• Journal of Chest Surgery
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• v.13 no.1
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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.

• Journal of Embryo Transfer
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• v.7 no.2
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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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• v.26 no.12
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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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• v.13 no.1
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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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• v.12 no.5
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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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• v.21 no.2
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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.

• YAKHAK HOEJI
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• v.29 no.2
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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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• v.32 no.2
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• pp.97-107
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• 1999

Background: This study was designed to develop a Korean version of the heparin-coated vascular bypass shunt by using a physical dispersing technique. The safety and effectiveness of the thrombo-resistant shunt were tested in experimental animals. Material and Method: A bypass shunt model was constructed on the descending thoracic aorta of 21 adult mongrel dogs(17.5-25 kg). The animals were divided into groups of no-treatment(CONTROL group; n=3), no-treatment with systemic heparinization(HEPARIN group; n=6), Gott heparin shunt (GOTT group; n=6), or Korean heparin shunt(KIST group; n=6). Parameters observed were complete blood cell counts, coagulation profiles, kidney and liver function(BUN/Cr and AST/ ALT), and surface scanning electron microscope(SSEM) findings. Blood was sampled from the aortic blood distal to the shunt and was compared before the bypass and at 2 hours after the bypass. Result: There were no differences between the groups before the bypass. At bypass 2 hours, platelet level increased in the HEPARIN and GOTT groups(p<0.05), but there were no differences between the groups. Changes in other blood cell counts were insignificant between the groups. Activated clotting time, activated partial thromboplastin time, and thrombin time were prolonged in the HEPARIN group(p<0.05) and differences between the groups were significant(p<0.005). Prothrombin time increased in the GOTT group(p<0.05) without having any differences between the groups. Changes in fibrinogen level were insignificant between the groups. Antithrombin III levels were increased in the HEPARIN and KIST groups(p<0.05), and the inter-group differences were also significant(p<0.05). Protein C level decreased in the HEPARIN group(p<0.05) without having any differences between the groups. BUN levels increased in all groups, especially in the HEPARIN and KIST groups(p<0.05), but there were no differences between the groups. Changes of Cr, AST, and ALT levels were insignificant between the groups. SSEM findings revealed severe aggregation of platelets and other cellular elements in the CONTROL group, and the HEPARIN group showed more adherence of the cellular elements than the GOTT or KIST group. Conclusion: Above results show that the heparin-coated bypass shunts(either GOTT or KIST) can suppress thrombus formation on the surface without inducing bleeding tendencies, while systemic heparinization(HEPARIN) may not be able to block activation of the coagulation system on the surface in contact with foreign materials but increases the bleeding tendencies. We also conclude that the thrombo-resistant effects of the Korean version of heparin shunt(KIST) are similar to those of the commercialized heparin shunt(GOTT).

• Korean Journal of Food Science and Technology
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• v.20 no.6
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• pp.762-768
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• 1988

The lipolytic enzyme of milk from hormone treated and non treated cows was isolated and purified, It was shown that the crude lipase extract from the milk before and after a hormone treatment of the cows was different in color, foaming properties, yield and specific activity. Final purification of the lipase system was achieved by affinity chromatography on Heparin-Sepharose CL-6B. The lipase bound by Heparin-Sepharose was then characterised. The pH-optimum of the purified enzyme was 8.5 for butteroil emulsion as a substrate and the optimum temperature was $30^{\circ}C$ respectively. The molecular weight. determined by SDS-polyacrylamidegel electrophoresis, was about 70,000. The activity increased by 10% hen 0.01% bovine serum albumin was added to the substrate. The results indicate the enzymes obtained by affinity chromatography from milk before and after hormone treatment had the similar characteristics. The second lipolytic active component that was not bound by Heparin-Sepharose must be the cause of spontaneous rancidity.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.16 no.2
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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.