• Journal of Chest Surgery
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• 제13권1호
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• pp.13-20
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• 1980

Heparin would have been used for preventing clotting of blood during extracorporeal circulation and subsequent use of protamine sulfate and made possible the neutralization of heparin. This procedure has been adopted for eliminating one of the great causes of bleeding, especially in cardiac surgery. In this experiment, the hypocoagulability of blood induced by heparin followed by neutralization with treatment of protamine sulfate were estimated by the Lee-White clotting time [CT], partial thromboplastin time [PTT] and protamine titration test. The results were as follows: 1] Comparison of clotting time between the heparinized [2.0 mg/kg] and non-heparinized dogs was done using CT and PT`I` of the blood. In heparinized group [Group I], the CT lasted infinitively and prolongation of PTT [4 times than normal] until 60 minutes. The CT [2 times] and PTT [3 times] has been shortened after 90 minutes, however they returned to normal limit level within 180 minutes. 2] The determination of appropriate ratio of heparin and protamine In vivo were performed. The group II [heparin 2.0 mg/kg, protamine 1.0 mg/kg] revealed rapid decrease of CT and PTT, but returned to normal after 120 minutes. The group III [heparin 2.0 mg/kg, protamine 2.0 mg/kg] returned rapidly to normal within 15 minutes. The group IV [heparin 2.0 mg/kg, protamine 3.0 mg/kg] recovered its normal level after 60 minutes. The group V [heparin 2.0 mg/kg, protamine 4.0 mg/kg] recovered its normal level after 90 minutes. 3] In the combined experimental study In vivo and vitro, the protamine titration test was done using the dog which were given 2.0 mg/kg and 3.0 mg/kg of heparin, respectively and coagulation time were checked after 15, 30, 60 and 120 minutes. The complete neutralization was showed to be heparin-protamine ratio of 1:1 to 1.5. 4] In vitro study, fresh blood was drawn into known amount of heparin content [20, 40, 60 and 100/ug per 1 ml of blood] syringe, thereafter protamine titration test was done. In all cases, the complete neutralization was found in heparin-protamine ratio of 1:0.85 to 1.5. 5] It was found by the present experiment that the ideal heparin-protamine ratio was 1:1 within 60 minutes and 1:0.5 after 60 minutes for avoiding the serious side effect due to overadministration of protamine sulfate.

• 한국수정란이식학회지
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• 제7권2호
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• pp.73-79
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• 1992

Effects of caffeine, heparin and caffeine-heparin treatments for in vitro capacitation of Korean Native Cattle sperm on acrosorne reaction and viability were studied using the methods of Wells-Awa and Dual stain. The results were summerized as follows: 1. The acrosome reaction of sperm when treated with caffeine after 0 to 4 hrs of preincubation were 11.0~75.7% for Wells-Awa stain, and 14.3~75.55% for Dual stain. True acrosome reaction of sperm for Dual stain was 3.0~29.2%. The viability of sperm was 62. 2~27.2%. 2. The acrosome reaction of sperm when treated with heparin after 0 to 4 hrs of preincubation were 17.0~81.2% for Wells-Awa, and 14.3~75.5% for Dual Stain. True acrosome reaction of sperm for Dual stain was 1.5~26.6%. The viability of sperm was 58.6~35. 8%. 3. The acrosome reaction of sperm when treated with caffeine-heparin after 0 to 4 hrs of preincubation were 13.0~83.2% for Wells Awa, and 11.0~78.5% for Dual stain. True acrosome reaction of for Dual stain was 5.1~26.3%. The viability of sperm was 60.5~30.1%.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1102-1108
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• 2003

We studied the effects of phytolaccosides, saponins from Phytolacca americana, on the intestinal absorption of heparin in vitro and in vivo. The absorption enhancing activity of these compounds (phytolaccosides B, $D_2$, E, F, G and I) was determined by changes in transepithelial electrical resistance (TEER) and the transport amount of heparin disaccharide, the major repeating unit of heparin, across Caco-2 cell monolayers. With the exception of phytolaccoside G, all of them decreased TEER values and increased the permeability in a dose-dependent and time-dependent manner. In vitro, phytolaccosides B,$D_2$, and E showed significant absorption enhancing activities, while effects by phytolaccoside F and I were mild. In vivo, phytolaccoside E increased the activated partial thromboplastin time (APTT) and thrombin time, indicating that phytolaccoside E modulated the transport of heparin in intestinal route. Our results suggest that a series of phytolaccosides from Phytolacca americana can be applied as pharmaceutical excipients to improve the permeability of macromolecules and hydrophilic drugs having difficulty in absorption across the intestinal epithelium.

• Asian-Australasian Journal of Animal Sciences
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• 제13권1호
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• pp.10-18
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• 2000

This paper describes the magnetic orientation of the intact and demembranated bull sperm treated by DTT or heparin in a 5,400 G static field. Semen samples collected from four bulls (Japanese Black) were mixed to the same sperm density. One percentage triton X-100 was used to extract the plasma membrane. The intact and demembranated sperm suspensions were treated with 20, 200, 2,000 mM DTT, 100, 1,000 or 10,000 units heparin solutions at $4{^{\circ}C}$ for 6 days. The decondensation of the sperm nuclei treated by DTT or heparin was examined by measuring the sperm head area at 1, 3, and 6 days. After measuring the area, each sperm sample was exposed to a 5,400 G static magnetic field generated by Nd-Fe-B permanent magnets for 24 hours at room temperature. Results showed that the decondensation of bull sperm nuclei was not induced by the heparin treatment, however, incomplete decondensation was induced by the DTT treatment. During the magnetic orientation, bull sperms treated by DTT or heparin had low percentages of long axis perpendicular to the magnetic lines of force. However, different aspects were obtained for long axis perpendicular orientations following treatment of DTT or heparin. Through the DTT treatment, the decline of long axis perpendicularly oriented percentages was due to the increase of long axis parallel orientation with the head of the flat plane perpendicular to the magnetic lines of force, whereas, using the heparin treatment, the decline of long axis perpendicular orientation was due to the increment of long axis parallel orientation with the head of the flat plane parallel to the magnetic lines of force. Also, percentages of the head of the flat plane perpendicular were decreased by the heparin treatment. These findings suggest that maintaining the structure of protamine in the chromatin is necessary for the sperm head to orient with its flat plane perpendicular, and maintaining the disulfide bond in the chromatin is necessary for the long axis of sperm to orient perpendicularly.

• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.231-236
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• 2008

Heparin is a well-known anticoagulant widely used in various clinical settings. Interestingly, recent studies have indicated that heparin also has anti-inflammatory effects on neuroinflammation-related diseases, such as Alzheimer's disease and meningitis. However, the underlying mechanism of its actions remains unclear. In the present study, we examined the anti-inflammatory mechanism of heparin in cultured cerebral endothelial cells (CECs), and found that heparin inhibited the tumor necrosis factor $\alpha$ ($TNF{\alpha}$)-induced and nuclear factor kappa B (NF-${\kappa}B$)-dependent expression of adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), which are crucial for inflammatory responses. Heparin selectively interfered with NF-${\kappa}B$ DNA-binding activity in the nucleus, which is stimulated by $TNF{\alpha}$. In addition, non-anticoagulant 2,3-O desulfated heparin (ODS) prevented NF-${\kappa}B$ activation by $TNF{\alpha}$, suggesting that the anti-inflammatory mechanism of heparin action in CECs lies in heparin's ability to inhibit the expression of cell adhesion molecules, as opposed to its anticoagulant actions.

• Journal of Chest Surgery
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• 제21권2호
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• pp.203-210
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• 1988

The clinical experience with the activated clotting time[A.C.T.] for the control of heparin and protamine therapy during cardiopulmonary bypass in 40 patients between April, 1987 and September, 1987 is reviewed retrospectively. All of patients used with cold blood potassium cardioplegia for myocardial protection under standard cardiopulmonary bypass, priming and perfusate techniques respectively. This study was divided into 2 groups of patients followed by cardiopulmonary bypass time. Twenty patients, within 60 minutes of cardiopulmonary bypass time[group A] were compared with twenty patients, from 60 to 120 minutes of cardiopulmonary bypass time[group B]. Using blood cardioplegia for myocardial protection, Author observed wide variation of A.C.T. in individual response to initial heparinization[2mg /kg] and no requirement of additional heparin during cardiopulmonary bypass until 120 minutes. Total heparin amount during cardiopulmonary bypass was not related to body weight and body surface area in the both groups. After cardiopulmonary bypass, amounts of protamine for neutralization of heparin were more required in group B.

• 약학회지
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• 제29권2호
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• pp.70-75
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• 1985

The influence of polyethylene glycol derivatives on heparin release from cylindrical monolithic type silicone segment devices was examined in physical saline solution. This water-soluble carrier caused the devices to absorb the water in aqueous media. The release rate of heparin from the devices was increased as molecular weight of polyethylene glycol was increased. Water soluble carrier incorporated into silitone segment devices permits controlled release of heparin that otherwise would be released extremly slowly from the polymer. Heparin released from the silicone segment containing polyethylene glycol showed the first-order kinetics. Without changing the release-pattern, the release rate of heparin could be controlled by varing molecular weight of polyethylene glycol, the water-soluble carrier and depleting polyethylene glycol on the outlayer of devices. The mechanism of release probably showed the creation of pore or microdomine through the devices secondary to the swelling.

• Journal of Chest Surgery
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• 제32권2호
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• pp.97-107
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• 1999

배경: 흉부대동맥 수술에 사용하는 헤파린 우회도관의 국산화를 위해, 헤파린 표면처리기법 중 물리분산법을 이용하여 제작한 우회도관의 동물실험을 통해 혈전저항성 및 안정성을 증명하고자 하였다. 대상 및 방법: 성견 21마리(17.5∼25 kg)를 대상으로 하행흉부대동맥 우회모델을 만들었다. 사용한 우회도관의 종류에 따라 무처리 우회도관군(CONTROL; n=3), 무처리 우회도관 및 전신 헤파린 처치군(HEPARIN; n=6), Gott 헤파린 우회도관군(GOTT; n=6), 국산 헤파린 우회도관군(KIST; n=6)로 분류하였다. 관찰지표는 말초혈액검사, 혈액응고검사, 신장 및 간기능검사, 표면전자현미경 소견 등이었다. 각 지표는 우회도관의 원위부 대동맥 혈액에서 검사하여 우회 전과 우회 후 2시간 째의 군내 변화와군간 차이를 비교하였다. 결과: 모든 관찰지표의 우회 전 기초치는 군간에 차이가 없었다. 말초혈액검사 중 혈소판치는 HEPARIN군과 GOTT군에서 유의하게 높아졌으나(p<0.05) 군간 차이는 유의하지 않았다. 기타 혈구세포의 변화는 각 군에서 군내변화와 군간차이가 유의하지 않았다. Activated clotting time, activated partial thromboplastin time, thrombin time은 HEPARIN군에서 현저히 증가하였고(p<0.05) 군간차이도 유의하였다(p<0.005). Prothrombin time은 GOTT군에서 유의하게 증가하였으나(p<0.05) 군간차이는 없었다. Fibrinogen은 각 군에서 군내변화와 군간차이가 유의하지 않았다. Antithrombin III는 HEPARIN군과 KIST군에서 유의하게 감소하였고(p<0.05) 군간차이도 유의하였다(p<0.05). Protein C는 HEPARIN군에서 유의하게 감소하였으나(p<0.05) 군간차이는 없었다. Blood urea nitrogen은 HEPARIN군과 KIST군에서 유의하게 증가하였으나(p<0.05) 군간차이는 없었다. Creatinine, aspartate aminotransferase, alanine aminotransferase는 각 군에서 군내변화와 군간차이가 유의하지 않았다. 표면전자현미경 소견에서 혈소판 및 혈구세포 응집정도는 CONTROL군이 가장 심했고, HEPARIN군은 GOTT군이나 KIST군에 비해 많았다. 결론: 이상의 결과에서 전신 헤파린 처치(HEPARIN)는 출혈경향을 증가시키면서 이물질 표면의 응고반응을 효과적으로 차단하지 못하는 반면, 헤파린 표면처리된 우회도관(GOTT & KIST)의 경우는 출혈경향 없이 표면의 응고반응을 충분히 억제하였다. 또한 국산(KIST) 헤파린 우회도관은 상용화된 외국산(GOTT)과 동등한 항혈전 성능을 보였다.

• 한국식품과학회지
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• 제20권6호
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• pp.762-768
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• 1988

우유의 지방분해 효소인 리파제를 분리 연구하기 위하여 홀몬처리 되지 않은 정상유와 홀몬 처리된 비정상유에서 리파제를 Heparin-Sepharose-CL-6B를 이용하여 분리 정제하였다. Heparin-Sepharose에 친화력을 조사한 결과 두 개의 효소활성이 있는 성분이 구분되었으며 한 성분은 Heparin-Sepharose-CL-6B에 결합되었고 다른 한 성분은 결합되지 않은 채 분리되었다. 친화성 크로마토그램에 결합되어 분리 정제된 리파제의 최적 온도, 최적 pH, 기질 특이성, 분자량 및 BSA의 활성제로서의 작용등 여러 가지 효소특성은 모두 동일한 것으로 나타났다. 그러나 홀몬처리된 소에서 얻은 우유의 경우에는 또 다른 호소활성 성분이 나타나 있음을 알았다. 이 lipolytic activity가 있는 성분은 Heparin-Sepharose-CL-6B에 친화력을 보이지 않았으므로 정상적인 milk lipase와는 구별된다. 따라서 홀몬처리된 소에서 얻은 우유에 함유된 성분중 Heparin-Sepharose에 결합된 효소는 유지방 자동산화에 영향을 끼치지 않으며 Heparin-Sepharose에 결합되자 않은 활성이 있는 성분은 자동산패에 영향을 크게 미친다고 볼 수 있다. 그 이유는 hormone의 불균형 상태로 인하여 생유에 자동산패가 일어날 수 있으며 이것은 비정상적으로 분비된 리파제 출현 사이에 연관관계가 있음을 의미한다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제16권2호
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• pp.116-122
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• 2013

Purpose: Preterm infants on parenteral nutrition are at a relatively high risk for hypertriglyceridemia because they have immature lipoprotein lipase activity. The purpose of this study was to analyze the clinical factors affecting lipid metabolism in preterm infants receiving parenteral nutrition and to evaluate the influence of intravenous heparin on serum triglycerides to determine the adequate heparin dose to prevent hypertriglyceridemia in preterm infants. Methods: A single-center retrospective review was conducted among preterm infants receiving parenteral nutrition between January 2006 and February 2011. In 75 patients, 110 determinations were performed within 28 days postnatal age. Demographic and clinical data, including laboratory parameters, the dose and the duration of lipid administration, and the amount of intravenous heparin, were analyzed. Results: Serum triglycerides were higher in the small for gestational age (SGA) infants than in the appropriate for gestational age infants ($185.5{\pm}134.9$ mg/dL vs. $126.9{\pm}101.9$ mg/dL, p=0.019). Birth weight, gestational age, and body weight were negatively correlated with serum triglyceride level (r=-0.289, p=0.002; r=-0.208, p=0.029; r=-0.287, p=0.002, respectively). The serum triglyceride level was statistically lower in preterm infants receiving 1 U/mL of heparin than in those receiving 0.5 U/mL heparin or no heparin. Conclusion: Preterm infants receiving parenteral nutrition, particularly SGA and extremely low birth weight infants, tend to have hypertriglyceridemia. Thus, administration of 1 U/mL of heparin rather than 0.5 U/mL or none may be helpful to prevent hypertriglyceridemia in preterm infants.