A novel approach for the characterisation of proteoglycans and biosynthetic enzymes in a snail model

Proteoglycans encompass a heterogeneous group of glycoconjugates where proteins are substituted with linear, highly negatively charged glycosaminoglycan chains. Sulphated glycosaminoglycans are ubiquitous to the animal kingdom of the Eukarya domain. Information on the distribution and characterisation of proteoglycans in invertebrate tissues is limited and restricted to a few species. By the use of multidimensional protein identification technology and immunohistochemistry, this study shows for the first time the presence and tissue localisation of different proteoglycans, such as perlecan, aggrecan, and heparan sulphate proteoglycan, amongst others, in organs of the gastropoda Achatina fulica. Through a proteomic analysis of Golgi proteins and immunohistochemistry of tissue sections, we detected the machinery involved in glycosaminoglycan biosynthesis, related to polymer formation (polymerases), as well as secondary modifications (sulphation and uronic acid epimerization). Therefore, this work not only identifies both the proteoglycan core proteins and glycosaminoglycan biosynthetic enzymes in invertebrates but also provides a novel method for the study of glycosaminoglycan and proteoglycan evolution. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)NIHUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, BrazilUniv Texas El Paso, Dept Biol Sci, Border Biomed Res Ctr, El Paso, TX 79912 USAUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, BrazilNIH: 2G12RR008124-16A1NIH: 2G12RR008124-16A1S1Web of Scienc

Low molecular weight heparins: Structural differentiation by spectroscopic and multivariate approaches

Various branded low molecular weight heparins (LMWHs) have been used for the treatment and prevention of thrombotic for over 20 years. With the introduction of generic LMWHs and the recent events involving heparin contamination, a great deal of effort is being expended in investigating ways of monitoring and regulating this class of complex drugs. in this paper, we present the characterization of different forms of LMWHs, as well as the comparison of 5 enoxaparin copies from different manufactures. the data suggests that, while some of these drugs are structurally comparable, specific analytical methods as well as biological and pharmacological tests may be used to address their similarity, quality and potential interchangeability. the proposed approach may also be useful in comparing biosimilar and branded LMWHs. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, SP, BrazilUniv Liverpool, Sch Biol Sci, Liverpool L69 7ZB, Merseyside, EnglandLoyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USAUniv Fed Parana, Lab Quim Carboidratos, Dept Bioquim & Biol Mol, BR-81531980 Curitiba, Parana, BrazilUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, SP, BrazilWeb of Scienc

A New Approach for Heparin Standardization: Combination of Scanning UV Spectroscopy, Nuclear Magnetic Resonance and Principal Component Analysis

The year 2007 was marked by widespread adverse clinical responses to heparin use, leading to a global recall of potentially affected heparin batches in 2008. Several analytical methods have since been developed to detect impurities in heparin preparations; however, many are costly and dependent on instrumentation with only limited accessibility. A method based on a simple UV-scanning assay, combined with principal component analysis (PCA), was developed to detect impurities, such as glycosaminoglycans, other complex polysaccharides and aromatic compounds, in heparin preparations. Results were confirmed by NMR spectroscopy. This approach provides an additional, sensitive tool to determine heparin purity and safety, even when NMR spectroscopy failed, requiring only standard laboratory equipment and computing facilities

A precisão do diagnóstico de depressão na doença de Parkinson: um estudo comparativo entre a UPDRS, a escala geriátrica de depressão e o inventário de depressão de Beck

OBJECTIVE: Evaluate the accuracy of diagnosis of major depression in patients with Parkinson's disease (PD) using the UPDRS, the 15-item Geriatric Depression Scale (GDS15) and the Beck Depression Inventory (BDI). METHOD: 50 consecutive patients with PD were evaluated. The diagnosis of major depression was made according to the DSM-IV criteria. RESULTS: We found a 24% prevalence of major depression. All depression scales were highly correlated but UPDRS depression item had the lowest diagnostic value. The GDS15 had the more appropriate "receiver operating characteristics" curve. The best cut-off scores for screening depression were 17/18 for BDI and 8/9 for GDS15. We did not find any correlation between the level of depression and intensity of motor symptoms, functional capacity and duration of the disease. CONCLUSION: GDS15 is better than the BDI and the UPDRS for screening depression in PD and depression is not related to the degree of parkinsonian symptoms.OBJETIVO: Avaliar a precisão do diagnóstico de depressão em pacientes com doença de Parkinson avaliados pela UPDRS, pela Escala Geriátrica de Depressão com 15 itens (EGD15) e pelo Inventário de Depressão de Beck (IDB). MÉTODO: 50 pacientes com DP foram avaliados. O diagnóstico de depressão maior foi feito segundo os critérios do DSM-IV. RESULTADOS: A prevalência de depressão foi 24%. As escalas de depressão tiveram elevada correlação entre si. A UPDRS apresentou a menor sensibilidade para o diagnóstico. A EGD15 mostrou uma curva ROC mais apropriada que o IDB. Os melhores escores-de-corte para diagnóstico de depressão foram 17/18 para o IDB e 8/9 para a EGD15. Não houve correlação entre os níveis de depressão e a intensidade do parkinsonismo, a capacidade funcional ou a duração da doença. CONCLUSÃO: A EGD15 é melhor que o IDB para diagnosticar depressão na DP. A depressão não está relacionada à gravidade dos sintomas parkinsonianos

Frequency and Characterization of Movement Disorders in Anti-IgLON5 Disease

Background and Objectives Anti-IgLON5 disease is a recently described neurologic disease that shares features of autoimmunity and neurodegeneration. Abnormal movements appear to be frequent and important but have not been characterized and are underreported. We describe the frequency and types of movement disorders in a series of consecutive patients with this disease. Methods In this retrospective, observational study, the presence and phenomenology of movement disorders were assessed with a standardized clinical questionnaire. Available videos were centrally reviewed by 3 experts in movement disorders. Results Seventy-two patients were included. In 41 (57%), the main reason for initial consultation was difficulty walking along with one or several concurrent movement disorders. At the time of anti-IgLON5 diagnosis, 63 (87%) patients had at least 1 movement disorder with a median of 3 per patient. The most frequent abnormal movements were gait and balance disturbances (52 patients [72%]), chorea (24 [33%]), bradykinesia (20 [28%]), dystonia (19 [26%]), abnormal body postures or rigidity (18 [25%]), and tremor (15 [21%]). Other hyperkinetic movements (myoclonus, akathisia, myorhythmia, myokymia, or abdominal dyskinesias) occurred in 26 (36%) patients. The craniofacial region was one of the most frequently affected by multiple concurrent movement disorders (23 patients [32%]) including dystonia (13), myorhythmia (6), chorea (4), or myokymia (4). Considering any body region, the most frequent combination of multiple movement disorders consisted of gait instability or ataxia associated with craniofacial dyskinesias or generalized chorea observed in 31 (43%) patients. In addition to abnormal movements, 87% of patients had sleep alterations, 74% bulbar dysfunction, and 53% cognitive impairment. Fifty-five (76%) patients were treated with immunotherapy, resulting in important and sustained improvement of the movement disorders in only 7 (13%) cases. Discussion Movement disorders are a frequent and leading cause of initial neurologic consultation in patients with anti-IgLON5 disease. Although multiple types of abnormal movements can occur, the most prevalent are disorders of gait, generalized chorea, and dystonia and other dyskinesias that frequently affect craniofacial muscles. Overall, anti-IgLON5 disease should be considered in patients with multiple movement disorders, particularly if they occur in association with sleep alterations, bulbar dysfunction, or cognitive impairment