• Korean Journal of Veterinary Research
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• v.44 no.3
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• pp.469-473
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• 2004

This study was performed to investigate the effects of calcium administration on the blood coagulation mechanism through APTT in the calf. Five male calves (70~90 kg) were used in this experiment. In the control group, heparinized normal saline (1 IU/kg/min) had been infusing into the jugular vein for 100 minutes. For the analysis of calcium effects on the APTT, the same solutions had been infusing during the first 40 minutes, subsequently the solution including calcium gluconate (3.3 mg/ml/min) had been infusing for 60 minutes. Blood samples were serially collected every 10 minutes for the APTT and platelets count and every 20 minutes for the calicum level during the infusion. In the calcium-treated group, after 70 minutes the APTT ratio (APTT heparin/APTT baseline) was higher than the therapeutic range. APTT was significantly increased at 50, 60 and 70 minutes in the calcium-treated group as compared to the control group (p<0.01). In the control group, calcium level was decreased significantly after heparin infusion (p<0.01). The platelet count was gradually decreased without significant variation in the both control and calcium-treated groups. These results suggested that APTT is slightly increased in combined heparin and calcium administration.

• Archives of Pharmacal Research
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• v.25 no.1
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• pp.86-92
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• 2002

The enhancement of paracellular transport of heparin disaccharide using several absorption enhancers across Caco-2 cell monolayers was tested . The cytotoxicity of these enhancers was also examined. The enhancing effects by Quillaja saponin, diponin glycyrrhizinate, $18{\beta}-glycyrrhetinic$ acid, sodium caprate and taurine were determined by changes in transepithelial electrical resistance (TEER) and the amount of heparin disaccharide transported across Caco-2 cell monolayers. Among the absorption enhancers, $18{\beta}-glycyrrhetinic$ acid arid taurine decreased TEER and increased the permeability of heparin disaccharide in a dose-dependent and time-dependent manner with little or negligible cytotoxicity. Our results indicate that these absorption enhancers can widen the tight junction, which is a dominant paracellular absorption route of hydrophilic compounds . It is highly possible that these absorption enhancers can be applied as pharmaceutical excipients to improve the transport of macromolecules and hydrophilic drugs having difficulty in permeability across the intestinal epithelium.

• Bulletin of the Korean Chemical Society
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• v.30 no.12
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• pp.3034-3038
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• 2009

A simple, rapid, practical and sensitive spectofluorimetric method was developed for the determination of trace amount of heparin (Hep). Under the Optimum conditions, we studied the interaction between NFLX-Ce$^{3+}$-Hep complex by using absorption and fluorescence spectra. It was observed that Hep remarkably enhance the fluorescence intensity of the NFLX-Ce$^{3+}$ complex at ${\lambda}$= 356 nm in the buffer solution of pH = 7.60 and the enhancement effect is shown to relate with the concentration of Hep. The linear range and detection limit for the determination of Hep was obtained. By the Rosenthal graphic method, the association constant (K) and binding numbers (N) of Hep with probe were investigated. This method is relatively free of interference from coexisting substances and successfully applied for the determination of heparin in heparin sodium injection samples. A suitable mechanism of fluorescence enhancement between NFLX-Ce$^{3+}$ and the NFLX-Ce$^{3+}$-Hep systems were proposed and discussed.

• Archives of Pharmacal Research
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• v.21 no.5
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• pp.576-580
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• 1998

When glycosaminoglycan (GAG)-degrating enzymes were measured in normal human stool suspensions, all 5 tested different stools degraded titrable heparin and acharan sulfate. GAG-degrading bacteria were screened from the isolates of human stools. Among them, HJ-15 had the most potent activities of heparinases (GAGs-degrading enzymes). However, HJ-15 produced the enzyme even if in the media without heparin. Acharan sulfate lyase was induced by acharan sulfate and heparin. Heparinase production was also induced by these GAGs. These enzymes, acharan sulfate lyase and heparinase, were produced in exponential and stationary phase of HJ-15 growth, respectively. Optimal pHs of the acharan sulfate lyase and heparinase activities were 7.2 and 7.5 respectively. the biochemical properties of HJ-15 was similar to those of B. stercoris. However, difference from B. stercoris was utilization of raffinose. this HJ-15 also degraded chondroitin sulfates A and C.

• Journal of Chest Surgery
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• v.35 no.6
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• pp.475-478
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• 2002

A 45 year old man was admitted for aggravated dyspnea, abdominal distension and poor oral intake. On Echocardiogram, mitral stenosis(severe), tricuspid regurgitaion(IV), and LA thrombus were diagnosed. We used heparin with continuous infusion for prevention of systemic thrombo embolism. On the 11th day of admission, the patient showed thrombocytopenia and we suspected Heparin-induced thrombocytopenia. Hirudin was used in this case as alternative anticoagulant during cardiopulmonary bypass to prevent serious complication of heparin. The patient was recovered without any complication as postoperative bleeding or systemic thromboembolism.

• The Journal of Health Technology Assessment
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• v.6 no.2
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• pp.133-141
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• 2018

Objectives: In the past, the pharmaceutical drug heparin was mostly used as the anticoagulant for continuous renal replacement therapy (CRRT), but the duration time is long to have the risk of a bleeding adverse effect, and in that case the drug therapy Nafamostat mesilate was utilized instead, as it is more safe in this case, with a short half-life and is increasing in use to permit lower concerns for bleeding incidents. However, there are insufficient number of large-scale studies on the comparison of Nafamostat mesilate and heparin. Methods: In this study, a systematic review are used to compare the bleeding risk of Nafamostat mesilate and Heparin, as subjected to patients and procedures for measuring risks performed with a CRRT, and the filter life span is to be evaluated as well in this patients. Results: As a result of literature review search, a total of 6 studies were included in systematic review. The reducing risk of bleeding and filter life span was analyzed. The retrospective cohort studies confirm that Nafamostat mesilate is less at risk of bleeding than heparin. And a cohort study confirms that Nafamostat mesilate is longer filter lifespan than heparin and randomized controlled trial studies show that Nafamostat mesilate is longer filter lifespan than not using the anticoagulants. Conclusion: Nafamostat mesilate is considered to be a good therapeutic option because it has a longer filter life span as well as the advantage of reducing bleeding.

• Journal of Chest Surgery
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• v.31 no.9
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• pp.867-872
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• 1998

Background: The fixed dose regimen with activated coagulation time(ACT) is the most commonly employed method for determining the required dosage of heparin and protamine during cardiopulmonary bypass(CPB). Material and Method: We performed a prospective study on a fixed dose regimen for analyzing adequate dosages of heparin and protamine, the incidence of heparin resistance and heparin-induced thrombocyt openia, factors affecting ACT during CPB, and changes of ACT during aprotinin usage. 300 units/kg of heparin were administered to patients, and ACTs were measured after 5 mins. ACTs were checked at 10 mins and 30 mins after the onset of CPB, and then at 30 min intervals thereafter. If the measured ACT was under 400 secs, we added 100 units/kg of heparin. The heparin was reversed with 1 mg of protamine for each 100 units administered. If the measured ACT was longer than 130 secs 30 mins after protamine administration or if there was definitive evidence of a coagulation defect, we administered a further 0.5 mg/kg of protamine. Result: We studied 80 patients(50 adults and 30 children) who underwent open heart surgery(OHS) at Seoul National University Hospital. Preoperative ACT was 114.3${\pm}$19.3 secs in adults, and 119.5${\pm}$18.2 secs in children. There were no differences in preoperative ACT due to age, body weight, body surface area, or sex. The preoperative ACT was not influenced by a positive past history of OHS. Ten adults(20%) and 3 pediatric patients(10%) needed additional doses of heparin to maintain the ACT above 400 secs. Additional protamine administration was needed in 9 adults(18%) and 10 children(33%). Heparin resistance was found in only two adults. Heparin-induced thrombocytopenia was detected in 2 adults and 1 child. During CPB, ACT was prolonged. 12 adult patients received a low dose of aprotinin and showed longer celite activated ACT compared to the control group.The kaolin activated ACT showed a lower tendency than the celite activated ACT in aprotinin users. Conclusion: In conclusion, fixed dose regimen of heparin and protamine can be used without significant problems, but the incidence of need of additional dosage remains unsatisfactory.

• Proceedings of the Polymer Society of Korea Conference
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• 2006.10a
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• pp.48-49
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• 2006

The incorporation of heparin to biomaterials has been widely studied to improve the biocompatibility (blood and cell) of biomaterials surfaces. In our laboratory, various kinds of heparinized polymers including heparinized thermosensitive polymers ($Tetronic^{(R)}$-PLA(PCL)-heparin copolymers) and star-shaped PLA-heparin copolymers have been developed as a novel blood/cell compatible material. These heparinized polymers have demonstrated their unique properties due to bound heparin, resulting in improved biocompatibility. These heparinized bioactive polymers can be applied as blood and tissue compatible biodegradable materials in variable medical application such as tissue engineering and drug delivery system.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.703-708
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• 2003

This study was carried out to compare the efficacy of carboxymethyl chitosan fabric (CMCF) with that of the combination of low molecular weight heparin (LMWH) and CMCF for the prevention of postoperative adhesions in the rat. Adhesions were induced by suturing both the ileal serosa and peritoneum scraped until petechial bleeding occurred. CMCF were sutured between two surfaces, and LMWH were instilled intraperitoneally immediately before closure of the peritoneomuscular layer. The adhesions were blindly assessed 2 weeks later by using a tensiometer. The mean tensile strength(Newton) of formed adhesions was $2.59{\pm}0.85$ in control group, $2.10{\pm}0.75$ in the CMCF group and $1.53{\pm}0.44$ in the CMCF+LMWH group. The most favorable prevention against adhesion was achieved in the CMCF+LMWH group. Therefore, we could conclude that CMCF+LMWH were effective in prevention against postoperative adhesion in the rat.

• Journal of Chest Surgery
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• v.51 no.2
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• pp.114-121
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• 2018

Background: Unfractionated heparin is commonly used for anticoagulation in extracorporeal membrane oxygenation (ECMO). Several studies have shown that nafamostat mesilate (NM) has comparable clinical outcomes to unfractionated heparin. This study compared anticoagulation with NM and heparin in a large-animal model. Methods: Beagle dogs (n=8; weight, 6.5-9 kg) were placed on venovenous ECMO. Blood samples were taken every hour and the following parameters were compared: hemoglobin level, activated partial thromboplastin time (aPTT), thromboelastography (TEG) data, platelet function, and inflammatory cytokine levels. Results: In both groups, the aPTT was longer than the baseline value. Although the aPTT in the NM group was shorter than in the heparin group, the TEG parameters were similar between the 2 groups. Hemoglobin levels decreased in both groups, but the decrease was less with NM than with heparin (p=0.049). Interleukin $(IL)-1{\beta}$ levels significantly decreased in the NM group (p=0.01), but there was no difference in the levels of tumor necrosis factor alpha or IL-10 between the 2 groups. Conclusion: NM showed a similar anticoagulant effect to that of unfractionated heparin, with fewer bleeding complications. NM also had anti-inflammatory properties during ECMO. Based on this preclinical study, NM may be a good alternative candidate for anticoagulation in ECMO.