AIM： To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin（LHT7） in a neovascularized mouse cornea using an in vivo optical ima...AIM： To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin（LHT7） in a neovascularized mouse cornea using an in vivo optical imaging system. METHODS： A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal neovascularization（CoNV） was induced in the inferior cornea（IC） of each animal by penetrating the stroma with two interrupted sutures. The development of CoNV was verified after one week and the area of each neovascularized region was measured. A near-infrared fluorescent probe of 20 μmol/L Cy5.5 labeled LHT7（LHT7-Cy5.5） in 0.02 mL solution was topically instilled onto the cornea in the experimental group（n=5）. Free-Cy5.5 of 20 μmol/L in 0.02 mL was instilled in the control group（n=5）. In vivo optical images were obtained before instillation and 5 min, 2, 4, and 6 h after instillation. The intensities were separately measured at the superior cornea（SC） and the IC. RESULTS： The mean CoNV areas were 1.97±0.17 mm^2 and 1.92±0.96 mm^2 in the experimental and control groups, respectively（P=0.832）. The SC remained normal in all 10 subject animals. The IC intensity of the LHT7-Cy5.5 was greater than the SC intensity at 5 min（P=0.038）, 2 h（P=0.041）, and 4 h（P=0.041） after application. The IC intensity fell to less than half of its initial value（42.9%±8.6%） at 6 h in the experimental group. In the control mice, here were no significant differences in the free-Cy5.5 intensity between the IC and SC. CONCLUSION： Topically administered LHT7 shows a high biodistribution in CoNV areas for 4 h and should be reapplied accordingly to maintain its effects. In vivo optical imaging can be a useful tool for evaluating the ocular biodistribution of a drug in an animal model.展开更多
目的探讨低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝在原发性肾病综合征(PNS)中的应用效果及安全性。方法回顾性选取2020年3月至2022年12月期间四川省凉山彝族自治州第一人民医院收治的188例PNS患者,根据肾穿刺活检病理结果及...目的探讨低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝在原发性肾病综合征(PNS)中的应用效果及安全性。方法回顾性选取2020年3月至2022年12月期间四川省凉山彝族自治州第一人民医院收治的188例PNS患者,根据肾穿刺活检病理结果及磷脂酶A2受体抗体分为膜性肾病组(n=73)与非膜性肾病组(n=115)。两组患者均根据血清白蛋白水平,采用低分子肝素钙或磺达肝癸钠序贯联合双嘧达莫抗凝。比较两组患者治疗前及治疗后4周、治疗后6个月的肾功能指标[白蛋白、尿素氮、血肌酐、肾小球滤过率(eGFR)和24 h尿蛋白定量(24 h PRO)],治疗前及治疗后4周的血栓弹力图指标[反应指数(R时间)、凝血时间(K时间)、血栓最大弹力度(MA)、凝血指数(CI)和α角],以及随访6个月记录血栓事件、出血事件。结果治疗后4周、6个月,两组的白蛋白、eGFR均较治疗前明显升高,尿素氮、血肌酐、24 h PRO均较治疗前明显降低,差异均有统计学意义(P<0.05),但两组治疗后各肾功能指标比较,差异均无统计学意义(P>0.05)。治疗后4周,两组患者的R时间、K时间均较治疗前明显延长,MA、CI值和α角均较治疗前明显降低,差异均有统计学意义(P<0.05),但两组患者治疗后4周的R时间、K时间、MA、CI值和α角比较,差异均无统计学意义(P>0.05)。膜性肾病组患者的血栓、出血事件发生率分别为6.85%、10.96%,均高于非膜性肾病组(0.87%、3.48%),但两组间血栓事件总发生率、出血事件发生率比较,差异均无统计学意义(P>0.05)。结论低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝有利于改善PNS患者的肾功能,缓解高凝状态,降低血栓栓塞事件发生率,且非膜性肾病患者获益较膜性肾病患者更明显,安全性更高。展开更多
基金Supported by a grant(No.2016-7026)from the Asan Institute for Life Science,Seoul,Republic of Korea
文摘AIM： To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin（LHT7） in a neovascularized mouse cornea using an in vivo optical imaging system. METHODS： A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal neovascularization（CoNV） was induced in the inferior cornea（IC） of each animal by penetrating the stroma with two interrupted sutures. The development of CoNV was verified after one week and the area of each neovascularized region was measured. A near-infrared fluorescent probe of 20 μmol/L Cy5.5 labeled LHT7（LHT7-Cy5.5） in 0.02 mL solution was topically instilled onto the cornea in the experimental group（n=5）. Free-Cy5.5 of 20 μmol/L in 0.02 mL was instilled in the control group（n=5）. In vivo optical images were obtained before instillation and 5 min, 2, 4, and 6 h after instillation. The intensities were separately measured at the superior cornea（SC） and the IC. RESULTS： The mean CoNV areas were 1.97±0.17 mm^2 and 1.92±0.96 mm^2 in the experimental and control groups, respectively（P=0.832）. The SC remained normal in all 10 subject animals. The IC intensity of the LHT7-Cy5.5 was greater than the SC intensity at 5 min（P=0.038）, 2 h（P=0.041）, and 4 h（P=0.041） after application. The IC intensity fell to less than half of its initial value（42.9%±8.6%） at 6 h in the experimental group. In the control mice, here were no significant differences in the free-Cy5.5 intensity between the IC and SC. CONCLUSION： Topically administered LHT7 shows a high biodistribution in CoNV areas for 4 h and should be reapplied accordingly to maintain its effects. In vivo optical imaging can be a useful tool for evaluating the ocular biodistribution of a drug in an animal model.
文摘目的探讨低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝在原发性肾病综合征(PNS)中的应用效果及安全性。方法回顾性选取2020年3月至2022年12月期间四川省凉山彝族自治州第一人民医院收治的188例PNS患者,根据肾穿刺活检病理结果及磷脂酶A2受体抗体分为膜性肾病组(n=73)与非膜性肾病组(n=115)。两组患者均根据血清白蛋白水平,采用低分子肝素钙或磺达肝癸钠序贯联合双嘧达莫抗凝。比较两组患者治疗前及治疗后4周、治疗后6个月的肾功能指标[白蛋白、尿素氮、血肌酐、肾小球滤过率(eGFR)和24 h尿蛋白定量(24 h PRO)],治疗前及治疗后4周的血栓弹力图指标[反应指数(R时间)、凝血时间(K时间)、血栓最大弹力度(MA)、凝血指数(CI)和α角],以及随访6个月记录血栓事件、出血事件。结果治疗后4周、6个月,两组的白蛋白、eGFR均较治疗前明显升高,尿素氮、血肌酐、24 h PRO均较治疗前明显降低,差异均有统计学意义(P<0.05),但两组治疗后各肾功能指标比较,差异均无统计学意义(P>0.05)。治疗后4周,两组患者的R时间、K时间均较治疗前明显延长,MA、CI值和α角均较治疗前明显降低,差异均有统计学意义(P<0.05),但两组患者治疗后4周的R时间、K时间、MA、CI值和α角比较,差异均无统计学意义(P>0.05)。膜性肾病组患者的血栓、出血事件发生率分别为6.85%、10.96%,均高于非膜性肾病组(0.87%、3.48%),但两组间血栓事件总发生率、出血事件发生率比较,差异均无统计学意义(P>0.05)。结论低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝有利于改善PNS患者的肾功能,缓解高凝状态,降低血栓栓塞事件发生率,且非膜性肾病患者获益较膜性肾病患者更明显,安全性更高。
