beraprost and Necrosis

To compare the efficacy of 6 to 12 months of beraprost sodium (BPS) therapy with placebo in the prevention of digital ulceration in patients with systemic sclerosis (SSc).. One hundred seven patients with SSc were randomized in a multicenter double blind prospective trial. The primary endpoints were the percentage of patients with new digital ulceration, and median survival without recurrence of digital ulceration. Other secondary outcome measures included disability due to Raynaud's phenomenon, overall patient well being, the need for hospitalization, and endothelial damage, evaluated by variations in biological markers and nailfold microscopy.. There was a trend towards fewer digital ulcerations in the BPS group than the placebo group (48.1 vs 58.8%, delta = 10.7%, p = 0.325), and median survival without recurrence of digital ulceration was longer in the BPS group (log-rank test, p = 0.233). Overall well being improved significantly more in the BPS group (p = 0.047), and von Willebrand factor decreased significantly more in the BPS group (p = 0.0001). The trend towards fewer digital ulcerations was more markedly in favor of BPS in the distal SSc group (delta for digital ulceration = 20.9%, p = 0.248) with a later onset (log-rank test, p = 0.057). Fewer patients were hospitalized in the BPS than the placebo group (4.0 vs 17.4%, p = 0.18). Side effects were mild.. Our study suggests that oral beraprost sodium may benefit patients with SSc. Such patients, especially those with distal SSc, tend to have fewer recurrent ischemic digital ulcerations in winter, and the onset of their ulceration is delayed.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Double-Blind Method; Epoprostenol; Female; Fingers; Humans; Ischemia; Male; Middle Aged; Necrosis; Outcome Assessment, Health Care; Prospective Studies; Scleroderma, Systemic; Ulcer

Beraprost sodium, a stable PGI2 analog, having antiplatelet aggregation and vasodilating actions, was tested in a rat subcutaneous heterotopic jejunal model for its ability to improve survival after vascular pedicle interruption. Forth Sprague-Dawley rats were divided into four groups: Group 1 (control, ligation of pedicle on postoperative day 5); Group 2 (Beraprost sodium, ligation on day 5); Group 3 (control, ligation on day 7); and Group 4 (Beraprost sodium, ligation on day 7). The resulting viability rates were: Group 1 = 0 percent, Group 2 = 40 percent, Group 3 = 30 percent, Group 4 = 90 percent. These results indicate that the administration of Beraprost sodium facilitates the neovascularization of the transferred intestine and shortens the time required for viability of the transferred tissue, after interruption of the vascular pedicle.

Topics: Abdominal Muscles; Animals; Epoprostenol; Graft Survival; Intestinal Mucosa; Jejunum; Necrosis; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; Transplantation, Heterotopic

Beraprost sodium is a chemically stable prostaglandin I2 analogue with antiplatelet and vasodilator actions. Burn injury causes thrombosis and vessel occlusion by increasing the blood viscosity and by thermal damage to the vascular network in the dermis. A vascular response also occurs in the uninjured dermis surrounding the site of injury. Diminished blood flow and spreading tissue oedema lead to progressive ischaemia and necrosis around the burn site (zone of stasis), with the final necrotic tissue area being larger than the initial one. If blood flow could be restored in the zone of stasis, secondary tissue damage would be minimized. In this study, we examined the effects of a prostaglandin I2 analogue, beraprost sodium (Procylin, Kaken Pharmaceutical Company, Tokyo, Japan) on burn injury in rats. Twenty male Sprague-Dawley rats weighing an average of 450 g were burned with a comb-shaped brass probe that produced a row of three burns measuring 10 x 30 mm each and two intervening unburned areas measuring 5 x 30 mm each. The rats were divided into two groups of 10 animals. One group received 0.015 mg of beraprost sodium intraperitoneally immediately after burn injury, while the control group received the same volume of saline. Skin blood flow was measured with a laser Doppler flowmeter, and the development of oedema as well as the area of necrotic tissue were also determined. The extent of skin necrosis and oedema were significantly reduced in the beraprost sodium-treated rats, and blood flow in the zone of stasis was increased. These findings demonstrate that prostaglandin I2 plays an important role in burn injury and that beraprost sodium can reduce secondary necrosis in the zone of stasis.

Topics: Animals; Biopsy, Needle; Burns; Disease Models, Animal; Dose-Response Relationship, Drug; Epoprostenol; Hemodynamics; Injections, Intraperitoneal; Male; Necrosis; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; Reference Values; Regional Blood Flow; Skin; Treatment Outcome

Endothelial cell damage causes massive hepatic necrosis as a result of fibrin deposition in the hepatic sinusoids. When a stable analog of prostaglandin I2, beraprost sodium, was administered to rats given either dimethylnitrosamine, carbon tetrachloride, or endotoxin following Corynebacterium parvum administration, the hepatic necrosis produced in each was attenuated, but to a greater extent in the dimethylnitrosamine and endotoxin/Corynebacterium parvum models, where fibrin deposition in the hepatic sinusoids occurs, as compared to the carbon tetrachloride model, where such fibrin deposition does not occur. Beraprost sodium reduced the expected increase of portal venous pressure in the endotoxin/Corynebacterium parvum model without affecting plasma thrombin-antithrombin III complex levels. Beraprost sodium also significantly reduced cell killing of both isolated rat hepatocytes and hepatic sinusoidal endothelial cells exposed to tert-butyl hydroperoxide when compared to controls. Beraprost sodium could prove to be a therapeutic candidate for the treatment of hepatic necrosis, particularly in cases associated with fibrin deposition in the hepatic sinusoids because of its fibrin clot-clearing action.

Topics: Animals; Antithrombin III; Capillaries; Carbon Tetrachloride; Cells, Cultured; Dimethylnitrosamine; Endothelium, Vascular; Endotoxins; Epoprostenol; Fibrin; Liver; Liver Diseases; Male; Necrosis; Peptide Hydrolases; Portal Pressure; Propionibacterium acnes; Prothrombin Time; Rats; Rats, Inbred F344