Viral detection in heart tissues has become a central issue for the diagnosis and exploration of the pathogenesis of idiopathic dilated cardiomyopathy (IDCM). In the present study, common cardiotropic viruses in 67 explanted heart samples of 31 IDCM adult patients were detected and semiquantified by using for the first time a new technology based on PCR assay coupled to electrospray ionization-time of flight mass spectrometry analysis (PCR-MS), with comparison to reference quantitative real-time PCR (RT-qPCR) assay. PCR-MS identified single or mixed enterovirus (EV) and parvovirus B19 (PVB19) infections in 27 (40.2%) of 67 samples, corresponding to 15 (48.3%) of the 31 patients, whereas RT-qPCR identified viral infections in 26 (38.8%) samples, corresponding to 16 (51.6%) of the patients. The PCR-MS results correlated well with EV and PVB19 detection by RT-qPCR (kappa = 0.85 [95% confidence interval {CI}, 0.72 to 1.00] and kappa = 0.82 [95% CI, 0.66 to 0.99], respectively). The levels of EV RNA (median, 550 [range, 178 to 3,200] copies/μg of total extracted nucleic acids) and of PVB19 DNA (median, 486 [range, 80 to 1,157] copies/μg of total extracted nucleic acids) were measured using PCR-MS and correlated with those obtained by RT-qPCR (r2 = 0.57, P = 0.002 and r2 = 0.64, P < 0.001 for EV and PVB19, respectively). No viruses other than EV and PVB19 strains were detected using the new PCR-MS technology, which is capable of simultaneously identifying 84 known human viruses in one assay. In conclusion, we identified single or mixed EV and PVB19 cardiac infections as potential causes of IDCM. The PCR-MS analysis appeared to be a valuable tool to rapidly detect and semiquantify common viruses in cardiac tissues and may be of major interest to better understand the role of viruses in unexplained cardiomyopathies. 相似文献
BACKGROUND & AIMS: Impaired mucosal barrier, cytokine imbalance, and dysregulated CD4(+) T cells play important roles in the pathogenesis of experimental colitis and human inflammatory bowel disease. Immunostimulatory DNA sequences (ISS-DNA) and their synthetic oligonucleotide analogs (ISS-ODNs) are derived from bacterial DNA, are potent activators of innate immunity at systemic and mucosal sites, and can rescue cells from death inflicted by different agents. We hypothesized that these combined effects of ISS-DNA could inhibit the damage to the colonic mucosa in chemically induced colitis and thereby limit subsequent intestinal inflammation. METHODS: The protective and the anti-inflammatory effect of ISS-ODN administration were assessed in dextran sodium sulfate-induced colitis and in 2 models of hapten-induced colitis in Balb/c mice. Similarly, these effects of ISS-ODN were assessed in spontaneous colitis occurring in IL-10 knockout mice. RESULTS: In all models of experimental and spontaneous colitis examined, ISS-ODN administration ameliorated clinical, biochemical, and histologic scores of colonic inflammation. ISS-ODN administration inhibited the induction of colonic proinflammatory cytokines and chemokines and suppressed the induction of colonic matrix metalloproteinases in both dextran sodium sulfate- and hapten-induced colitis. CONCLUSIONS: As the colon is continuously exposed to bacterial DNA, these findings suggest a physiologic, anti-inflammatory role for immunostimulatory DNA in the GI tract. Immunostimulatory DNA deserves further evaluation for the treatment of human inflammatory bowel disease. 相似文献
Essential thrombocythemia (ET) and polycythemia vera (PV) are myeloproliferative neoplasms (MPN) with an increased risk of arterial and venous thrombosis. Aspirin is recommended to reduce this risk, but resistance to antiplatelet therapy seems to hamper its efficacy in some patients. We have previously shown that multiple electrode aggregometry (MEA) was a valuable tool to assess aspirin resistance in MPN. In this study, MEA was used to assess the reduction in aspirin resistance after bi-daily (BID) aspirin intake or cytoreduction.
Fifty one MPN patients (31 ET and 20 PV) receiving 75 mg aspirin once daily (OD) or BID, with or without cytoreductive treatment, were analyzed. Aspirin resistance was assessed using whole blood MEA (Multiplate®, Roche Diagnostics, Meylan, France).
In all patients, global aspirin resistance consisted mainly of turnover resistance (TOR). 94% of patients with OD aspirin intake and without cytoreduction displayed biological aspirin resistance. By switching to a BID aspirin regimen, the proportion of resistant patients reduced to 47%. Cytoreduction also contributed to reduce aspirin resistance in a similar way (50% of aspirin resistant patients). Combining cytoreduction and BID aspirin regimen was the most efficient way to reduce aspirin resistance yielding to 12% resistant patients. Moreover, a nonlinear correlation was observed between TOR and naive platelet counts regardless of aspirin regimen. Last, mutational status did not seem to affect TOR.
This study confirmed that BID aspirin is biologically more effective than OD aspirin in reduction of aspirin resistance. The latter was achieved through a reduction in TOR which was also decreased by cytoreductive therapy. 相似文献
The objective of this prospective study was to examine the association between serum levels of TNF (tumor-necrosis factor) and IL-6 (interleukin-6) and left ventricular mass in hypertensive patients. Hypertensive patients currently receiving medical therapy were eligible. All subjects underwent echocardiography with measurements of left ventricular (LV) mass and ejection fraction (EF) and had serum levels of TNF and IL-6 measured by ELISA immunoassay. 35 subjects (20F, 15M; mean age 56.4 +/- 10.5 yrs) were studied. 19 patients (54%) had elevated LV mass. Of these patients, 6 (32%) had detectable serum TNF levels and 1 (7%) had detectable IL-6 levels, (p = NS). Hypertensive patients with elevated LV mass do not consistently exhibit elevated cytokine levels when compared to those with normal LV mass. 相似文献