High plasma N-terminal pro-brain natriuretic peptide level found in diabetic patients after myocardial infarction is associated with an increased risk of in-hospital mortality and cardiogenic shock.

AIMS: No studies have yet been conducted concerning plasma N-terminal pro-brain natriuretic peptide (Nt-pro-BNP) levels after Myocardial Infarction (MI) and their relationship with short-term outcomes in diabetic patients. METHODS AND RESULTS: Five hundred and sixty patients hospitalized for MI from the RICO survey, including 199 diabetic and 361 non-diabetic subjects, were included in the study. Plasma Nt-pro-BNP levels were measured on admission. Median Nt-pro-BNP levels were significantly higher in diabetic patients compared with non-diabetic patients [245 (81-77) vs. 130 (49-199) pmol/L, P<0.0001]. This difference remained highly significant after adjustment for age, female gender, creatinine clearance, left ventricular ejection fraction (LVEF), plasma peak troponin, anterior wall necrosis, and hypertension. In multivariable analysis, Nt-pro-BNP levels were negatively associated with creatinine clearance (P<0.0001) and LVEF (P<0.0001) and positively associated with plasma peak troponin (P<0.0001), age (P=0.0029), diabetes (P=0.0031), and female gender (P=0.0102). Diabetic patients showed a 4.7-fold increase in hospital mortality (15.6 vs. 3.3%, P<0.0001) and a 2.2-fold increase in cardiogenic shock (17.6 vs. 7.7%, P=0.0004). In multivariable analysis, diabetes was an independent factor for mortality [OR: 1.79 (1.45-2.20); P=0.0064] and cardiogenic shock [OR: 1.45 (1.22-1.72); P=0.0364] when the variable Nt-pro-BNP level was not introduced into the model, but was less significantly associated with mortality [OR: 1.73 (1.39-2.16); P=0.0107] and no longer associated with cardiogenic shock when Nt-pro-BNP was in the model. CONCLUSION: After MI, diabetes is independently associated with high plasma Nt-pro-BNP levels. This elevated Nt-pro-BNP is strongly associated with the increased incidence of in-hospital mortality and cardiogenic shock observed in diabetes. Our findings clearly indicate that plasma Nt-pro-BNP provides highly valuable prognostic information on in-hospital outcome after MI, in particular in diabetic patients.

The extent of myocardial damage assessed by contrast-enhanced MRI is a major determinant of N-BNP concentration after myocardial infarction.

AIMS: To evaluate the relationship between N-terminal Pro-Brain Natriuretic Peptide (N-BNP) level and contrast-enhanced MRI in patients after acute myocardial infarction (MI). METHODS: Eighty-two patients were studied. Venous blood samples were obtained 3 days after MI and MRI was performed from 2 to 7 days after MI, with determination of left ventricular function and acquisition of perfusion data after injection of gadolinium-DTPA. First-pass images (FPI) and Delayed contrast-enhanced (CE) images were analyzed using a 17-segment model, and the extent of transmurality was determined by a visual score. RESULTS: Univariate analysis showed that age (P<0.001), sex (P<0.02), Left Ventricular Ejection Fraction (LVEF) <45% (P<0.002), creatinine (P<0.05) and delayed CE-MR images (P<0.006) were predictors of a supramedian N-BNP level. FPI was not a predictor in this univariate analysis (P<0.078). In a multivariate model, only age, LVEF <45% and delayed CE-MRI were associated with an increased N-BNP level. CONCLUSION: After MI, high N-BNP levels are dependent on the LVEF but also on the myocardial infarct size derived from the delayed CE-MR images.

Determination of queuosine derivatives by reverse-phase liquid chromatography for the hypomodification study of Q-bearing tRNAs from various mammal liver cells.

Three queuosine derivatives (Q-derivatives) have been found at position 34 of four mammalian so-called Q-tRNAs: queuosine (Q) in tRNA(Asn) and tRNA(His), mannosyl-queuosine (manQ) in tRNA(Asp), and galactosyl-queuosine (galQ) in tRNA(Tyr). An analytical procedure based on the combined means of purified tRNA isolation from liver cells and ribonucleoside analysis by reverse-phase high performance liquid chromatography coupled with real-time UV-spectrometry (RPLC-UV) was developed for the quantitative analysis of the three Q-derivatives present in total tRNA from liver tissues and liver cell cultures. Using this analytical procedure, the rates of Q-tRNA modification were studied in total tRNAs from various mammalian hepatic cells. Our results show that the four Q-tRNAs are fully modified in liver tissues from adult mammals, regardless of the mammal species. However, a lack in the Q-modification level was observed in Q-tRNAs from newborn rat liver, as well in Q-tRNAs from normal rat liver cell cultures growing in a low queuine content medium, and from a rat hepatoma cell line. It is noteworthy that in all cases of Q-tRNA hypomodification, our analytical procedure showed that tRNA(Asp) is always the least affected by the hypomodification. The biological significance of this phenomenon is discussed.

Medically assisted reproduction and second-trimester maternal serum marker screening for Down syndrome.

OBJECTIVES: To evaluate the effect of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) on total hCG, free ss-hCG, AFP and unconjugated estriol (uE3) used as markers for second-trimester Down syndrome maternal serum screening. METHODS: Second-trimester maternal sera from 1515 singleton pregnancies (970 by IVF, 545 by ICSI) were compared with control sera (21 014 cases). Free ss-hCG, total hCG, AFP and uE3 were compared between the control group and the medically assisted reproduction groups. The percentages of at-risk patients (>/=1/250) were also compared. RESULTS: No differences in values of the maternal serum markers were observed between the medically assisted and control groups. When maternal age was taken into account, the screen-positive rate for Down syndrome screening did not differ between the two groups. CONCLUSION: Patients undergoing assisted reproduction techniques can be counseled for maternal serum Down syndrome screening with the same efficacy as patients with naturally conceived pregnancies.

Recognition by tryptophanyl-tRNA synthetases of discriminator base on tRNATrp from three biological domains.

To study the recognition by tryptophanyl-tRNA synthetase (TrpRS) of tRNA(Trp) discriminator base, mutations were introduced into the discriminator base of Bacillus subtilis, Archeoglobus fulgidus, and bovine tRNA(Trp), representing the three biological domains. When B. subtilis, A. fulgidus, and human TrpRS were used to acylate these tRNA(Trp), two distinct preference profiles regarding the discriminator base of different tRNA(Trp) substrates were found: G>A>U>C for B. subtilis TrpRS, and A>C>U>G for A. fulgidus and human TrpRS. The preference for G73 in tRNA(Trp) by bacterial TrpRS is much stronger than the modest preferences for A73 by the archaeal and eukaryotic TrpRS. Cross-species reactivities between TrpRS and tRNA(Trp) from the three domains were in accordance with the view that the evolutionary position of archaea is intermediate between those of eukarya and bacteria. NMR spectroscopy revealed that mutation of A73 to G73 in bovine tRNA(Trp) elicited a conformational alteration in the G1-C72 base pair. Mutation of G1-C72 to A1-U72 or disruption of the G1-C72 base pair also caused reduction of Trp-tRNA(Trp) formation. These observations identify a tRNA(Trp) structural region near the end of acceptor stem comprising A73 and G1-C72 as a crucial domain required for effective recognition by human TrpRS.