration are fundamental properties of the cells involved. Disturbed interaction of leukocytes with microvascular endothelial cells has been proposed to be a central pathogenic factor in chronic venous insufficiency. This disease may therefore serve to elucidate dysregulated modulation of adhesion molecule expression in conditions of chronic inflammation and impaired wound healing. In this study, we determined how the expression of ICAM-1/VCAM-1 on endothelial cells and their ligands LFA-1/VLA-4 on leukocytes is modulated in skin of progressing stages of chronic venous insufficiency. Immunohistochemical staining of skin biopsies revealed an increase in the expression of ICAM-1 and VCAM-1 on endothelial cells in an early stage of venous disease such as stasis dermatitis. Such protein expression correlated with an increase of corresponding mRNA in skin biopsies. Expression of these CAMs on endothelial cells was accompanied by the occurrence of a marked perivascular infiltration of leukocytes, which expressed increased levels of LFA-1 and VLA-4. In progressing stages of chronic venous insufficiency, characterized by hyperpigmentation and lipodermatosclerosis, which precede skin ulceration, all these CAMs remained upregulated on endothelial cells and infiltrating leukocytes. Our findings indicate that following an initial peak expression during stasis dermatitis, vascular ICAM-1 and VCAM-1 expression is not downmodulated to baseline levels, but remains upregulated. This possibly promotes tissue damage by a perpetuated, upregulated influx of activated leukocytes, finally leading to skin ulceration.
Adult↗
Metastasizing porocarcinoma of the head with lethal outcome.
Porocarcinoma is a very rare malignant tumor arising from the duct of eccrine sweat glands. Its prognosis is variable. We report on a patient who developed lymph node and multiple distant metastases, and who died of this malignancy only 6 months after the initial diagnosis.
Abdominal Neoplasms↗