Biomechanical and histological characterization of MPS I mice femurs.

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder characterized by alpha-L-iduronidase (IDUA) deficiency, an enzyme responsible for glycosaminoglycan degradation. Musculoskeletal impairment is an important component of the morbidity related to the disease, as it has a major impact on patients' quality of life. To understand how this disease affects bone structure, morphological, biomechanical and histological analyses of femurs from 3- and 6-month-old wild type (Idua +/+) and MPS I knockout mice (Idua -/-) were performed.

Analysis of motor performance and histomorphometry of skeletal muscles of rats exercised after cerebral ischemia.

Introduction: Cerebral ischemia causes muscle atrophy and motor incoordination in animals, impairing motor performance.

Objective: Thus, the objective of the present study was to analyze the motor performance and histomorphometry of the biceps brachii, soleus, and anterior tibialis muscles of rats submitted to a treadmill training program after induction of cerebral ischemia by the transient occlusion of the middle cerebral artery (MCAO).

Materials And Methods: To do so, twenty-four 30-day-old Wistar rats were utilized.

Effects of exercise training and stem cell therapy on the left ventricle of infarcted rats.

Introduction And Objectives: Stem cell therapy and aerobic exercise are non-pharmacological therapies following myocardial infarction. The aim of this study was to test whether aerobic exercise training enhances the benefits of mesenchymal stem cell (MSC) therapy on remodeling of the extracellular matrix and fetal gene expression in the left ventricle of infarcted rats.

Methods: Myocardial infarction was surgically induced in six-week old male Wistar rats.

CASE SERIES OF PATIENTS UNDER BIWEEKLY TREATMENT WITH LARONIDASE: A REPORT OF A SINGLE CENTER EXPERIENCE.

Objective: To report the stabilization of urinary glycosaminoglicans (GAG) excretion and clinical improvements in patients with mucopolysaccharidosis type I (MPS I) under an alternative dose regimen of laronidase of 1.2 mg/kg every other week.

Methods: We participated in a dose-optimization trial for laronidase in MPS-I patients using four alternative regimens: 0.

Lysosomal Acid Lipase Deficiency: Report of Five Cases across the Age Spectrum.

Lysosomal acid lipase (LAL) deficiency is an autosomal recessive lysosomal storage disorder caused by mutations in the gene that leads to premature organ damage and mortality. We present retrospective data from medical records of 5 Brazilian patients, showing the broad clinical spectrum of the disease.

Differential expression of microRNAs from miR-17 family in the cerebellum of mucopolysaccharidosis type I mice.

Mucopolysaccharidosis type I (MPS I) is caused by deficiency of α-l-iduronidase, involved in degradation of glycosaminoglycans. Clinical manifestations are widely variable and patients with severe phenotype present developmental delay and cognitive decline, among other systemic alterations. MPS I patients present secondary accumulation of gangliosides in neuronal cells, besides accumulation of undegraded glycosaminoglycans.

The Underexploited Role of Non-Coding RNAs in Lysosomal Storage Diseases.

Non-coding RNAs (ncRNAs) are a functional class of RNA involved in the regulation of several cellular processes which may modulate disease onset, progression, and prognosis. Lysosomal storage diseases (LSD) are a group of rare disorders caused by mutations of genes encoding specific hydrolases or non-enzymatic proteins, characterized by a wide spectrum of manifestations. The alteration of ncRNA levels is well established in several human diseases such as cancer and auto-immune disorders; however, there is a lack of information focused on the role of ncRNA in rare diseases.

α- L-iduronidase gene-based therapy using the phiC31 system to treat mucopolysaccharidose type I mice.

Background: Mucopolysaccharidose type I (MPSI) is a lysosomal monogenic disease caused by mutations in the gene for α- L-iduronidase (IDUA). MPSI patients need a constant supply of IDUA to alleviate progression of the disease. IDUA gene transfer using integrative vectors might provide a definitive solution and support advancement to clinical trials, although studies have not yet been satisfactory.

Brazilian reference values for MPS II screening in dried blood spots--a fluorimetric assay.

Objectives: Mucopolysaccharidosis II (MPS II), or Hunter Syndrome, is a lysosomal storage disorder that is caused by the deficiency or absence of iduronate-2-sulfatase (IDS) enzyme; in this disease, early diagnosis is essential to provide higher life expectancy for patients. This study validates a fluorimetric assay that is used to assess IDS enzyme activity using dried blood spot (DBS) samples and presents the reference interval for the Brazilian population.

Design And Methods: Venous blood sample was collected in heparin tubes for leukocyte extraction and DBS preparation.

Acute and chronic observations of complete atrioventricular block in rats.

The mechanisms of production, and gross, microscopic and electrocardiograhic findings of surgically-induced complete heart block (CHB) in the adult rat are presented. This is an effective in vivo model for establishing alternative methods to electronic pacemakers and for providing detailed information aimed at replacement, reduction and refinement of the technique. Sternal thoracotomy was employed to identify the epicardial fat pad by the aortic root, used as a landmark for cauterization of the atrioventricular (AV) node.

Mesenchymal stem cells do not prevent antibody responses against human α-L-iduronidase when used to treat mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPSI) is an autosomal recessive disease that leads to systemic lysosomal storage, which is caused by the absence of α-L-iduronidase (IDUA). Enzyme replacement therapy is recognized as the best therapeutic option for MPSI; however, high titers of anti-IDUA antibody have frequently been observed. Due to the immunosuppressant properties of MSC, we hypothesized that MSC modified with the IDUA gene would be able to produce IDUA for a long period of time.

Apoptosis status and proliferative activity in mucopolysaccharidosis type I mice tongue mucosa cells.

Background: Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of alfa-iduronidase (IDUA), which leads to intralysosomal accumulation of glysosaminoglycans. Evidences point secondary events like oxidative stress on lysosomal storage diseases including MPS I. Patients with MPS I present a wide range of oral clinical manifestations, including tongue hypertrophy, hypertrophyc alveolar process, and carious teeth.

Differentiation of adipose tissue-derived mesenchymal stem cells into cardiomyocytes.

Background: Cardiomyocytes have small potential for renovation and proliferation in vivo. Consequently, the heart muscle has limited capacity of self-renewal. Mesenchymal stem cells (MSC) therapy, as well as MSC differentiated into cardiomyocytes, has been used in the attempt to minimize the effects of ischemic-hypoxic lesions and those affecting the electrical conduction system of the heart.

Evaluation of oxidative stress markers and cardiovascular risk factors in Fabry Disease patients.

Fabry Disease, an X-linked inborn error of metabolism, is characterized by progressive renal insufficiency, with cardio and cerebrovascular involvement. Homocysteine (Hcy) is considered a risk factor for vascular diseases, but the mechanisms by which it produces cardiovascular damage are still poorly understood. Regarding the vascular involvement in FD patients, the analysis of factors related to thromboembolic events could be useful to improving our understanding of the disease.

Treatment of adult MPSI mouse brains with IDUA-expressing mesenchymal stem cells decreases GAG deposition and improves exploratory behavior.

Background: Mucopolysaccharidosis type I (MPSI) is caused by a deficiency in alpha-L iduronidase (IDUA), which leads to lysosomal accumulation of the glycosaminoglycans (GAGs) dermatan and heparan sulfate. While the currently available therapies have good systemic effects, they only minimally affect the neurodegenerative process. Based on the neuroprotective and tissue regenerative properties of mesenchymal stem cells (MSCs), we hypothesized that the administration of MSCs transduced with a murine leukemia virus (MLV) vector expressing IDUA to IDUA KO mouse brains could reduce GAG deposition in the brain and, as a result, improve neurofunctionality, as measured by exploratory activity.

Genomic instability in blood cells from murine model of mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of alfa-iduronidase (IDUA), which leads to intralysosomal accumulation of glycosaminoglycans. Some studies have revealed that oxidative stress plays an important role in MPS I. However, the mechanisms by which these alterations occur are still not fully understood.

Evaluation of α-iduronidase in dried blood spots is an accurate tool for mucopolysaccharidosis I diagnosis.

Background: Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of the α-L-iduronidase (IDUA), which leads to the accumulation of glycosaminoglycans in lysosomes. MPS I patients present a spectrum ranging from a severe to an attenuated phenotype. Once clinical suspicion is present, diagnosis of MPS I can be performed by enzyme activity determination and/or molecular analysis.

Reference values for lysosomal enzymes activities using dried blood spots samples - a Brazilian experience.

Background: Lysosomal storage diseases (LSD) are inherited disorders caused by deficiency of lysosomal enzymes in which early diagnosis is essential to provide timely treatment. This study reports interval values for the activity of lysosomal enzymes that are deficient in Mucopolysaccharidosis type I, Fabry, Gaucher and Pompe disease, using dried blood spots on filter paper (DBS) samples in a Brazilian population.

Results: Reference activity values were obtained from healthy volunteers samples for alpha-galactosidase A (4.

Evidence of lysosomal membrane permeabilization in mucopolysaccharidosis type I: rupture of calcium and proton homeostasis.

Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of alpha-iduronidase (IDUA), which leads to intralysosomal accumulation of glysosaminoglycans. Patients with MPS I present a wide range of clinical manifestations, but the mechanisms by which these alterations occur are still not fully understood. Genotype-phenotype correlations have not been well established for MPS I; hence, it is likely that secondary and tertiary alterations in cellular metabolism and signaling may contribute to the physiopathology of the disease.

Mutational and oxidative stress analysis in patients with mucopolysaccharidosis type I undergoing enzyme replacement therapy.

Background: Mucopolysaccharidosis type I (MPS I) patients present a wide range of clinical manifestations, which could be due to the high molecular heterogeneity of the IDUA gene and to pathological events besides the enzyme deficiency. The aim of this study was to identify the most common MPS I causing mutations and to evaluate some oxidative stress markers in Brazilian patients.

Methods: 3 common mutations in the IDUA gene were searched in 11 MPS I patients by PCR-RFLP.

Molecular analysis of homocystinuria in Brazilian patients.

Background: Cystathionine beta-synthase (CBS) deficiency is the most common cause of homocystinuria. However, no data are available concerning the molecular basis of this disease in Brazilian populations.

Methods: We studied 14 Brazilian patients from 11 unrelated families using a combined screening approach, involving restriction analysis, single-strand conformational polymorphism (SSCP) scanning, and sequencing.