Biomedical subjects
Publications and source records attributed to Giovanni Russo.
A systematic low-temperature NMR study of a glycosylation reaction was performed in the presence of different ionic liquids and acidic catalysts. The influence of the triflate anion derived from [emim][OTf] on the stereochemistry of the glycosylation products was evaluated.
TGF-beta proteins are main regulators of blood vessel development and maintenance. Here, we report an unprecedented link between TGF-beta signaling and arterial hypertension based on the analysis of mice mutant for Emilin1, a cysteine-rich secreted glycoprotein expressed in the vascular tree. Emilin1 knockout animals display increased blood pressure, increased peripheral vascular resistance, and reduced vessel size. Mechanistically, we found that Emilin1 inhibits TGF-beta signaling by binding specifically to the proTGF-beta precursor and preventing its maturation by furin convertases in the extracellular space. In support of these findings, genetic inactivation of Emilin1 causes increased TGF-beta signaling in the vascular wall. Strikingly, high blood pressure observed in Emilin1 mutants is rescued to normal levels upon inactivation of a single TGF-beta1 allele. This study highlights the importance of modulation of TGF-beta availability in the pathogenesis of hypertension.
Arterial hypertension is not only a major risk factor for cerebrovascular accidents, such as stroke and cerebral hemorrhage, but is also associated to milder forms of brain injury. One of the main causes of neurodegeneration is the increase in reactive oxygen species (ROS) that is also a common trait of hypertensive conditions, thus suggesting that such a mechanism could play a role even in the onset of hypertension-evoked brain injury. To investigate this issue, we have explored the effect of acute-induced hypertensive conditions on cerebral oxidative stress. To this aim, we have developed a mouse model of transverse aortic coarctation (TAC) between the two carotid arteries, which imposes acutely on the right brain hemisphere a dramatic increase in blood pressure. Our results show that hypertension acutely induced by aortic coarctation induces a breaking of the blood-brain barrier (BBB) and reactive astrocytosis through hyperperfusion, and evokes trigger factors of neurodegeneration such as oxidative stress and inflammation, similar to that observed in cerebral hypoperfusion. Moreover, the derived brain injury is mainly localized in selected brain areas controlling cognitive functions, such as the cortex and hippocampus, and could be a consequence of a defect in the BBB permeability. It is noteworthy to emphasize that, even if these latter events are not enough to produce ischemic/hemorrhagic injury, they are able to alter mechanisms fundamental for maintaining normal brain function, such as protein synthesis, which has a prominent role for memory formation and cortical plasticity.
INTRODUCTION: Congestive heart failure (CHF) and atrial fibrillation (AF) are frequently linked, and when associated produce additive deleterious effects. In this prospective study, the effects of catheter ablation for AF in patients with impaired left ventricular (LV) function are presented. METHODS: Baseline data and clinical outcome have been prospectively collected in 105 consecutive patients who underwent pulmonary vein ablation for the control of AF. We evaluated 40 patients affected by LV dysfunction with ejection fraction (EF)<40% and compared them to the remaining 65 patients with normal ventricular function in terms of changes in LV function, maintenance of sinus rhythm, and quality of life during follow-up. RESULTS: After a mean follow-up of 14+/-2 months, 87% of patients with impaired LV function and 92% of patients with normal ventricular function were in sinus rhythm, with or without antiarrhythmic therapy (P=NS). A significant improvement in LVEF and fractional shortening was documented in patients with CHF (33+/-2% vs 47+/-3%, and 19+/-4% vs 30+/-3%, P<0.01 for both comparisons). Evaluation of exercise capacity and quality of life documented better improvements in patients with CHF compared to patients without CHF. CONCLUSIONS: Catheter ablation in patients with LV dysfunction is feasible, not associated with higher procedural complications, and provides a significant improvement in LV performance, symptoms, and quality of life during follow-up.
BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. The natural history of this disturbance and its effect on survival is still not known in patients with implantable cardioverter defibrillators (ICDs). METHODS AND RESULTS: Several controlled trials for both secondary and primary prevention of sudden death using ICDs have been published in literature, and meta-analysis of them provided useful clinical information on the outcome during the follow-up of this population. AF occurs in about 25% of the patients with secondary prevention indication for ICD implantation. The prevalence of AF in patients with primary prevention indication for ICD implantation is much more difficult to define; it seems to be higher in patients with left ventricular dysfunction due to nonischemic etiology (ranging from 15% to 25%), and is lower in patients with ischemic etiology (about 5-10%). However, data from clinical registries, which are expected to better reflect clinical practice than randomized trials, seem to show a substantial difference as compared to the latter ones. A history of AF episodes in patients with an ICD indication for both primary and secondary prevention is probably associated with a higher risk of death. This is particularly evident in secondary prevention in ICD recipients, while it is still controversial in patients who received an ICD for primary prevention, particularly when patients with nonischemic etiology of their left ventricular dysfunction are considered. In a population of patients implanted with an ICD, there are several other clinical factors (ejection fraction, New York Heart Association functional class, age) that can interfere with the risk of death much more than AF itself. CONCLUSIONS: Further large-scale registries are needed to further characterize the population receiving ICD implantation, assessing the course of risk of death with regard to clinical variables and to evaluate the degree of acceptance of trials in clinical practice.
[reactions: see text] The glycosylation with trichloroacetimidates derived from different glycopyranoses bearing a nonparticipating group at C-2 was explored in different ionic liquids as solvents. The stereoselectivity of the reaction was significantly affected by the reaction media and by the anomeric configuration of the donor.
Different techniques have been proposed to treat atrial fibrillation (AF) by catheter ablation. This study compares a new three-dimensional (3D) nonfluoroscopic navigation system with conventional fluoroscopy to guide pulmonary vein (PV) isolation. A total of 60 consecutive patients with paroxysmal or persistent AF were randomly assigned to 3D-guided ablation (group 1, n = 30), versus conventional fluoroscopy guidance ablation (group 2, n = 30). Complete PV isolation was achieved in both groups. The mean duration of fluoroscopy exposure (22 +/- 8 vs 56 +/- 10 minutes), and radiofrequency delivery (5 +/- 1 vs 10 +/- 3 minutes) were significantly shorter in group 1 than in group 2, P < 0.05 for both comparisons). The mean procedural time in group 1 was longer (225 +/- 15 minutes) than in group 2 (156 +/- 10 minutes, P < 0.05) due to the learning curve and time spent to generate the 3D maps. Over a mean follow-up of 7 +/- 2 months, 6 patients (20%) in group 2 had AF recurrences compared to 3 patients (10%) in group 1 (ns). The new nonfluoroscopic 3D system allows a high-resolution reconstruction of the left atrium and PVs. It significantly reduces the mean radiofrequency delivery and fluoroscopy times as opposed to ablation performed under fluoroscopy guidance.
The hypothesis that the sex composition of an applicant pool affects the hiring probabilities of individual job applicants was tested using gender-distinctive information on accepted and rejected job applicants in The Netherlands. The evidence supports this hypothesis, although the effect sizes are moderate. Both men and women have a lower probability of being hired when the applicant pool contains fewer applicants from their own sex.
It has been suggested that a reentrant circuit confined to the posterior extensions of the atrioventricular node underlies both fast-slow and slow-slow types of atrioventricular nodal reentrant tachycardia (AVNRT). According to this hypothesis the fast-slow reentrant circuit would be formed by two slow pathways, located in the rightward and leftward posterior extension of the atrioventricular node. Thus, the fast pathway would act as a bystander with respect to the reentrant circuit. We describe the case of a 40-year-old woman with several episodes of palpitations unresponsive to antiarrhythmic drugs. The ECG during symptoms showed a narrow QRS tachycardia with a long ventriculo-atrial interval and a negative P wave in the inferior leads. Electrophysiological study showed the inducibility of a slow-slow AVNRT which rapidly shifted to a fast-slow AVNRT without any change in the duration of the tachycardia cycle. Our observation is in agreement with the hypothesis that the fast-slow reentrant circuit consists of two slow pathways with the fast pathway acting as a bystander.
The G protein-coupled, receptor-activated phosphoinositide 3-kinase gamma (PI3Kgamma) mediates inflammatory responses and negatively controls cardiac contractility by reducing cAMP concentration. Here, we report that mice carrying a targeted mutation in the PI3Kgamma gene causing loss of kinase activity (PI3KgammaKD/KD) display reduced inflammatory reactions but no alterations in cardiac contractility. We show that, in PI3KgammaKD/KD hearts, cAMP levels are normal and that PI3Kgamma-deficient mice but not PI3KgammaKD/KD mice develop dramatic myocardial damage after chronic pressure overload induced by transverse aortic constriction (TAC). Finally, our data indicate that PI3Kgamma is an essential component of a complex controlling PDE3B phosphodiesterase-mediated cAMP destruction. Thus, cardiac PI3Kgamma participates in two distinct signaling pathways: a kinase-dependent activity that controls PKB/Akt as well as MAPK phosphorylation and contributes to TAC-induced cardiac remodeling, and a kinase-independent activity that relies on protein interactions to regulate PDE3B activity and negatively modulates cardiac contractility.
To screen for vancomycin-resistant enterococci (VRE) colonization in hospitalized patients and to study molecular evolution and alterations of Tn1546-like elements in VRE among potentially at-risk patients, a 3-year surveillance protocol in an Intensive Care Unit was performed. A total of 397 patients were screened in the period June, 1997-June, 2000, and VRE were isolated from rectal swabs taken at admission, weekly, and when clinically indicated. The susceptibility of the enterococci was determined by the disk diffusion and broth dilution methods. The presence of vancomycin-resistance genes (vanA, vanB, and vanC) was assessed by polymerase chain reaction (PCR); genetic clonality of isolates was assessed by pulsed-field gel electrophoresis (PFGE); Tn1546 types were obtained by restriction fragment length polymorphism (RFLP) analysis of Tn1546 PCR fragments. Thirty-four strains, 31 identified as Enterococcus faecium and 3 strains as E. faecalis, were isolated from 12 of the 397 patients (3.0%); all strains were VanA as assessed by PCR and were resistant to the other antibiotics tested and showed high-level resistance to aminoglycosides. Enterococci isolated during the study period showed that different genetic backgrounds of strains, determined by PFGE combined with RFLP of Tn1546, are present in all the strains isolated in the study. PFGE type B was predominant in 1998 and 1999, and insertion sequence movements were found to have a role in the evolution of VanA resistance elements found in all strains. This study demonstrates that single patients may be colonized by closely related VRE with several PFGE types containing a wide variety of VanA elements. Moreover, isolates with identical PFGE types may contain different VanA elements reflecting rearrangements mediated by insertion sequences in VRE strains during their stay in the gastrointestinal tract.
The synthesis of protected fucosylated derivatives of a Galbeta(1-->3)GlcNAc and of lactosamine Galbeta(1-->4)GlcNAc building blocks contained in human milk oligosaccharides is described. Both chemical and enzymatic methods have been exploited for selective protection of the disaccharide. Fucosylation of the appropriate derivatives allowed an easy and relatively short access to different products from common precursors.
We describe a chemo-enzymatic synthesis of 3'- and 6'-O-sialyllactose, two trisaccharides occurring in the 'acidic fraction' of the human milk oligosaccharides and endowed with potential antiadhesive activity. The key step is the highly regioselective 6'-O-acylation of benzyllactoside, which gave access to suitably protected lactose building blocks to be used as acceptors in the sialylation reaction. Moreover, the synthesis of the carboxymethyl and sulfo analogues of the title compounds is reported.
Carbapenems are beta-lactam antibiotics characterised by the presence of a beta-lactam ring with a carbon instead of sulfone in the 4-position of the thyazolidinic moiety. The first carbapenem to be utilised in therapy was imipenem, the N-formimidoyl derivative of thienamycin. Imipenem is coadministered with cilastatin, an inhibitor of human renal dehydropeptidase I, as imipenem is hydrolysed by this enzyme. Meropenem was the first carbapenem with a 1-beta-methyl group and 2-thio pyrrolidinyl moiety, which renders this antibiotic stable to renal dehydropeptidase I. Other carbapenems for parenteral administration later discovered include biapenem, panipenem, ertapenem, lenapenem, E-1010, S-4661 and BMS-181139. Carbapenems which are orally administered include sanfetrinem, DZ-2640, CS-834 and GV-129606. Carbapenems have an ultra-broad spectrum of antibacterial activity and stability to almost all clinically relevant beta-lactamases. This differentiates them from all other currently available classes of beta-lactam antibiotics. However, Class B beta-lactamases, along with some rare Class A and D enzymes, are able to hydrolyse these antibiotics. Although Class B enzymes are generally chromosomally-encoded (isolated from Stenotrophomonas maltophilia, Aeromonas spp., Bacillus cereus, Bacteroides fragilis, Flavobacterium spp. and Legionella gormanii), plasmid-metallo-beta-lactamases now are appearing in B. fragilis, Pseudomonas aeruginosa, Acinetobacter baumannii and members of Enterobacteriaceae such as Serratia marcescens and Klebsiella pneumoniae. The number of these enzymes compared to the number of other beta-lactamase types is still low, however, it is likely that they will spread due to the increased selective pressure of carbapenem use. The very broad spectrum of antimicrobial activity associated with a good clinical efficacy and a favourable safety profile makes the carbapenems valuable as 'first-line' antibiotics in initial empirical therapy for the treatment of severe infections.
BACKGROUND: The use of abciximab (c7E3 Fab; ReoPro , Eli Lilly & Company, Indianapolis, Indiana) during percutaneous coronary intervention (PCI) decreases the incidence of early (30-day) and late (6-month to 1 year) adverse cardiac ischemic events. In a high-risk population, abciximab also reduced the need for target lesion revascularization. PCI of lesions with complex morphology, particularly long lesions, is associated with more complicated outcomes. The use of multiple and/or long intracoronary stents to cover long coronary lesions may lower the incidence of acute or subacute occlusion, but is still limited by a high late restenosis rate. We characterized patients undergoing elective implantation of long or multiple overlapping coronary stents and determined the impact of abciximab administration on clinical and angiographic outcomes. METHODS AND RESULTS: In a prospective, single-center randomized trial, a total of 107 patients undergoing elective implantation of long or multiple overlapping coronary stents were randomly assigned to receive either standard-dose heparin (n = 53) or abciximab plus low-dose heparin (n = 54). The use of abciximab was not associated with an increased incidence of bleeding or vascular complications compared to standard heparin regimen (3.7% versus 3.8%, respectively; p = NS). A 68% reduction in composite in-hospital cardiac events (i.e., death, myocardial infarction, urgent revascularization) was observed in the abciximab group (3.7% versus 11.5%, p = 0.1). At 6-month follow-up, a 48% reduction of target lesion revascularization (11% versus 21%; p = 0.1) and a decrease in binary angiographic restenosis were observed for abciximab-treated patients (17% versus 34%; p < 0.05). CONCLUSION: The peri-procedural use of abciximab during implantation of long or multiple overlapping coronary stents is safe and effective, as it does not increase bleeding or vascular complications compared to standard heparin anticoagulation and reduces the incidence of in-hospital adverse cardiac events; moreover, abciximab improves 6-month clinical and angiographic outcomes in such a complex setting.
Coronary artery disease does not occur in all the patients with acute myocardial infarction. Coronary artery diseases occurs in 97% of cases; in the other 3% of cases, myocardial infarction is caused by coronary spasm (40%, intracoronary thrombosis (60%) due to platelet hyperreactivity, peripartum thrombophilia or use of oral contraceptives. Myocardial infarction in young women is an infrequent event. Spontaneous coronary artery dissection is a rare cause of acute myocardial infarction that typically occurs during the peripartum period. A few cases of myocardial infarction in premenopausal women with no risk factors for coronary artery disease and normal coronary arteries have been reported. We describe 2 consecutive cases of acute myocardial infarction occurred in young, premenopausal women, without risk factors for cardiovascular diseases.