Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent reports demonstrated the expression of inducible-type NO synthase in the heart of viral myocarditis. Since NO has multiple biological actions, a substantial amount of NO produced in the diseased heart may act either as a cytotoxic or as a cytoprotective molecule in the process of myocarditis. In the present study, we examined the effect of inhibition of NO synthesis on the mortality and the extent of myocardial injury in a murine model of coxsackievirus B3-induced myocarditis. We fed the infected mice drinking water containing a relatively low concentration (0.37 mmol/L) of N omega-nitro-L-arginine methyl ester (L-NAME) for 14 days after virus inoculation. This dose of L-NAME did not change virus titers in the heart. However, L-NAME-fed mice showed a significant reduction in mortality compared with those fed normal drinking water (nontreated mice). On the contrary, mice given a higher concentration of L-NAME (3.7 mmol/L) exhibited increased mortality. In addition, mice fed a low concentration of L-NAME showed reductions in the severity of heart failure and in the area of myocardial necrosis. Although systemic blood pressure was reduced in nontreated mice, in mice fed a low concentration of L-NAME, it was maintained at a level similar to that in uninfected control mice, L-NAME-treated mice also exhibited a reduction in the degree of inflammatory cell infiltration associated with decreased production of tissue prostaglandin E2 levels in the heart compared with nontreated mice. Therefore, NO is likely to be involved in the pathogenic mechanisms of myocardial injury and resultant cardiac dysfunction in a murine model of coxsackievirus B3-induced viral myocarditis.
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PMID:Low-dose N omega-nitro-L-arginine methyl ester treatment improves survival rate and decreases myocardial injury in a murine model of viral myocarditis induced by coxsackievirus B3. 931 31

It was previously demonstrated that administration of the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) aggravated viral myocarditis in mice. In the current study, the effects of l-arginine, a precursor of nitric oxide, on congestive heart failure (CHF) in myocarditis were evaluated. Dietary l-arginine and l-arginine plus l-NAME (l-arginine + l-NAME group) were administered to encephalomyocarditis virus-infected BALB/c mice over 4 weeks (experiment I) and to encephalomyocarditis virus-infected DBA/2 mice from the 4th through 12th weeks after the virus inoculation (experiment II). An infected control was prepared in each experiment. In experiment I, survival was higher in the l-arginine group compared with the other two groups, and cardiac damage was less, as was incidence of CHF. In addition, extravasated fibrin was less prominent in the l-arginine group. Plasma concentrations of l-arginine and nitric oxide were elevated in the l-arginine group. In experiment II, plasma cardiomyopathic lesions in the l-arginine group were less prominent and were associated with lower plasma catecholamine and lower myocardial collagen concentrations compared with the other two groups. l-arginine treatment may be effective in preventing the development of CHF in viral myocarditis by modifying postmyocarditic architectural remodeling.
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PMID:Oral administration of L-arginine prevents congestive heart failure in murine viral myocarditis. 1207 71

We have previously demonstrated that administration of nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), aggravated murine coxsackievirus B3 myocarditis. In the present study, we evaluated the effects of L-arginine, a precursor of NO, upon acute and chronic myocarditis. Dietary L-arginine and L-arginine plus L-NAME (L-arginine+L-NAME group) were administered to coxsackievirus B3 (CB3)-infected C(3)H/He mice for 2 weeks (experiment I), and to CB3-infected mice from the second week until the fourth week after virus inoculation (experiment II). Infected control was prepared in each experiment. In experiment I, survival was higher in the L-arginine group compared with the other two groups, and cardiac damage was less. In addition, plasma concentrations of L-arginine and NO were elevated in the L-arginine group. In experiment II, cardiomyopathic lesion in the L-arginine group was less prominent associated with lower plasma catecholamine and lower myocardial collagen concentrations compared with the other two groups. Thus, L-arginine treatment may be effective not only in preventing the development of acute CB3 myocarditis but in ameliorating cardiac dysfunction in chronic myocarditis.
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PMID:Oral L-arginine prevents murine coxsackievirus B3 myocarditis. 1241 66

The antiviral effect of nitric oxide (NO)-releasing compounds was investigated. Using bacterially expressed and purified proteinases 2A and 3C of coxsackievirus B3, in vitro assays demonstrated the inhibition of the 2A proteinase activity in the presence of S-nitroso- N-acetyl-penicillamine (SNAP), 3-morpholinosydnonimine (SIN-1), 4-phenyl-3-furoxancarbonitrile (PFC), glyceryl trinitrate (GTN), and isosorbide dinitrate (ISDN). Sodium nitroprusside (SNP), which releases NO after metabolization, had no effect. The 3C proteinase was inactivated by SNAP, GTN, and ISDN. The vasodilators GTN and ISDN, widely used in the treatment of angina pectoris, exhibited antiviral activity in CVB3-infected GMK cells. CVB3-infected NMRI outbred mice showed significantly reduced signs of myocarditis after treatment with GTN or ISDN. Inhibitors of the cellular inducible NO synthase (iNOS) such as N(G)-nitro-L-arginine methyl ester (L-NAME), N(G)-nitro-L-arginine (L-NNA), and S-methyl-isothiourea (SMT), had no deleterious effect on CVB3-infected NMRI mice, indicating that endogenous NO synthesis is unlikely to be a major defense mechanism after enterovirus infection of outbred mice.
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PMID:Nitric oxide donors inhibit the coxsackievirus B3 proteinases 2A and 3C in vitro, virus production in cells, and signs of myocarditis in virus-infected mice. 1451 74

The effect of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) on Trypanosoma cruzi multiplication and nitric oxide (NO) production in cardiac myocytes was investigated. Cardiac myocyte cultures were obtained from neonatal Wistar rat hearts, infected with T. cruzi, and treated with IL-1beta, TNF-alpha, IFN-gamma, or N-monomethyl-L-arginine (L-NAME) for 72 h. Parasite growth was calculated from the number of infected cells in Giemsa-stained smears. Nitric oxide production was determined with the Griess reagent. Inducible nitric oxide synthase (iNOS) expression by cardiac myocytes was detected by Western blot. The results showed that the percentages of cardiac myocytes containing T. cruzi amastigotes in cytokine-treated cultures were significantly lower than in nontreated cultures. The addition of L-NAME reversed the inhibitory effect on parasite growth of IL-1beta and TNF-alpha but not of IFN-gamma. Nitrite levels released by T. cruzi-infected and noninfected cardiac myocyte cultures after 72 h of stimulation with IL-1beta were significantly higher than those produced upon treatment with TNF-alpha, IFN-gamma, or medium alone, regardless of the infection status. Nitrite levels in TNF-alpha-stimulated infected cultures were significantly higher than in untreated infected cultures and TNF-alpha-treated noninfected cultures. L-NAME inhibited IL-1beta- but not TNF-alpha-induced NO production, indicating the presence of iNOS-dependent and iNOS-independent mechanisms for NO formation in this experimental system. iNOS expression was detected in infected and noninfected cardiac myocytes stimulated with IL-1 beta and TNF-alpha but not with IFN-gamma. These results suggest an important role for cardiac myocytes and locally secreted cytokines in the control of parasite multiplication in T. cruzi-induced myocarditis.
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PMID:Intracellular growth of Trypanosoma cruzi in cardiac myocytes is inhibited by cytokine-induced nitric oxide release. 1468 16

Myocarditis is a common inflammatory heart disease in children and young adults that may result in chronically dilated cardiomyopathy. Coxsackievirus B3 is the major etiologic agent of this disease. Current treatments for patients with viral myocarditis are almost entirely supportive. In recent years, some promising therapeutic candidates have emerged, including novel treatments and improvements of existing drugs. Among these are molecules that specially target virus entry, such as pleconaril, WIN 54954 and CAR-Fc; nucleic acid-based antiviral agents that inhibit viral translation and/or transcription, such as antisense oligodeoxynucleotide and short interfering RNA; and immunomodulatory agents that augment the host-protective immune responses to effectively clear viruses from target tissues, including interferons and immunoglobulins. In addition, certain new antiviral strategies, still in the early stages, include modulation of signal transduction pathways responsible for viral replication using enzyme inhibitors, which have revealed potential therapeutic targets for viral myocarditis. Finally, the progress in cellular cardiomyoplasty for end-stage therapy, in particular the preliminary clinical trials, is also discussed with respect to its potential future application.
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PMID:Coxsackievirus-induced myocarditis: new trends in treatment. 1610 2

It was previously shown that administration of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) aggravated murine viral myocarditis by increasing myocardial virus titres. Experimental autoimmune myocarditis in mice and rats mimics human fulminant myocarditis. The effects of L-arginine, a precursor of nitric oxide, upon heart failure in experimental autoimmune myocarditis were evaluated. Dietary L-arginine (L-arginine group) and L-arginine plus N(G)-nitro-L-arginine methyl ester (L-arginine + l-NAME group) were administered to C57BL/6 mice immunized with porcine cardiac myosin over 3 weeks. An untreated myocarditis group was prepared. Cardiac damage was less in the L-arginine group compared with the other two groups, as was incidence of heart failure. In addition, extracellular matrix change was less prominent in the L-arginine group. Plasma concentrations of nitric oxide were elevated in the L-arginine group. Cytotoxic activities of lymphocytes were lower in L-arginine group than in other two groups. L-arginine treatment may be effective in preventing the development of heart failure in experimental myocarditis by maintaining extracellular matrix and reducing the cytotoxic activity of lymphocytes.
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PMID:L-arginine ameliorates experimental autoimmune myocarditis by maintaining extracellular matrix and reducing cytotoxic activity of lymphocytes. 1880 30

We systematically investigated serial efficacy of granulocyte colony-stimulating factor (G-CSF) therapy upon experimental autoimmune myocarditis (EAM) in rats treated with and without the inhibition of nitric oxide (NO) with the analyses of tissue regeneration. G-CSF could mobilize multipotent progenitor cells of bone marrow into the peripheral blood and may improve ventricular function. A rat model of porcine myosin-induced EAM was used. After the immunization of myosin, G-CSF (10 microg/kg/day) or saline was injected intraperitoneally on days 0-21 in experiment 1 and on days 21-42 in experiment 2. Additional myosin-immunized rats were orally given 25 mg/kg/day of N(G)-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS), in each experiment (each group; n=8-21). Serum cytokines and peripheral blood cell counts were measured in each group. In experiment 1, G-CSF treatment aggravated cardiac pathology associated with increased macrophage inflammatory protein-2 (MIP-2) and interleukin-6 (IL-6) levels and enhanced superoxide production. In experiment 2, G-CSF treatment reduced the severity of myocarditis with increased capillary density and improved left ventricular ejection fraction. In the rats with EAM treated with G-CSF associated with oral L-NAME treatment in experiment 2, the severity of myocarditis was not reduced. Myocardial c-kit(+) cells were demonstrated only in G-CSF-treated group in experiment 2 but not in other groups. G-CSF has differential effects on EAM in rats associated with the modulation of cytokine network. The overwhelming superoxide production by G-CSF administration in the acute stage may worsen the disease. G-CSF therapy improved cardiac function via NO system in a rat model of myocarditis in the chronic stage, but not in the acute stage, possibly through the myocardial regeneration and acceleration of healing process.
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PMID:Therapy with granulocyte colony-stimulating factor in the chronic stage, but not in the acute stage, improves experimental autoimmune myocarditis in rats via nitric oxide. 2017 Jun 62

Coxsackievirus B3 (CVB3) is associated with several different acute and chronic forms of human disease, including myocarditis, aseptic meningitis, and pancreatitis. Moreover, CVB3 also infects immune cells like CD19+ B lymphocytes, but the viral uptake mechanism into these cells is not well understood. Therefore, primary murine and human CD19+ B cells were isolated by magnetic-activated cell separation technology and analyzed for virus receptor expression, antibody-dependent enhancement of viral infection, and different cellular surface proteins, that might be involved in mechanisms of viral uptake. Western blot analysis of these cells revealed no significant expression of the coxsackievirus-adenovirus receptor CAR. But incubation of CVB3 with serum dilutions, which exhibited binding but not neutralizing characteristics, increased viral uptake and replication significantly in a dose-dependent manner. Viral entry was reduced when Fc portions of immunoglobulins were blocked by protein A treatment. Moreover, the classical complement system rather than Fc-gamma-receptor-mediated mechanisms could be involved in viral uptake. Taken together, these data suggest an antibody-dependent enhancement of CVB3 infection of primary murine and human CD19+ B cells.
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PMID:Antibody-dependent enhancement of coxsackievirus B3 infection of primary CD19+ B lymphocytes. 2071 77

Coxsackievirus B1, a member of the Picornaviridae family is a non-enveloped single-stranded RNA virus associated with human diseases including myocarditis and pancreatitis. Infection of the intestinal mucosa, lined by polarized epithelial cells, requires interaction of coxsackievirus with apically located DAF (decay-accelerating factor) before transport to the basolaterally located CAR (coxsackie and adenovirus receptor), where entry is mediated by endocytosis. As with many other non-enveloped viruses, coxsackievirus has to induce lysis of host cells in order to perpetuate infection. However, recent evidence indicates that virus spread to secondary sites is not only achieved by a lytic mechanism and a non-lytic cell-cell strategy has been suggested for coxsackievirus B3. A physical interaction between infected and non-infected cells has been shown to be an efficient mechanism for retroviral transmission and one type of extracellular vesicle, the exosome, has been implicated in HIV-1 transmission. HIV-1 also takes advantage of depolymerization of actin for spread between T-cells. Calpain-mediated depolymerization of the actin cytoskeleton, as a result of increases in intracellular calcium concentration during coxsackievirus infection, would result in a release of host cell-derived microvesicles. If so, we speculate that maybe such microvesicles, increasingly recognized as major vehicles mediating intercellular communication, could play a role in the intercellular transmission of non-enveloped viruses.
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PMID:Coxsackievirus B transmission and possible new roles for extracellular vesicles. 2335 1


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