ll thickening without significant dilatation, and LV hypertrophy. Systolic function is largely preserved in most affected individuals, but diastolic dysfunction is a relatively common finding even at early stage of the disease. In the mouse model, we found LV functional alterations with mild alteration of diastolic function, as depicted with Tissue Doppler interrogation, and no systolic alteration. This is very similar to the findings in human at early stages of the cardiac disease. Moreover, a good relationship was shown between tissue Doppler echocardiographic data and mechanical properties of human cardiac myofilaments obtained from myocardial biopsies. The findings that the mouse model has mild cardiac involvement detectable with tissue Doppler suggest that this specific MedChemExpress Celgosivir interrogation in human has to be performed for early detection of cardiac involvement, inasmuch as the efficiency of the replacement therapy is dependent on early onset of treatment. We also found evidence of cardiac remodeling at the molecular level, with increased mRNA levels, for atrial natriuretic factor brain natriuretic peptide, plasminogen activator inhibitor-1; connective tissue growth factor, and thrombospondin 2. Our results suggest that atrial arrhythmias could be associated with early cardiac involvement in Fabry disease. Although more than 60% of patients with Fabry disease have evidence of cardiac involvement, the prevalence and clinical significance of arrhythmia in Fabry disease are unknown. Shah and colleagues studied 78 consecutive patients with Fabry disease. Three 9600591 patients had persistent atrial fibrillation, and 8 had paroxysmal atrial fibrillation. Five males had nonsustained ventricular tachycardia with a maximal left ventricular wall thickness.20 mm. Age, left atrial diameter, maximal left ventricular wall thickness, left ventricular mass index, 22694778 and angina were univariate predictors of atrial fibrillation. During follow-up, there was 1 sudden cardiac death, 4 patients received pacemakers for bradyarrhythmias, and 1 patient received a biventricular pacemaker and an internal cardiac defibrillator. The high incidence of arrhythmias and pacemaker implantation and sudden cardiac death suggests that arrhythmia has a significant impact on the natural history of Fabry disease. The mouse model did not, however, displayed ventricular arrhythmias possibly because the mice were relatively young. Long term treatment with ERT has been shown to reduce LV hypertrophy, and suggested that early treatment may yield better long-term cardiac outcomes and exercise capacity. Whether or not these abnormalities in heart rhythm or rate, as well as the cardiac remodeling will respond to ERT, and/or other forms of adjunctive therapy are questions that can be addressed in the Fabry KO mouse despite the limitations of the model. We have found changes in the cellular phenotype in this model, 3 weeks following a single intravenous injection of 3 mg/kg agalsidase-beta, a dose and interval chosen to maximize the reduction in cardiac GL3 content. Rozenfeld et al. observed improvement in left ventricular contractility following longer treatment periods of a much lower dose of ERT . Bacteria can encounter numerous environments in 
which chemical and physical factors such as osmotic pressure, temperature, pH and carbon source availability can change considerably and unpredictably. To adapt to changing conditions, bacteria possess an array of mechanisms which sense external factor
