Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Daflon 500 mg (S-5682) is a purified, micronized flavonoid fraction containing 90% diosmin and 10% hesperidin that is currently used to treat chronic venous insufficiency and hemorrhoidal disease. Thus, it seemed of interest to evaluate the effects of S-5682 on ischemia/reperfusion, ie, the changes in mean internal diameter and blood flow of arterioles and venules and the functional capillary density (FCD) during reperfusion after ninety minutes of total ischemia in the hamster cheek pouch microvasculature. Different doses of S-5682 (5, 20, 80, and 160 mg/kg body weight/day), suspended in 10% lactose solution or vehicle (10% lactose) were administered orally to male hamsters for ten days twice a day. The cheek pouch preparation was placed under an intravital microscope coupled to a closed-circuit TV system. A ninety-minute local ischemia was obtained by a cuff mounted around the neck of the everted pouch where it left the mouth of the hamster. Mean arteriolar and venular internal diameters were determined by means of an image-shearing device, IPM model 907; red blood cell (RBC) velocity was measured by the dual-slit photometric technique; microvessel volume flow was calculated from diameters and RBC velocities; and FCD was defined as the number of red-cell-perfused capillaries per observation field. During reperfusion, placebo-treated animals showed significant vasodilatation concomitant with a decrease in blood flow and FCD compared with preischemic values and an impairment of the myogenic response. In S-5682-treated animals, there was a significant dose-dependent improvement in all these parameters including the myogenic tonus. These results clearly demonstrated that oral administration of different doses of S-5682 for ten days improved the microvascular reactivity and FCD after ischemia/reperfusion in a dose-dependent fashion in the hamster cheek pouch microvasculature.
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PMID:Microvascular reactivity after ischemia/reperfusion in the hamster cheek pouch: beneficial effects of different oral doses of S-5682 (Daflon 500 mg). 899 41

The precapillary resistance in the skin of the foot increases with standing. This mechanism, termed the venoarterial reflex (VAR) restricts arterial inflow, and avoids an excessive rise in capillary pressure. This study tests the hypothesis that there is microcirculatory compensation to atherosclerotic disease of increasing severity. Foot skin perfusion (FSP) was measured in 100 limbs with a laser Doppler placed on the plantar aspect of the great toe. Limbs were categorized as normal (n = 31) with an ankle brackial index (ABI) > or = 0.96, claudicants (n = 42) ABI 0.5-0.86, and critical ischemia (n = 27) with an ABI < or = 0.49 or a pulse volume recording consistent with severe peripheral vascular disease and symptoms of rest pain or tissue loss. Segmental Doppler pressures and pulse volume recordings were performed prior to laser Doppler measurements. Subjects with clinical signs or symptoms of chronic venous insufficiency were excluded. The resting foot skin perfusion was measured in the horizontal and dependent position, with the patient supine and sitting. Comparisons within categories were done using Wilcoxon matched pairs signed rank test and between groups with Mann-Whitney U test for unpaired data. Differences were considered significant if they exceeded the 95% confidence level (p value < or = 0.05). Resting supine skin perfusion was similar between nondiabetic normals and claudicants and diabetic normals and claudicants. There was a significant decrease in the foot skin perfusion (mean FSP +/- SEM) in the normal limb with a change from the supine (7.8 +/- 2.2 ml/min/100 g) to the dependent (2.8 +/- 0.6 ml/min/100 g) position indicating an intact VAR. This was absent in 33% of the limbs with claudication. Limbs with critical ischemia demonstrated an increase in FSP with dependency (supine 4.0 +/- 1.0 ml/min/100 g) versus dependent (8.4 +/- 1.8 ml/min/100 g) and was present in both diabetic and nondiabetic limbs. Microcirculatory compensation occurs early in atherosclerotic limbs. Although supine FSP is similar in normals and claudicants, a greater percentage of claudicants demonstrate a loss of the VAR. Critically ischemic limbs have increased FSP in the dependent position. These observations indicate that there are microcirculatory alterations in limbs with claudication and assist in explaining why patients with ischemic rest pain obtain relief and develop edema with dependency.
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PMID:Microcirculatory compensation to progressive atherosclerotic disease. 906 Nov 39

Small vessel investigative laboratories for the in vivo study of the human microcirculation are few. Everyone believes that the combination of clinical examination. Doppler scanning and radiology ensures thorough investigation of peripheral vascular diseases. Capillaroscopy, plethysmography, oximetry, thermography, laser-Doppler, volumetry, and measurement of ambulatory venous pressure are rarely used for these diseases in routine practice, because they are often considered expensive, time consuming, inaccurate and eventually without practical consequences for patients. The aim of the present study is to summarize the 20-year-experience of such a small vessel laboratory, and to demonstrate its usefulness, both in research and in the routine practice of Vascular Medicine. Raynaud's phenomenon, critical ischemia, and chronic venous insufficiency will serve as examples for this demonstration.
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PMID:[Laboratory for exploration of small vessels: its utility in vascular diseases]. 916 8

The authors report the salvage of a lower limb with recalcitrant venous stasis ulcers by "sequential" free flaps in a patient with co-existing chronic venous insufficiency and arterial occlusive disease. This presentation is interesting for inclusion of the following: (1) treatment of a recalcitrant venous ulcer by the combination of free-tissue transfer and valvular transplantation; (2) thrombosis of the free flap pedicle at an indeterminate time postoperatively without flap loss or leg ischemia; and (3) performance of a second free flap to the peroneal artery-only, to a one-vessel leg with an excellent clinical outcome at long-term follow-up.
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PMID:Lower-limb salvage in a patient with recalcitrant venous ulcerations. 927 6

Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is an immune-mediated response to the administration of heparin that results in life-threatening thrombosis. The pathophysiology of HITTS remains controversial. The onset of clinical symptoms and laboratory changes is usually delayed 1-2 weeks after exposure to heparin. Thrombosis occurs in both the arterial and venous circulation with significant morbidity and mortality. Complications include deep venous thrombosis, pulmonary embolus, stroke, myocardial infarction, chronic venous insufficiency, extremity ischemia, gangrene, and death. Diagnostic criteria for HITTS include thrombocytopenia during heparin exposure, exclusion of other causes such as sepsis or medications, resolution of thrombocytopenia after withdrawal of heparin, demonstration of in vitro heparin-dependent platelet antibodies, and development of vascular thrombosis. Despite having several disadvantages, the carbon-14-serotonin release assay is the most sensitive and specific test for HITTS. Angiography as an adjunct to other imaging modalities can document the presence, location, and extent of thrombus. Optimal treatment has not yet been defined but should include immediate discontinuation of use of all heparin products and heparin-coated catheters. In addition, alternate methods of antithrombotic therapy should be considered. In severe cases, thrombolysis or thrombectomy may be warranted. Familiarity with the pathophysiology, clinical manifestations, complications, diagnostic criteria, and treatment options associated with HITTS will enable timely recognition and facilitate prompt and effective treatment.
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PMID:Heparin-induced thrombocytopenia and thrombosis syndrome. 946 Jan 12

A growing body of evidence indicates that neutrophils play a critical role in disrupting the microvascular barrier in skeletal muscle. Recent studies from our laboratory and by others indicate that administration of antibodies directed against P-selectin, ICAM-1, or the common subunit (CD18) of CD11/CD18 was as effective as neutrophil depletion in attenuating ischemia/reperfusion (I/R)-induced microvascular barrier disruption and edema formation in skeletal muscle. These studies have important implications with regard to the pathogenesis of leg ulceration in view of our more recent work indicating that the increase in tissue pressure induced by edema formation secondary to microvascular barrier disruption may lead to the development of capillary no-reflow. The resulting maldistribution of blood flow during reperfusion exacerbates muscle injury induced by ischemia. Daflon 500 mg is a purified, micronized flavonoid fraction that exhibits a number of anti-inflammatory properties and is used clinically to treat venous insufficiency. In view of these actions and the demonstrated role of neutrophil adhesion in the pathogenesis of I/R, we sought to determine whether this agent would prevent leukocyte adhesion and microvascular barrier disruption in postischemic rat cremaster muscles and small bowel. Rats were treated with Daflon 500 mg (80 mg/kg/day by gavage) or its vehicle for 2 (cremaster studies) or 10 (mesenteric studies) days prior to the experiments. Leukocyte/endothelial cell interactions and venular protein leakage were quantitated using intravital microscopic techniques in rat cremaster muscles and mesenteries subjected to ischemia (60 min for cremaster, 20 min for mesentery) and reperfusion (60 min). The results indicated that Daflon 500 mg was as effective as the anti-adhesive monoclonal antibodies in reducing postischemic leukocyte adhesion and emigration and venular protein leakage in these models.
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PMID:Postischemic leukocyte/endothelial cell interactions and microvascular barrier dysfunction in skeletal muscle: cellular mechanisms and effect of Daflon 500 mg. 947 39

One possible mechanism that accounts for the alterations observed in varicose veins is the activation of endothelial cells by ischemia occurring in the leg veins during blood stasis and the cascade of reactions that follows. Because in vitro data suggest that endothelium alteration is a key event in the development of the pathology, it was important to confirm this hypothesis in patients. We used the number of circulating endothelial cells detached from the vascular wall as a criterion of the endothelium injury. We first compared the number of circulating endothelial cells (CECs) in patients with chronic venous insufficiency (CVI) with those of a control population. A twofold increase in the CEC count (1,001+/-127 CEC/ml of plasma compared with 514+/-82 CECs/ml) was observed in CVI patients, which indeed suggests an alteration of the endothelium in this disease. Second, the protective effect of a venotropic drug, Ginkgo biloba extract, troxerutine, and heptaminol (Ginkor Fort), was tested by a randomized double-blind, placebo-controlled clinical trial. In the active-treatment group, the mean values of the CEC count decreased by 14.5% after a 4-week treatment, whereas in the placebo group, the decrease was less (8.4%). The decrease from week 0 to the end of treatment was significantly higher in the active-treatment group than in the placebo group. These results confirm the important role of the endothelium alterations in the development of varicose veins and suggest a potential beneficial action of a venotropic drug on the venous wall.
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PMID:Increase in circulating endothelial cells in patients with primary chronic venous insufficiency: protective effect of Ginkor Fort in a randomized double-blind, placebo-controlled clinical trial. 989 Mar 90

A complex symptom complex developed in a 76-year-old man with atherosclerotic right artery ililaca communis aneurysm and was caused by retroperitoneal rupture. It was characterized by incomplete small intestinal ileus, progressive hydronephrosis, ischemia and chronic venous insufficiency of the right leg.
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PMID:[Rupture of an atherosclerotic aneurysm of the common iliac artery]. 1019 5

Wound healing is a complicated process that recruits at least 4 distinct cell types. Though the process is continuous, it is commonly referred to as occurring in "phases." The main phases of wound healing include coagulation, which begins immediately after injury; inflammation, which initiates shortly thereafter; a migratory and proliferative process, which begins within days and includes the major processes of healing; and a remodeling process, which may last for up to a year and is responsible for scar tissue formation and development of new skin. Wound healing is affected by several factors. These include local factors (growth factors, edema and ischemia, low oxygen tension, and infection), regional factors (arterial insufficiency, venous insufficiency, and neuropathy), systemic factors (inadequate perfusion and metabolic disease), and other miscellaneous factors, such as nutritional state, preexisting illnesses, exposure to radiation therapy, and smoking. In general, chronic wounds may be managed by preventing or medically treating infections through debridement and occlusive dressings. For wounds that are unresponsive to such interventions, the use of skin replacements is becoming a viable option. In this regard, a product such as Graftskin (APLIGRAF, Organogenesis Inc, Canton, MA, and Novartis Pharmaceuticals Corporation, East Hanover, NJ), a bilayered living skin construct with allogeneic dermis and epidermis, is a positive development.
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PMID:Physiology of wound healing. 1107 96

Impaired cutaneous wound healing is a common complication in diabetes, ischemia and venous insufficiency of lower extremities, and in long-term treatment with corticosteroids or other immunosuppressive agents. In development of gene therapy for wound repair, expression of therapeutic transgenes should be precisely targeted and controlled. Here, we describe a recombinant adenovirus RAdFiRE-EGFP, in which a growth factor inducible element (FiRE) of the murine syndecan-1 gene controls the expression of enhanced green fluorescent protein (EGFP) reporter gene. Treatment of RAdFiRE-EGFP-transduced murine epidermal keratinocytes in culture with FiRE-activating growth factor markedly enhanced the expression of EGFP. In ex vivo organ culture of wounded murine skin transduced with RAdFiRE-EGFP, the EGFP expression was specifically detected in wound margin keratinocytes, but not in intact skin. Activity of EGFP was first detected 2 days after a single application of RAdFiRE-EGFP and persisted up to 10 days. Similarly, FiRE-driven EGFP expression was detected specifically in epidermal keratinocytes in the edge of incisional wounds in murine skin transduced with RAdFiRE-EGFP. In contrast, adenovirus-mediated lacZ expression driven by CMV promoter was detected scattered in epidermal, dermal and subcutaneous layers in ex vivo and in vivo wounds, as well as in intact skin. These data demonstrate the feasibility of FiRE as a tool for transcriptional targeting of adenovirus-mediated transgene expression to cutaneous wound edge keratinocytes.
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PMID:Transcriptional targeting of adenoviral gene delivery into migrating wound keratinocytes using FiRE, a growth factor-inducible regulatory element. 1108 72


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