Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impaired mononuclear leucocyte (MNL) motility can be found both in vascular and autoimmune diseases. Pentoxifylline (PTX) has a well-known therapeutic effect in vascular diseases, which is based on the rearrangement of blood cell cytoskeleton and thus increased microcirculatory flow. Most data on PTX concern red blood cells and granulocytes so now the effect of PTX on previously decreased MNL migration and chemotaxis was investigated in vitro. The results of MNL chemotaxis studies described here suggest that this drug enhances impaired MNL motility in obliterative atherosclerosis and systemic lupus erythematosus and thus may also be introduced in the treatment of certain polysystemic autoimmune diseases with decreased in vitro MNL chemotaxis.
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PMID:Effect of pentoxifylline on decreased in vitro mononuclear leucocyte chemotaxis in vascular and polysystemic autoimmune diseases. 195 Aug 15

To assess the clinical effectiveness of pentoxifylline (Trental) in the treatment of intermittent claudication and ischemic rest pain, 129 patients were retrospectively interviewed with respect to compliance and improvement of symptoms. Risk factors for the development of atherosclerosis were tabulated, as was the severity of symptomatic lower extremity peripheral vascular insufficiency. The duration of pentoxifylline treatment was 35.8 +/- 45.0 weeks (mean +/- 1 S.D.). Forty-eight percent of the patients discontinued pentoxifylline on their own, most commonly because of side effects (13%) or perceived lack of improvement (23%). Of those patients taking pentoxifylline for eight weeks or more (n = 110), 64% noted some improvement, with 31% reporting increased claudication distance and 52% reduced claudication pain. Pentoxifylline provided pain relief in 52% of patients with ischemic rest pain (n = 27). Neither diabetes, hypertension, concomitant antiplatelet therapy, the severity of claudication, nor pretreatment ankle-brachial Doppler pressures were related to treatment outcome. Increased daily walking exercise during treatment was associated with successful outcome (p = 0.04). Clinical response to pentoxifylline was inversely related to the number of cigarettes smoked daily in those with 1 block claudication (n = 71, p = 0.05). Pentoxifylline was not very effective in increasing reported claudication distance. This review suggests that pentoxifylline may be of value for patients with ischemic rest pain when arterial reconstruction is not possible. Whether pentoxifylline is useful adjunctive therapy for intermittent claudication requires further scrutiny.
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PMID:Pentoxifylline in the nonoperative management of intermittent claudication. 199 79

Pentoxifylline is a methylxanthine derivative used to increase blood flow in peripheral atherosclerosis. Pentoxifylline is known to increase whole blood filtration rate, and recent evidence suggests that pentoxifylline increases the filtration rate of polymorphonuclear leukocytes (PMNs). The purpose of this study was to directly observe and quantitate the effect of pentoxifylline on the flow of individual PMNs into a model capillary. Short-term incubation of human PMNs with 10 mM pentoxifylline inhibited cell activation, as judged by a significant reduction in the number of neutrophils forming pseudopods. Furthermore, incubation of PMNs from 6 healthy men with 0.1, 1.0 and 10 mM pentoxifylline significantly decreased the time required for individual cells to be aspirated into a 4 microns pipet under constant pressure by 16 +/- 5%, 21 +/- 7%, and 41 +/- 8%, respectively (mean +/- SEM, p less than or equal to 0.05), compared with control. These experiments are the first direct demonstration of increased deformability in neutrophils treated with pentoxifylline. The results are consistent with the hypothesis that the beneficial effect of pentoxifylline on microvascular perfusion is partly due to an inhibition of PMN stiffness and activation.
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PMID:Effect of pentoxifylline on the flow of polymorphonuclear leukocytes through a model capillary. 233 24

Pentoxifylline has been used for several years in various types of peripheral and cerebrovascular diseases because of its hemorheological properties: pentoxifylline improves the red cell deformability, decreases platelet and red cell aggregation, decreases fibrinogen and plasma viscosity. Its new properties on the leukocyte function can lead to new therapeutical ways. Adherence and peroxidative free radicals production are induced by inflammatory cytokines (IL1, TNF) and can induce vascular tissue damages and development of atherosclerosis. Pentoxifylline has no effect on the normal leukocyte function. However, in all inflammatory diseases, Pentoxifylline acts on the activated neutrophil function: Pentoxifylline decreases adherence to endothelial cells or other surfaces, the superoxide and lysozyme release, and increases chemotaxis. In some animal models of shock and infection, pentoxifylline decreases cellular and tissue damages, mediated by activated neutrophils. Furthermore, in inhibiting neutrophil adhesion to cultured endothelium cells, pentoxifylline, modulates leukocyte-endothelium and leukocyte-platelets interactions which are important factors in the development of inflammation and thrombosis. Pentoxifylline increases the leukocytes mediated activation of fibrinolytic pathways and could play an important role in the prevention of thrombosis. In addition to its well-known effects on chronic vascular diseases, pentoxifylline is also effective in some acute injuries in animal models. This can lead to new research fields allowing a better understanding of atheromatous processes.
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PMID:[New aspects of the pharmacology of pentoxifylline]. 265 14

Indices of the system of hemostasis, the levels of glycolysated hemoglobin were studied in 67 patients suffering from non-insulin-dependent diabetes mellitus with lower limb angiopathies (aged 40 to 60). Rheovasography of the lower limbs was performed. The patients were treated with antidiabetic drugs per os (with the exception of hydroxydione sodium succinate), platelet aggregation inhibitors (pentoxifylline, acetylsalicylic acid) and vasodilators (xanthinol nicotinate, solcoseryl and cinnarizine). The use of pentoxifylline after therapy increased the rate of platelet aggregation inhibition and decreased the prothrombin index, not influencing the other indices of the system of hemostasis. Pentoxifylline combined with acetylsalicylic acid at small doses normalized not only platelet indices but also the other indices of the system of hemostasis. Positive changes in the system of hemostasis were accompanied by a rise of the rheographic index in patients with vascular functional changes. In obliterating atherosclerosis the rheographic index was not on an increase indicating the necessity of corrective therapy of vascular lesions, first of all in the system of hemostasis, in the early period of diabetes mellitus.
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PMID:[Characteristics of disturbances in the hemostasis system in patients with insulin-dependent diabetes mellitus with angiopathies of the vessels of the lower extremities]. 321 77

Pentoxifylline was used in the treatment of 90 patients with atherosclerosis-induced chronic peripheral arterial occlusive disease and diabetic vascular disorders in the lower extremities (clinical Fontaine Stages III and IV) for whom surgical reconstructive treatment was not indicated and who had shown inadequate response to previous therapy. In 20 initially hospitalized patients, treatment was started with pentoxifylline intravenous infusions for 1 week (increased gradually from 500 mg to 1000 mg per day) and afterwards continued for a further 8 weeks by oral administration of the drug (400 mg 3-times daily). In 70 patients, oral treatment (400 mg 2 to 3-times daily) was carried out from the beginning for 3 to 6 months or longer. The majority (74%) of the patients showed good or very good results in respect of the clinical parameters. Pentoxifylline abolished or decreased rest pain and consumption of analgesic drugs, accelerated healing of leg ulcers, produced a statistically significant increase in mean pain-free walking distance (approximately 500%) and reduced concomitant symptoms. Definite improvement was achieved in 16 patients with initial intravenous treatment and in 62 patients on oral therapy alone. Haemodynamic measurements, as well as whole blood viscosity assessment using a middle and high shear rate viscosimeter, revealed only small and insignificant improvements. No essential changes could be found in the chemical blood parameters studied.
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PMID:Clinical investigation of the effects of pentoxifylline in patients with severe peripheral occlusive vascular disease. 405 74

We studied 27 non-insulin-dependent diabetics without apparent atherosclerosis (AS) to investigate whether abnormal platelet function is related to asymptomatic atherosclerosis in diabetes mellitus. The degree of AS was quantitatively evaluated by determining the intimal plus medial thickness (IMT) of the carotid artery wall with ultrasound high-resolution B-mode imaging. Based on our previous finding that the upper threshold of the IMT was 1.1 mm in healthy subjects, the patients were divided into the AS-positive group with the IMT > 1.1 mm, (n = 17) and the AS-negative group with the IMT < 1.1 mm (n = 10). Among five variables measured as the factors concerned with thrombogenesis, only plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were significantly higher in the AS-positive group than in the AS-negative group. Chronic administration of pentoxifylline (300 mg/day) significantly reduced the abnormally high plasma levels of beta-TG and PF4 in 7 patients of the AS-positive group to normal levels, without lowering the normal plasma beta-TG and PF4 levels in the remaining 10 patients. Pentoxifylline treatment did not affect the plasma levels of the 3 other variables, von Willebrand factor, 6-keto prostaglandin F1 alpha and thromboxane B2. This study suggests that the progress of atherosclerosis in diabetes mellitus is associated with in vivo platelet activation and platelet activation does not occur in diabetics without carotid atherosclerosis. Pentoxifylline may impede the vicious cycle in which atherosclerosis is accelerated by platelet activation.
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PMID:Platelet activation in diabetic patients with asymptomatic atherosclerosis. 795 14

Pentoxifylline versus nicergoline therapy has been studied in 56 patients with atherosclerosis of major cerebral arteries who had ischemic apoplexy. Pentoxifylline enhances circulation primarily in the stenotic vessels, while nicergoline in the intact cerebral arteries. The former is more potent in inducing antiaggregation inhibiting spontaneous platelet and red cell aggregation and reducing blood viscosity. The results of the study suggest better response in case of pentoxifylline treatment of patients with hypo- and eukinetic circulation, while in nicergoline treatment hyperkinetic hemodynamics patients benefit more in view of the drug cardiodepressive activity.
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PMID:[The effect of pentoxifylline and nicergoline on the systemic and cerebral hemodynamics and on the blood rheological properties in patients with an ischemic stroke and atherosclerotic lesions of the major cerebral arteries]. 804 84

A sixty-six-year-old man with known severe atherosclerosis was admitted with painful feet and nonblanching purpuric lesions of his toes. He had undergone cardiac catheterization and coronary artery bypass five and three months, respectively, prior to admission. Initial treatment included: stopping the patient's lisinopril, increasing his nifedipine dose, and adding pentoxifylline 400 mg po tid. Within twenty-four hours pain was markedly decreased. Skin biopsy confirmed a diagnosis of cholesterol embolism. Pentoxifylline was stopped and intravenous heparin therapy was initiated. Within twenty-four hours, pain returned. Nitrol paste applied to the top of each foot had no effect. After forty-eight hours, pentoxifylline was restarted. Once again, pain relief was noted within twenty-four hours, and after forty-eight hours both feet were visibly improved. Heparin and analgesics were discontinued. On the ninth hospital day, the patient was able to walk and was discharged to home. The innocuous nature of the intervention combined with the prompt nature of the therapeutic response support a short trial of pentoxifylline in patients with cholesterol emboli who are not responding to other therapy.
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PMID:Pain relief and clinical improvement temporally related to the use of pentoxifylline in a patient with documented cholesterol emboli--a case report. 828 87

Pentoxifylline, a new trisubstituted methylxanthine derivative, is the most well known of a new group of hemorheologic agents. It has been shown to improve hemorheologic abnormalities associated with diabetes and atherosclerosis. The authors examined the role of pentoxifylline in the treatment of diabetic foot ulcers. Forty diabetic patients with foot ulcerations were included in the study, 20 of whom received conventional therapy and 20 received pentoxifylline (400 mg three times a day) in addition. Healing of ulcers after eight weeks of treatment was significantly higher in those on pentoxifylline, and the patients needed less mutilating surgery. Administration of pentoxifylline in addition to conventional therapy was significantly superior in the management of diabetic foot ulcers.
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PMID:Hemorheologic approach in the treatment of diabetic foot ulcers. 834 78


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