Tetrahydrobiopterin: Beyond Its Traditional Role as a Cofactor.

Tetrahydrobiopterin (BH4) is an endogenous cofactor for some enzymatic conversions of essential biomolecules, including nitric oxide, and monoamine neurotransmitters, and for the metabolism of phenylalanine and lipid esters. Over the last decade, BH4 metabolism has emerged as a promising metabolic target for negatively modulating toxic pathways that may result in cell death. Strong preclinical evidence has shown that BH4 metabolism has multiple biological roles beyond its traditional cofactor activity. We have shown that BH4 supports essential pathways, e.g., to generate energy, to enhance the antioxidant resistance of cells against stressful conditions, and to protect from sustained inflammation, among others. Therefore, BH4 should not be understood solely as an enzyme cofactor, but should instead be depicted as a cytoprotective pathway that is finely regulated by the interaction of three different metabolic pathways, thus assuring specific intracellular concentrations. Here, we bring state-of-the-art information about the dependency of mitochondrial activity upon the availability of BH4, as well as the cytoprotective pathways that are enhanced after BH4 exposure. We also bring evidence about the potential use of BH4 as a new pharmacological option for diseases in which mitochondrial disfunction has been implicated, including chronic metabolic disorders, neurodegenerative diseases, and primary mitochondriopathies.

An Exploratory Survey on the Care for Ataxic Patients in the American Continents and the Caribbean.

Little is known about access of rare disease carriers to health care. To increase this knowledge, the Pan American Hereditary Ataxia Network (PAHAN) conducted an exploratory survey about care for hereditary ataxias in American continents and the Caribbean. A questionnaire was sent to health professionals about the hereditary ataxias identified; access to care; and local teaching and research. The number of ataxics under current care per 100,000 inhabitants was subtracted from the expected overall prevalence of 6/100,000, to estimate the prevalence of uncovered ataxic patients. Local Human Development Indexes (HDI) were used to measure socio-economic factors. Twenty-six sites participated. Twelve sites had very high, 13 had high, and one site had medium HDI. Participants reported on 2239 and 602 patients with spinocerebellar ataxias and recessive forms under current care. The number of patients under current care per inhabitants varied between 0.14 and 12/100,000. The estimated prevalence of uncovered ataxic patients was inversely proportional to HDIs (rho = 0.665, p = 0.003). Access to diagnosis, pre-symptomatic tests, and rehabilitation were associated with HDIs. More and better molecular diagnostic tools, protocols and guidelines, and professional training for ataxia care were the top priorities common to all respondents. Evidence of inequalities was confirmed. Lower HDIs were associated with high potential numbers of uncovered ataxic subjects, and with lack of molecular diagnosis, pre-symptomatic testing, and rehabilitation. More and better diagnostic tools, guidelines, and professional training were priorities to all sites. PAHAN consortium might help with the last two tasks.

Idiopathic inflammatory myopathies in childhood: a brief review of 27 cases.

The most common idiopathic inflammatory myopathies in children include juvenile dermatomyositis, juvenile polymyositis, and myositis associated with another autoimmune disease (overlap myositis). Idiopathic inflammatory myopathies manifest different characteristics affecting children. Only a few investigations of childhood idiopathic inflammatory myopathies were reported, involving 27 patients. In addition, clinical findings, serum muscular enzyme levels, results of electromyography studies, muscle biopsy features, and treatment responses were studied. Seventeen female and 10 male were classified as exhibiting juvenile dermatomyositis (n = 19), juvenile polymyositis (n = 6), or overlap myositis (n = 2). Overlap myositis was associated with systemic sclerosis and systemic erythematous lupus. The mean age at onset was 6.1 years for juvenile dermatomyositis, 4.9 years for juvenile polymyositis, and 8.5 years for overlap myositis. The most common signs included proximal weakness and myalgia. The serum creatine kinase level was increased in 48.2% of patients. An electromyography study revealed myopathic features in 85% of patients. Muscle biopsies led to observations of inflammatory infiltrates with preferential perivascular involvement in the juvenile dermatomyositis group, and endomysial involvement in the juvenile polymyositis group. Fiber atrophy was predominantly perifascicular in the juvenile dermatomyositis group. Treatment with prednisone improved the findings in 81.5% of children.

Lesado medular. Estudo prospectivo de 92 casos / Spinal cord lesions: a prospective study of 92 cases

O objetivo do trabalho foi avaliar de forma seriada a função neurológica de pacientes com traumatismo de coluna vertebral e medula espinal, correlacionando-a à reabilitação neurológica durante a internação e a terapêutica estabelecida. Foram estudados, de forma prospectiva, 92 pacientes portadores de traumatismo de coluna vertebral, durante o período de agosto de 2001 a março de 2003. As informações analisadas incluíram: classificação do déficit neurológico nas escala ASIA e de Frankel, na admissão e alta, tratamento adotado, resultados obtidos e a evolução neurológica. Dos 92 casos, 67 estavam intactos neurologicamente, 16 tinham déficit neurológico completo, e, em 8 casos, o déficit era incompleto na admissão. A escala ASIA dos 24 pacientes com déficit neurológico atingiu um índice motor médio de 41,7 (admissão) e 52,06 (alta), com uma diferença de 10,3 pontos. O índice sensitivo foi de 63,4 na admissão e de 82,4 na alta, com diferença de 19 pontos. Dos 38 casos cirúrgicos, 16 tinham déficit neurológico e 22 não. Destes, 21 permaneceram sem déficit com o tratamento cirúrgico e em um caso houve piora neurológica após a cirurgia, com recuperação posterior. Nos 16 casos com dano neurológico verificou-se que 9 melhoraram neirologicamente, 6 mantiveram-se inalterados e 1 piorou. O tratamento conservador foi adotado em 54 casos; entre esses, 4 apresentavam lesão neurológica completa e outros 4, lesão incompleta. Foi indicado quando havia contusão medular e as fraturas eram estáveis, consistindo em colete cervical ou lombar, repouso e analgesia. Seis evoluíram para melhora neurológica e dois permaneceram inalterados. O tratamento realizado (cirúrgico ou conservador) em 24 casos com déficit neurológico levou à melhora de 10,3 pontos no índice motor e de 19 pontos no índice sensitivo.