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11.
Brooks MB 《Veterinary clinical pathology / American Society for Veterinary Clinical Pathology》2004,33(4):208-214
BACKGROUND: Unfractionated heparin (UFH) has a complex pharmacologic profile that necessitates patient monitoring to prevent inadequate anticoagulation or overdosage and hemorrhage. Factor Xa inhibitory assays (to measure anti-Xa activity) are used to adjust UFH dosage and define safe and effective regimens for specific thrombotic disorders in humans. OBJECTIVE: In this study, the accuracy, linearity, and clinical utility of a chromogenic assay were assessed for monitoring UFH anti-Xa activity in canine plasma samples. METHODS: A commercial assay (Rotachrom Heparin, Diagnostica Stago, Parsippany, NJ, USA) was used to measure anti-Xa activity in canine plasma samples spiked with different concentrations of UFH. Background absorbance and assay linearity were compared for canine and human plasmas. Percentage recovery of UFH anti-Xa activity and intra- and interassay imprecisions were investigated by multiple measurements of canine plasma to which known amounts of UFH were added. The spiked plasma samples also were used to determine the heparin sensitivity of an activated partial thromboplastin time (aPTT) test. RESULTS: Canine plasma samples were assayed at a higher dilution than were human plasma samples (3:8 versus 4:8) to eliminate higher background anti-Xa activity in canine plasma. Using this modification, the recovery of anti-Xa activity in canine plasma was linear (R2 > .9) at concentrations of 0 - 0.75 U/mL UFH. Intra- and interassay imprecisions for plasma samples containing 0.5 U/mL UFH were <10%, whereas samples containing 0.25 U/mL UFH had imprecisions of 13% and 24%, respectively. The anti-Xa activity range of 0.5 - 0.75 U/mL caused prolongation of aPTTs to 1.5 - 2.5 times the assay mean. CONCLUSION: Plasma anti-Xa activity of dogs treated with UFH can be accurately monitored using this commercially available chromogenic assay. 相似文献
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[目的]采用木瓜蛋白酶对土鳖虫蛋白质进行酶解,制备土鳖虫多肽,并对获得的多肽进行抗凝血的作用研究。[方法]利用酶解法制备土鳖虫多肽,以水解度为考察指标,确定多肽的最佳制备工艺;通过试剂盒测定不同浓度的多肽对小鼠凝血酶时间(TT)、凝血酶原时间(PT)、活化部分凝血激酶时间(APTT)的影响。[结果]木瓜蛋白酶水解制备土鳖虫多肽的最佳工艺条件为pH 8.0,酶用量1.0%,酶解温度55℃,酶解时间3.5 h;获得的土鳖虫多肽显著延长了小鼠TT和APTT,对PT无明显影响。[结论]在最佳酶解条件下获得了土鳖虫多肽,且证明其具有抗凝血作用。 相似文献
13.
羊栖菜硫酸多糖的抗凝血活性研究 总被引：1，自引：0，他引：1
[目的]探讨羊栖菜硫酸多糖的抗凝血活性。[方法]从水提液中提取羊栖菜硫酸多糖,通过体内和体外的抗凝血试验系统地研究其抗凝血活性。[结果]利用葡聚糖凝胶G-75分离纯化所提取的羊栖菜硫酸多糖F1,得到5个不同组分。在2.0 g/L的受试条件下,组分F12抗凝血活性的最强,其延长小白鼠的出血时间和凝血时间、大白兔的凝血活酶时间、凝血酶时间、凝血酶原时间分别为粗多糖F0的174.2%、153.7%、311.9%1、57.8%和218.2%。羊栖菜硫酸多糖F1与抗凝血效果有显著的量效关系。在受试条件下(浓度为0.5~2.0g/L),多糖的浓度与小白鼠的抗凝血指标、与大白兔体外抗凝血指标之间均呈现良好的直线回归关系。[结论]该研究为羊栖菜类保健品及临床药物的开发提供理论基础。 相似文献
14.
将家蚕丝素蛋白通过化学接枝反应制备具有抗凝血功效的硫酸化丝素蛋白医用材料。经动物的热原试验、皮内刺激试验、皮肤致敏试验、急性毒性试验以及体外溶血试验,对硫酸化丝素蛋白进行生物相容性评价。结果表明:3只注射受试硫酸化丝素蛋白溶液后的家兔体温仅升高0.2、0.3、0.1℃,未引起热原反应;家兔试验部位和周边组织出现的少量红斑或红肿在72 h后自然消退,无刺激反应;涂抹受试溶液后连续3 d,小鼠的试验部位和周边组织均未出现红斑、水肿等致敏反应;小鼠腹腔注射受试溶液后生理活动及生长正常,无毒性反应;受试溶液在体外溶血试验中无溶血现象。各项试验结果提示:硫酸化丝素蛋白材料有良好的生物相容性,具有在生物医学材料领域应用的前景。 相似文献
15.
Mette Drude Markussen Carsten Alsbo Sakari Kauppinen Michael Kristensen 《Pesticide biochemistry and physiology》2007,88(3):284-295
To examine the role of xenobiotic relevant genes in bromadiolone resistance in wild Norway rats (Rattus norvegicus) we compared the constitutive liver gene expression and expression upon bromadiolone administration in bromadiolone resistant and anticoagulant susceptible female rats using a LNA microarray and quantitative PCR. Resistant rats showed significantly higher constitutive expression of the cytochrome P450 genes Cyp2c13 and Cyp3a2 and lower expression of Cyp2e1 and Gpox1 compared to the susceptible rats. The Cyp1a2, Cyp2c13, Cyp2e1, Cyp3a2 and Cyp3a3 genes were significantly higher expressed in resistant than susceptible rats upon bromadiolone exposure. To establish how bromadiolone affected xenobiotic gene expression in the two strains we compared bromadiolone expression profiles to saline profiles of both strains. Bromadiolone mediated significant up-regulation of Cyp2e1 and Cyp3a3 expression in the resistant rats whereas the rodenticide conferred down-regulation of Cyp2e1, Cyp3a3 and Gpox1 and induction of Cyp2c12 expression in susceptible rats. Cyp2c13 and Cyp3a2 expression were markedly suppressed in both strains upon treatment. This suggests that xenobiotic relevant enzymes play a role in bromadiolone resistance in the Norway rat. A high constitutive expression of Cyp2c13 and Cyp3a2 and induction of Cyp1a2, Cyp2e1 and Cyp3a3 expression during bromadiolone exposure may increase the resistance to bromadiolone presumably by facilitating increased detoxification and decreased liver injury. 相似文献
16.
Hiroshi Kamitakahara Fusako Nishigaki Yuji Mikawa Michiko Hori Shigetomo Tsujihata Takashi Fujii Fumiaki Nakatsubo 《Journal of Wood Science》2002,48(3):204-209
Chemically synthesized (1 5)--d-glucofuranan, (1 5)--d-galactofuranan, (1 5)--d-xylofuranan, (1 5)--L-arabinofuranan, natural xylan, and curdlan were sulfated to investigate their inhibitory activities on B16-BL6 lung metastasis and anticoagulant activities. (1 5)--d-Glucofuranan sulfate, (1 5)--d-galactofuranan sulfate, xylan sulfate, and curdlan sulfate had binding abilities with B16-BL6 melanoma lysate. The inhibitory activities of sulfated polysaccharides on B16-BL6 lung metastasis selected by heparin binding assay were in the order (1 5)--d-galactofuranan sulfate > (1 5)---d-glucofuranan sulfate > xylan sulfate curdlan sulfate. Furthermore, (1 5)--d-galactofuranan sulfate, (1 5)--d-glucofuranan sulfate, and xylan sulfate had not only high inhibitory activity on B16-BL6 lung metastasis but also low anticoagulant activity. The correlation between chemical structure and biological activity is discussed.Part of this paper was presented at the 10th International Synposium on Wood and Pulping Chemistry, Yokohama, Japan, June 1999 相似文献
17.
Schultze AE Sullivan JM 《Veterinary clinical pathology / American Society for Veterinary Clinical Pathology》2007,36(2):123-136
BACKGROUND: Veterinary clinical and anatomic pathologists play a critical role in assessing the safety of new molecules. The process for evaluation of candidate molecules in drug discovery may vary markedly, depending on the unique characteristics of the compound class. OBJECTIVES: The goal of this report is to describe the evaluation process for assessing the potential toxicity of 2 anticoagulant compounds that were representative of molecules tested in early screening studies in Fisher rats, and to use these studies as an example of the strategic approach used by veterinary pathologists in pharmaceutical safety assessment. METHODS: Groups of 3 rats were given vehicle alone or one of several doses of compound A or B by oral gavage daily for 4 consecutive days. Survival; clinical signs; body and organ weight measurements; hematologic, coagulation, and clinical biochemical testing; and gross and histologic findings at necropsy were assessed. Transmission electron microscopy was used to characterize unique findings in the liver of rats treated with compound B. RESULTS: Both compounds caused dose-dependent prolongation of the prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin clotting time (TCT). Hepatobiliary and intestinal toxicity were identified by alterations in serum chemistry data, and by histopathologic findings. Electron microscopy and tissue inorganic phosphorus analysis revealed phospholipidosis in rats treated with compound B. CONCLUSIONS: Pharmacologically mediated or "on target" effects for these molecules were characterized by dose-progressive prolongation of the PT, APTT, and TCT. Nonpharmacologically mediated or "off-target" toxicity consisted of hepatoxicity and enterotoxicity. These liabilities required that scientists alter the original molecular scaffold to reach the desired therapeutic target and minimize toxicity. 相似文献
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鱼类血液极易凝结,经抗凝剂处理后的血液可充分满足各项生理指标检测,为衡量鱼体各项生理机能提供重要参考,同时,鱼类种属多样,在抗凝剂的选择和使用上存在一定差异。基于此,本研究以欧亚养殖良种大菱鲆(Scophthalmus maximus)为研究对象,选用乙二胺四乙酸二钾、肝素钠和柠檬酸钠3种抗凝剂,通过对大菱鲆正常状态和急性低氧胁迫条件下[溶解氧浓度为(1.2±0.3) mg/L]抗凝效果评价、血细胞形态观察和血液生理生化指标分析,筛选急性低氧胁迫条件下最佳血液抗凝剂。结果显示,正常溶解氧状态下,乙二胺四乙酸二钾抗凝效果显著,急性低氧胁迫下静置6 h和12 h后,抗凝效果显著抗凝剂分别为乙二胺四乙酸二钾和肝素钠。正常溶解氧状态肝素钠抗凝剂下血细胞出现双核现象,柠檬酸钠和乙二胺四乙酸二钾抗凝剂下分别出现嗜酸性、嗜碱性粒细胞和嗜碱性粒细胞,急性低氧胁迫导致乙二胺四乙酸二钾、肝素钠、柠檬酸钠抗凝剂均观察到双核血细胞,其中,肝素钠和柠檬酸钠抗凝剂还分别出现微核和无核血细胞。急性低氧胁迫处理后,3种抗凝剂作用下血液白细胞数目均显著增高(P<0.05),乙二胺四乙酸二钾和肝素钠抗凝作用下,红细胞数目和血红蛋白含量显著升高(P<0.05),而柠檬酸钠抗凝剂作用下,红细胞数目和血红蛋白含量显著降低(P<0.05)。3种抗凝剂作用下血浆葡萄糖和皮质醇浓度显著增高(P<0.05),但肝素钠抗凝剂作用下,葡萄糖和皮质醇浓度显著低于柠檬酸钠和乙二胺四乙酸二钾(P<0.05)。综上所述,乙二胺四乙酸二钾可作为急性低氧胁迫条件下大菱鲆血液学分析的首选抗凝剂。 相似文献
19.
鱿鱼肝脏活性肽的制备及生物活性研究 总被引：1，自引：0，他引：1
[目的]为鱿鱼肝脏的高值化利用提供基础研究数据。[方法]以鱿鱼肝脏蛋白为原料,通过蛋白酶水解来制备生物活性肽,研究了多种蛋白酶水解鱿鱼肝脏制得水解液的抗凝血活性、抑制血管紧张素Ⅰ转换酶（ACE）活性及抗氧化活性。[结果]当鱿鱼肝脏水解液浓度为5 mg/ml时,中性蛋白酶的水解液对ACE抑制率为68.0%;APTT值为59.8 s,TT值为34.2 s,比空白对照组分别延长26.7和20.6 s,表明鱿鱼肝脏的中性蛋白酶水解液具有抗凝血活性。中性蛋白酶解液对Fe3＋的还原力为0.588,羟自由基清除能力为64.5%,说明鱿鱼肝脏中性蛋白酶水解液具有较好的抗氧化活性;而其余的木瓜蛋白酶、酸性蛋白酶、碱性蛋白酶、胰蛋白酶的鱿鱼肝脏水解液的抗凝血活性和ACE抑制活性均低于中性蛋白酶水解液的酶解液活性。[结论]鱿鱼肝脏蛋白质具有较好的综合利用价值。 相似文献
20.