Search results for "Ceramidase"
showing 10 items of 24 documents
Evaluation of treatment response to enzyme replacement therapy with Velaglucerase alfa in patients with Gaucher disease using whole-body magnetic res…
2015
Abstract Objective This was a retrospective data analysis to evaluate the treatment response to enzyme replacement therapy (ERT) with Velaglucerase alfa using whole-body magnetic resonance imaging (MRI). Materials and methods A baseline and follow-up MRI were performed on 18 Gaucher Type 1 patients at an interval of 11.6 months. The MRI score systems determined the Bone-Marrow-Burden (BMB) score, the Dusseldorf-Gaucher score (DGS), and the Vertebra-Disc-Ratio (VDR). The Severity Score Index Type 1 (GD-DS3) was also assessed. Results The baseline MRI medians were: BMB, 7.00; DGS, 3.00; and VDR: 1.70; while, the follow-up MRI medians were: BMB, 7.00; DGS, 3.00; and VDR: 1.73. The baseline GD-…
Fluorinated Chaperone−β-Cyclodextrin Formulations for β-Glucocerebrosidase Activity Enhancement in Neuronopathic Gaucher Disease
2017
Amphiphilic glycomimetics encompassing a rigid, undistortable nor-tropane skeleton based on 1,6-anhydro-L-idonojirimycin and a polyfluorinated antenna, when formulated as the corresponding inclusion complexes with β-cyclodextrin (βCD), have been shown to behave as pharmacological chaperones (PCs) that efficiently rescue lysosomal β- glucocerebrosidase mutants associated to the neuronopathic variants of Gaucher disease (GD), including the highly refractory L444P/L444P and L444P/P415R single nucleotide polymorphs, in patient fibroblasts. The body of work here presented includes the design criteria for the PC prototype, the synthesis of a series of candidates, the characterization of the PC:βC…
Involvement of caspase-3 and GD3 ganglioside in ceramide-induced apoptosis in Farber disease.
2000
Farber's disease (FD) is a rare genetic disorder caused by ceramidase deficiency, which results in ceramide accumulation in lung, liver, colon, skeletal muscle, cartilage, and bone. Although this disease has been symptomatically characterized, little is known about its molecular pathogenetic process. Because recent studies reported that ceramide accumulation induces GD3 ganglioside formation and apoptosis, we investigated, in tissue obtained via colonoscopy from seriously involved patients, the possible involvement of ceramide in FD colonocyte destruction. Histochemical and TUNEL analyses of paraffin-embedded sections revealed that 45 ± 4.3% of FD colonocytes showed morphological signs of …
Cholelithiasis in Patients with Gaucher Disease type 1: Risk Factors and the Role of ABCG5/ABCG8 Gene Variants
2016
Background & Aim: Patients with Gaucher disease type 1 (GD1) show an altered lipid profile and a certain degree of insulin resistance, which might contribute to cholelithiasis (CL) and could possibly be associated with ABCG5/ABCG8 gene variants. We aimed to investigate the prevalence of CL in Caucasian adult patients with GD1 and the possible risk factors, including gene variants of the ABCG5/ABCG8 genes.
 Methods: 61 Caucasian patients with GD1 (38 female/23male), aged 18-62 years and 61 healthy subjects matched for age, gender and BMI, without CL, for comparison of lipid profiles. Data before start of enzyme replacement therapy (ERT) were recorded: clinical, haematological, sever…
Relationship Between Glucocerebrosidase Activity and Clinical Response to Enzyme Replacement Therapy in Patients With Gaucher Disease Type I
2018
The quantification of enzyme activity in the patient treated with enzyme replacement therapy (ERT) has been suggested as a tool for dosage individualization, so we conducted a study to evaluate the relationship between glucocerebrosidase activity and clinical response in patients with Gaucher disease type I (GD1) to ERT. The study included patients diagnosed with GD1, who were being treated with ERT, and healthy individuals. Markers based on glucocerebrosidase activity measurement in patients' leucocytes were studied: enzyme activity at 15 min. post-infusion (Act75 ) reflects the amount of enzyme that is distributed in the body post-ERT infusion, and accumulated glucocerebrosidase activity …
Outcome of type III Gaucher disease on enzyme replacement therapy: review of 55 cases.
2007
The European Task Force for Neuronopathic Gaucher Disease (NGD) met in 2006 to review its 2001 guidelines. Fifty-five patients from five European countries were reviewed; 29 were male and 26 female. The majority of the patients were homozygous for the L444P mutation. All had been on enzyme replacement therapy (ERT). However, there was considerable variation in the dose of ERT, as well as an uneven distribution of risk factors. Thus, the oldest patients were on the lowest doses, and several had had a total splenectomy, while the youngest patients had a high proportion of compound heterozygosity and were on the highest doses, and very few had had a splenectomy. This heterogeneity rendered ana…
Outcome of enzyme replacement therapy in patients with Gaucher disease type I. The Romanian experience
2007
This study reports the first evaluation of therapeutic response in Romanian patients with Gaucher disease type I, after therapy with Cerezyme recently became available in our country.24 patients (11-50 years) received Cerezyme 20-60 U/kg every two weeks for at least 18 months. Haemoglobin, platelet count, volume of the liver and spleen, plasma chitotriosidase and the severity score were assessed every 6 months; skeletal radiography and osteodensitometry were also monitored.Eleven patients were splenectomized before start of therapy. Eight patients had anaemia (mean haemoglobin 9.4 g/dl) and 14 patients, of whom 13 were without splenectomy, had thrombocytopenia (mean 65,692/mm3). Haemoglobin…
Baseline characteristics and outcome in Romanian patients with Gaucher disease type 1.
2009
Abstract Background/aim To present clinical and genetic characteristics of all Romanian patients with Gaucher disease type 1, in whom specific diagnosis has been confirmed by enzymatic and molecular methods and to analyze their outcome with and without enzymatic replacement therapy (ERT). Patients, methods There are fifty patients (F/M — 1.63/1) with Gaucher disease type 1. Clinical status, haemoglobin, thrombocytes, hepatic/splenic volume, bone mineral density and severity score were assessed at baseline and every six months thereafter. Thirty-nine patients (78%) received imiglucerase (44.4 ± 13.6 U/kg/2 weeks) for 3.1 +/− 1.4 years. Results Based on general prevalence data, our group repr…
Development and application to clinical practice of a validated HPLC method for the analysis of β-glucocerebrosidase in Gaucher disease.
2014
The main objective of our study is to develop a simple, fast and reliable method for measuring ß-glucocerebrosidase activity in Gaucher patients leukocytes in clinical practice. This measurement may be a useful marker to drive dose selection and early clinical decision making of enzyme replacement therapy. We measure the enzyme activity by high-performance liquid chromatography with ultraviolet detection and 4-nitrophenyl-ß-d-glucopyranoside as substrate. A cohort of eight Gaucher patients treated with enzyme replacement therapy and ten healthy controls were tested; median enzyme activity values was 20.57mU/ml (interquartile range 19.92-21.53mU/ml) in patients and mean was 24.73mU/ml (24.12…
A case of lipogranulomatosis Farber: some clinical and ultrastructural aspects
1985
A 20-month-old girl showed typical clinical signs of Farber disease: hoarseness since birth, and periarticular subcutaneous painful nodules. Complete deficiency of acid ceramidase activity was found in cultured skin fibroblasts. An electron microscopic examination of a dermal nodule disclosed pathognomonic tubular inclusions in histiocytes. In epidermal cells zebra-body-like and needle-like lysosomal inclusions were found. Their ultrastructure is different from that of the intrahistiocytic lysosomal inclusions. Probably three clinical types of Farber disease may be distinguished according to the symptomatology and the course of the disease: a severe type, an intermediate type and a relative…