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

We investigated the effects of low-dose Beraprost sodium (BPS), a stable prostaglandin I2 (PGI2) analogue, on microvascular permeability and the plasma concentrations of thromboxane and adenosine 3',5'-cyclic monophosphate (cAMP) in blood-perfused rabbit lungs subjected to ischemia-reperfusion (I/R). After an ischemic insult for 2 h, saline as a vehicle, 3 pmol/L of BPS (BPS-1), 150 to 300 pmol/L of BPS (BPS-2), 900 pmol/L of BPS (BPS-3), or 60 micromol/L of indomethacin (IND) was administered into the reservoir, then the lungs were reperfused and reventilated for 1 h. Vascular permeability was assessed by determining the microvascular filtration coefficient (Kf, ml/min/mm Hg/100 g wet lung). I/R resulted in increases in vascular resistance, Kf, and thromboxane. BPS-2, BPS-3, and IND inhibited the increase in vascular resistance, and BPS-3 and IND attenuated the increases in Kf and thromboxane. BPS-3 increased, but IND decreased, the concentrations of cAMP in the perfusate. Perfusate thromboxane released after reperfusion was significantly correlated with Kf. We conclude that cyclooxygenase products play a critical role in I/R-induced lung vascular injury and that 900 pmol/L of BPS inhibits the production of thromboxane and enhances the permeability barrier via a cAMP-elevating effect. However, vasodilatory action of BPS may exacerbate the reperfused lung injury by increasing the flow through injured capillaries via inhibition of thromboxane-induced vasoconstriction.
 ...
PMID:Effects of low-dose Beraprost sodium, a stable prostaglandin I2 analogue, on reperfusion injury to rabbit lungs. 981 23

The digestion of pancreatic tissue with collagenase is an essential part of the islet isolation procedure. However, the process exposes islets to various types of harmful factors, including collagenase contaminants, enzymes released from the acinar cells, warm ischemia, and mechanical agitation. Nitrogen oxide production and cytokine release may also contribute to islet cell damage. Protection of islets from such damage would improve the islet yield, survival, and function. Beraprost sodium (BPS) is a prostaglandin I2 analogue, is stable in aqueous solution, and has a cytoprotective effect on various types of cells. BPS has been shown to improve the yield and function of cryopreserved and/or cultured islets. These findings prompted us to examine its cytoprotective effect on islets during the islet isolation process. Canine islets were isolated by means of a two-step digestion method and purified on Euro-Ficoll density gradient solutions (the procedure used for human islets). BPS at a concentration of 100 nM was added to the collagenase solution. After purification, the islet yield was 434,561 +/- 35.691 islet number expressed as 150 microm equivalent size (IEQ)/pancreas or 8,799 +/- 345 IEQ/g of pancreas in the BPS group and 349,987 +/- 52,887 IEQ/pancreas or 7,998 +/-1610 IEQ/g of pancreas in the control group (n = 8, each). The percent viability was 88.5 +/- 0.7% in the BPS group and 82.0 +/-0.9% in the control group (P < 0.01). Therefore, the recovery of viable islets (calculated by islet number x % viability) was 384,586 +/- 46,804 IEQ/pancreas (7,743 IEQ/g) in the BPS group and 286,989 +/- 43,367 IEQ/pancreas (6,558 IEQ/g) in the control group (P < 0.02). After culture, significantly higher numbers of islets were also recovered in the BPS group than in the control group. The islet insulin content was significantly higher in the BPS group than controls (237.8 +/- 38.5 versus 92.3 +/- 25.6 microU/IEQ; P < 0.02), although islets of both groups responded with high stimulation indices (>6). These results indicate that the addition of BPS to the collagenase solution increases the recovery of viable islets, and improves beta cell function.
 ...
PMID:Increased islet viability by addition of beraprost sodium to collagenase solution. 1145 Nov 49

Renal blood flow decreases with the progression of chronic glomerulonephritis (CGN). This disease induces medullary ischemia and further renal dysfunction in patients with chronic renal insufficiency (CRI). Prostacyclin (PGI2), with its vasodilative action, increases renal blood flow (RBF) without increasing glomerular filtration rate (GFR). We therefore examined the possibility that PGI2 would mitigate the progression of renal dysfunction by increasing RBF in patients with CRI. Sixteen patients with progressive renal insufficiency (serum creatinine: 2.14+/-0.89 mg/dl) due to CGN were prospectively chosen for this study. The blood pressure was already under control using calcium channel blockers before and during this study in nine hypertensive patients. In the first 6 months the patients received a low-protein (0.6 g/kg/day) and low-salt (5.0 g/day) diet. In the next 6 months they received 60 microg/day of PGI2 analogue (Beraprost sodium) orally. GFR was determined by 24-hour creatinine clearance, and effective renal plasma flow (ERPF) was determined by 99mTc-MAG3 scintigraphy. Glomerular capillary pressure, the resistance ratio of afferent and efferent arterioles (R(A)/R(E)), and the other hemodynamic parameters from Gomez's estimation equation were determined at the start of this study, just before the administration of Beraprost and at the end of the study. The levels of GFR and ERPF were 34.6+/-12.4 and 140.6+/-52.1 ml/min at the start of this study respectively, and decreased to 28.0+/- 12.0 and 115.6+/-45.3 ml/min after the first 6 months without Beraprost. The levels of GFR and ERPF stayed at 28.1+/-15.7 and 119.2+/-57.6 ml/min after the next 6 months with Beraprost in the same patients. R(A)/R(E) increased in the first 6 months from 7.9+/-3.6 to 10.8+/-8.6, but remained constant during 6 months of Beraprost administration, at 10.5+/-8.0. These data indicate that PGI2 analogue diminishes the vascular resistance of glomerular afferent and efferent arterioles regulating the decrease of renal blood flow without glomerular hyperfiltration, thus mitigating the progression rate of renal dysfunction.
 ...
PMID:PGl2 analogue mitigates the progression rate of renal dysfunction improving renal blood flow without glomerular hyperfiltration in patients with chronic renal insufficiency. 1172 76

This paper provides an update on the mechanisms of vascular impairment associated with insulin resistance and the pathogenesis of diabetic nephropathy and peripheral artery disease (PAD). It also considers the optimal treatment strategies for systemic vascular protection in light of recent findings. This area is of major clinical importance given the ongoing global epidemic of type 2 diabetes and the pivotal role played by insulin resistance in the mechanism of vascular impairment that manifests as macroangiopathy and microangiopathy. Timely diagnosis and intervention is critical in patients with systemic arteriosclerotic disease. Therefore, treatment strategies are aimed not only at targeting the presenting pathology, but also at reducing the risk of cardiovascular events. These efforts can help reduce the risk of both cardiovascular events and mortality. Treatment for PAD includes pharmacotherapy, endovascular treatment, and vascular reconstruction, along with exercise therapy. Because PAD can cause ischemia in the lower extremities, typical drug approaches include use of vasodilators and antiplatelet agents. Beraprost sodium and cilostazol are common choices in Japan, and their risks and benefits are discussed. Of note, beraprost has several therapeutic properties, including vascular endothelial protection, and antiplatelet and anti-inflammatory effects, in addition to vasodilatory activity. In patients with PAD, these activities improve the pathological process in the lower extremities and reduce the incidence of systemic vascular events. Recent preclinical findings indicate that beraprost improves not only ischemic extremities through its vasodilatory properties, but also reduces the insulin resistance which affects vascular endothelium. In this way, beraprost may contribute to an overall systemic vascular protective action. The use of agents, such as beraprost, which are capable of improving insulin resistance and resulting vascular endothelial function at an earlier disease stage, may ultimately contribute to increasing the life expectancy of patients with PAD.
 ...
PMID:Treatment strategy for type 2 diabetes from the perspective of systemic vascular protection and insulin resistance. 2291 Jul 31

A 66-year-old man was hospitalized for diverticular bleeding of the colon. Anticoagulant drugs (Dabigatran and Beraprost sodium), which had been taken for chronic underlying atrial fibrillation, were interrupted for three days. After two months, he presented with acute pancreatitis and a pancreatic pseudocyst. The contrast-enhanced CT scan revealed an atrial thrombus and localized splenic infarction. Consequently, we suspected ischemic acute pancreatitis secondary to thrombus. Anticoagulant drug interruption and the resultant local ischemia were potential factors contributing to ischemic pancreatitis.
 ...
PMID:[A case report of suspected ischemic acute pancreatitis caused by temporary interruption of anticoagulant drugs for diverticular bleeding of the colon]. 2988 89