Effect of Granulocyte Colony-Stimulating-Factor Administration on Tissue Regeneration Due to Thioacetamide-Induced Liver Injury in Rats

It has been shown recently that granulocytecolony-stimulating factor (G-CSF) accelerates andenhances the hepatocyte proliferative capacity ofpartially hepatectomized rats. In the present study, weinvestigated the effect of G-CSF administration in a ratmodel of liver injury and regeneration, induced bythioacetamide (TAA) injection. TAA (300 mg/kg bodyweight) was injected intraperitoneally in male Wistarrats, and this was followed by administration ofeither saline (group A) or G-CSF at a dose of 150g/kg body weight (group B), 24 hr later. The animalswere killed at different time points after TAA treatment and the rate of tritiated thymidineincorporation into hepatic DNA, the activity of theenzyme thymidine kinase (EC 2.7.1.21) in the liver, andthe assessment of the mitotic index of hepatocytes, wereemployed to estimate liver regeneration. Theadministration of TAA caused severe hepatic injury,recognized histopathologically and by the raisedactivities of the serum hepatic enzymes aspartate andalanine aminotransferases. The hepatic injury, which peaked 36 hr afterTAA injection, was followed by a regenerative process ofhepatocytes presenting peaks at time points of 48 and 60hr (group A). The administration of G-CSF 24 hr after the injection of TAA (group B) causeda statistically significantly increase in the hepatocyteproliferation indices examined (P < 0.001), comparedto those found in group A at the same time points. It was concluded that G-CSFadministration enhanced the hepatocyte proliferativecapacity in this model of liver injury induced by TAAadministration.     

A Synthetic Selective Inhibitor of Factor Xa, DX-9065a, Reduces Monocyte Chemoattractant Protein-1 Expression After Ischemia-Reperfusion Injury in Rat Liver

Activated factor X (FXa) is a trypsinlike serineprotease involved in the cascade of blood coagulation.The monocyte chemoattractant protein-1 (MCP-1) may beimportant in the pathophysiology of liverischemia-reperfusion injury. We investigated the effects of aselective FXa inhibitor, DX-9065a, on MCP-1 expressionafter ischemia-reperfusion in the rat liver. Liverischemia was induced in rats by occluding the portalvein for 30 min. DX-9065a was injected intravenously5 min before vascular clamping. Serum concentrations ofMCP-1 were measured by enzyme-linked immunosorbentassay. The levels of MCP-1 mRNA in the liver after reperfusion were determined by northern blotanalysis. In vitro MCP-1 production by peritonealmacrophages in response to alpha-thrombin was examined.Serum concentrations of MCP-1 increased and peaked at 6 hr after reperfusion. However,pretreatment of animals with DX-9065a resulted insignificantly smaller increases in the serumconcentration of MCP-1 after reperfusion in adose-dependent manner. Pretreatment with DX-9065a significantly reduced MCP-1 mRNAlevels in the liver after ischemia-reperfusion. In vitroMCP-1 production by peritoneal macrophages was enhancedby alpha-thrombin. In addition, DX-9065a significantly reduced tissue factor mRNA levels in peripheralmonocytes after ischemiareperfusion, compared tountreated animals. In conclusion, a selective inhibitorof FXa, DX-9065a, limited MCP-1 production after ischemia-reperfusion of the ratliver.     

清热解毒法治疗急性冠脉综合征55例

观察清热解毒法对急性冠脉综合征的临床干预效果及干预机制,以探讨急性冠脉综合征与炎症的关系。【方法】将55例急性冠脉综合征患者按3:1随机分为2组,观察组41例,对照组14例。对照组给予抗凝、抗血小板聚集、抗心肌缺血等常规治疗,观察组在对照组治疗基础上加用三黄片(由大黄、黄芩、黄连组成)口服,4片／次,2次／d,两组均以2周为1个疗程。以计分法比较两组治疗后胸痛、胸闷、气短、心悸、发热、自汗、不寐、疲倦乏力、畏寒肢冷等症状的改善情况,以及治疗前后两组炎症性指标的变化情况。【结果】治疗后观察组症状计分减少程度大于对照组(P<0．05);血中 C反应蛋白(CRP)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)的下降程度亦均大于对照组(P<0．05)。服药期间,两组均未发现明显的不良反应。【结论】以清热解毒法干预急性冠脉综合征有效,说明急性冠脉综合征与炎症反应有关。     

针刺百会、大椎穴对局灶性脑缺血大鼠皮层脑源性神经营养因子表达的影响

[目的]观察电针对不同时间段局灶性脑缺血大鼠缺血区皮层脑源性神经营养因子(BDNF)的影响。[方法]SD大鼠36只,随机分为6组,分别为假手术2周与5周组、缺血2周与5周模型组、电针2周与5周组;除假手术组外.其他动物均采用热凝闭大鼠大脑中动脉法复制局灶性脑缺血模型,观察缺血2周和5周后缺血区皮层BDNF的变化规律及针刺对其影响。[结果]假手术组大鼠相应区域仅见少量BDNF阳性细胞,且强度较弱;脑缺血2周及5周组大鼠缺血区BDNF的免疫阳性细胞数量比假手术组增多(P<0.01),但脑缺血2周组与5周组大鼠缺血区脑片比较,BDNF阳性细胞数量无显著性差异(P>0.05);电针2周组与5周组脑片中免疫阳性细胞数量增加,与模型组比较有显著性差异(P<0.01),但随着时间的推移,此表达呈下降趋势。[结论]电针可以通过提高BDNF在缺血区周围皮层的表达,保护缺血性脑损伤,并可能与大脑可塑性的形成有一定的关系。     

针药结合对围绝经期模型大鼠性激素及胰岛素样生长因子的影响

[目的]探讨电针加雌激素(E2)治疗对围绝经期模型大鼠性激素和胰岛素样生长因子(IGF)的影响.[方法]选用雌性未孕Wistar大鼠随机分为正常组、模型组、假手术组、雌激素组(剂量为0.04 mg·kg-1·d-1),电针组(电针肾俞、太溪、足三里、三阴交),电针加雌激素组(电针方法同电针组,雌激素剂量减半),采用双侧...     

Mice Lacking Wnt9a or Wnt4 Are Prone to Develop Spontaneous Osteoarthritis With Age and Display Alteration in Either the Trabecular or Cortical Bone Compartment

Osteoarthritis (OA) is a common degenerative disease of the joint, with a complex multifactorial not yet fully understood etiology. Over the past years, the Wnt signaling pathway has been implicated in osteoarthritis. In a recent genomewide association study (GWAS), the chromosomal location on chromosome 1, linked to the Wnt3a-Wnt9a gene locus, was identified as the most significant locus associated with a thumb osteoarthritis endophenotype. Previously, it was shown that WNT9a is involved in maintaining synovial cell identity in the elbow joint during embryogenesis. Here, we report that the conditional loss of Wnt9a in the Prx1-Cre expressing limb mesenchyme or Prg4-CreER expressing cells predispositions the mice to develop spontaneous OA-like changes with age. In addition, the trabecular bone volume is altered in these mice. Similarly, mice with a conditional loss of Wnt4 in the limb mesenchyme are also more prone to develop spontaneously OA-like joint alterations with age. These mice display additional alterations in their cortical bone. The combined loss of Wnt9a and Wnt4 increased the likelihood of the mice developing osteoarthritis-like changes and enhanced disease severity in the affected mice. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Effect of growth factors and extracellular matrix materials on the proliferation and differentiation of microencapsulated myoblasts

An alternative approach to gene therapy via non-autologous somatic gene therapy is to implant genetically-engineered cells protected from immune rejection with microcapsules to deliver a therapeutic gene product. This delivery system may be optimized by using myoblast cell lines which can undergo terminal differentiation into myotubes, thus removing the potential problems of tumorigenesis and space restriction. However, once encapsulated, myoblasts do not proliferate or differentiate well. We now report the use of extracellular matrix components and growth factors to improve these properties. Addition of matrix material collagen, merosin or laminin all stimulated myoblast proliferation, particularly when merosin and laminin were combined; however, none, except collagen, stimulated differentiation. Inclusion of basic fibroblast growth factor (bFGF) within the microcapsules in the presence of collagen stimulated proliferation of C₂C₁₂ myoblasts, as well as differentiation into myotubes. Inclusion of insulin growth factor (IGF-II) in the microcapsules had no effect on proliferation but accelerated myoblasts differentiation. When the above matrix material and growth factors were provided in combination, the use of merosin and laminin together with bFGF and IGF-II stimulated myoblast proliferation but had no effect on differentiation. In contrast, the cocktail containing bFGF, IGF-II and collagen induced increased myoblasts proliferation and subsequent differentiation. Hence, the combination of bFGF, IGF-II and collagen appears optimal in improving proliferation and differentiation in encapsulated myoblasts.     

A Prospective Study of Prognostic Value of Type IV Collagenase Activity in Colorectal Cancer Tissue

The purpose of this prospective study was toevaluate the prognostic value of the type IV collagenase(IVase) activity in colorectal cancer tissue ondisease-free and overall survival in 31 colorectalcancer patients. The clinicopathologic factors studiedfor prognostic value were age, tumor location, tumordifferentiation, preoperative serum levels ofcarcinoembryonic antigen, Dukes' stage, and IVaseactivity in colorectal cancer tissue. IVase activitiesin colorectal cancer tissue were significantly higher inthe group of patients with recurrences than in the groupwithout recurrences (P = 0.019). Patients with high IVase activity in colorectal cancer tissuehad a significantly shorter disease-free survival (P =0.0016) and overall survival (P = 0.022) time than thosewith low IVase activity. Univariate and multivariate analysis showed that significant prognosticfactors for disease-free survival were Dukes' stage (P= 0.029, P = 0.046, respectively) and IVase activitystatus (P = 0.0016, P = 0.0026, respectively). Withrespect to overall survival, only IVase activity statusprovided significant predictive value in multivariateanalysis (P = 0.041). This prospective study suggeststhat IVase activity is a valuable prognostic factor in colorectal cancer patients.     

Helicobacter pylori Infection and Atrophic Gastritis (A Nested Case-Control Study in a Rural Town in Japan)

A seroepidemiologic, nested case-control studywas conducted to evaluate the risk for atrophicgastritis associated with Helicobacter pylori infection.Atrophic gastritis was diagnosed on the basis of serum pepsinogen levels: pepsinogen I level70 ng/ml and pepsinogen I/pepsinogen II ratio3.0. Cases were 23 men and 39 women who were notdiagnosed with atrophic gastritis in 1987, but who were diagnosed with the condition in 1992. Controlswere the 120 men and 282 women who did not meet theserologic criteria for atrophic gastritis in either timeperiod. Neither cases nor controls had a history of upper gastrointestinal operations.Helicobacter pylori infection at the initial survey wasassociated with a significantly increased risk ofatrophic gastritis incidence for both sexes combined(odds ratio = 3.72; 95% confidence interval,1.78-7.79; P = 0.0005). Cigarette smoking andconsumption of alcohol and green-yellow vegetables werenot associated with incidence of atrophicgastritis.