Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients followed within the MPS Brazil Network

Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alpha-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5 years later (T2; n = 24/34). The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype). For all variables in which there was no between-group difference at baseline, a delta of ≥ ± 20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.

Mucopolysaccharidoses in northern Brazil: targeted mutation screening and urinary glycosaminoglycan excretion in patients undergoing enzyme replacement therapy

Mucopolysaccharidoses (MPS) are rare lysosomal disorders caused by the deficiency of specific lysosomal enzymes responsible for glycosaminoglycan (GAG) degradation. Enzyme Replacement Therapy (ERT) has been shown to reduce accumulation and urinary excretion of GAG, and to improve some of the patients' clinical signs. We studied biochemical and molecular characteristics of nine MPS patients (two MPS I, four MPS II and three MPS VI) undergoing ERT in northern Brazil. The responsiveness of ERT was evaluated through urinary GAG excretion measurements. Patients were screened for eight common MPS mutations, using PCR, restriction enzyme tests and direct sequencing. Two MPS I patients had the previously reported mutation p.P533R. In the MPS II patients, mutation analysis identified the mutation p.R468W, and in the MPS VI patients, polymorphisms p.V358M and p.V376M were also found. After 48 weeks of ERT, biochemical analysis showed a significantly decreased total urinary GAG excretion in patients with MPS I (p < 0.01) and MPS VI (p < 0.01). Our findings demonstrate the effect of ERT on urinary GAG excretion and suggest the adoption of a screening strategy for genotyping MPS patients living far from the main reference centers.

Padronização e aplicação da técnica de ELISA (Enzyme-linked immunosorbent assay) indireto com anticorpo de captura para a detecção de anticoepos contra o cicovírus suíno tipo 2

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

DNA for nano-bio scale computation of chemical formalisms using Higher Order Logic (HOL) and analysis using an interdisciplinary approach

Bio-molecular computing, 'computations performed by bio-molecules', is already challenging traditional approaches to computation both theoretically and technologically. Often placed within the wider context of ´bio-inspired' or 'natural' or even 'unconventional' computing, the study of natural and artificial molecular computations is adding to our understanding of biology, physical sciences and computer science well beyond the framework of existing design and implementation paradigms. In this introduction, We wish to outline the current scope of the field and assemble some basic arguments that, bio-molecular computation is of central importance to computer science, physical sciences and biology using HOL - Higher Order Logic. HOL is used as the computational tool in our R&D work. DNA was analyzed as a chemical computing engine, in our effort to develop novel formalisms to understand the molecular scale bio-chemical computing behavior using HOL. In our view, our focus is one of the pioneering efforts in this promising domain of nano-bio scale chemical information processing dynamics.

A liquid-phase-blocking concanavalin A enzyme-linked immunosorbent assay for the detection of antibodies against Newcastle disease virus in serum of free-ranging pigeons

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cyclodextrin Production by Bacillus lehensis Isolated from Cassava Starch: Characterisation of a Novel Enzyme

The properties of a previously unknown enzyme, denominated cyclodextrin glycosyltransferase, produced from Bacillus lehensis, were evaluated using affinity chromatography for protein purification. Enzyme characteristics (optimum pH and temperature; pH and temperature stability), the influence of substances on the enzyme activity, enzyme kinetics, and cyclodextrin production were analysed. Cyclodextrin glycosyltransferase was purified up to 320.74-fold by affinity chromatography using beta-cyclodextrin as the binder and it exhibited 8.71% activity recovery. This enzyme is a monomer with a molecular weight of 81.27 kDa, as estimated by SDS-PAGE. Optimum temperature and pH for cydodextrin glycosyltransferase were 55 degrees C and 8.0, respectively. The Michaelis-Menten constant was 8.62 g/l during maximum velocity of 0.858 g/l.h.

Estimating outcomes in newborn infants using fuzzy logic

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Citrus pulp and enzyme complex for growing and finishing pigs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Logic TK: algebric notions from Tarski's consequence operator

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Deconstructing the DGAT1 enzyme: Binding sites and substrate interactions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of Three Enzyme Immunoassays for Diagnosis of Clostridium difficile-Associated Diarrhea in Foals

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

ENDO-OLIGOPEPTIDASE-A, A PUTATIVE ENKEPHALIN-GENERATING ENZYME, IN THE VERTEBRATE RETINA

Endo-oligopeptidase A, EC 3.4.22.19, converts small enkephalin-containing peptides into the corresponding enkephalins in vitro. We investigated the presence of endooligopeptidase A in the retina and its possible colocalization with enkephalins in retinal neurons. The specific activity of endo-oligopeptidase A found in pigeon retinae (30.3 +/- 7.3 mU/mg, mean +/- standard deviation) was four times higher than in rabbit retinae (7.0 +/- 1.1 mU/mg). The enzyme activity was not modified by EDTA, but it was enhanced by dithiothreitol and inhibited by zinc and 5,5'-dithiobis(2-nitrobenzoic acid). Immunohistochemical experiments with a purified antiserum against rabbit endo-oligopeptidase A revealed labeled neurons in both the inner nuclear layer and the ganglion cell layer of pigeon and rabbit retinae. Double-labeling immunofluorescence experiments demonstrated that about 90% of neurons containing endo-oligopeptidase A-like immunoreactivity also contained [Leu5]-enkephalin-like immunoreactivity. These colocalization results may represent an important step toward the demonstration of the possible involvement of endo-oligopeptidase A in enkephalin generation in vivo.