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Aims: S100A8/A9 is expressed in activated monocytes/macrophages and assumed to be heavily involved in the pathogenesis of acute inflammation. Although several studies have asserted that S100A8/A9 has a proinflammatory function, the exact biological function of S100A8/A9 is yet to be described. We examined the anti-inflammatory effects of S100A8/A9 on experimental autoimmune myocarditis (EAM) in rats.Methods and Results: Experimental autoimmune myocarditis was induced in Lewis rats by immunization with porcine cardiac myosin. The recombinant (R-) S100A8/A9 was injected intraperitoneally into EAM rats. R-S100A8/A9 attenuated the severity of myocarditis, as evidenced by echocardiographic and histological findings. In addition, we found that not only the mRNA expression of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumour necrosis factor (TNF)-alpha] in the myocardium, but also their serum concentrations were suppressed in EAM rats treated with R-S100A8/A9. Nuclear factor-kappa B expression in inflammatory cells was also suppressed in the treated rats. To elucidate the mechanistic function of S100A8/A9 on proinflammatory cytokines in vivo, we used an ELISA on the supernatant of homogenized heart tissue treated with R-S100A8/A9. The findings revealed high-affinity binding of R-S100A8/A9 with IL-1beta, IL-6, and TNF-alpha in the myocardium, suggesting the trapping of proinflammatory cytokines by R-S100A8/A9.Conclusion: S100A8/A9 attenuates EAM through modulation of the proinflammatory cytokine network. [ABSTRACT FROM AUTHOR]

To better define the reported increased digitalis-like immunoreactive substances (DLIS) in neonatal plasma, we studied the relation among plasma DLIS level, blank intensity (BLK-I) value at FPIA measurement and plasma total bilirubin level.The DLIS levels were measured in 10 neonates with or without jaundice and 10 infants in good health, using fluorescence polarization immunoassay (FPIA) and microparticle enzyme immunoassay (MEIA). BLK-I value and plasma total bilirubin level were also measured simultaneously.In neonates with jaundice, DLIS using FPIA, BLK-I and total bilirubin level were 0·58 ±0·13 ng/mL, 2598 ± 408, and 17·98 ± 1·13 mg/dL, respectively, before phototherapy, and 0·33 ±0·06 ng/mL, 1886 ± 237, and 15·16 ± 2·07 mg/dL after phototherapy. Corresponding values in neonates without jaundice were (DLIS: 0·34 ±0·04 ng/mL; BLK-I: 1,764 ± 278; total bilirubin: 10·37 ± 4·54 mg/dL); in healthy infants (0·12 ±0·06 ng/mL, 400·7 ± 4·6 and 0·42 ± 0·13 mg/dL, respectively) and in healthy volunteers (0·10 ±0·07 ng/mL, 403·1 ± 8·4, and 0·58 ± 0·30 mg/dL, respectively). Using MEIA, DLIS was not detected in 10 neonates, 10 infants and 20 healthy volunteers.A fluorescent compound related to bilirubin increased the BLK-I value in the measurement of neonatal plasma using FPIA. The fluorescence was not the result of endogenous digitalis-like factors. [ABSTRACT FROM AUTHOR]

Idiopathic dilated cardiomyopathy (IDC) is a myocardial disease characterised by ventricular dilatation, impaired contractility, and the symptoms of congestive heart failure. Although the causes of IDC remain uncertain, much interest has been focused on the enteroviral infection in the myocardium in the pathogenesis of this disease. Enteroviral RNA has been demonstrated in the myocardium at all stages of IDC. Recent studies using sequence analysis of enteroviral polymerase chain reaction (PCR) products have shown that the viruses detected in hearts of patients with IDC are coxsackie B. In addition, active coxsackieviral RNA replication in the myocardium has been demonstrated by strand-specific detection of viral RNA. Viral antigen has also been found in hearts with IDC by immunohistochemical techniques. In tissue culture experiments and transgenic mice, it has been shown that restricted coxsackieviral RNA replication, and not infectious virus progeny, in the myocardium can impair cardiac contractile function and lead to dilated cardiomyopathy. Coxsackieviral RNA in the myocardium can be a marker of a poor clinical outcome after partial left ventriculectomy, and might influence prognosis after heart transplantation. Therefore, there is a therapeutic need to detect replicating coxsackieviral RNA in the myocardium, and a specific therapy for coxsackie B viruses is indicated in the management of patients with virus-positive IDC. [ABSTRACT FROM AUTHOR]

Aims Although increased digitalis-like immunoreactive substances have been found in cases of hypertension and heart failure, no information is available about digitalis-like immunoreactive substances in patients with hypertrophic cardiomyopathy. We investigated digitalis-like immunoreactive substances in the plasma and biopsied specimens of patients with hypertrophic cardiomyopathy.Methods and Results In 40 patients with hypertrophic cardiomyopathy (27 with the non-obstructive type and 13 with the obstructive type), the plasma concentration of digitalis-like immunoreactive substances was studied by fluorescence polarization immunoassay. Right ventricular endomyocardial biopsy specimens were analysed immunohistochemically, using a monoclonal antibody against digoxin. An increase in digitalis-like immunoreactive substances of more than 0·2ng.ml−1in plasma was found in six of 27 patients with non-obstructive hypertrophic cardiomyopathy (22·2%) and five of 13 with obstructive hypertrophic cardiomyopathy (38·4%). Under light microscopy, positive staining against the antibody was observed heterogeneously on some cardiocytes. In non-obstructive hypertrophic cardiomyopathy, digitalis-like immunoreactive substances in the plasma correlated with the left atrial dimension and inversely with the cardiac index. In obstructive hypertrophic cardiomyopathy, plasma and myocardial digitalis-like immunoreactive substances were positively correlated; they also correlated with left ventricular end-diastolic pressures. Under electron microscopy, digitalis-like immunoreactive substances were detected at the sarcolemma in the free wall, T-tubules, intercalated discs and Z-bands of cardiocytes.Conclusions Increased digitalis-like immunoreactive substances in plasma and cardiocytes, which may have been caused by pressure and/or volume overload, were found in patients with hypertrophic cardiomyopathy. Digitalis-like immunoreactive substances may act on the sarcolemma of cardiocytes and be transported into the cytoplasm. [ABSTRACT FROM PUBLISHER]

Light- and electron-microscopic studies and immunohistochemical procedures were carried out on blood eosinophils and left ventricular endomyocardial biopsies from a 68-year-old man with an eosinophilia of 8.2 × 10/l and congestive cardiac failure due to eosinophilic endomyocardial disease. Some blood eosinophils were vacuolated and degranulated, and reversal of the normal staining pattern of eosinophil granules was seen by means of electron microscopy. The biopsies showed degenerative changes in the cardiac myocytes, with interstitial fibrosis and infiltration by numerous eosinophils, mast cells, and macrophages. Eosinophils infiltrating the myocardium showed a decrease in the number of granules, many of which were indistinct or contained dissolving crystalloids, which occasionally were seen to be discharged onto the surface of adjacent cardiac myocytes. Immunohistochemical studies of the endomyocardial biopsies with a monoclonal antibody, which is specific for activated eosinophils and binds to the secreted forms of eosinophil cationic protein (ECP) and eosinophil protein-X (EP-X), demonstrated that the lesions contained numerous activated eosinophils and secreted ECP and EP-X. These findings support the concept that in eosinophilic endomyocardial disease, activated eosinophils infiltrate and degranulate in the myocardium, releasing eosinophil cationic proteins which then damage adjacent myocardial cells. [ABSTRACT FROM AUTHOR]

DBA/2 inbred mice spontaneously develop myocarditis and a unique form of subepicardial inflammation of the right ventricle characterized by a prominent eosinophilic infiltrate with calcinosis. We studied this myocarditis using light microscopy and both transmission and analytical X-ray electron microscopy, paying particular attention to eosinophil-associated cardiocyte injury. At 5 weeks of age, many eosinophils and mononuclear cells (MNCs) were seen in the subepicardium of the right ventricle. Electron microscopy showed that cardiocytes underwent degenerative changes, including myofibrillar lysis, accumulation of Z-band material and mitochondrial inclusions, and rupture of plasma membranes. The infiltrating eosinophils appeared to be activated, and cells with cytoplasmic vacuoles, suggestive of degranulation, were noted. The myocardial injury was most severe in the 7th week and healed with myocardial fibrosis and calcinosis by the 8th week. Analytical X-ray electron microscopy showed that the calcinosis was initiated in mitochondrial inclusions of injured cardiocytes. The peripheral eosinophil count did not increase during the course of the disease, but there was a positive correlation between the ratio of eosinophils to infiltrated white blood cells (Eo/WBCs) in the right ventricle and the severity of myocardial damage. Eosinophils may play a significant part in subepicardial cardiocyte injury seen in DBA/2 mice. [ABSTRACT FROM AUTHOR]

The bacterial cell-wall peptidoglycan peptides and related compounds coupled with some fatty acids were synthesized, and their immunostimulating property was examined by carbon clearance assay. All the new compounds ( 2-6) proved to possess significant potencies superior to that of FK-156 ( 1). [ABSTRACT FROM AUTHOR]

An abstract of the article "Intranasala Administration of atrial natriutetic peptide attenuates left ventricular remodeling and dysfunction associated with acute myocardial infarction in rats," by T. Kono and colleagues is presented.

An abstract of the article "Low-dose rather than high-dose erythropoietin may be effective in a rat model of dilated cardiomyopathy that is not anaemic," by T. Kono and colleagues is presented