Effects of Beraprost Sodium Evaluated by Digital Infrared Thermal Imaging in Diabetic Patients with Peripheral Arterial Disease / 대한족부족관절학회지

PURPOSE: This study examined the effects of beraprost sodium on digital infrared thermal images in patients with peripheral arterial disease caused by type 2 diabetes mellitus. MATERIALS AND METHODS: Twenty-five diabetic patients with peripheral arterial disease were treated with beraprost sodium in a prospective, multicenter, cohort study from February 2013 to December 2014. Beraprost sodium (40 μg) was administered orally 3 times daily (120 μg/day) for 6 months. The visual analogue scale (VAS) and digital infrared thermal imaging (DITI) were performed to compare the blood flow improvement between before and after dosing. RESULTS: Among the 25 patients included in the evaluation, 22 patients completed the study. A significant increase in body temperature was observed in the front and left side, particularly in the plantar side in DITI compared to that before and after administration. An increase in body temperature was observed at the frontal part from 28.1℃±2.3℃ to 29.1℃±2.1℃ (p=0.021), at the left side from 27.8℃±2.4℃ to 28.6℃±1.9℃ (p=0.028), at the plantar part at 24.0℃±1.5℃, and at the plantar part at 27.1℃±2.4℃ (p < 0.01). The VAS decreased significantly from 5.4±1.3 to 2.7±2.0 after 6 months of treatment (p < 0.01). CONCLUSION: Beraprost sodium is a safe and easy-to use oral medication for diabetes peripheral arterial disease. It can be expected to increase the blood flow and decrease the lower extremity pain statistically after being taken for 6 months.

Effects of Beraprost Sodium on Subjective Symptoms in Diabetic Patients with Peripheral Arterial Disease

BACKGROUND: This study evaluated the effects of Beraprost sodium (Berasil) on subjective leg symptoms in patients with peripheral arterial disease caused by diabetes mellitus. METHODS: Ninety-four diabetic patients with peripheral arterial disease were treated with Beraprost in a fixed-dose, prospective, multicenter, cohort study. Beraprost (40 microg) was administered orally 3 times daily (120 microg/day) for 12 weeks. We developed a new disease-specific symptom questionnaire, which evaluated the effect of peripheral arterial disease on leg discomfort in daily life and assessed therapeutic responses to treatment. Patients were asked for their subjective assessment of symptoms on a written questionnaire before treatment and after 12 weeks of therapy. RESULTS: There was significant improvement in all estimated subjective symptoms (burning, coldness, edema, exertional pain, stabbing, and paresthesias) in the lower extremities at 12 weeks (p < 0.001). There were 18 patients with neuropathy in whom significant improvement was noted for 6 subjective symptoms at 12 weeks (p < 0.05). Adverse events considered to be drug-related were observed in 4 patients (4.3%), all of which were mild and resolved with discontinuation of the medication. CONCLUSIONS: Beraprost is effective as a treatment for improving various subjective symptoms in the lower extremities, such as burning, coldness, edema, exertional pain, stabbing, and paresthesias, in diabetic patients with peripheral arterial disease.

Clinical Research on Correlation between SOD and TXB_2/6-k-PGF_(l?) in Stroke Patients / 中国中医药信息杂志

Objective To research the correlation between SOD and TXB2/6-k-PGF1? and relationship with TCM syndrome in stroke patients. Methods A contrast test on blood SOD and plasma TXB2 and 6-k-PGF1? was given separately to two groups, one group was 74 cases with stroke and the control group was 36 cases in health. Results Content of b1ood SOD in stroke group reduced remarkably compared with the health group (P

Effect of Jiuqiang Naoliqing on the TXA_2 and PGI_2 level in spontaneous hypertension rat plasma / 中国康复理论与实践

@#ObjectiveTo investigate the effect of Jiuqiang Naoliqing(JNQ) on the TXA2 and PGI2 level in spontaneous hypertension rat (SHR) plasma.MethodsThe plasma was separated after the SHR and Wistar rats were treated with JNQ at the dose of 0.133g/kg,0.265g/kg,0.530g/kg and 1% carboxymethyl cellulose respectively for 5 weeks. The level of TXB2 and 6 keto PGF1α ,stable metabolin of TXA2 and PGI 2,in SHR plasma was tested by radioimmunoassay.ResultsThe level of TXB2 and the ratio of TXB2/6 keto PGF1α (T/P) in SHR plasma increased significantly(P<0.01),and there was no significant difference in the concentration of 6 keto PGF1α between Wistar rats and SHR plasma(P>0.05). JNQ could increase the generation of 6 keto PGF1α and decrease the level of TXB2 and T/P in SHR plasma after treated with different dosages for 5 weeks.ConclusionJNQ may improve the balance between TXA2 and PGI2 in SHR plasma.

Different response of antisense IRAK-2 oligonucleotides to PGI2 release induced byIL-1 and TNF / 中国免疫学杂志

To explore the effects of artisense IRAK-2 oligonucleotide on the prostacyclin (PGI2) synthesis in human umbilicalvein endothelial cells (HUVEC) induced by interleukin-1 (IL-1) and tumor necrosis factor (TNF).Methods:The HUVECs were transfectedwith antisense interleulkin-1 receptor associated kinase-2 oligonucleotide (IRAK-20DN) and stimulated with IL-1 and TNF. The levels of PGI2release were analyzed by competitive ELISA. Results: Pre-transfection with antisense IRAK-20DN could remarkably decrease the levels ofPGI2 synthesis induced by IL-1 in time- and dose-dependent manner, whereas it could not attenuate the one stimulated by TNF. Conclusion:The response of antisense IRAK-2 ODN to IL-1 and TNF-stimulated PGI2 release were different. IRAK-2 plays a key role in the IL-1 signalingevents leading to PGI2 release.

Establishment of Canine Partial Liver Autotransplantation Model and Protective Effect of Prostaglandin I2 on the Ischemia-Reperfusion Injury / 대한이식학회지

BACKGROUND: The pathogenesis of primary non function or delayed graft function after liver transplantation is not yet clearly defined. However it is presumed that these unhappy events most likely attributes to the Kupffer cell-mediated, reperfusion injury aggravating the sinusoidal endothelial cell damage following preformed ischemic insults. Prostaglandin (PG) I2 and its analogues were reported to protect the liver against ischemic injury thereby be efficacious for the use during the preservation of harvested liver. Prevention of platelet aggregation, vasodilation, stabilization of lysosomal membranes, and inhibition of thromboxane generated by platelets may be the attributable biological activities of PGI2. PURPOSES: We designed this experimental study to assess the effect of continuous PGI2 infusion during in situ liver splitting on the bile flow from liver segment during resection and after reimplantation, and to establish our unique autotransplantation model in mongrel dogs before warming-up of living donor partial liver transplantation in the clinic. METHODS: Mongrel dogs weighing 15-25 kg were used after fasting for 12 hours. After endotracheal intubation under monitoring, abdomen was opened through the Chevron incision extending to xiphoid process. Initially, the right hepatic duct was ligated and divided. The common bile duct was divided, the end being cannulated proximally and drained. Basal bile flow was measured for 1 hour as a reference value. The left partial graft including the right medial, quadrate, left medial, left lateral lobe, and the papillary process of caudate lobe was resected en bloc. After cold flushing ex vivo, the harvested segment was immediately reimplanted orthotopically. In PGI2 group, PGI2 50 microgram was slowly infused through splenic venous cannulation. After closing the abdomen, the bile flow was measured continuously. RESULTS: Eleven out of 24 dogs were alive 12 hours after surgery; 5 in PGI2 and 6 in control group. Basal mean bile flow (BF) rate were 2.9 ml/hr/100 gm of liver tissue in control vs. 2.5 ml/hr/100 gm in PGI2 group. This difference did not reach the statistical significance. However, postoperative BF increased significantly in PGI2 group; 0.45 ml/hr/100 gm in contro vs. 1.71 ml/hr/100 gm in PGI2 group (p=0.04). CONCLUSION: Continuous infusion of PGI2 through the splenic vein during the harvest of the liver could mitigate the manipulation injury. The BF reflecting the quality of resected liver segment was relatively well preserved in PGI2 group after canine autotransplantation model. This model is not complicated, and will be useful for the mastery of surgical techniques for the living donor partial liver transplantation in the clinic.

The Effect of Anoxia and Reoxygenation on the Production of Prostaglandin I2 from the Endothelial Cells of Umbilical Vein

The successful revascularization and reperfusion of ischemia are still associated with high systemic complication rates and severe local tissue injuries. The morality rates after revascularization have been reported to range from 10% to 20% and the amputation rates from 12% to 22%. It is well recognized that the microvasculature is highly sensitive to ischemia-reperfusion (I/R) and that the initial damage of endothelial cells contributes to I/R-induced tissue injury. In an effort to define the mechanisms responsible for reperfusion-induced vascular injury number of in vitro models have been developed to stimulate the responses of endothelial cells to I/R. Because of its simplicity, many investigators have used monolayers of cultured endothelial cells exposed to anoxia and reoxygenation as a model system to minic I/R-induced vascular changes in vivo. The endothelium serves as an important modulator of vascular homeostases by secreting various levels of both thrombotic and antithrombotic agents. One of the important product of endothelial cells, prostaglandin I2 or prostacyclin (PGI2) helps to maintain hemostasis through its involvement in coagulation, platelet activation, leukocyte migration and adhesion, vascular tone regulation and growth control. PGI2 synthesis is a readily quantifiable index of endothelial cell perturbation and thus serves as a marker for the identification of injurious stimuli. Endothelial cells were isolated from human umbilical vein and cultured in M-199 medium plus 20% fetal calf serum. Purity of culture was determined by immunological fluorescent staining of factor VIII related antigen, phase-contrast microscopy. TRK 790 radio-immunoassay kit was used for the measuring of 6-keto-PGF1 alpha released by endothelial cells. The results were as follows: 1) The concentration of PGI(2) released from the cultured endothelial cells was 33.44 +/- 2.26 pg/1 105 cells/mL 2) Incubation of endothelial cells with anoxia and reoxygenation resulted in PGI(2) release of 42.98 +/- 2.29 pg/1x10(5) cells/ml and 62.44 2.11 pg/1 105 cells/ml, respectively. 3) Incubation of endothelial cells with allopurinol (20 mumol/L) decreased the PGI(2) release to 40.68 +/- 2.99 pg/1x10(5) cells/ml. In conclusion, our data showed that the damage of endothelial cells in reoxygenotion group was significantly increased comparing anoxia group (p<0.005) and that allopurinol can inhibit reoxygenation-induced injury of endotheial cells.

The Effects of Prostaglandin I2, Prostaglandin E1, and Nitroglycerin on Hemodynamics and Blood Gas Exchanges in Pulmonary Hypertension in Dogs / 대한마취과학회지

BACKGREOUND: The ideal drug for treatment of pulmonary hypertension would be a vasodilator which acts preferentially on the pulmonary vascular bed. The aim of this study was to compare the effects of prostaglandin I2 (PGI2) on central hemodynamics and right ventricular function with the more widely used vasodilators, prostaglandin E1 (PGE1) and nitroglycerin (NTG) and to investigate whether PGI2 is more selective to the pulmonary vascular bed compared with PGE1 and NTG in dogs. METHODS: We have used a method for producing sustained pulmonary hypertension in vivo by continuous infusion of U46619 adjusting the infusion rate until a mean pulmonary artery pressure (PAP) exceeded 25 mmHg. And the pulmonary and systemic effects of the three pulmonary vasodilators were compared at doses producing equivalent, lowered approximately 20% of mean arterial pressures (MAP) or mean PAP returned to baseline. RESULTS: After infusion of the three vasodilators, heart rate, cardiac output, and mean PAP/MAP ratio were significantly increased, but there was no statistical significant differences among the three vasodilators. PGI2 and PGE1 significantly increased (worsened) the PVR/SVR ratio, but NTG decreased. However there was no significant difference among the three vasodilators. After infusion of the three vasodilators, the arterial oxygen tension (PaO2), mixed venous oxygen tension (PO2), O2 deliver, and O2 uptake were increased, and shunt ratio (s/t(%)) were significantly decreased, but there were no significant differences among three vasodilators. CONCLUSIONS: PGI2, PGE1, and NTG all decreased both PVR and SVR. None of these vasodilatorswere more selective to the pulmonary vascular bed, myocardial performance, and improved gas exchange.