α-Synuclein dimerization in erythrocytes of Gaucher disease patients: correlation with lipid abnormalities and oxidative stress.

Several observations suggest that disturbed homeostasis of α-Synuclein (α-Syn) may provide a link between Gaucher disease (GD) and Parkinson's disease (PD). We recently reported increased dimerization of α-Syn in the red blood cell (RBC) membrane of patients with GD. Several studies indicate a crucial relationship between lipids, oxidative stress and α-Syn status.

Feasibility study of needle placement in percutaneous vertebroplasty: cone-beam computed tomography guidance versus conventional fluoroscopy.

Objective: To investigate the accuracy, procedure time, fluoroscopy time, and dose area product (DAP) of needle placement during percutaneous vertebroplasty (PVP) using cone-beam computed tomography (CBCT) guidance versus fluoroscopy.

Materials And Methods: On 4 spine phantoms with 11 vertebrae (Th7-L5), 4 interventional radiologists (2 experienced with CBCT guidance and two inexperienced) punctured all vertebrae in a bipedicular fashion. Each side was randomization to either CBCT guidance or fluoroscopy.

Quantification of arterial flow using digital subtraction angiography.

Purpose: In this paper, a method for the estimation of arterial hemodynamic flow from x-ray video densitometry data is proposed and validated using an in vitro setup.

Methods: The method is based on the acquisition of three-dimensional rotational angiography and digital subtraction angiography sequences. A modest contrast injection rate (between 1 and 4 ml/s) leads to a contrast density that is modulated by the cardiac cycle, which can be measured in the x-ray signal.

MPI Cell Tracking: What Can We Learn from MRI?

Magnetic resonance imaging (MRI) cell tracking has become an important non-invasive technique to interrogate the fate of cells upon transplantation. At least 6 clinical trials have been published at the end of 2010, all of which have shown that real-time monitoring of the injection procedure, initial engraftment, and short-term biodistribution of cells is critical to further advance the field of cellular therapeutics. In MRI cell tracking, cells are loaded with superparamagnetic iron oxide (SPIO) particles that provide an MRI contrast effect through microscopic magnetic field disturbances and dephasing of protons.

Therapeutic goals in the treatment of Gaucher disease.

Gaucher disease, the most common lysosomal storage disorder, is a heterogeneous multisystem condition. Patients with non-neuronopathic (type 1) Gaucher disease may suffer from hepatomegaly, splenomegaly, thrombocytopenia, bleeding tendencies, anemia, hypermetabolism, skeletal pathology, growth retardation, pulmonary disease, and decreased quality of life. Enzyme replacement therapy (ERT) with mannose-terminated glucocerebrosidase reverses or ameliorates many of the manifestations of type 1 Gaucher disease.

Design and synthesis of 2-acetamidomethyl derivatives of isofagomine as potential inhibitors of human lysosomal beta-hexosaminidases.

As part of a program towards the development of specific inhibitors of human lysosomal beta-hexosaminidase for use as chemical chaperones in therapy of G(M2) gangliosidosis related diseases, the synthesis of 2-acetamidomethyl derivatives of isofagomine has been undertaken. Key event in this synthesis is the conversion of a C-2 substituted gluconolactone derivative into the corresponding lactam, followed by reduction to the corresponding amine. The 1-N-imino-2 acetamidomethyl derivative 5 proved to be a rather selective inhibitor with a K(i) of 2.

Plasma level of the macrophage-derived soluble CD163 is increased and positively correlates with severity in Gaucher's disease.

Recently, soluble CD163 (sCD163) has been identified as a macrophage/monocyte-specific plasma protein and increased concentrations have been measured in patients with infection and myeloid leukaemia. In the present study we investigated the levels of sCD163 in patients with Gaucher's disease, an inherited lysosomal storage disorder characterised by hepato- and splenomegaly due to excessive accumulation of macrophages. The sCD163 plasma levels, median (25-75 percentiles), were far above the levels in normal subjects [7.

Correlation of bone marrow response with hematological, biochemical, and visceral responses to enzyme replacement therapy of nonneuronopathic (type 1) Gaucher disease in 30 adult patients.

Purpose: This investigation correlates the marrow response with the degree of increase in hemoglobin (Hb) and platelet count (Plt); decrease in concentrations of plasma tartrate-resistant acid phosphatase, serum angiotensin-converting enzyme (ACE), serum ferritin, and plasma chitotriosidase; and decrease in liver and spleen size, measured by ultrasonography.

Methods: Thirty adult patients with nonneuronopathic (type 1) Gaucher disease (23% splenectomized) were followed for mean periods of 12 and 36 months.

Results: The series achieved highly significant mean responses in all hematological, biochemical, and visceral parameters over both observation periods; over a mean 36 months, 19 (63%) had a marrow response, 11 (37%) did not.