This study determined the levels of serum soluble intercellular adhesion molecule-1 (sICAM-1) 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 sICAM-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 sICAM-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 controls. 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 sICAM-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 sICAM-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 sICAM-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 sICAM-1 and sVCAM-1 suggests the progression of inflammation in KD. sICAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function. The increased serum sICAM-1 and sVCAM-1 in KD patients may be related to CBV infection.
Cardiomyopathies/*blood ; Cardiomyopathies/etiology ; Cardiomyopathies/*virology ; Coxsackievirus Infections/*complications ; Enterovirus B, Human ; Intercellular Adhesion Molecule-1/*blood ; Selenium/blood ; Vascular Cell Adhesion Molecule-1/blood ; Young Adult

OBJECTIVE: To explore etiology and pathogenesis of viral myocarditis (VMC) and dilated cardiomyopathy (DCM). METHODS: The expression of Coxsackie B virus and adenovirus receptors (CAR) were detected with modified immunohistochemical (IHC) technique in myocardium of left ventricle, right ventricle, interventricular septum, and septal papillary muscle from 28 patients with viral myocarditis, 31 patients with dilated cardiomyopathy and 17 control patients (including normal, hypertension heart disease, myocardial infarction and coronary atherosclerotic heart disease). RESULTS: The brown staining on the cell membrane of myocardium represents positive result. 100% (28 of 28) of VMC patients (IHC surface integral: 4.3975 +/- 0.0365) and 84% (26 of 31) of DCM patients (4.2064 +/- 0.052 6) had prevalent CAR expression compared to 0% (0 of 19) control patients (0.073 1 +/- 0.0362). There were statistically significant differences between VMC/DCM and control patients (P < 0.05). CONCLUSION The prevalence of CAR expression was significantly higher in VMC and DCM patients (100% and 84% vs. 0% in control). In contrast, there was no difference found between VMC and DCM patients. These results suggest that both VMC and DCM involve viral etiology and could share a similar pathogenesis.
Adenovirus Infections, Human/complications* ; Cardiomyopathy, Dilated/virology* ; Case-Control Studies ; Coxsackie and Adenovirus Receptor-Like Membrane Protein ; Coxsackievirus Infections/complications* ; Death, Sudden, Cardiac ; Female ; Humans ; Immunohistochemistry ; Male ; Myocarditis/virology* ; Myocardium/pathology* ; Receptors, Virus/metabolism*

OBJECTIVETo investigate the relationship between coxsackievirus infection and type 1 diabetes mellitus (T1DM), and observe the changes of T lymphocyte subsets in the development of T1DM.

METHODSWe detected Coxsackievirus RNA by reverse transcription PCR, and measured the change in T-lymphocyte subsets by flow cytometry in 22 cases of newly diagnosed T1DM (group I), 30 patients with diabetes for some time (group II), and 30 healthy subjects (group III).

RESULTSThe positivity rate of coxsackie virus RNA in groups I, II, and III was 55.55%, 23.33%, and 6.67%, respectively, showing a significant difference among the 3 groups (P<0.01). Patients with upper respiratory tract infection had a higher positivity rate for coxsackie virus RNA than those without upper respiratory tract infection in group I (P<0.05). Compared with the control group, the percentage of CD3, CD4 and CD4/CD8 ratio decreased significantly in groups I and II (P<0.01 or P<0.05). CD3, CD4 and CD4/CD8 tended to increase in group II in comparison with group I, and there was an significant difference in CD3 and CD4 between the two groups (P<0.01 or P<0.05). Compared with the control group and CVBRNA-negative group, CVBRNA-positive group showed significantly lowered CD3, CD4, CD8 and CD4/CD8 (P<0.01 or P<0.05).

CONCLUSIONThe occurrence and development of type 1 diabetes is closely related to coxsackie virus infection, and the changes in T lymphocyte subsets serves as a probable mechanism of its pathogenicity.

Adolescent ; Adult ; CD4-CD8 Ratio ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Coxsackievirus Infections ; complications ; immunology ; Diabetes Mellitus, Type 1 ; complications ; virology ; Female ; Humans ; Lymphocyte Count ; Male ; T-Lymphocyte Subsets ; immunology ; Young Adult

OBJECTIVETo investigate the correlations among persistent viral infection, heart function and Chinese medicine (CM) difined-syndromes in patients with dilated cardiomyopathy (DCM).

METHODSFifty patients with DCM in the First Affiliated Hospital of Zhejiang Chinese Medical University from October 2009 to December 2011 were selected as the research subjects, and 30 healthy people were simultaneously selected as the normal control group to detect persistent viral infections after admission. The CM syndrome type and grade of heart function were then evaluated. The expression level of Coxsackie adenovirus receptor (CAR) was detected using the flow cytometry (FCM) technique, coxsackie virus RNA (CVB-RNA) using reverse transcription polymerase chain reaction (RTPCR), and the plasma brain natriuretic peptide (BNP) level with a Triage meter plus diagnosis instrument. Finally, the parameters such as left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by ultrasonic cardiogram. Person correlation analysis was used for measured data, Spearman correlation analysis for rating data, and the Chi-square test for numerical data.

RESULTSCVB-RNA was positive in 22 patients (44%) with DCM, while only 6 cases (20%) were CVB-RNA-positive in the normal control group, with a significant difference between the two groups (P<0.01). The expression level of CAR was significantly elevated in the DCM group compared with the normal control group (P<0.01). In CVB-RNA-positive patients (22 cases), the expression level of CAR was significantly higher than in CVB-RNA-negative patients (28 cases; P<0.01). In the DCM patients, there was a positive correlation between the CAR expression and the BNP level (r=0.34, P<0.05), while no significant difference was found between the CAR expression and the LVEF and LVEDd (r=-0.32, 0.30, P>0.05). There was no clear correlation between virus infection and the CM syndrome types in DCM patients (r=-0.22, P>0.05). According to the sequence of syndrome types: phlegm → qi deficiency → blood stasis → hydroretention with asthenic yang (from low to high), a positive correlation was existed between the BNP levels and CM syndrome types (r=0.139, P<0.05).

CONCLUSIONThe expression of CAR on the surface of white cells could be used to detect persistent viral infection. The expression level of CAR and heart function in DCM patients were highly correlated. The expression level of BNP may serve as an objective index for differentiating CM syndromes for patients with DCM.

Adult ; Aged ; Cardiomyopathy, Dilated ; blood ; complications ; physiopathology ; virology ; Coxsackie and Adenovirus Receptor-Like Membrane Protein ; Coxsackievirus Infections ; blood ; complications ; physiopathology ; Female ; Heart Function Tests ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; RNA, Viral ; blood ; Syndrome

OBJECTIVETo investigate the association of Coxsackie B virus (CBV) with habitual abortion.

METHODSCBV IgM antibody, viral RNA and virions were detected in 86 women with habitual abortion and 40 with induced abortion by means of enzyme-linked immunosorbent assay (ELISA), RT-PCR and virus isolation, respectively.

RESULTSThe positivity rate of CBV IgM were 87.2% and 35% in the two groups, respectively, and the detection rate of the viral RNA was 53.5% and 17.5% in blood lymphocytes, and 59.3% and 17.5% in the placentas. The virions were found in the placentas in 41.9% and 6.9% of the women, respectively. The positivity rates of CBV IgM, viral DNA and virions showed significant difference between the two groups (P<0. 01).

CONCLUSIONCBV might be one of the causes responsible for habitual abortion.

Abortion, Habitual ; blood ; etiology ; Adult ; Antibodies, Viral ; blood ; Coxsackievirus Infections ; complications ; virology ; Enterovirus B, Human ; immunology ; isolation & purification ; Female ; Humans ; Immunoglobulin M ; blood ; Lymphocytes ; ultrastructure ; virology ; Microscopy, Electron ; Pregnancy ; Pregnancy Complications, Infectious ; blood ; virology ; RNA, Viral ; blood

OBJECTIVETo explore the role of interleukin-17 (IL-17) in the evolution of viral myocarditis (VMC) into dilated cardiomyopathy (DCM).

METHODSA mouse model of VMC was established in 100 male Balb/c mice by intraperitoneal injection of coxsackievirus B3. The expression of IL-17 protein in the cardiac tissue of the mice was detected immunohistochemically, and IL-17 mRNA in the splenocytes was examined by reverse transcription-polymerase chain reaction (RT-PCR). IL-17 levels in the plasma, peripheral blood mononuclear cell (PBMC) culture supernatants, and phytohemagglutinin (PHA)-stimulated PBMC culture supernatants were measured in 30 DCM patients, 26 non-DCM patients and 20 normal adults using enzyme-linked immunosorbent assay (ELISA), and IL-17 mRNA expression in the PBMCs was detected using RT-PCR.

RESULTSThe levels of IL-17 mRNA in the splenocytes of the mice with VMC were significantly higher at 4 and 6 weeks than those at 8 weeks (P<0.01), but not detected at 2 weeks. No IL-17 expression was found in the ventricular tissue of the mice at 2 weeks, but peaked at 4 weeks followed by gradual decrease (P<0.01). IL-17 level in PHA-stimulated PBMC culture supernatants but not the plasma, and its mRNA level in PHA-stimulated PBMCs but not the PBMC culture supernatants, were significantly elevated in DCM patients as compared with those in non-DCM patients and normal control subjects.

CONCLUSIONSThe mouse model of VMC in the chronic phase and DCM patients express high levels of IL-17, which may contribute to the transition from VMC to DCM.

Adult ; Animals ; Cardiomyopathy, Dilated ; etiology ; metabolism ; pathology ; Coxsackievirus Infections ; complications ; metabolism ; Enterovirus B, Human ; Female ; Humans ; Interleukin-17 ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Myocarditis ; complications ; metabolism ; virology ; RNA, Messenger ; genetics ; metabolism

OBJECTIVE: In order to improve accuracy and reliability of forensic diagnosis of sudden cardiac death, pathogenesis and relationship between the viral myocarditis (VMC) and dilated cardiomyopathy (DCM) were investigated. METHODS: Improved immunohistochemical technique was used to detect the expression of the CAR in myocardium samples, including 22 deceased with VMC, 20 deceased with DCM and 16 control deceased. RESULTS: The brown staining on the cell membrane of myocardium showed positive result. There was a prominent CAR expression in VMC group and DCM group, which were statistically significant difference compared with control group (P < 0.05). CONCLUSION The CAR expression showed significantly higher in VMC and DCM groups. The viral infection can result in myocardial necrosis and impaired cardiac functions. These abnormalities can trigger a cascade of events that contributed to the progress of VMC to DCM.
Cardiomyopathy, Dilated/pathology* ; Case-Control Studies ; Coxsackie and Adenovirus Receptor-Like Membrane Protein ; Coxsackievirus Infections/complications* ; Death, Sudden, Cardiac ; Female ; Forensic Pathology ; Humans ; Immunohistochemistry ; Male ; Myocarditis/virology* ; Myocardium/pathology* ; Receptors, Virus/metabolism* ; Staining and Labeling

OBJECTIVETo investigate the myocardial protective effect of L-carnitine in children with hand, foot and mouth disease (HFMD) caused by Coxsackie A16 virus and possible mechanisms.

METHODSA total of 60 HFMD children with abnormal myocardial enzyme after Coxsackie A16 virus infection were enrolled and randomly divided into L-carnitine group and fructose-1,6-diphosphate group (fructose group), with 30 children in each group. The two groups were given L-carnitine or fructose diphosphate in addition to antiviral and heat clearance treatment. Another 30 healthy children who underwent physical examination were enrolled as control group. The changes in myocardial zymogram, malondialdehyde (MDA), superoxide dismutase (SOD), and apoptosis factors sFas and sFasL after treatment were compared between groups.

RESULTSThere was no significant difference in treatment response between the L-carnitine group and the fructose group (P>0.05). One child in the fructose group progressed to critical HFMD, which was not observed in the L-carnitine group. Before treatment, the L-carnitine group and the fructose group had significantly higher indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significantly lower level of SOD than the control group (P<0.05), while there were no significant differences in these indices between the L-carnitine group and the fructose group (P>0.05). After treatment, the L-carnitine group and the fructose group had significant reductions in the indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significant increase in the level of SOD (P<0.05); the fructose group had a significantly higher level of creatine kinase (CK) than the control group and the L-carnitine group, and there were no significant differences in other myocardial enzyme indices, MDA, sFas, and sFasL between the L-carnitine group and the fructose group, as well as between the L-carnitine and fructose groups and the control group (P>0.05). SOD level was negatively correlated with aspartate aminotransferase, lactate dehydrogenase (LDH), CK, and creatine kinase-MB (CK-MB) (r=-0.437, -0.364, -0.397, and -0.519 respectively; P<0.05), and MDA level was positively correlated with LDH and CK-MB (r=0.382 and 0.411 respectively; P<0.05).

CONCLUSIONSL-carnitine exerts a good myocardial protective effect in children with HFMD caused by Coxsackie A16 virus, possibly by clearing oxygen radicals and inhibiting cardiomyocyte apoptosis.

Carnitine ; therapeutic use ; Child, Preschool ; Coxsackievirus Infections ; complications ; Female ; Hand, Foot and Mouth Disease ; drug therapy ; etiology ; metabolism ; Heart ; drug effects ; Humans ; Infant ; Male ; Malondialdehyde ; analysis ; Myocardium ; metabolism ; pathology ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the effect of astragaloside (Astr), one of the active components of the Chinese medical herb Astragulus membranaceus, on cardiac fibrosis in chronic myocarditis and its relevant mechanisms.

METHODSEighty mice were randomized into 3 groups, the control group (n=20), the model group (n=30) and the Astr group (n=30). Mice in the model group and the Astr group were monthly intraperitoneally inoculated with CVB3, but to the control group equal amount of culture fluid was given instead. Mice in the control and the model group were fed with drinking water while those in the Astr group with drinking water containing Astr-sodium carboxymethycellulose at a concentration of 300 mg/L. All the survived mice were sacrificed 3 months later. Heart tissue of mice was stained by picrosirius red for calculating collagen volume fraction (CVF) with an automatic image analysis system. Expressions of transforming growth factor beta1 (TGF-beta1), platelet derived growth factor (PDGF), matrix metalloproteinase 1 (MMP-1), tissue inhibitor of metalloproteinase 1 (TIMP-1), MMP-13 and MMP-14 in heart tissue were detected by Western blot analysis.

RESULTSAs compared with the model group, in the Astr group, the mortality and CVF were significantly lower (53.3% vs. 23.3%, chi2 = 4.23, P < 0.05), and (17.4 +/- 1.2% vs. 8.6 +/- 0.9%, chi2 = 5.38, P < 0.05), respectively. As compared with the control group, Western blot analysis showed that expression of TGF-beta1 was decreased, MMP-1 and TIMP-1 were down-regulated, while expressions of MMP-13 and MMP-14 were up-regulated after Astr treatment.

CONCLUSIONAstr could lower the mortality and alleviate the myocardial fibrosis of mice with chronic myocarditis. Its antifibrotic effect might be realized by way of inhibiting TGF-beta1 expression and up-regulating the expressions of MMP-13 and MMP-14 in the heart tissues.

Animals ; Blotting, Western ; Chronic Disease ; Coxsackievirus Infections ; complications ; Drugs, Chinese Herbal ; therapeutic use ; Endomyocardial Fibrosis ; etiology ; metabolism ; prevention & control ; Male ; Matrix Metalloproteinase 13 ; metabolism ; Matrix Metalloproteinase 14 ; metabolism ; Mice ; Mice, Inbred BALB C ; Myocarditis ; complications ; drug therapy ; virology ; Random Allocation ; Saponins ; therapeutic use ; Transforming Growth Factor beta ; metabolism ; Triterpenes ; therapeutic use

PURPOSE: This study investigated the possible relationship between viral infection and first trimester pregnancy loss. MATERIALS AND METHODS: A prospective study was performed on 51 gravidas with missed abortion, fetal anomaly, pre-term delivery, and full-tem delivery at Hanyang University Hospital. Enteroviruses were detected by semi-nested reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in abortive tissues and placentas. Enterovirus serotypes were confirmed by genome sequencing. Herpesviruses were detected by PCR. RESULTS: Coxsackievirus B3 (CVB3) was detected in 8 of 14 missed abortion cases, 1 of 27 full-term cases, and none of the 9 pre-term cases. Coxsackievirus B1 (CVB1) was detected in an encephalocele case. Herpes simplex virus type 1 was found in 4 full-term cases, 3 pre-term cases, and none of the missed abortion cases. CONCLUSION: The prevalence of CVB3 was significantly higher in missed abortion cases compared to full-term or pre-term delivery cases. CVB infection may therefore be an important etiological agent of missed abortion.
Abortion, Missed/*etiology ; Adult ; Coxsackievirus Infections/complications/*diagnosis/virology ; Enterovirus B, Human/genetics/*isolation & purification ; Female ; Humans ; Immunohistochemistry ; Placenta/virology ; Pregnancy ; Pregnancy Complications, Infectious/*virology ; Pregnancy Trimester, First ; Prevalence ; Prospective Studies ; Republic of Korea ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Uterus/*virology