Phosphatidylinositol 3-kinase gamma is a critical mediator of myocardial ischemic and adenosine-mediated preconditioning.

Ischemic preconditioning (IPC) is a potent cellular protective mechanism whereby brief periods of sublethal ischemia protect the myocardium from prolonged ischemia-induced injury. We demonstrate the selective role of phosphatidylinositol 3-kinase (PI3K) isoforms in IPC. Hearts from PI3Kgamma knockout mice (PI3Kgamma(-/-)) displayed poorer functional recovery and greater tissue injury following IPC compared to wild-type and PI3Kgamma(+/-) hearts.

Evaluation of an international emergency medicine intervention in Tuscany.

Objective: To measure the effectiveness of a 9-month emergency medicine 'train the trainers' program in Tuscany, Italy.

Methods: A total of 81 physicians with emergency department experience completed a training course in Italy. The course included 120 h of didactic lectures, 700 h of clinical rotations and 30 h of practical workshops.

Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways.

Background: The glucagon-like peptide 1 receptor (GLP-1R) is believed to mediate glucoregulatory and cardiovascular effects of the incretin hormone GLP-1(7-36) (GLP-1), which is rapidly degraded by dipeptidyl peptidase-4 (DPP-4) to GLP-1(9-36), a truncated metabolite generally thought to be inactive. Novel drugs for the treatment of diabetes include analogues of GLP-1 and inhibitors of DPP-4; however, the cardiovascular effects of distinct GLP-1 peptides have received limited attention.

Methods And Results: Here, we show that endothelium and cardiac and vascular myocytes express a functional GLP-1R as GLP-1 administration increased glucose uptake, cAMP and cGMP release, left ventricular developed pressure, and coronary flow in isolated mouse hearts.

Enteral glutamine: a novel mediator of PPARgamma in the postischemic gut.

Early enteral nutrition supplemented with glutamine, arginine, omega-3 fatty acids, and nucleotides has been shown to decrease infection complications in critically injured patients. Concern has been raised, however, that under conditions of hyperinflammation, these diets may be injurious through the induction of inducible NO synthase by enteral arginine. In a rodent model of gut ischemia/reperfusion, inflammation and injury are intensified by enteral arginine and abrogated by glutamine.

BCR-ABL1 mediates up-regulation of Fyn in chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) invariably progresses to blast crisis, which represents the most proliferative phase of the disease. The BCR-ABL1 oncogene stimulates growth and survival pathways by phosphorylating numerous substrates, including various Src family members. Here we describe up-regulation, in contrast to activation, of the ubiquitously expressed Src kinase, Fyn, by BCR-ABL1.

[Expression and exon 3 mutation of beta-catenin in human hepatocellular carcinoma].

Background & Objective: South Guangxi is an area with high incidence of hepatocellular carcinoma (HCC), and with severe contamination of dietary aflatoxin B1 (AFB1). The activation of beta-Catenin is involved in many cancers. AFB1 may play a key role in hepatocarcinogenesis.

Loss of Emi1-dependent anaphase-promoting complex/cyclosome inhibition deregulates E2F target expression and elicits DNA damage-induced senescence.

Expression of the anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 is required for the accumulation of APC/C substrates crucial for DNA synthesis and mitotic entry. We show that in vivo Emi1 expression correlates with the proliferative status of the cellular compartment and that cells lacking Emi1 undergo cellular senescence. Emi1 depletion leads to strong decreases in E2F target mRNA and APC/C substrate protein abundances.

The Tuscan Emergency Medicine Initiative.

Italy lacks standardized specialty training in emergency medicine. There is no system of national or regional accreditation of the knowledge base or skill set of physicians working in regional emergency departments (ED), which results in variability of emergency medical care delivery not only between hospital EDs but also within individual EDs. To address this need, the Tuscan Minister of Health chose to develop a partnership with emergency medicine specialists from the United States to help expedite the growth of the specialty in Tuscany.

Candidate genes responsible for human hepatocellular carcinoma identified from differentially expressed genes in hepatocarcinogenesis of the tree shrew (Tupaia belangeri chinesis).

Aim: To explore gene expression profiles during hepatocarcinogenesis of the tree shrew, and to find the genes responsible for human hepatocellular carcinoma (HCC).

Methods: Tree shrews were used as an animal model for HCC induction employing aflatoxin B(1) (AFB(1)) alone or AFB(1) plus hepatitis B virus (HBV) as etiological factors. Gene expression profiles from the tissues of HCC, HCC-surrounding liver tissues (para-HCC) and the corresponding biopsies taken from the same animals before HCC had developed (pre-HCC) were analyzed by cDNA microarray assay to identify differentially expressed genes.

Real-time three dimensional echo-guided closure of atrial septal defect: an experimental model.

Real-time 3D echo may open the way to off-pump closure of an atrial septal defect with a robotic surgery technique without remnant of closure device. We report the preliminary results of 3D echo-guided closure of defect in an experimental model. A sheet with an oval defect immersed in water was visualized with 3D echo as well as surgical instruments.

The END network couples spindle pole assembly to inhibition of the anaphase-promoting complex/cyclosome in early mitosis.

Cyclin-dependent kinase 1 (Cdk1) initiates mitosis and later activates the anaphase-promoting complex/cyclosome (APC/C) to destroy cyclins. Kinetochore-derived checkpoint signaling delays APC/C-dependent cyclin B destruction, and checkpoint-independent mechanisms cooperate to limit APC/C activity when kinetochores lack checkpoint components in early mitosis. The APC/C and cyclin B localize to the spindle and poles, but the significance and regulation of these populations remain unclear.

NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells.

The proteasome has been successfully targeted for the treatment of multiple myeloma and mantle cell lymphoma; however, in other hematologic malignancies, bortezomib has been less effective as a single agent. Here, we describe effects of NPI-0052, a novel proteasome inhibitor, in leukemia model systems. In cell lines, NPI-0052 inhibits all 3 proteolytic activities associated with the proteasome: chymotrypsin-, trypsin-, and caspase-like.

Building a trauma center and system in Tuscany, Italy.

Background: Growing evidence supports the premise that adult trauma centers lower the risk of death for severely injured patients. The same principles have been applied to the pediatric population and mounting research suggests that, as in the adult population, gravely injured children have better outcomes at pediatric trauma centers where personnel trained and experienced in the specific needs and unique physiology of injured children provide care. As in the United States, acute traumatic injury represents an important public healthcare concern to the Tuscan regional government whose goal is to maximize clinical outcomes within available resources.

Difficult airway management.

Airway management is unequivocally the most important responsibility of the emergency physician. No matter how prepared for the task, no matter what technologies are utilized, there will be cases that are difficult. The most important part of success in the management of a difficult airway is preparation.