Major 5'terminally deleted enterovirus populations modulate type I IFN response in acute myocarditis patients and in human cultured cardiomyocytes.

Major 5'terminally deleted (5'TD) group-B enterovirus (EV-B) populations were identified in heart biopsies of patients with fulminant myocarditis or dilated cardiomyopathy suggesting that these 5'TD forms are key drivers of host-cell interaction in EV cardiac infections. To date, early emergence of EV-B 5'TD forms and its impact on type 1 IFN response during acute myocarditis remains unknown. Using quantitative RACE-PCR assay, we identified major EV-B 5'TD RNA populations in plasma or heart samples of acute myocarditis cases. Deletions identified within the 5' non-coding region of EV-B populations only affected secondary-structural elements of genomic RNA domain I and were distinguished in two major groups based on the extent of RNA structural deletions. Proportions of these two respective EV-B 5'TD population groups were positively or negatively correlated with IFN-ß levels in plasma samples of myocarditis patients. Transfection of synthetic CVB3/28 RNAs harboring various 5'terminal full-length or deleted sequences into human cultured cardiomyocytes demonstrated that viral genomic RNA domain I possessed essential immunomodulatory secondary-structural elements responsible for IFN-ß pathway induction. Overall, our results highlight the early emergence of major EVB-TD populations which deletions affecting secondary-structures of RNA domain I can modulate innate immune sensing mechanisms in cardiomyocytes of patients with acute myocarditis.

Influence of cell age and ketoaminic linkage on rapid glycosylation of hemoglobin in human red cells in vitro.

In vitro the rate of synthesis of the aldiminic linkage between Hb and glucose depends on glucose concentration, length of incubation and some other physiological factors. To understand better the regulation of this synthesis and to verify the role of cell age and of basal HbA1 levels on the rate of synthesis of pre-A1, we studied red cells from 7 normal controls and 7 diabetics, with high HbA1 levels. We found that the content of HbA1 (stable glycosylated hemoglobin) is able to negatively affect the rate of synthesis of new pre-A1, according to a curvilinear model. These results suggest that in vitro the glycosylation process is saturable, and that elevated values of HbA1 are able to slow the synthesis of pre-A1 in vitro.

[Special aspects of the curve of the oral glucose tolerance test]. / Aspetti particolari della curva da carico di glucosio per os.

The insulin response of 10 lean and 23 obese subjects with lag-type and borderline O.G.T.T. has been studied. The O.G.T.T. was interpreted according to the criteria of Fajans and Conn. The maximum increase and the area of increase were examined both for blood glucose and plasma I.R.I., and the corresponding I.R.I./glucose ratios calculated. The shape of the insulin response curve is similar to that of glucose curve. The I.R.I./glucose ratios are decreased in the lag-type curves as compared to borderline in the lean subjects while we observed opposite results in obese ones. A possible physiopathological interpretation of this curves is proposed.