ABSTRACT
BACKGROUND: Coenzyme Q10 (CoQ10 or ubiquinone) deficiency can be due either to mutations in genes involved in CoQ10 biosynthesis pathway, or to mutations in genes unrelated to CoQ10 biosynthesis. CoQ10 defect is the only oxidative phosphorylation disorder that can be clinically improved after oral CoQ10 supplementation. Thus, early diagnosis, first evoked by mitochondrial respiratory chain (MRC) spectrophotometric analysis, then confirmed by direct measurement of CoQ10 levels, is of critical importance to prevent irreversible damage in organs such as the kidney and the central nervous system. It is widely reported that CoQ10 deficient patients present decreased quinone-dependent activities (segments I + III or G3P + III and II + III) while MRC activities of complexes I, II, III, IV and V are normal. We previously suggested that CoQ10 defect may be associated with a deficiency of CoQ10-independent MRC complexes. The aim of this study was to verify this hypothesis in order to improve the diagnosis of this disease. RESULTS: To determine whether CoQ10 defect could be associated with MRC deficiency, we quantified CoQ10 by LC-MSMS in a cohort of 18 patients presenting CoQ10-dependent deficiency associated with MRC defect. We found decreased levels of CoQ10 in eight patients out of 18 (45 %), thus confirming CoQ10 disease. CONCLUSIONS: Our study shows that CoQ10 defect can be associated with MRC deficiency. This could be of major importance in clinical practice for the diagnosis of a disease that can be improved by CoQ10 supplementation.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Ataxia/genetics , Electron Transport/genetics , Mutation , Mitochondrial Diseases/genetics , Muscle Weakness/genetics , Ubiquinone/analogs & derivatives , Ubiquinone/deficiency , Ataxia/diagnosis , Ataxia/metabolism , Biopsy , Cells, Cultured , Chromatography, Liquid , Fibroblasts/enzymology , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/metabolism , Muscle Weakness/diagnosis , Muscle Weakness/metabolism , Muscles/pathology , Spectrophotometry/methods , Tandem Mass Spectrometry/methods , Ubiquinone/biosynthesis , Ubiquinone/genetics , Ubiquinone/metabolismABSTRACT
The purpose of this ex vivo study was to determine, in "open" and "closed" systems, whether the design has an influence on the penetration length of sodium hypochlorite mixed with a radiopaque contrast medium, measured in millimeters, when delivered using positive pressure (PP) and using sonic (SI) or passive ultrasonic (PUI) activation. Sixty single-rooted teeth were divided into two groups: open and closed systems (n=30). Root canal shaping was performed to a working length of 17 mm. The samples were divided into three sub-groups (n=10) according to irrigant delivery and activation: PP, and SI or PUI activation. By using radiographs, penetration length was measured, and vapor lock was assessed. For the closed group, the penetration distance means were: PP 15.715 (±0.898) mm, SI 16.299 (±0.738) mm and PUI 16.813 (±0.465) mm, with vapor lock occurring in 53.3% of the specimens. In the open group, penetration to 17 mm occurred in 97.6% of the samples, and no vapor lock occurred. Irrigant penetration and distribution evaluation using open and closed systems provide significantly different results. For closed systems, PUI is the most effective in delivering the irrigant to working length, followed by SI.
O objetivo deste estudo in vivo foi determinar, para os sistemas "abertos" e "fechados", se o design tem influência na penetração, em milímetros, do hipoclorito de sódio misturado com um meio radiopaco quando empregado na ativação com pressão positiva (PP) e ativação sônica (SI) ou ultrassônica passiva (PUI). Sessenta dentes unirradiculares foram divididos em dois grupos: sistema aberto e sistema fechado (n=30). Os canais radiculares foram trabalhados até um comprimento de trabalho de 17 mm. Os grupos foram subdivididos em três subgrupos (n=10) de acordo com a solução irrigadora e a ativação: PP, e ativação SI ou PUI. Usando radiografias, a distância de penetração foi medida e avaliado o vapor contido. Para o grupo fechado, as distâncias médias de penetração foram PP 15,715 (±0,898) mm, SI 16,299 (±0,738) mm e PUI 16,813 (±0,465) mm e houve vapor contido em 53,3% das amostras. No grupo aberto, houve penetração de 17 mm em 97.6% das amostras, sem contenção de vapor. A penetração do irrigante e avaliação da distribuição usando sistemas aberto e fechado produziram resultados significativamente diferentes. Para os sistemas fechados, PUI é mais eficaz para levar o irrigante até preencher o comprimento de trabalho, seguido por SI.
Subject(s)
Animals , Mice , Ubiquinone/metabolism , /analogs & derivatives , /chemical synthesis , Diffusion , Electron Transport , Fluorescent Dyes , Liposomes , Mice, Inbred ICR , Mitochondria, Liver/metabolism , Phosphatidylethanolamines , Ubiquinone/analogs & derivatives , Ubiquinone/biosynthesis , Ubiquinone/chemical synthesisABSTRACT
The development of new drugs is one strategy for malaria control. Biochemical pathways localised in the apicoplast of the parasite, such as the synthesis of isoprenic precursors, are excellent targets because they are different or absent in the human host. Isoprenoids are a large and highly diverse group of natural products with many functions and their synthesis is essential for the parasite's survival. During the last few years, the genes, enzymes, intermediates and mechanisms of this biosynthetic route have been elucidated. In this review, we comment on some aspects of the methylerythritol phosphate pathway and discuss the presence of diverse isoprenic products such as dolichol, ubiquinone, carotenoids, menaquinone and isoprenylated proteins, which are biosynthesised during the intraerythrocytic stages of Plasmodium falciparum.