Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uniform view of chronic venous diseases has been formed in the last 3 decades. Chronic venous insufficiency (CVI) is a functional disorder of the venous system of the lower limb. The basis of the pathology is always the venous hypertension caused by valvular insufficiency and reflux with or without venous outflow obstruction. Epifascial, subfascial and transfascial forms of CVI can be distinguished. In the practice these forms are almost always combined. The consistent venous hypertension is the initiating factor in alterations in the microcirculation which leads to skin changes and venous ulceration. The precise mechanism of the development of venous leg ulcer is still uncertain. A recent hypothesis suggests that leukocytes are trapped in the capillaries and attaching to the endothel they become activated and release proteolytic enzymes, free radicals which have destructive effects on lipid membranes, proteins as well as on many connective tissue compounds. The endothelium plays active role in the complex mechanism. Increased expression of tissue metalloproteinases has been observed in the periulcer skin. The presence of perivascular leukocyte infiltration and fibrin cuff is a reflexion of an inflammatory process. The clinical stages of CVI are likely to be the results of a systemic inflammatory response to a period of venous hypertension.
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PMID:Pathomechanism of chronic venous insufficiency and leg ulcer. 1548 13

Initially, the progression of chronic venous insufficiency is related to venous hypertension. The earliest complaints or symptoms, as well as vessel wall deterioration, valve restructuring, and, eventually, varicose veins, result not only from elevation of pressure, but also from a cascade of biochemical events related to both the macro- and the microcirculation. Thickening and remodelling of the venous wall are influenced by two parameters: abnormal shear stress and hypoxia that activate the endothelium first at the level of valve cusps and then in large veins. Hypoxia leads to activation of the endothelium and leukocyte accumulation. By inhibiting endothelial activation, micronized purified flavonoid fraction (MPFF) (Daflon 500 mg), an edema-protective agent, can prevent the inflammatory cascade resulting from the leukocyte-endothelium interaction. This subsequently delays the appearance of reflux and inhibits the initiation of the vicious circle ending in enhanced venous pressure. This is how Daflon 500 mg relieves patients from symptoms and edema and possibly also prevents the appearance of varicose veins. Rheological disturbances also play a major role in the appearance of these disorders. Furthermore, venous hypertension provokes leakage from the vessels and capillaries exhibiting increased permeability, leading to increases in hydrostatic load, and overloading of the lymphatic network, which subsequently results fluid exudation causing edema. Microcirculatory dysfunction leads to capillary damage, skin changes and venous leg ulcers. The clinical efficacy of Daflon 500 mg in venous leg ulcers has been demonstrated by several randomised controlled studies, in which the rate of ulcer healing was significantly shortened. An explanation for the ability to speed ulcer healing comes from the protection Daflon 500 mg exerts on the microcirculation.
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PMID:Micronized purified flavonoid fraction (MPFF): a review of its pharmacological effects, therapeutic efficacy and benefits in the management of chronic venous insufficiency. 1564 40

Patients with venous leg ulcers usually have extensive symptoms both related to their venous insufficiency and to the wound itself, often combined with a reduced quality of life. Prevalence of venous leg ulcers varies from 0.1 to 1.0%. Treatment costs are high and may amount to 1.5% of a nation's total spending on health care. Venous hypertension is the common denominator for all patients with venous leg ulcers. Isolated superficial as well as deep or combined venous insufficiency with or without insufficient perforators may cause ulceration. In the microcirculation, inflammation is involved, but the exact mechanisms behind the ulcer formation remain unresolved. During the examination, a presence of superficial venous insufficiency accessible for superficial resection must be established. In addition to a clinical examination, venous pressure measurements/plethysmography and colour duplex scanning is recommended in order to locate and evaluate the significance of the venous insufficiency. The key element in the treatment of venous ulcers is to reduce oedema and venous hypertension by adequate compression and elevation. If primary superficial venous insufficiency is established, venous resection is recommended. This may improve healing and reduce recurrences. In selected patients, deep venous reconstruction is an alternative approach.
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PMID:[Venous leg ulcers]. 1581 37

Recent histologic and immunocytochemical evidence of venous leg ulcers supports the hypothesis that lesions observed at different stages of chronic venous insufficiency may be associated with, and possibly caused by, an inflammatory process. Evidence has been obtained that venous valve deficiency may be associated with leukocyte infiltration into valve leaflets; therefore, it is hypothesized that an essential event in the inflammatory cascade is the enzymatic degradation of the valve leaflets and venous wall. The metalloproteinases (MMP) in veins exposed to elevated pressures up to 6 weeks were examined in a rat femoral fistula model with venous hypertension. Zymography shows increased activity of pro-MMP-2 at 3 and 6 weeks. MMP-2 and MMP-9 activity was predominantly observed at days 7 and 21 after creation of the fistula. The degree of extracellular matrix remodeling correlates with the morphological finding of macroscopic lesions. Therefore, the MMP-2 and MMP-9 activation is already present in veins days after exposure to elevated blood pressure and coincides with periods of early alterations in the valve morphology and early forms of reflux.
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PMID:Venous hypertension and the inflammatory cascade: major manifestations and trigger mechanisms. 1619 24

Recent histological and immunocytochemical analyses of venous leg ulcers suggest that lesions observed in the different stages of chronic venous insufficiency (CVI) may be related to an inflammatory process. This inflammatory process leads to fibrosclerotic remodeling of the skin and then to ulceration. The vascular network of the most superficial layers of the skin appears to be the target of the inflammatory reaction. Hemodynamic forces such as venous hypertension, circulatory stasis, and modified conditions of shear stress appear to play an important role in an inflammatory reaction accompanied by leukocyte activation which clinically leads to CVI: venous dermatitis and venous ulceration. The leukocyte activation is accompanied by the expression of integrins and by synthesis and release of many inflammatory molecules, including proteolytic enzymes, leukotrienes, prostaglandin, bradykinin, free oxygen radicals, cytokines, and possibly other classes of inflammatory mediators. The inflammatory reaction perpetuates itself, leading to liposclerotic skin and subcutaneous tissue remodeling. In light of the mechanisms of venous ulcer formation cited above, therapy in the future might be directed against leukocyte activation in order to diminish the magnitude of the inflammatory response. With this in mind, the attention of many investigators has been drawn to two different drugs with an anti-inflammatory effect: pentoxifylline and flavonoids.
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PMID:Microcirculation and venous ulcers: a review. 1624 8

Leg ulceration is a chronic condition affecting about 1-2% of the adult population. The main causes of leg ulceration are venous hypertension, arterial insufficiency, diabetes, or a combination of these aetiologies (causes) or malignancy. Venous ulcers account for approximately 80% of all leg ulcers and are a result of venous hypertension. The current mainstay of treatment of venous ulcers is the application of graduated compression bandaging to the limb. In spite of the application of the best evidence-based therapy, healing rates for venous leg ulcers remain disappointing, at 50-70% after 12 weeks of treatment, depending on initial size and chronicity of the ulcer. Thus, a large number of ulcers are unhealed by this time, and many patients suffer from long-term leg ulceration, some remaining for years, and those that heal often recur. There is an obvious need to develop new treatments that would improve healing rates. This review provides a complete overview of the anatomy of venous circulation and the physiology pertaining to it, the pathophysiology of venous disease, the pathogenesis of ulceration, and a review of treatments currently employed in healing venous leg ulcers and their supporting evidence. The aim of this article is to encourage a fresh look at this chronic problem and stimulate ideas on how healing rates can be improved.
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PMID:A review of technological approaches to venous ulceration. 1639 Mar 12

Venous leg ulcer is the most severe expression of chronic venous insufficiency. Venous ulcerations are always associated with venous ambulatory hypertension, but the exact mechanism leading from pathological hemodynamics in venous circulation to the necrotic lesions in the skin still remains undiscovered. It has been shown that tissue injury in venous ulcer patients was induced by leukocytes. However, though infiltrating leukocytes have at their disposal a powerfully cytotoxic arsenal, it has not been discovered which molecular mechanisms may contribute to the skin damage. The search for this hypothetical factor responsible for the development of ulceration should be focused on mechanisms leading to apoptosis of keratinocytes, on pathogenesis of related dermatological pathologies, on other pathologies associated with epithelial lesions, and on mechanisms responsible for the expression of adhesion molecules. A thorough review of the literature, with special regard to cytokines, has revealed that proinflammatory cytokine--interferon-gamma (INFgamma)--could be a pivotal cytokine in the pathogenesis of venous ulceration. This cytokine, however, has not been investigated in venous leg ulcer patients before. INFgamma is a glycoprotein with numerous immunological and antiproliferative activities. The most important message from recent investigations is the fact that INFgamma seems to be the main mediator of keratinocyte apoptosis. INFgamma mediates also leukocyte chemotaxis, and enhances the expression of adhesion molecules involved in the pathophysiology of chronic venous insufficiency. Therapeutic injections of interferons can result in skin necrosis. If it were proven that INFgamma was responsible for the development of venous leg ulcers, this fact would have important clinical consequences. In such a case, anti-INFgamma agent could be used, either in the management of active ulceration, or in the prevention of recurrent ulcer.
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PMID:A potential role of interferon-gamma in the pathogenesis of venous leg ulcers. 1673 95

The successful management of patients who have leg ulcers related to chronic venous disease requires optimal management of the wound bed, elimination of edema with compression, and correction of venous hypertension whenever possible. Healing of the wound itself requires compression, debridement, bacterial control, and stimulation of the wound bed. Prevention of ulcer recurrence is most effective if the patient is amenable to correction of the venous insufficiency. This is most successful when the superficial or perforator veins are the primary source. Quality diagnostic studies are critical in determining the anatomy and hemodynamic importance of various venous abnormalities and can guide appropriate interventional treatment. Venous corrective procedures usually can be performed using minimally invasive endovenous methods, which are associated with fewer complications and more rapid recovery than are major surgical techniques.
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PMID:Evaluation and treatment of leg ulcers associated with chronic venous insufficiency. 1796 25

This paper presents a hypothetical model of role for iron in the development of venous leg ulcers and multiple sclerosis. Elevated concentrations of iron were found in the skin affected by venous hypertension and also in the areas of brain with multiple sclerosis lesions. Individuals with hemochromatosis gene (HFE) mutations: C282Y and H63D, which result in a less efficient transport of iron by macrophages, are characterized by an increased risk for venous leg ulcer and multiple sclerosis. Multiple sclerosis is a T cell-mediated disease, and T cells probably participate in the development of venous ulcers. This deleterious role of ferric ions could be related to the regulation of T cell proliferation and apoptosis. Under normal conditions excessive accumulation of T cells cannot take place, because nitric oxide and interferon-gamma drive these cells toward apoptosis. However, in tissues with a high concentration of iron, T lymphocytes proliferate instead of undergoing apoptosis. This is possible due to the internalization of the INF-gammaR2 chain of the interferon-gamma receptor, the downregulation of inducible nitric oxide synthase expression in macrophages and the inactivation of the active site of caspases. Yet, it should be emphasized that this hypothesis does not claim for the increased concentration of iron as a direct causal factor for the development of venous ulcerations or multiple sclerosis, but rather, iron is a factor that modulates and exaggerates the autoimmune process. Iron chelators, administered systemically or locally, should potentially exhibit therapeutic and prophylactic activity against venous leg ulcers and multiple sclerosis.
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PMID:Hypothetical molecular mechanisms by which local iron overload facilitates the development of venous leg ulcers and multiple sclerosis lesions. 1840 Apr 14

Chronic venous leg ulcers (CVLU) are chronic wounds, associated with long-standing venous hypertension, which have a poor prognosis for healing. In the process of wound healing the first step is represented by platelet aggregation and subsequent release of growth factors and other mediators, which play a key role in the repair response. Platelet gel (PG), a hemocomponent obtained by mixing platelets, thrombin, and calcium, is able, when applied topically, to release platelet mediators that likely favor CVLU healing. However, unstandardized protocols have been described in studies utilizing PG for the regeneration of a number of tissues, including CVLU; the relative clinical outcomes were hence highly variable. In our experience the topical use of PG, together with the strict adherence to the principles of good wound care, quickly promoted increased granulation tissue, followed by a complete CVLU epithelization. Although further studies and trials are needed to establish the major outcome affecting rules for optimal indications, preparation, and use of PG for CVLU treatment, PG can be undoubtedly considered a useful tool, able to improve the management of CVLU.
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PMID:Treatment of chronic venous leg ulcers by platelet gel. 1872 10


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