牛磺酸对实验性小鼠Coxsackie B3病毒性心肌炎的疗效研究

用Coxsackie B3病毒(CV B3)感染BALB/C小鼠建立实验性病毒心肌炎(VMC)模型,观察了牛磺酸对此模型的作用.结果发现,牛磺酸能减少感染病毒后小鼠的死亡只数,减轻心肌组织病理损害,减少感染CVB3后ECG的异常变化,加快血清及心肌CVB3RNA转阴,感染CVB3后血清牛磺酸浓度明显增加.本实验结果显示,牛磺酸对实验性VMC具有良好的保护作用.

CoxsackieB＿3病毒对小鼠Ⅱ导联QRS波群功率谱的影响

将健康Ｂａｌｂ／ｃ小鼠腹腔注射Ｃｏｘｓａｃｋｉｅ病毒（ＣＢ＿３Ｖ），对其种毒前及种毒后第１，３，５，７天的高频心电图（ＨＦ－ＥＣＧ）Ⅱ导联ＱＲＳ波群的功率谱进行分析。结果表明，种毒后低频（０－８０Ｈｚ）相对能量较种毒前降低，而高频（７８０Ｈｚ）各频段相对能量均较种毒前升高，即病毒使心电活动的高频相对能量升高，对照组无此变化。结果提示：功率谱可能成为检测病毒性心肌炎的一项新的辅助指标。

Coxsackie B组病毒研究

Coxsackie B 病毒有6个血清型,可引起人的一系列严重疾病。为推动对该组病毒的研究,我们采用原代猴肾（MK）、人胚肾（HK）细胞,以及传代细胞 LLc-Mk2、Veto、MA104.BSC-1.Hela.F1.R66、pK15等十种细胞,比较对该组病毒的敏感性,以 CPE 及感染滴度为指标,结果以 HK 最敏感,F1不敏感,Hela 也较敏感。可用 Hela 繁殖病毒、测血清抗体等。

Oxidative Stress in Patients With Acute Coxsackie Virus Myocarditis

Objective To study the state of oxidative stress in patients with acute coxsackie virusmyocarditis (ACM), and to investigate the pathological chain reactions of a series of freeradicals and oxidative and lipoperoxidative damages in their bodies. Methods Eighty ACMpatients and 80 healthy adult volunteers (HAV) were enrolled in a case-control study, inwhich concentrations of nitric oxide (NO) in plasma, lipoperoxides (LPO) in plasma andLPO in erythrocytes (RBC), vitamin C (VC), vitamin E (VE) and b-carotene (b-CAR) inplasma as well as activities of superoxide dismutase (SOD), catalase (CAT) and glutathioneperoxidase (GSH-Px) in RBC were determined by using spectrophotometric assays. ResultsCompared with the average values (AV) of the above biochemical parameters (BP) in theHAV group, the AV of NO in plasma, and LPO in plasma and RBC in the ACM group weresignificantly increased (P=0.0001), while the AV of VC, VE, b-CAR, SOD, CAT and GSH-Px in the ACM group were significantly decreased (P=0.0001). The values of the above BPwere used to estimate the relative risk ratio (RR) between the ACM group and the HAVgroup; the RR and its 95 % confidence interval were 12.467 (5.745~27.051), 4.333(2.126~8.834), 6.517 (3.225~13.618), 3.310 (1.598~6.858), 31.000 (12.611~76.201),4.663 (2.228~9.759), 11.769 (5.440~25.462), 3.043 (1.486~6.229) and 6.594 (3.045~14.281)respectively, and their P levels ranged from 0.002 to 0.0001. The results were asfollows: D = 22.143 - 0.017SOD + 0.008NO + 0.244LPO in RBC, Eigenvalue = 13.659,Canonical correlation = 0.965, Wilks’λ= 0.068, c2 = 420.212, P = 0.0001. The correct rateof discrimination to the ACM group and to the HAV group was 87.5% and 95.0 %, respectively,and 91.3 % of originally grouped cases was correctly classified. Conclusion The findingsin this study suggested that the oxidative stress in bodies of ACM patients was severelyaggravated, and marked high oxidative constituents and low antioxidants and antioxidasesin the human body might increase the relative risk of inducing acute coxsackie virusmyocarditis, and measuring the values of NO in plasma, SOD and LPO in RBC mightincrease the correct rates of discriminatory analysis of the ACM.

Experimental infection of tree shrews(Tupaia belangeri) with Coxsackie virus A16

Coxsackie virus A16(CA16) is commonly recognized as one of the main human pathogens of hand-foot-mouth disease(HFMD). The clinical manifestations of HFMD include vesicles of hand, foot and mouth in young children and severe inflammatory CNS lesions. In this study, experimentally CA16 infected tree shrews(Tupaia belangeri) were used to investigate CA16 pathogenesis. The results showed that both the body temperature and the percentages of blood neutrophilic granulocytes / monocytes of CA16 infected tree shrews increased at 4-7 days post infection. Dynamic distributions of CA16 in different tissues and stools were found at different infection stages. Moreover, the pathological changes in CNS and other organs were also observed. These findings indicate that tree shrews can be used as a viable animal model to study CA16 infection.

Circulating Adhesion Molecules in Patients with Keshan Disease and Their Relationship with Coxsackie B Virus Infection

This study determined the levels of serum soluble intercellular adhesion molecule-1 （sI-CAM-l） and soluble vascular cell adhesion molecular-1 （sVCAM-1） in patients with different types of Keshan disease （KD）, examined the relationship between Coxsackie B virus-specific IgM antibody （CBV-IgM） and slCAM-1 or sVCAM-1 in KD patients, and investigated the role of these adhesion molecules in the pathogenesis of KD and their clinical implications. The levels of serum slCAM-1, sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in 22 patients with chronic Keshan disease （CKD）, 27 with latent Keshan disease （LKD） and 28 healthy controis. The subjects in different groups were adjusted for sex and age. Echocardiography was adopted to determine left ventricular ejection fraction （LVEF） in 22 patients with CKD. The results showed that CKD patients had significantly higher levels of slCAM-1 and sVCAM-1 than LKD patients and healthy controls （P〈0.01 for all）. And there was significant difference in the levels of the 2 adhesion molecules between LKD patients and healthy controls （P〈0.05）. A negative correlation was found between LVEF and slCAM-1 or sVCAM-1 in CKD patients. The percentage of CBV-specific IgM positive individuals in KD patients was significantly higher than that of healthy controls. In CVB-specific IgM positive patients, the levels of serum slCAM-1 and sVCAM-1 were significantly greater than those in CBV-specific IgM negative counterpart. It was concluded that the increase in the levels of slCAM-1 and sVCAM-1 suggests the progression of inflammation in KD. slCAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function. The increased serum slCAM-1 and sVCAM-1 in KD patients may be related to CBV infection.

Expression of Coxsackievirus and Adenovirus Receptor in Human Lung Cancer： Possible Clinical Significance

OBJECTIVE To explore the relationship between CAR and the development of human lung cancer, as well as to provide the basis for the clinical treatment of lung cancer using an adenovirus vector-based gene therapy. METHODS CAR expression was assessed immunohisto- chemically in tumoral, paraneoplastic and normal samples from 112 lung cancer patients. At the same time, the mRNA and protein expression of CAR in 32 cases were determined by RT-PCR and Western blot. The relationship between CAR expression and clinicopathologic parameters was statistically analyzed. RESULTS There was no expression of CAR in normal lung tissue but a little in paraneoplastic tissue. The positive rate was 43% in squamous cell carcinoma, and 70% in adenocarcinoma. Both were much significantly higher than that in paraneoplastic tissue. The CAR expression level in adenocarcinoma was higher than that in squamous cell cancer, mRNA expression by RT-PCR and protein expression by Western blot were consistent with immunohistochemistry results. CONCLUSION CAR is overexpressed in human lung cancer, especially in adenocarcinoma. This data offer the reliable basis for adenovirus-mediated gene therapy of lung cancer; more important, CAR may take part in the formation or development of lung cancer; this may be exploitable for the development of antibody-directed therapy in human lung cancer.

Design,synthesis and biological activity of some novel benzimidazole derivatives against Coxsackie virus B_3

A series of novel benzimidazole derivatives was synthesized and their anti-Coxsackie virus B3 （CVB3） activity was evaluated in VERO ceils. Compounds 9 and 10 exhibited better inhibitory activity than those of ribavirin （RBV） with IC50 values of 5.30 and 1.06 μg/mL, respectively. ？2009 Xian Jin Luo. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Inhibitory Effect of Coxsackie Adenovirus Receptor on Invasion and Metastasis Phenotype of Ovarian Cancer Cell Line SKOV3

Full-length coxsackie adenovirus receptor (CAR) eukaryotic expression plasmid was transfected into an ovarian cell line, SKOV3, and its effect on the change of malignant metastasis phenotype was explored. CAR mRNA and protein expression levels among 4 ovarian cancer cell lines (A2780, SKOV3, SW626, CAOV3) and the positive control 293 (a transformed human embryo kidney cell line) was detected by using semi-quantitative RT-RCR and Western blot and compared. CAR-negative SKOV3 was transfected with the eukaryotic expression plasmid containing a full-length CAR cDNA and mock-vector respectively. The positive clones were screened by G418. The biological behavior changes of positive transfected cells were gauged by colony formation in soft agar assay and cell adhesion assay. Among the cell lines, there were obviously different CAR expression levels. CAR could not be detected in SKOV3. In transfected cell group, CAR expression was enhanced obviously as compared with non-transfected or mock-transfected groups. Cell adhesion in the transfected group was promoted. The number of colony formation was reduced significantly in transfected groups (25.32±8.91) as compared with that in non-transfected group (88.75±13.98) and mock-transfected group (82.53±19.37). Among the 4 ovarian cancer cell lines, CAR expression level was variable. Exogenous CAR expression had a potential role in inhibiting the malignant metastasis phenotype of ovary cancer cells.

Expression of coxsackie and adenovirus receptor in small cell lung cancer

Objective: We explored the expression of coxsackie and adenovirus receptor (CAR) in small cell lung cancer (SCLC) tissue. Methods: CAR expression in 31 SCLC was assessed in formaldehyde-fixed, paraffin-embedded tissue according to the EnVision immunohistochemistry procedure, while 3 samples of surgical specimens of non-malignant lung disease were taken as the negative control. Results: We observed that the expression of CAR was detectable positive in all the 31 cases from the small cell lung cancer tissue, in contrasting that non-malignant lung tissue control. Conclusion: The high expression of CAR appeared in SCLC tissue indicates that it play an important role in of adenovirus vector-based gene therapy in SCLC.

Design, Synthesis and Inhibitory Properties against Coxsackie B3/B6 of Some Novel Triazole Derivatives

A series of 1,2,4-triazole derivatives were synthesized, and their abilities to inhibit the in vitro replication of Coxsackie B3/B6 were evaluated. Among the 1,2,4-triazole derivatives, compound 3 g displayed potent activity, with a high antiviral potency (IC50 = 1.71 μM (against CVB3), 1.43 μM (against CVB6)). The structures of all the new synthesized compounds were confirmed by 1H-NMR spectra, mass spectra and elemental analyses.

Expression and Significance of Coxsackie and Adenovirus Receptor in Renal-Cell Carcinoma

OBJECTIVE To investigate the expression of Coxsackie and Adenovirus receptor （CAR） in renal-cell carcinoma and the relationship of the CAR to the biological behavior of the carcinomas. METHODS The immunohistochemical SP method was used to detect the expression of Coxsackie and Adenovirus receptor in 48 cases of renal- cell carcinoma and in 12 cases of normal renal tissue 2 cm away from the tumor tissue. RESULTS The positive rates of CAR were 100% in 12 cases of para-tumor normal renal tissue and 35.4% in 48 cases of renal-cell carcinoma respectively. The difference of CAR expression between them was significant （P〈0.05）. The grades of the tumor were as follows： 22 in Grade Ⅰ, 17 in Grade Ⅱ and 9 in Grade Ⅲ with the CAR positive rate being 54.5%, 23.5% and 11.1%, respectively. There was a negative correlation between CAR expression and tumor grading （P〈0.05）. In addition, the number of the cases in stages I to IV were 19, 13, 11 and 5 respectively, with the respective positive rates being 57.9%, 30.8%, 18.2% and 0.0%, i.e. there also was a negative relationship between CAR expression and the stage （P〈0.05）. CONCLUSION CAR expression is down-regulated in renal-cell carcinoma compared with normal tissue. The level of CAR may be a sensitive predictor of differentiation, invasion and metastasis. Loss of CAR expression correlates with the invasive phenotype in our analysis of renal-cell carcinoma.

Expression of Coxsackie and Adenovirurus Receptor and its Significance in Human Lung Cancer

OBJECTIVE To study the relationship between the coxsackie and adenovirus receptor （CAR） and the development of human lung cancer. To optimize adenovirus vector-based gene therapy.METHODS The expression of CAR in 112 cases of lung cancer was examined using immunohistochemistry. At the same time, the relationship between CAR expression and clinicopathologic characteristics was analyzed,RESULTS ：lhere is a little expression of CAR in normal lung tissue. Compared with paraneoplastic epithelial tissue of the lung, the expression of CAR is generally up-regulated in tumor tissues showing a significant dif- ference （P〈0.01）. The positive rate of CAR expression in squamous cell carcinoma was 43.1%, and in adenocarcinoma 70.2%, with the difference between the two rates being statistically significant （P〈0.01）. Compared to the paraneoplastic tissues, the difference in CAR positive expression was 35.4% for squamous cell carcinoma and 38.3% for adenocarcinoma. But the difference in different stages of squamous cell carcinoma had no statistical significance （P〉0.05）. However, the expression of CAR was at a high level in the bronchioalveolar carcinomas as 80.4% were CAR positive. This research showed that there was a specially high expression of CAR in adenocarcinomas.CONCLUSION CAR is expressed in human lungs at a low level and up-regulated in the tumor tissues, suggesting that there is a relationship between adenocarcinoma and CAR. This research provides a basis for planning a regimen of gene therapy using an adenovirus vector,

辽宁省手足口病病原—Coxsackie A_(16)病毒的研究

1985年4—7月间,辽宁省沈阳、铁岭两市发生了手足口病（Hand Foot and Mou-th Disease,简称 HFMD）的首次大流行,经病原学研究证实是由于肠道病毒柯萨奇 A 组16型(Coxsackie A16,简称 CoxA16)病毒感染所致,报告如下。

Microarray analysis of extracellular matrix genes expression in myocardium of mouse with Coxsackie virus B_3 myocarditis

Background Extracellular matrix (ECM) orchestrates cell behaviour including growth, death, apoptosis, adhesion, migration, and invasion by activating several signalling pathways Certain components of ECM, such as integrins, may act as receptors or co-receptors of enterovirus ECM-activated gene expressions in myocardium of viral heart disease including myocarditis and partial cardiomyopathy remain elusive This study was to investigate the expression of ECM-activated genes in myocardium of mouse with viral myocarditis Methods BALB/c mice were infected with Coxsackie virus B 3 (CVB 3) to establish an animal model of myocarditis Uninfected mice were also prepared and served as controls Specific mRNA expression pattern in myocarditic mouse heart was analysed by an in-house cDNA microarray containing 8192 genes Overexpressed ECM genes were selected and subsequently confirmed by Northern blot analysis Results Nine ECM genes were isolated, from the array of 8192 genes, as overexpressed genes in hearts of myocarditic mice in comparison with controls Subsequent Northern blot analysis confirmed that four of the nine genes were highly expressed Expression of these four genes, Fin15, ILk, Lamr1 and ADAMTS-1, has not been reported previously to be induced by Coxsackie virus Conclusion CVB 3-induced myocarditis is associated with gene expression profiles of certain ECM components

流产妇女CoxsackieB病毒感染

流产妇女ＣｏｘｓａｃｋｉｅＢ病毒感染［英］／［Ａｘｅｌｓ－ｓｏｎＣ．．．ＪＭｅｄＶｉｒｏｌ，－１９９３，２８２－３９］为了研究ＣｏｘｓａｃｋｉｅＢ病毒１－５型（ＣＢＶ１－５）作为流产的病原学因素，对９７名流产妇女用放射免疫分析检测了ＣＢＶ－ＩｇＭ，并...

Effect of Astragalus membranacaus on Electrophysiological Activities of Acute Experimental Coxsackie B3 Viral Myocarditis in Mice

ＥｆｆｅｃｔｏｆＡｓｔｒａｇａｌｕｓｍｅｍｂｒａｎａｃａｕｓｏｎＥｌｅｃｔｒｏｐｈｙｓｉｏｌｏｇｉｃａｌＡｃｔｉｖｉｔｉｅｓｏｆＡｃｕｔｅＥｘｐｅｒｉｍｅｎｔａｌＣｏｘｓａｃｋｉｅＢ３ＶｉｒａｌＭｙｏｃａｒｄｉｔｉｓｉｎＭｉｃｅＲｕｉＴａｏ（芮涛）；...

心康口服液防治小鼠急性病毒性心肌炎

目的 在小鼠实验性病毒性心肌炎模型上，观察心康口服液抑制病毒，保护心肌及免疫组织的效果。方法用嗜心肌柯萨奇病毒B3（CVB3m)腹腔感染10d龄小鼠诱发急性病毒性心肌炎，以30g·kg^-1·d^-1和12g·kg^-1·d^-1的心康口服液分2次灌胃给药，间隔8h。预防观察在小鼠感染病毒前接受2d的保护性用药（组2，3)；治疗观察在小鼠感染病毒后2h用药（组4，5），病毒感染对照（组1）口服相同容量的无菌饮用水替代安慰用药。并设非感染病毒的正常药物和正常小鼠对照（组6，7）。结果 心康口服液对CVB3m病毒感染小鼠诱发心肌炎病变有明显的预防和治疗作用。表现在用药后经巨检及光镜病毒形态学检查，其心肌病毒程度，病灶范围及组织机构改变等明显较病毒对照组为轻；心肌病变面积亦明显低于病毒对照组，且心肌炎症反应轻。结论 心康口服液具有抑制病毒复制，保护心肌，降低心肌炎发生率，对胸腺淋巴组织具有保护等作用。

Down-regulation of Coxsakie and Adenovirus Receptor during Embryo Implantation

In this study,real-time PCR and immunohistochemistry were used to detect coxsakie and adenovirus receptor (CAR) expression.Both localization and quantity were evaluated in the uteri ob-tained at days post coitus (dpc) 2.5,4.5,6.5,8.5.Outcome of PCR was assessed by 2-ΔΔCt method.Im-age Pro-Plus 6.0 software was used for quantifying mean density of CAR expression in immunohisto-chemical sections.We found relatively weak CAR expression in the mouse uteri during implantation window.PCR and immunohistochemistry revealed highest CAR expression was detected on dpc 2.5 followed by down-regulation of CAR at dpc 4.5 and 6.5 (with significant difference).At dpc 8.5,CAR expression was increased slightly again.It is concluded that during implantation,the expression of CAR mRNA and protein is declined,resulting in the impairment of tight junction between cavity epithelium cells.After implantation window closure,CAR appears again to maintain epithelium stability.CAR might play an important role during embryo implantation procedure.

EFFECT OF VERAPAMIL ONCa^（2＋） INFLUX ANDCVB3－RNA REPLICATION IN CULTURED NEONATALRAT HEART CELLS INFECTED WITH CVB3

The effect of verapamil on Ca2+ influx across the myocardial plasma membrane and coxsackie virus B3 ( CVB3)-RNA replication in cultured neonatal rat heart cells infected with CVB3 was investigated. It was found that the Ca2+ influx could be inhibited significantly (P<O. 01) by verapamil (1 μmol/L) after infection of heart cells for 48h. However, when the cultured heart cells infected with CVB3 and treated with verapamil (Iμmol/L and 10 nmo/L) at the same time for 48h, the amounts of CVB3-RNA in myocytes were significantly higher than that in infected control group (P<O. 05). These phenomena suggest that the increase of Ca2+ influx of cultured heart cells infected with CVB3 could be inhibited by some calcium antagonists, e. g. verapamil at the early stage. On the other hand, verapamil might accelerate viral replication in myocardium. Thus, although verapamil could be beneficial for decreasing the secondary Ca2+ damages and improve the myocardial electric activity, it isn’t a sensible choice for therapy in early stage of virus infection with cardiac symptoms.