Effects of flavonoids on glycosaminoglycan synthesis: implications for substrate reduction therapy in Sanfilippo disease and other mucopolysaccharidoses

Sanfilippo disease (mucopolysaccharidosis type III, MPS III) is a severe metabolic disorder caused by accumulation of heparan sulfate (HS), one of glycosaminoglycans (GAGs), due to a genetic defect resulting in a deficiency of GAG hydrolysis. This disorder is characterized as the most severe neurological form of MPS, revealing rapid deterioration of brain functions. Among therapeutic approaches for MPS III, one of the most promising appears to be the substrate reduction therapy (SRT). Genistein (5, 7-dihydroxy-3- (4-hydroxyphenyl)-4H-1-benzopyran-4-one) is an isoflavone that has been used in SRT for MPS III. In this report, we tested effects of other flavonoids (apigenin, daidzein, kaempferol and naringenin) on GAG synthesis. Their cytotoxicity and anti-proliferation features were also tested. We found that daidzein and kaempferol inhibited GAG synthesis significantly. Moreover, these compounds were able to reduce lysosomal storage in MPS IIIA fibroblasts. Interestingly, although genistein is believed to inhibit GAG synthesis by blocking the tyrosine kinase activity of the epidermal growth factor receptor, we found that effects of other flavonoids were not due to this mechanism. In fact, combinations of various flavonoids resulted in significantly more effective inhibition of GAG synthesis than the use of any of these compounds alone. These results, together with results published recently by others, suggest that combination of flavonoids can be considered as a method for improvement of efficiency of SRT for MPS III

Biology of human hair: Know your hair to control it

Hair can be engineered at different levels—its structure and surface—through modification of its constituent molecules, in particular proteins, but also the hair follicle (HF) can be genetically altered, in particular with the advent of siRNA-based applications. General aspects of hair biology are reviewed, as well as the most recent contributions to understanding hair pigmentation and the regulation of hair development. Focus will also be placed on the techniques developed specifically for delivering compounds of varying chemical nature to the HF, indicating methods for genetic/biochemical modulation of HF components for the treatment of hair diseases. Finally, hair fiber structure and chemical characteristics will be discussed as targets for keratin surface functionalization

Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness

Life & Brain GmbH; the BONFOR programme of the University of Bonn; and the Agency for Science, Technology and Research (A*STAR). M.M.N. is a member of the DFG Excellence Cluster ImmunoSensation

Fluxograma diferencial entre a artrite séptica e sinovite transitória do quadril em crianças Flowchart distinguishing between septic arthritis and transitory synovitis of the hip in children

O diagnóstico diferencial entre a artrite séptica e a sinovite transitória do quadril não é fácil de ser realizado, pois não há um exame que seja simples, nem satisfatoriamente sensível e específico para diferenciá-las. Sendo assim, é muitas vezes utilizada uma propedêutica armada de exames que demanda maior custo e requer melhor infra-estrutura da instituição de saúde. Perante isso, torna-se evidente a necessidade de uma análise multifatorial dos dados clínicos e laboratoriais envolvidos para a proposição de um fluxograma em que se possa racionalizar exames visando a correta abordagem e evitar a indicação de procedimentos, muitas vezes, desnecessários como a ressonância magnética ou mais invasivos como a artrocentese e a própria drenagem cirúrgica. Realizamos uma ampla revisão da literatura nas bases de dados do Pubmed e Cochrane até maio de 2009 em que foi analisada a importância do exame clínico, dos testes laboratoriais e de imagem para a diferenciação entre as duas afecções. Mediante o cruzamento dos dados foi elaborado um fluxograma para o diagnóstico e conduta na criança e no adolescente, com idade de seis meses a dezoito anos, com sintoma de dor no quadril, na suspeita de quadro inflamatório. Nivel de Evidência III, estudos diagnósticos, investigação de um exame para diagnóstico.<br>The distinguishing diagnosis between the septic arthritis and the transitory synovitis of a hip is not easy to be carried through; therefore, there is not a simple, nor sensible and satisfactorily specific examination to differentiate them. Thus, the use of a propedeutic set of examinations becomes necessary to demand greater cost and depend on a bigger infrastructure of the health institution. First of all, the necessity of a multifactorial analysis on a flowchart is evident, so it can rationalize the indication of unnecessary or more invasive procedures as artrocentesis, magnetic resonance and the surgical draining. A revision of literature on the databases of Pubmed and Cochrane until May of 2009 was carried through, and the importance of the clinical examination, laboratorial tests and imaging exams was analyzed. By studies on the data, it was elaborated a flowchart for the diagnosis and the conduction of the management on the patient, between the ages of six months and eighteen years old, with complaint of pain on the hip under suspicion of inflammatory picture. Level of Evidence: Level III, diagnostic studies - investigating a diagnostic test