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.

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.

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

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.

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.

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.

TAURINE INFLUX IN CULTURED RAT CARDIOMYOCYTES AND CHANGES AFTER CVB3 INFECTION

Monolayer culture of spontaneously contracting rat heart cells was obtained from newborn SD rats andseeded intO culture plates. 1OOTCID50 of coxsackie virus B3 (CVB3) (Nancy strain )was added as the infectedgroup. The dynamics of taurine transport across membrane of normal heart cells and changes after infectionwere examined by using radioactive isotope tracing techniques. The results demonstrated that: (1)two uptake systems of taurine with different affinities and capacities were present in the Plasma membrane of cul-tured rat cardiOmyocytes,the K. of high and low affinity were 9. 5 X 10-5mol/l, and l. 3 X 1 O 2 mol/l,,respectively; (2)taurine transport across membrane was sodium-dependent with a positive linear relationshipbetween amount of taurine influx and extracellular concentration of sOdium;in addition,it was alsO regulat-ed by osmOlarity; (3) fyalanine,a carboxylic analog of taurine,could inhibit the uptake of taurine in dosedependently; (4)taurine influx was decreased in cultured rat cardiomyocytes after infected with CVB3. (5)the lnhibition ratio of taurine transport was enhanced as the infected time prolonged. This experiment pro-vides a basis fOr further investigation of kinetic test of taurine transport and more study should be carriedout to learn the effect of taurine in viral myocarditis.

Glucosylated caffeoylquinic acid derivatives from the flower buds of Lonicera japonica

Three new glucosylated caffeoylquinic acid isomers (1-3), along with six known compounds, have been isolated from an aqueous extract of the flower buds of Lonicera japonica. Structures of the new compounds were determined by spectroscopic and chemical methods as (-)-4-O-(4-O-beta-D-glucopyranosylcaffeoyl)quinic acid (-)-3-O-(4-O-beta-D-glucopyranosylcaffeoyl)quinic acid (2), and (-)-5-O-(4-O-beta-D-glucopyranosylcaffeoyl)quinic acid (3), respectively. In the preliminary in vitro assays, two known compounds methyl caffeate and 2'-O-methyladenosine showed inhibitory activity against Coxsackie virus B3 with IC50 values of 3.70 mu mol/L and 6.41 mu mol/L and SI values of 7.8 and 12.1, respectively. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

Phenolic constituents from the roots of Alangium chinense

Three new phenolics（1–3） and twenty-eight known compounds（4–31） were isolated from an ethanolic extract of roots of Alangium chinense. Compound 11 exhibited antiviral activity against Coxsackie virus B3 with IC50 values of 16.89 mmol/L. Compounds 1, 10–17, 19–21, and 23 showed strong antioxidant activity against Fe^2＋-cysteine-induced rat liver microsomal lipid peroxidation, with IC50 values of 0.14–8.18 mmol/L.

Design, synthesis, and antiviral properties of 2-aryl-1H- benzimidazole-4-carboxamide derivatives

A series of new benzimidazole derivatives were designed and synthesized.Their chemical structures were testified by 1 H NMR,infrared spectroscopy(IR),mass spectrography(MS),and elemental analysis.Their potent antiviral properties indicated the prospect of new drugs.Compound 13,16,18,19,21,22,and 23 were identified as novel antivirus with much better selective activity and inhibitory activity than the comparable ribavirin against Coxsackie virus B_(3) in VERO cells.

Clinical and Experimental Study on Huodan Tablet (藿丹片) in Treating Infantile Viral Myocarditis

Objective: To study the effect of Huodan tablet (藿丹片, HDT) in treating infantile viral myocarditis. Methods: Clinical manifestations and physical signs as well as laboratory examinations have been observed. Results: The markedly effective rate was 68%, and total effective rate 91.67% in the treated group, while in the control group, the markedly effective rate was 30.83%, and the total effective rate 70.84%. According to Ridit analysis, significant difference was shown between the two groups. r-treated group=0.5000, r-control group=0.295+2×0.025 respectively. Conclusion: HDT has no toxic side-effect and can be taken safely and conveniently, it conforms to the demands of WHO on new drug for prevention and cure of myocarditis.