Until recently,anti-platelet/coagulation therapy had not been recommended for patients with cirrhosis.Although venous thrombosis is one of the representative complications of cirrhosis and ischemic disorders associate...Until recently,anti-platelet/coagulation therapy had not been recommended for patients with cirrhosis.Although venous thrombosis is one of the representative complications of cirrhosis and ischemic disorders associated with atherosclerosis are not infrequent in cirrhotic patients,many clinicians have tended to hesitate to introduce anti-platelet/coagulation therapy to their patients.Undoubtedly,this is due to the increased risk of hemorrhagic diathesis in cirrhotic patients.However,accumulating evidence has revealed the benefits of anti-platelet/coagulation therapy for cirrhotic patients.In addition to the safety of the therapy carried out against cardiovascular diseases in cirrhotic patients,some clinical data have indicated its preventive effect on venous thrombosis.Moreover,the efficacy of antiplatelet/coagulation therapy against cirrhosis itself has been demonstrated both clinically and experimentally.The conceptual basis for application of anti-platelet/coagulation therapy against cirrhosis was constructed through two pathologic studies on intrahepatic thrombosis in cirrhotic livers.It may be better to use thrombopoietinreceptor agonists,which have been tested as a treatment for cirrhosis-related thrombocytopenia,in combination with anti-platelet drugs to reduce the risk of venous thrombosis.During the last decade,the World Journal of Gastroenterology,a sister journal of World Journal of Hepatology,has been one of the main platforms of active discussion of this theme.展开更多
Seventeen novel ilexgenin A hybrids（lA-aspirin） and（IA-NO）,as donor hybrids（IA-NO will release NO in vivo and function as NO donor）,were designed and synthesized in order to develop new multi-targeting agents fo...Seventeen novel ilexgenin A hybrids（lA-aspirin） and（IA-NO）,as donor hybrids（IA-NO will release NO in vivo and function as NO donor）,were designed and synthesized in order to develop new multi-targeting agents for the treatment of platelet disorders.Their in vitro activities against ADP,AA and thrombin were evaluated.As a result,IA hybrids achieved substantial increases in the three tested pathways compared with IA.Encouragingly,the most potent hybrid compounds 6d and 14d displayed about 8-fold higher potency than aspirin,and 3-fold higher potency than the simultaneous administration of aspirin and IA in inhibiting ADP-induced aggregation with IC_（50） values of 0.15 mmol/L and 0.14 mmol/L,respectively. The results suggest these IA hybrids are good candidates for multi-target therapies,and especially,may be considered as promising ADP agonists.展开更多
BACKGROUND We report the case of a postmenopausal female with a hemorrhagic Bartholin’s cyst who has been using an antiplatelet medication.CASE SUMMARY A postmenopausal woman,84 years of age,had a medical history of ...BACKGROUND We report the case of a postmenopausal female with a hemorrhagic Bartholin’s cyst who has been using an antiplatelet medication.CASE SUMMARY A postmenopausal woman,84 years of age,had a medical history of hypertension,diabetes mellitus,coronary artery disease(three-vessel disease),chronic kidney disease(stage 3),and dementia.The patient has been taking clopidogrel,an antiplatelet medication,for several years.She presented at our outpatient clinic complaining of painful swelling over her left vulva for several days.A Bartholin’s cyst over the left vulva was suspected,and the patient underwent marsupialization under local anesthesia,which was well-tolerated.During the incision procedure,bright-red blood with some blood clots was discharged,and a hemorrhagic Bartholin’s cyst was observed.There was no recurrence of the hemorrhagic Bartholin’s cyst during the 6-mo subsequent follow-up period.CONCLUSION Hemorrhagic Bartholin’s cysts rarely occur.We report the case of a postmenopausal female with a hemorrhagic Bartholin’s cyst who had been on antiplatelets and was successfully treated with marsupialization.No recurrence was noted during the 6-mo follow-up period.Older females taking antiplatelets should be cautious of bleeding when presenting with a Bartholin’s cyst.展开更多
On the propose of searching for the SAR and obtaining novel antiplatelet aggregating drugs,we have described the synthesis procedure and the activities in vitro on antiplatelet aggregation of two series of derivatives...On the propose of searching for the SAR and obtaining novel antiplatelet aggregating drugs,we have described the synthesis procedure and the activities in vitro on antiplatelet aggregation of two series of derivatives,which contain both 18 N.N＇-di（2- substitutedphenyl）-4-methoxyisophthalamides（2a-2r） of the 2 series and nine N,N＇-di（2-substitutedphenyl）-4-methoxybenzene- 1,3-disulfonamides（3a-3i） of the 3 series.The results showed that three compounds 2e,2i and 3g emerged as significant activities of antiplatelet aggregation,superior to two reference drugs picotamide and aspirin,and eight compounds 2j,2k,21,2o,2p,2q,2r and 3i merely superior to picotamide.The preliminary SAR shows that it is favorable for the 2 series to increase the activities via the steric hindrance substituents attached to the two side chain benzene rings at 2-positions.And the arylamides of the 2 series have better the activity values than the arylsulfonamides of the 3 series respective except for 3b and 3g.On the contrary,electrostatic factors would not contribute evidently to the activities of the two series.The structures of 15 compounds newly synthesized have been established by MS and ~1H NMR and been first reported in this paper.展开更多
Background The clinical characteristics of stroke patients treated with double anti-platelet therapy （DAPT） after percutaneous coronary intervention （PCI） is not clear. Methods In total, 2675 patients under- went ...Background The clinical characteristics of stroke patients treated with double anti-platelet therapy （DAPT） after percutaneous coronary intervention （PCI） is not clear. Methods In total, 2675 patients under- went PCI and DAPT in Guangdong General Hospital, and 68 out of them were hospitalized due to suspected stroke, of whom 23 were diagnosed as having stroke. Data of the 23 stroke patients were collected and tradi- tional risk factors associated with stroke were analyzed retrospectively. Results The mean age of these pa- tients was 75.6± 8.7 years, and 20 （87.0%） were males. Notably, 19 patients were complicated with hyper- tension, 7 with diabetes mellitus, 7 with previous history of stroke, none with atrial fibrillation （AF） or patent foramen ovale （PFO）. Specifically, 22 patients were diagnosed with ischemic stroke, and 1 patient with hemorrhagic stroke. Conclusion Stroke in patients treated with DAPT after PCI was correlated with ad- vanced age, gender, hypertension, diabetes mellitus, stroke history. Long term electrocardiography （ECG） may be needed for the diagnosis of AF, while trans-esophageal echocardiography （TEE） may be needed for PFO.展开更多
Fetal liver tissues obtained from 28 human fetuses with gestation age from 3 to 6 months and fetal bone marrow from 35 human fetuses from 3 to 7 months were observed by immunochemical staining with anti-platelet GPⅡ ...Fetal liver tissues obtained from 28 human fetuses with gestation age from 3 to 6 months and fetal bone marrow from 35 human fetuses from 3 to 7 months were observed by immunochemical staining with anti-platelet GPⅡ b / Ⅲa monoclonal antibody and ABC technique. In the fetal liver, megakaryocytes were wholly located among growing fetal liver cells and near foci of hemopoiesis. Some megakaryocytes in the fetal liver were small7890- lymphoid-like megakaryocytes. The size of megakaryocytes both in the fetal liver (14.79 ± 4.52μm) and in the fetal bone marrow (16.08±7.39 μm) was small, which did not vary significantly over the gestation age ranging from 3 to 6 or 7 months. However, the maturation stage of megakaryocytes in the fetal liver shifted to more mature stage with the advancement of gestation, although the maturation stage of megakaryocytes in the fetal bone marrow did not change with the advancement of gestation from 4 to 7 months, the megakaryocyte in the fetal bone marrow was less mature展开更多
Platelets play a known role in the maintenance of vascular homeostasis, but these cells are emerging as important cellular mediators of acute and chronic inflammatory diseases. Platelets are key elements in the pathog...Platelets play a known role in the maintenance of vascular homeostasis, but these cells are emerging as important cellular mediators of acute and chronic inflammatory diseases. Platelets are key elements in the pathogenesis of acute and chronic liver disease associated with hepatitis B virus （HBV） infection by promoting the accumulation of virus-specific CD8＋ T cells and nonspecific inflammatory cells into the liver parenchyma. This review discusses major platelet functions in immune and inflammatory responses, with an emphasis on recent pre-clinical studies that suggest that the inhibition of platelet activation pathways represent an alternative therapeutic strategy with potential use in the reduction of virus-specific T cell-mediated chronic inflammation, liver fibrosis and hepatocellular carcinoma in patients who are chronically infected with HBV.展开更多
OBJECTIVES and BACKGROUNDS： Cardiovascular events occure as a result of various risk factors, such as uric acid （UA）, inflammation, hormones and other materials that induce C- reactive protein （CRP） expression. T...OBJECTIVES and BACKGROUNDS： Cardiovascular events occure as a result of various risk factors, such as uric acid （UA）, inflammation, hormones and other materials that induce C- reactive protein （CRP） expression. These factors lead to complement activation, and endothelial damages. Damaged endothelial cells release heparan sulfate which inhibits tissue factor activity and von Willed brand factor （VWVF） and causes aggregation. Finally this cascade of events cause platelets aggregation and leads to heart ischemia and cardiovascular events. DISCUSSION： Anti-platelet therapy is an interesting premise. Anti-platelet resistance patients and bleeding as a result of using ticagrelor and prasugrel should be considered in this treatment methods. Anti-platelet drugs such as clopidogrel are prescribed in cardiovascular events. Platelets have VWF receptors and P2Y12 receptors on their surface, and thus, targeting these receptors can be useful in treatment. The active metabolites of clopidogrel bind to P2Y12R and inhibit ADP binding; thus, clopidogrel inhibits aggregation by interfering in several events as a result of the inhibition of ADP attachment to P2Y12R of the platelet. However, the polymorphisms of P2~ 12 and other genes mentioned in Table 1 showed treatment resistance in anti-platelet therapy, highlighting that these SNPs can be helpful in anti-platelet therapy. CONCLUSION： The knowledge of these SNPs may decrease the number of unwanted effects that endanger patients with cardiovascular diseases and avoids ineffective anti-platelet therapy in several patients. Clopidogrel, ticagrelor, prasugrel, and aspirin and CYP2C19 and their SNPs are very important subjects in anti-platelet therapy. To present the importance of using phannacogenetics in anti-platelet therapy, we discuss here the association between these drugs and the SNPs for therapeutic resistance.展开更多
Poly（ethylene glycol） monoacrylate （PEGMA） is grafted onto polycarbonateurethane （PCU） surface via ultraviolet initiated photopolymerization. The hydroxyl groups of poly（PEGMA） on the surface react with one NC...Poly（ethylene glycol） monoacrylate （PEGMA） is grafted onto polycarbonateurethane （PCU） surface via ultraviolet initiated photopolymerization. The hydroxyl groups of poly（PEGMA） on the surface react with one NCO group of isophorone diisocyanate （IPD1） and another NCO group of IPDI is then hydrolyzed to form amino terminal group, which is further grafted with phosphorylcholine glyceraldehyde to establish a biocompatible hydrophilic structure on the surface. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirm the successful grafting of both PEG and phosphorylcholine functional groups on the surface. The decrease of the water contact angle for the modified film is caused by synergic effect of PEG and phosphorylcholine, which both have the high hydrophilicity. Furthermore, the number of platelets adhered is relative low on the synergetically modified PCU film compared with the PCU film modified only by poly（PEGMA）. Our synergic modification method using both PEG and phosphorylcho- line may be applied in surface modification of bloodcontacting biomaterials and some relevant devices.展开更多
文摘Until recently,anti-platelet/coagulation therapy had not been recommended for patients with cirrhosis.Although venous thrombosis is one of the representative complications of cirrhosis and ischemic disorders associated with atherosclerosis are not infrequent in cirrhotic patients,many clinicians have tended to hesitate to introduce anti-platelet/coagulation therapy to their patients.Undoubtedly,this is due to the increased risk of hemorrhagic diathesis in cirrhotic patients.However,accumulating evidence has revealed the benefits of anti-platelet/coagulation therapy for cirrhotic patients.In addition to the safety of the therapy carried out against cardiovascular diseases in cirrhotic patients,some clinical data have indicated its preventive effect on venous thrombosis.Moreover,the efficacy of antiplatelet/coagulation therapy against cirrhosis itself has been demonstrated both clinically and experimentally.The conceptual basis for application of anti-platelet/coagulation therapy against cirrhosis was constructed through two pathologic studies on intrahepatic thrombosis in cirrhotic livers.It may be better to use thrombopoietinreceptor agonists,which have been tested as a treatment for cirrhosis-related thrombocytopenia,in combination with anti-platelet drugs to reduce the risk of venous thrombosis.During the last decade,the World Journal of Gastroenterology,a sister journal of World Journal of Hepatology,has been one of the main platforms of active discussion of this theme.
基金supported by a grant from the Postgraduate Innovation Project of Jiangsu Province,China(No. CX09B_284Z)the Natural Science Foundation of Jiangsu Province,China(No.BK2012378)
文摘Seventeen novel ilexgenin A hybrids（lA-aspirin） and（IA-NO）,as donor hybrids（IA-NO will release NO in vivo and function as NO donor）,were designed and synthesized in order to develop new multi-targeting agents for the treatment of platelet disorders.Their in vitro activities against ADP,AA and thrombin were evaluated.As a result,IA hybrids achieved substantial increases in the three tested pathways compared with IA.Encouragingly,the most potent hybrid compounds 6d and 14d displayed about 8-fold higher potency than aspirin,and 3-fold higher potency than the simultaneous administration of aspirin and IA in inhibiting ADP-induced aggregation with IC_（50） values of 0.15 mmol/L and 0.14 mmol/L,respectively. The results suggest these IA hybrids are good candidates for multi-target therapies,and especially,may be considered as promising ADP agonists.
文摘BACKGROUND We report the case of a postmenopausal female with a hemorrhagic Bartholin’s cyst who has been using an antiplatelet medication.CASE SUMMARY A postmenopausal woman,84 years of age,had a medical history of hypertension,diabetes mellitus,coronary artery disease(three-vessel disease),chronic kidney disease(stage 3),and dementia.The patient has been taking clopidogrel,an antiplatelet medication,for several years.She presented at our outpatient clinic complaining of painful swelling over her left vulva for several days.A Bartholin’s cyst over the left vulva was suspected,and the patient underwent marsupialization under local anesthesia,which was well-tolerated.During the incision procedure,bright-red blood with some blood clots was discharged,and a hemorrhagic Bartholin’s cyst was observed.There was no recurrence of the hemorrhagic Bartholin’s cyst during the 6-mo subsequent follow-up period.CONCLUSION Hemorrhagic Bartholin’s cysts rarely occur.We report the case of a postmenopausal female with a hemorrhagic Bartholin’s cyst who had been on antiplatelets and was successfully treated with marsupialization.No recurrence was noted during the 6-mo follow-up period.Older females taking antiplatelets should be cautious of bleeding when presenting with a Bartholin’s cyst.
基金the Committee of Science and Technology of Tianjin of China for the financial support from the Prop Up Research Project(No.10ZCKFSH00500)
文摘On the propose of searching for the SAR and obtaining novel antiplatelet aggregating drugs,we have described the synthesis procedure and the activities in vitro on antiplatelet aggregation of two series of derivatives,which contain both 18 N.N＇-di（2- substitutedphenyl）-4-methoxyisophthalamides（2a-2r） of the 2 series and nine N,N＇-di（2-substitutedphenyl）-4-methoxybenzene- 1,3-disulfonamides（3a-3i） of the 3 series.The results showed that three compounds 2e,2i and 3g emerged as significant activities of antiplatelet aggregation,superior to two reference drugs picotamide and aspirin,and eight compounds 2j,2k,21,2o,2p,2q,2r and 3i merely superior to picotamide.The preliminary SAR shows that it is favorable for the 2 series to increase the activities via the steric hindrance substituents attached to the two side chain benzene rings at 2-positions.And the arylamides of the 2 series have better the activity values than the arylsulfonamides of the 3 series respective except for 3b and 3g.On the contrary,electrostatic factors would not contribute evidently to the activities of the two series.The structures of 15 compounds newly synthesized have been established by MS and ~1H NMR and been first reported in this paper.
文摘Background The clinical characteristics of stroke patients treated with double anti-platelet therapy （DAPT） after percutaneous coronary intervention （PCI） is not clear. Methods In total, 2675 patients under- went PCI and DAPT in Guangdong General Hospital, and 68 out of them were hospitalized due to suspected stroke, of whom 23 were diagnosed as having stroke. Data of the 23 stroke patients were collected and tradi- tional risk factors associated with stroke were analyzed retrospectively. Results The mean age of these pa- tients was 75.6± 8.7 years, and 20 （87.0%） were males. Notably, 19 patients were complicated with hyper- tension, 7 with diabetes mellitus, 7 with previous history of stroke, none with atrial fibrillation （AF） or patent foramen ovale （PFO）. Specifically, 22 patients were diagnosed with ischemic stroke, and 1 patient with hemorrhagic stroke. Conclusion Stroke in patients treated with DAPT after PCI was correlated with ad- vanced age, gender, hypertension, diabetes mellitus, stroke history. Long term electrocardiography （ECG） may be needed for the diagnosis of AF, while trans-esophageal echocardiography （TEE） may be needed for PFO.
文摘Fetal liver tissues obtained from 28 human fetuses with gestation age from 3 to 6 months and fetal bone marrow from 35 human fetuses from 3 to 7 months were observed by immunochemical staining with anti-platelet GPⅡ b / Ⅲa monoclonal antibody and ABC technique. In the fetal liver, megakaryocytes were wholly located among growing fetal liver cells and near foci of hemopoiesis. Some megakaryocytes in the fetal liver were small7890- lymphoid-like megakaryocytes. The size of megakaryocytes both in the fetal liver (14.79 ± 4.52μm) and in the fetal bone marrow (16.08±7.39 μm) was small, which did not vary significantly over the gestation age ranging from 3 to 6 or 7 months. However, the maturation stage of megakaryocytes in the fetal liver shifted to more mature stage with the advancement of gestation, although the maturation stage of megakaryocytes in the fetal bone marrow did not change with the advancement of gestation from 4 to 7 months, the megakaryocyte in the fetal bone marrow was less mature
文摘Platelets play a known role in the maintenance of vascular homeostasis, but these cells are emerging as important cellular mediators of acute and chronic inflammatory diseases. Platelets are key elements in the pathogenesis of acute and chronic liver disease associated with hepatitis B virus （HBV） infection by promoting the accumulation of virus-specific CD8＋ T cells and nonspecific inflammatory cells into the liver parenchyma. This review discusses major platelet functions in immune and inflammatory responses, with an emphasis on recent pre-clinical studies that suggest that the inhibition of platelet activation pathways represent an alternative therapeutic strategy with potential use in the reduction of virus-specific T cell-mediated chronic inflammation, liver fibrosis and hepatocellular carcinoma in patients who are chronically infected with HBV.
文摘OBJECTIVES and BACKGROUNDS： Cardiovascular events occure as a result of various risk factors, such as uric acid （UA）, inflammation, hormones and other materials that induce C- reactive protein （CRP） expression. These factors lead to complement activation, and endothelial damages. Damaged endothelial cells release heparan sulfate which inhibits tissue factor activity and von Willed brand factor （VWVF） and causes aggregation. Finally this cascade of events cause platelets aggregation and leads to heart ischemia and cardiovascular events. DISCUSSION： Anti-platelet therapy is an interesting premise. Anti-platelet resistance patients and bleeding as a result of using ticagrelor and prasugrel should be considered in this treatment methods. Anti-platelet drugs such as clopidogrel are prescribed in cardiovascular events. Platelets have VWF receptors and P2Y12 receptors on their surface, and thus, targeting these receptors can be useful in treatment. The active metabolites of clopidogrel bind to P2Y12R and inhibit ADP binding; thus, clopidogrel inhibits aggregation by interfering in several events as a result of the inhibition of ADP attachment to P2Y12R of the platelet. However, the polymorphisms of P2~ 12 and other genes mentioned in Table 1 showed treatment resistance in anti-platelet therapy, highlighting that these SNPs can be helpful in anti-platelet therapy. CONCLUSION： The knowledge of these SNPs may decrease the number of unwanted effects that endanger patients with cardiovascular diseases and avoids ineffective anti-platelet therapy in several patients. Clopidogrel, ticagrelor, prasugrel, and aspirin and CYP2C19 and their SNPs are very important subjects in anti-platelet therapy. To present the importance of using phannacogenetics in anti-platelet therapy, we discuss here the association between these drugs and the SNPs for therapeutic resistance.
基金Acknowledgements This work has been financially supported by Ministry of Science and Technology of China （Grants No. 2013DFG52040 and 2008DFA51170）, National Natural Science Foundation of China （Grant No. 31370969）, and Ph.D. PrograFns Foundation of Ministry of Education of China （No. 20120032110073）.
文摘Poly（ethylene glycol） monoacrylate （PEGMA） is grafted onto polycarbonateurethane （PCU） surface via ultraviolet initiated photopolymerization. The hydroxyl groups of poly（PEGMA） on the surface react with one NCO group of isophorone diisocyanate （IPD1） and another NCO group of IPDI is then hydrolyzed to form amino terminal group, which is further grafted with phosphorylcholine glyceraldehyde to establish a biocompatible hydrophilic structure on the surface. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirm the successful grafting of both PEG and phosphorylcholine functional groups on the surface. The decrease of the water contact angle for the modified film is caused by synergic effect of PEG and phosphorylcholine, which both have the high hydrophilicity. Furthermore, the number of platelets adhered is relative low on the synergetically modified PCU film compared with the PCU film modified only by poly（PEGMA）. Our synergic modification method using both PEG and phosphorylcho- line may be applied in surface modification of bloodcontacting biomaterials and some relevant devices.
