Manejo perioperatorio y periprocedimiento del tratamiento antitrombótico: documento de consenso de SEC,SEDAR, SEACV,SECTCV, AEC,SECPRE, SEPD,SEGO, SEHH,SETH, SEMERGEN,SEMFYC, SEMG,SEMICYUC, SEMI,SEMES, SEPAR,SENEC, SEO,SEPA, SERVEI,SECOT y AEU

During the last few years, the number of patients receiving anticoagulant and antiplatelet therapy has increased worldwide. Since this is a chronic treatment, patients receiving it can be expected to need some kind of surgery or intervention during their lifetime that may require treatment discontinuation. The decision to withdraw antithrombotic therapy depends on the patient's thrombotic risk versus hemorrhagic risk. Assessment of both factors will show the precise management of anticoagulant and antiplatelet therapy in these scenarios. The aim of this consensus document, coordinated by the Cardiovascular Thrombosis Working Group of the Spanish Society of Cardiology, and endorsed by most of the Spanish scientific societies of clinical specialities that may play a role in the patient-health care process during the perioperative or periprocedural period, is to recommend some simple and practical guidelines with a view to homogenizing daily clinical practice.Full English text available from: www.revespcardiol.org/en     

WJC,WJGE,WJGO,WJGS,WJH,WJR6本期刊被PMC收录

本刊讯我们于2010-08-17收到PubMed Central(PMC)的通知,经过美国国立医学图书馆机构咨询委员会The Literature Selection Technical Review Committee评定,决定WJC,WJGE,WJGO,WJGS,WJH,WJR6本期刊被PMC收录.PMC是一个提供生命科学期刊文献的全文数据库,他是由隶属美国国立医学图书馆(National Library of Medicine)的国家生物技术信息中心(National Center for Biotechnology Information)所创建与管理的.(常务副总编辑:张海宁2011-01-08)     

WJC,WJGE,WJGO,WJGS,WJH,WJR 6本期刊被PMC收录

本刊讯我们于2010-08-17收到PubMed Central(PMC)的通知,经过美国国立医学图书馆机构咨询委员会The Literature Selection Technical Review Committee评定,决定WJC,WJGE,WJGO,WJGS,WJH,WJR6本期刊被PMC收录.PMC是一个提供生命科学期刊文献的全文数据库,他是由隶属美国国立医学图书馆(National     

WJC,WJGE,WJGO,WJGS,WJH,WJR 6本期刊被PMC收录

本刊讯我们于2010-08-17收到PubMed Central(PMC)的通知,经过美国国立医学图书馆机构咨询委员会The Literature Selection Technical Review Committee评定,决定WJC,WJGE,WJGO,WJGS,WJH,WJR6本期刊     

WJC,WJGE,WJGO,WJGS,WJH,WJR6本期刊被PMC收录

本刊讯我们于2010-08-17收到PubMed Central(PMC)的通知,经过美国国立医学图书馆机构咨询委员会TheLiterature Selection Technical Review Committee评定     

WJC,WJGE,WJGO,WJGS,WJH,WJR6本期刊被PMC收录

本刊讯我们于2010-08-17收到PubMed Central(PMC)的通知,经过美国国立医学图书馆机构咨询委员会The Literature Selection Technical Review Committee评定,决定WJC,WJGE,WJGO,WJGS,WJH,WJR6本期刊     

WJC,WJGE,WJGO,WJGS,WJH,WJR6本期刊被PMC收录

本刊讯我们于2010-08-17收到PubMed Central(PMC)的通知,经过美国国立医学图书馆机构咨询委员会TheLiterature Selection Technical Review Committee评定,决定WJC,WJGE,WJGO,WJGS,WJH,WJR6本期刊被PMC收录.PMC是一个提供生命科学期刊文献的全文数据库,他是由隶属美国国立医学图书馆(National     

WJC,WJGE,WJGO,WJGS,WJH,WJR 6本期刊被PMC收录

本刊讯我们于2010-08-17收到PubMed Central(PMC)的通知,经过美国国立医学图书馆机构咨询委员会The Literature Selection Technical Review Committee评定,决定WJC,WJGE,WJGO,WJGS,WJH,WJR6本期刊     

WJC,WJGE,WJGO,WJGS,WJH,WJR6本期刊被PMC收录

本刊讯我们于2010-08-17收到PubMed Central(PMC)的通知, 经过美国国立医学图书馆机构咨询委员会The Literature Selection Technical Review Committee评定, 决定WJC, WJGE, WJGO, WJGS, WJH, WJR 6本期刊     

ACEI attenuates the progression of CCl4-induced rat hepatic fibrogenesis by inhibiting TGF-β1, PDGF-BB, NF-κB and MMP-2,9

AIM: Angiotensin Ⅱ has pro-fibrotic function in the liver.Blockade of the renin-angiotensin-aldosterone-system (RAAS) attenuates hepatic fibrosis. The aim of the present study was to determine the mechanism of angiotensinconverting enzyme inhibitor (ACEI) on the progression of rat hepatic fibrosis.METHODS: Forty male Wistar rats were divided into three groups. Model group (Mo): The rats were injected subcutaneously with 40% of CCl4 0.25 mL/100 g. Perindopril group (Pe): The rats were injected subcutaneously with administrated. Control group (Nc): the rats were treated with olive oil only. After 4 and 6 wk, the rats were killed.The liver sections were stained with Masson. The protein expressions of AT1R, TGF-β1 and PDGF-BB were examined by Western blot. Nuclear factor κB (NF-κB) DNA binding activity was examined by EMSA (Electrophoretic gel mobility shift assay). Matrix metalloproteinase-2,9(MMP-2,9) activity was assessed by zymography. Serum laminin (LN) and hyaluronic acid (HA) were measured using radioimmunoassays.RESULTS: Using Western blot, we clearly provided direct evidence for the expression of AT1R in liver. The expression was up-regulated when fibrogenesis occurred. Perindopril treatment significantly reduced mean fibrosis score,protein levels of AT1R, TGF-β1 and PDGF-BB, serum levels of HA and LN, and the activity of MMP-2,9. NF-κB DNA binding activity markedly increased in model group, perindopril treatment considerably reduced NF-κB DNA binding activity.CONCLUSION: Perindopril attenuates CCl4-induced hepatic fibrogenesis of rat by inhibiting TGF-β1, PDGF-BB,NF-κB and MMP-2,9.     

培哚普利抗实验性大鼠肝纤维化的实验研究

目的 研究血管紧张素转化酶抑制剂-培哚普利对实验性肝纤维化的影响,并探讨其作用机制。 方法 取雄性大鼠40只,随机分为3组。模型组:40％ CCl4油0.25 g/L皮下注射,每周2次;培哚普利治疗组:40％CCl4油0.25 g/L皮下注射,2次/周,同时予以培哚普利2 mg/kg灌胃,1次/d。对照组:橄榄油皮下注射。于第4、6周取材。光镜下动态观察组织学改变,检测血管紧张素Ⅱ1型受体(A T 1 R)、转化生长因子β1(TGF—β1)、血小板衍生性生长因子-BB(PDGF—BB)蛋白的表达、金属蛋白酶-2(MMP-2)的活性和血清透明质酸(HA)、层黏连蛋白(LN)的含量。 结果 培哚普利治疗组肝组织炎症程度明显减轻,纤维间隔较为细小,血清HA、LN(μg/L)含量分别为82.07±13.66和94.84±3.54,模型组分别为147.86±18.92和113.72±2.14,t=2.27～2.87,P<0.05;培哚普利治疗组AT1R mRNA和蛋白质表达水平、TGF-β1和PDGF—BB蛋白质的表达低于模型组;模型组MMP-2活性高于培哚普利组。 结论 培哚普利对实验性大鼠肝纤维化具有抑制作用。     

Antifibrotic effects of interleukin-10 on experimental hepatic fibrosis

BACKGROUND/AIMS: To study the effects of interleukin-10 on hepatic stellate cells and liver tissue in experimental rats hepatic fibrosis. METHODOLOGY: Rat hepatic fibrosis model induced by carbon tetrachloride was established. Liver tissues were harvested from the rats administered CCl4 with or without IL-10 treatment and the animals of the control group. The expression of TGF-beta1, MMP-2 and TIMP-1 in the liver tissues was measured by S-P immunohistochemistry. In addition, another model was established; HSCs in rats in each group were isolated. RT-PCR was employed to analyze TGF-beta1, MMP-2 and TIMP-1 mRNA expression in cells and immunocytochemistry was performed to detect protein expression of alpha-SMA, NF-kappaB, TGF-beta1, MMP-2 and TIMP-1 in HSCs. RESULTS: Rat hepatic fibrosis was developed successfully. The fibrosis changes were partially reversed by simultaneous administration of IL-10. The positive signals of TGF-beta1, MMP-2 and TIMP-1 were observed more frequently (P<0.05) in the CCl4-treated group compared to those in the IL-10-treated group and the control group. HSCs were successfully isolated. TGF-beta1, MMP-2 and TIMP-1 mRNA in HSCs increased obviously during the course of hepatic fibrosis, and their levels were decreased after the treatment with IL-10 (P<0.05). The immunocytochemistry positive levels for TGF-beta1, MMP-2, TIMP-1, alpha-SMA and NF-kappaB in the fibrogenesis group were increased significantly compared to the normal group (P<0.01). The positive signals decreased significantly (P<0.05) after the treatment with IL-10. CONCLUSIONS: The expression of TGF-beta1, MMP-2 and TIMP-1 increased in liver or in HSC of hepatic fibrosis rats and decreased after treatment with IL-10. The IL-10 could inhibit the activation of HSCs and make an antifibrogenic process come into effect in this way.     

Diagnostic value of platelet derived growth factor-BB, transforming growth factor-β1,matrix metalloproteinase-1, and tissue inhibitor of matrix metaUoproteinase-1 in serum and peripheral blood mononuclear cells for hepatic fibrosis

AIM: Noninvasive diagnosis of hepatic fibrosis has become the focus because of the limited biopsy, especially in the surveillance of treatment and in screening hepatic fibrosis. Recently, regulatory elements involved in liver fibrosis, such as platelet derived growth factor-BB (PDGF-BB), transforming growth factor-β1(TGF-β1), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), have been studied extensively. To determine whether these factors or enzymes could be used as the indices for the diagnosis of hepatic fibrosis, we investigated them by means of receiver operating characteristic (ROC) curve. METHODS: Serum samples from sixty patients with chronic viral hepatitis B and twenty healthy blood donors were assayed to determine the level of PDGF-BB, TGF-β1, MMP-1, and TIMP-1 with ELISA, and HA, PCIII, C-IV, and LNlevel with RIA. The message RNA (mRNA) expression of TIMP-1 and MMP-1 in peripheral blood mononuclear cells (PBMCs) was detected by RT-PCR and Northern blot hybridization. Liver biopsy was performed in all patients. The biopsy samples were histopatholocjically examined. The trial was double-blind controlled. RESULTS: The serum level of PDGF-BB, TIMP-1, the ratio of TIMP-1 and MMP-1 (TIMP-1/MMP-1), mRNA expression of TIMP-1 (TIMP-lmRNA), and the ratio of TIMP-lmRNA and MMP-lmRNA (TIMP-lmRNA/MMP-lmRNA) in patients was significantly higher than those in the healthy blood donors (t=2.514-11.435, P=0.000-0.016). The serum level of PDGF-BB, TIMP-1, TIMP-1/MMP-1, and TIMP-lmRNA was positively correlated with fibrosis stage and inflammation grade (r=0.239-0.565, P=0.000-0.033), while the serum level of MMP-1 was negatively correlated with fibrosis stage and inflammation grade, and TIMP-lmRNA/MMP-lmRNA was positively correlated with inflammation grade. Through the analysis by ROC curve, serum PDGF-BB was the most valuable marker, and its sensitivity was the highest among the nine indices. The markers with the highest specificity were TIMP-lmRNA and TIMP-lmRNA/MMP-lmRNA in PBMCs. The area under the curve (AUC) of PDGF-BB, TIMP-lmRNA, TIMP-lmRNA/MMP-lmRNA, TIMP-1/MMP-1, HA, PCIII, TIMP-1, C-IV, and LN was 0.985, 0.876, 0.792, 0.748, 0.728, 0.727, 0.726, 0.583, and 0.463, respectively. The sensitivity and the specificity in the parallel test was 99.0% and 95.0 % when serum PDGF-BB, TIMP-lmRNA and TIMP-lmRNA/MMP-lmRNA was detected simultaneously. CONCLUSION: Serum level of PDGF-BB, TIIVIP-lmRNA, TIMP-lmRNA/MMP-lmRNA in PBMCs, and serum level of TIMP-1 and TIMP-1/MMP-1 can be used as the indices for the diagnosis of hepatic fibrosis, but the former three are more useful. The combination of serum PDGF-BB, TIMP-lmRNA and TIMP-lmRNA/MMP-lmRNA in PBMCs is even more efficient in screening liver fibrosis.     

Therapeutic effects and molecular mechanisms of anti-fibrosis herbs and selenium on rats with hepatic fibrosis

AIM:To study the therapeutic effects of anti-fibrosis herbs and selenium on hepatic fibrosis induced by carbon tetrachloride (CCl4) in rats and the underlining molecular mechanisms.METHODS:Fifty-three Wistar rats were randomly divided into:normal control group, model control group, colchicine group, anti-fibrosis herbs group (AF group) and anti-fibrosis herbs plus selenium group (AS group).The last four groups were administered with CCl4 at the beginning of experiment to induce hepatic fibrosis. Then colchicine, anti-fibrosis herbs and selenium were used to treat them. The normal control group and the model control group were given normal saline at the same time. At the end of the 6^th week, rats in each group were sacrificed. Blood and tissue specimens were taken. Serum indicators (ALT, AST, HA, LN) were determined and histopathological changes were graded. Lymphocyte CD4 and CD8 were examined by flow cytometry. Expression of TGF-β1 and NF-κB was detected by immunohistochemistry and expression of TGF-β1 mRNA was detected by semiquantified RT-PCR.RESULTS: Histological grading showed much a smaller degree of hepatic fibrogenesis in AS group and AF group than that in colchicine group and model control group.The serum content of ALT, AST, HA and LN in AF group and AS group were significantly lower than that in colchicine group (ALT:65.8&#177;26.5, 67.3&#177;18.4 and 96.2&#177;20.9 in AF, AS and colchicine groups respectively; AST: 150.8&#177;34.0, 154.6&#177;27.3 and 215.8&#177;24.6 respectively; HA: 228&#177;83, 216&#177;58 and 416&#177;135 respectively; LN:85.9&#177;15.0, 80.6&#177;18.6 and 106.3&#177;14.2 respectively) (P&lt;0.05). The level of CD4 and CD4/CD8 ratio in AF group and AS group was significantly higher that those in cochicine group (CD4:50.8&#177;3.8, 52.6&#177;3.4 and 40.2&#177;2.1 in AF, AS and colchicine groups respectively;CD4/CD8 ratio:1.45,1.46 and 1.26, respectively (P&lt;0.05).The expression level of NF-κB and TGF-β1 in the liver tissues of AF and AS treatment groups was markedly decreased compared with that in cochicine group, and TGF-β1 mRNA was also markedly decreased (1.07&#177;0.31 and 0.98&#177;0.14 vs2.34&#177;0.43, P&lt;0.05).CONCLUSION: Anti-fibrosis herbs and selenium have beneficial effects on hepatic fibrosis in rats by enhancing immunity and inhibiting NF-κB and TGF-β1 expressions.     

Effects of AT1 receptor antagonist, losartan, on rat hepatic fibrosis induced by CCl(4)

AIM:To investigate effect of losartan, an AT1 receptor antagonist, on hepatic fibrosis induced by CCl(4); and to determine whether or not AT1 receptors are expressed on hepatic stellate cells. METHODS AND RESULTS:Fifty male Sprague-Dawley rats, weighing (180 plus minus20)g, were randomized into five groups (control group, model group, and three losartan treated groups), in which all rats were given the subcutaneous injection of 40% CCl(4)(every 3 days for 6 weeks) except for rats of control group. Rats of losartan-treated groups were treated with losartan (20 mg/kg, 10 mg/kg, 5 mg/kg, daily gavage). After 6 weeks liver tissue and serum samples of all rats were examined. Serum hyaluronic acid (HA), procollagen type III (PC III) were detected by radioimmunoassays. van Giesion collagen staining was used to evaluate the extracellular matrix of rats with liver fibrosis. The expression of AT1 receptors, transforming growth factor-beta (TGF-beta), and alpha-smooth muscle actinalpha-SMA) in liver tissue were determined by immunohistochemical techniques. Compared with model group, serum ALT and AST of losartan-treated groups were significantly reduced (italic>t = 4.20,P < 0.01 and italic>t = 4.57,P < 0.01). Serum HA and PC III also had significant differences (italic>t = 3.53,P<0.01 and t=2.20, P<0.05). The degree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors, TGF-beta, and alpha-SMA in liver tissue.CONCLUSION:AT1 receptor antagonist, losartan, could limit the progression of the hepatic fibrosis induced by CCl(4). The mechanism may be related to the decrease in the expression of AT1 receptors and TGF-beta, ameliorating the injury of hepatocytes; activation of local renin-angiotensin system might relate to hepatic fibrosis; and during progression of fibrosis, activated hepatic stellate cells might express AT1 receptors.     

Therapeutic effect of interleukin-10 on CCl4-induced hepatic fibrosis in rats

AIM: To study the therapeutic effect of exogenous interleukin-10 on CCl4-induced hepatic fibrosis in rats and its possible mechanisms. METHODS: Fourty-seven SD rats were randomly divided into control group (group N) and CCl4-induced hepatic fibrosis model group (group C). After CCl4 was given for 9 wk, the model group was divided into three groups. Rats in group M were put to death immediately,rats in group T were treated with IL-10 for another three wk and then put to death, rats in group R recovered after three weeks and were then killed. The degree of hepatic fibrosis was measured by HE staining and histological activity index (HAI). Histological activity index (HAI), change of collagen types I and III were measured by Picrosirius staining. The expression of TNF-alpha, MMP-2 and TIMP-1 in liver tissue was measured by S-P immunohistochemistry. RESULTS: CCl4- induced experimental rat hepatic fibrosis model was established successfully. The degree of hepatic fibrosis was markedly lower in group T than in groups M and R, and there was no difference between the two groups.The expression of collagen types I and III was significantly suppressed in group T and was slightly suppressed in groups M and R. The positive levels of TNF-alpha, MMP-2 and TIMP-1 in group M increased significantly compared to those in group N (P<0.01). The positive signals decreased significantly in groups T and R (P<0.01),but positive score was significantly lower in group T than in group R (P<0.01). CONCLUSION: Exogenous IL-10 can reverse CCl4-induced hepatic fibrosis in rats. IL-10 may exert its reversible effects on hepatic fibrosis by blocking CCl4-induced inflammation,inhibiting expression of MMP-2 and TIMP-1 and promoting resolution of collagen types I and III.     

Diagnostic value of platelet derived growth factor-BB, transforming growth factor-β1,matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinase-1 in serum and peripheral blood mononuclear cells for hepatic fibrosis

AIM: Noninvasive diagnosis of hepatic fibrosis has become the focus because of the limited biopsy, especially in the surveillance of treatment and in screening hepatic fibrosis.Recently, regulatory elements involved in liver fibrosis, such as platelet derived growth factor-BB (PDGF-BB), transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), have been studied extensively. To determine whether these factors or enzymes could be used as the indices for the diagnosis of hepatic fibrosis, we investigated them by means of receiver operating characteristic (ROC) curve.METHODS: Serum samples from sixty patients with chronic viral hepatitis B and twenty healthy blood donors were assayed to determine the level of PDGF-BB, TGF-β1, MMP-1, and TIMP-1 with ELISA, and HA, PCIII, C-IV, and LN level with RIA. The message RNA (mRNA) expression of TIMP-1 and MMP-1 in peripheral blood mononuclear cells (PBMCs) was detected by RT-PCR and Northern blot hybridization. Liver biopsy was performed in all patients.The biopsy samples were histopathologically examined. The trial was double-blind controlled.RESULTS: The serum level of PDGF-BB, TIMP-1, the ratio of TIMP-1 and MMP-1 (TIMP-1/MMP-1), mRNA expression of TIMP-1 (TIMP-1mRNA), and the ratio of TIMP-1mRNA and MMP-1mRNA (TIMP-1mRNA/MMP-1mRNA) in patients was significantly higher than those in the healthy blood donors (t=2.514-11.435, P=0.000-0.016). The serum level of PDGF-BB, TIMP-1, TIMP-1/MMP-1, and TIMP-1mRNA was positively correlated with fibrosis stage and inflammation grade (r=0.239-0.565, P=0.000-0.033), while the serum level of MMP-1 was negatively correlated with fibrosis stage and inflammation grade, and TIMP-1mRNA/MMP-1mRNA was positively correlated with inflammation grade. Through the analysis by ROC curve, serum PDGF-BB was the most valuable marker, and its sensitivity was the highest among the nine indices. The markers with the highest specificity were TIMP-1mRNA and TIMP-1mRNA/MMP-1mRNA in PBMCs. The area under the curve (AUC) of PDGF-BB, TIMP-1mRNA, TIMP-1mRNA/MMP-1mRNA, TIMP-1/MMP-1, HA,PCIII, TIMP-1, C-IV, and LN was 0.985, 0.876, 0.792, 0.748,0.728, 0.727, 0.726, 0.583, and 0.463, respectively. The sensitivity and the specificity in the parallel test was 99.0 %and 95.0 % when serum PDGF-BB, TIMP-1mRNA and TIMP1mRNA/MMP-1mRNA was detected simultaneously.CONCLUSION: Serum level of PDGF-BB, TIMP-1mRNA,TIMP-1mRNA/MMP-1mRNA in PBMCs, and serum level of TIMP-1 and TIMP-1/MMP-1 can be used as the indices for the diagnosis of hepatic fibrosis, but the former three are more useful. The combination of serum PDGF-BB, TIMP-1mRNA and TIMP-1mRNA/MMP-1mRNA in PBMCs is even more efficient in screening liver fibrosis.     

Effect of Losartan, an Angiotensin II Antagonist, on Hepatic Fibrosis Induced by CCl4 in Rats

In addition to regulating blood pressure and body fluid homeostasis, the renin-angiotensin system (RAS) is also involved in hepatic fibrogenesis. We aimed to investigate the effect of losartan, an angiotensin II (Ang II) antagonist, on CCl4-induced hepatic fibrosis in rats. Hepatic fibrosis was induced by a subcutaneous injection with 50% CCl4 in Sprague-Dawley rats. The amount of CCl4 administered was 1 mg/kg. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in plasma and hydroxyproline (Hyp) contents in liver tissue were assayed by spectrophotometry. Hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels in culture supernatants of Kupffer cells (KCs) stimulated with Ang II was determined by ELISA. Liver samples collected after 12 weeks of CCl4 treatment were stained with hematoxylin and eosin, then scored. Losartan (2.5, 5, and 10 mg x kg(-1), ig) and captopril (100 mg x kg(-1), ig) significantly decreased liver and spleen indexes, serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. Histopathological scores showed that losartan had an inhibitory effect on the progression of hepatic fibrosis. In in vitro experiments, losartan (1 x 10(-9) - 1 x 10(-5) M) significantly reduced TNF-alpha and TGF-beta1 levels in culture supernatants of KCs, but captopril (1 x 10(-5) M) did not. The results showed that losartan significantly inhibited the progression of hepatic fibrosis induced by CCl4, and the inhibitory effect of losartan on hepatic fibrosis might be associated with its ability to inhibit the production of TNF-alpha and TGF-beta1 by activated KCs.