beraprost and Ischemia

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

BACKGROUND To investigate the combination of beraprost sodium (BPS) and aspirin in the treatment of acute ischemic stroke (AIS). MATERIAL AND METHODS 308 patients with acute cerebral infarction were randomly divided into two groups: experimental group (n=154), treated with BPS (40 μg, tid) and aspirin (100 mg, qd); control group (n=154), treated with 100 mg of aspirin, qd). The antiplatelet therapy remained unchangeable until six months after hospital discharge. RESULTS Initially, no significant differences were found between the two groups. After six months, the relapse-free survival rate was similar between the treatment group (98.1%) and the control group (97.4%). One patient died from AIS in the control group. However, glomerular filtration rate was significantly higher; neurological function and functional ability of patients were better in patients treated with BPS plus aspirin (experimental group) than that in aspirin alone group. No significant difference was found in the function of the coagulation system, suggesting that BPS plus aspirin treatment did not increase the risk of bleeding. Serious adverse events did not occur in both groups. Facial flushing (one case) and mild gastrointestinal reaction (one case) were found in the treatment group without influencing treatment. CONCLUSIONS In our trial involving patients with acute cerebral infarction, BPS plus aspirin was not found to be superior to aspirin in reducing the recurrence of cerebral infarction or death. However, BPS plus aspirin treatment could improve renal function and neurological function without increasing the risk of bleeding.

Topics: Aged; Aged, 80 and over; Aspirin; Brain Ischemia; Cerebral Infarction; Drug Therapy, Combination; Epoprostenol; Female; Glomerular Filtration Rate; Humans; Ischemia; Male; Middle Aged; Platelet Aggregation Inhibitors; Stroke; Treatment Outcome

Implantation of autologous bone marrow (BM) mononuclear cells (MNCs) has been shown to augment neovascular formation in ischemic tissues in experimental animals and in humans. Prostaglandin derivatives improve the symptoms of patients with critical limb ischemia, possibly by their vasodilating and antiplatelet actions. We therefore examined whether therapeutic angiogenesis by implantation of autologous BM-MNCs would be enhanced by beraprost sodium (BPS), using a rabbit ischemic hindlimb model. Ischemia was induced by surgical resection of the left femoral artery. Twenty-five New Zealand white rabbits were divided into four groups. The first group (BM group, n = 4) received autologous BM-MNCs (2 x 10(6)/animal) implanted into the ischemic tissue 1 week after limb ischemia. The second group (BM+BPS group, n = 8) received BPS injected into the dorsal skin (300 microg/kg daily) starting 1 week before limb surgery. This group received BM-MNC implantation 1 week after surgery. Daily injection of BPS was continued until the end of the protocol. The third group (BPS group, n = 8) received BPS injected into the dorsal skin (600 microg/kg daily) starting 1 week before limb surgery. The fourth group received saline as a control (n = 4). The extent of angiogenesis in the ischemic hindlimb was assessed using the angiographic score (AS), ischemic/normal limb calf blood pressure ratio (CBPR), and tissue capillary density. Four weeks after limb ischemia, the ischemic/normal CBPR was highest in the BM+BPS group, followed by the BPS, BM, and control groups (0.56 +/- 0.16, 0.51 +/- 0.25, 0.44 +/- 0.15, and 0.30 +/- 0.10, respectively). The AS was also the greatest in the BM+BP group, followed by the BM, BP, and S group (1.63 +/-0.21, 1.31 +/- 0.25, 1.26 +/- 0.21 and 0.80 +/- 0.10, respectively). The TCD was greatest in the BM+BP group, followed in by the BM, BP, and S group? (46 +/- 4.1, 34 +/- 0.7, 33 +/- 6.9, and 19 +/- 1.8 per field, respectively). BP treatment is an effective means to enhance the efficacy of therapeutic angiogenesis induced by autologous BM-MNCs implantation in ischemic hindlimb tissues.

Topics: Angiogenesis Inducing Agents; Animals; Blood Pressure; Bone Marrow Transplantation; Capillaries; Collateral Circulation; Disease Models, Animal; Epoprostenol; Hindlimb; Ischemia; Male; Muscle, Skeletal; Neovascularization, Physiologic; Rabbits; Radiography; Time Factors; Transplantation, Autologous

Topics: Animals; Dogs; Epoprostenol; Ischemia; Kidney