Femoral arterial closure devices are now commonly used after both diagnostic and therapeutic coronary procedures. They have been shown to reduce the time to ambulation and to decrease the length of the hospital stay. Angioseal is a commercially available femoral artery closure device that has been approved by the Food and Drug Administration (FDA). The device sandwiches an intra-arterial absorbable anchor on the luminal side of the vessel and a thrombin plug on the surface of the vessel with using a self-cinching stitch. We report here on three patients who presented with acute and delayed arterial occlusive complications that were found to be due to an Angioseal anchor that was not appropriately reabsorbed.
Femoral Artery ; Glycosaminoglycans ; Humans ; Length of Stay ; Phenobarbital ; Thrombin ; United States Food and Drug Administration ; Walking

Angioplasty, Balloon, Coronary ; Heart Injuries ; drug therapy ; etiology ; Humans ; Thrombin ; administration & dosage

BACKGROUND: Bivalirudin is a direct thrombin inhibitor for patients with unstable angina undergoing percutaneous coronary intervention. METHODS: A sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of bivalirudin, in human plasma using nafarelin as internal standard (IS). Chromatographic separation was performed using a Shiseido MG3 mm column (2.0 x 50 mm) with a gradient mobile phase consisting of water and acetonitrile containing 0.1 % formic acid at a flow rate of 0.4 mL/min, and total run time was within 5 min. Detection and quantification was performed by the mass spectrometer using a multiple reaction-monitoring mode at m/z 1091.0 --> 650.3 for bivalirudin, and m/z 662.1 --> 249.3 for IS. RESULTS: The assay was linear over a concentration range of 10 - 10000 ng/mL with a lower limit of quantification of 10 ng/mL in human plasma. CONCLUSION: This method was successfully applied for pharmacokinetics study after intravenous administration of bivalirudin to healthy Korean male volunteers.
Administration, Intravenous ; Angina, Unstable ; Chromatography, Liquid ; Humans* ; Male ; Mass Spectrometry ; Methods ; Nafarelin ; Percutaneous Coronary Intervention ; Pharmacokinetics ; Plasma* ; Thrombin ; Water

BACKGROUND AND OBJECTIVES: In a previous study, LB30057 was found to inhibit smooth muscle cell proliferation in a dose dependent manner, and prolonged 1 4-day oral administration of LB30057 is effective in reducing the neointimal hyperplasia in a rat carotid balloon injury model. The prolonged administration of LB30057, an orally active direct thrombin inhibitor, was evaluated and found to be a potential inhibitor of restenosis in a porcine coronary injury model. MATERIALS AND METHODS: An oversized balloon injury and a stent injury were given to the right coronary artery and left anterior descending artery, respectively, in the porcine model. LB30057 (50mg/kg) or a placebo was administrated for 28 days, using an osmotic pump, starting 6 hours prior to the injury until sacrifice on the 28th day. The drug concentration and antithrombotic effects (aPTT, thrombin-anti thrombin complex levels) were measured, and a histo-morphometric analysis performed 28 days later. RESULTS: The drug concentrations were 271+/-1 24 and 67+/-52 ng/mL on days 1 and 28 after injury in the drug group. The TAT (thrombin-antithrombin complex) levels were significantly lower in the drug than the control group on the 2nd and 7th days after injury (p<0.05). There were no significant differences in the injury scores, and the luminal, intimal and medial areas between the two groups. CONCLUSION: Prolonged administration of LB30057, using an osmotic pump, was not effective in reducing the restenosis in our pig coronary injury model.
Administration, Oral ; Animals ; Arteries ; Coronary Disease ; Coronary Restenosis ; Coronary Vessels ; Hyperplasia ; Myocytes, Smooth Muscle ; Phenobarbital ; Rats ; Stents ; Thrombin*

BACKGROUND: Recent data showed prolonged administration of direct thrombin inhibitor might be needed to counteract the persistent thrombin activity and reduce the neointimal hyperplasia after arterial injury. We hypothesized that prolonged administration of LB30057, orally active direct thrombin inhibitor, might inhibit the vascular smooth muscle cell (SMC) proliferation in vitro and neointimal hyperplasia in rat carotid injury model. METHODS: In phase I, thrombin stimulated [methyl-3H] thymidine uptake was measured after LB30057 administration in cell culture study using rat aortic SMC. In phase II, LB30057 (low-dose: 5mg/kg, bid: mid-dose: 25mg/kg, bid: high-dose: 50mg/kg, bid) or placebo was administrated orally twice a day starting from 30minutes before injury until sacrifice for 14days in separated 2 sets of experiment. The histo-morphometric analysis for lumen area, intimal area, medial area, intima-to-medial ratio was performed. RESULTS: In vitro rat aortic SMC culture study, LB30057 inhibited thrombin-induced thymidine uptake. The mean neointimal area was significantly less in high-dose and mid-dose group than placebo group (high-dose vs. placebo: 0.14+/-0.02mm2 vs. 0.25+/-0.02mm2: mid-dose vs. placebo: 0.16+/-0.02mm2 vs. 0.29+/-0.03mm2, p<0.005) respectively and the mean ratio of neointima to medial area were significantly less in high-dose and mid-dose group than in placebo group (high-dose vs. placebo: 1.20+/-0.57 vs. 1.94+/-0.67, mid-dose vs. placebo: 1.58+/-0.29 vs. 2.39+/-0.27, p<0.05). There was no significant difference in the mean area of internal elastic lamina, external elastic lamina and mean luminal area between groups. In 2nd set experiment, the mean neointimal area (placebo: 0.29+/-0.03mm2, mid-dose: 0.16+/-0.02mm2: p<0.005), the mean area of internal elastic lamina and external elastic lamina were significantly less in mid-dose group than in placebo group. The mean ratio of neointima to medial area was significantly less in mid-dose group(1.58+/-0.29) than in placebo group (2.39+/-0.27) (p<0.05). CONCLUSION: LB30057 inhibits SMC proliferation in a dose dependent manner. Prolonged 14-day oral administration of LB30057 is effective in reducing the neointimal hyperplasia in rat carotid balloon injury model.
Administration, Oral ; Animals ; Cell Culture Techniques ; Cell Proliferation* ; Hyperplasia* ; Muscle, Smooth, Vascular* ; Neointima ; Phenobarbital ; Rats* ; Thrombin* ; Thymidine

BACKGROUNDThe non-operation treatment of intra-abdominal trauma guided contrast enhanced ultrasound (CEUS) is one of the hottest research topic. Gelatin/thrombin/calcium (GTC) was developed as a novel haemostatic agent for non-operable intra-abdominal trauma. We hypothesized that GTC can achieve haemostasis (without the use of pressure) within a short time in a large wound model by percutaneous injection under CEUS guidance.

METHODSForty Wister rats received large liver injuries by haemostatic clamp and were randomly divided into four groups, according to the haemostatic agent used. These included normal saline (NS) group A, lyophilising thrombin powder (LTP) group B, GTC group C, and absorbable α-cyanoacrylate (ACNA) group D. Each injury site was treated with one of the above materials and total bleeding time was recorded. All liver wounds were evaluated using CEUS at three periods: pre-injury, injury and post-treatment. The liver wounds were also evaluated by histology 3, 6, and 9 days after injury and the extents of abdominal adhesions were recorded.

RESULTSThe sensitivity of CEUS (100%) in detecting blunt traumatic liver lesions was significantly higher than conventional ultrasound (42.5%). Bleeding times at the injury site in the GTC group C ((129.3 ± 14.0) seconds) and ACNA group D ((5.2 ± 1.0) seconds) were significantly shorter than those in the NS group A ((369.5 ± 48.8) seconds, P < 0.01) and LTP group B ((324.7 ± 52.22) seconds, P < 0.01). The LTP group B showed no significant difference compared with the NS group A. Gross examination of liver tissue revealed that there were fewer intra-abdominal adhesions in the GTC group C (10%) than in the ACNA group D (100%). Histopathologic examination showed that GTC was completely absorbed after nine days.

CONCLUSIONSGTC, delivered by percutaneous injection under CEUS, may achieve haemostasis (without the use of pressure) within a short time in a large wound model. GTC is absorbable and may prevent intra-abdominal adhesions. Therefore, it may be the optimal choice for first aid treatment of large abdominal wounds in the setting of blunt trauma.

Animals ; Calcium ; administration & dosage ; therapeutic use ; Gelatin ; administration & dosage ; therapeutic use ; Hemorrhage ; diagnostic imaging ; drug therapy ; Hemostatics ; administration & dosage ; therapeutic use ; Injections ; Liver ; diagnostic imaging ; injuries ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Thrombin ; administration & dosage ; therapeutic use ; Ultrasonography

During the past decade, many studies using platelet-rich plasma (PRP) or adipose-derived stem cells (ASCs) have been conducted in various medical fields, from cardiovascular research to applications for corneal diseases. Nonetheless, there are several limitations of practical applications of PRP and ASCs. Most reports of PRP are anecdotal and few include controls to determine the specific role of PRP. There is little consensus regarding PRP production and characterization. Some have reported the development of an antibody to bovine thrombin, which was the initiator of platelet activation. In the case of ASCs, good manufacturing practices are needed for the production of clinical-grade human stem cells, and in vitro expansion of ASCs requires approval of the Korea Food and Drug Administration, such that considerable expense and time are required. Additionally, some have reported that ASCs could have a potential risk of transformation to malignant cells. Therefore, the authors tried to investigate the latest research on the efficacy and safety of PRP and ASCs and report on the current state and regulation of these stem cell-based therapies.
Consensus ; Corneal Diseases ; Humans ; Korea ; Mesenchymal Stromal Cells ; Platelet Activation ; Platelet-Rich Plasma ; Stem Cells ; Thrombin ; Treatment Outcome ; United States Food and Drug Administration

Carotid Artery Diseases ; drug therapy ; Carotid Artery, Internal ; Child ; Female ; Humans ; Injections ; Leukemia, Promyelocytic, Acute ; complications ; Rupture, Spontaneous ; Thrombin ; administration & dosage ; Ultrasonography, Interventional

OBJECTIVE: To explore the effect of the cerebral thrombin preconditioning on the thrombin-induced brain edema, to detect the expression of tumor necrosis factor-alpha (TNF-alpha), and to analyse the relationship between TNF-alpha and the thrombin-induced brain edema. METHODS: Forty SD rats were randomly divided into a ST group and a TT group. The rats received 50 L saline (ST group) or 1 U thrombin infusion (TT group), and received the second infusion (10 U thrombin) 24 h later. The rats were sacrificed at 24 and 72 h after the second infusion in order to examine the changes of brain water and sodium contents as well as the expression of TNF-alpha in the brain. RESULTS: The brain water and sodium contents in the ST group were significantly higher than those on the TT group, and those on the 1st day were higher than those on the 3 th day. The positive expression of TNF-alpha and in the change of water content were identical in the TT group and the ST group. CONCLUSION Thrombin preconditioning can alleviate the thrombin-induced brain edema. The increase of TNF-alpha expression after thrombin treatment may be related to the thrombin-induced brain edema.
Animals ; Brain ; metabolism ; Brain Edema ; etiology ; metabolism ; therapy ; Ischemic Preconditioning ; Male ; Rats ; Rats, Sprague-Dawley ; Thrombin ; administration & dosage ; adverse effects ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism

AIMTo investigate the pharmacokinetics and the anticoagulation action of recombinant hirudin-2 (rHV2) nasal spray after administration of the preparation.

METHODSrHV2 concentration in plasma was determined by chromogenic substrate method and the relative bioavailability was calculated. The anticoagulation action of rHV2 spray after intranasal administration in normal rats and DIC model rabbits after intranasal administration of rHV2 spary were studied.

RESULTSThe in vivo course of rHV2 in rats fitted to the one-compartment model after intranasal administration of rHV2 spray and the relative bioavailability was 28.53%. Coagulating times of APTT and TT were significantly prolonged in normal rats, and APTT in DIC model rabbits was significantly shortened and was close to the normal values after administration of rHV2 nasal spray.

CONCLUSIONrHV2 spray could be an effective nasal preparation of rHV2.

Administration, Intranasal ; Animals ; Area Under Curve ; Biological Availability ; Disseminated Intravascular Coagulation ; physiopathology ; Hirudins ; administration & dosage ; pharmacokinetics ; pharmacology ; Male ; Partial Thromboplastin Time ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; administration & dosage ; pharmacokinetics ; pharmacology ; Thrombin Time