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Mutations in the ATP6 gene are reported to be associated with Leber hereditary optic neuropathy, bilateral striatal necrosis, coronary atherosclerosis risk and neuropathy, ataxia and retinitis pigmentosa ( NARP)/maternally inherited Leigh syndromes. Here, we present a patient with NARP syndrome, in whom a previously undescribed mutation was detected in the ATP6 gene: m. 8839G>C. Several observations support the concept that m. 8839G>C is pathogenically involved in the clinical phenotype of this patient: (1) the mutation was heteroplasmic in muscle; (2) mutation load was higher in the symptomatic patient than in the asymptomatic carriers; (3) cybrids carrying this mutation presented lower cell proliferation, increased mitochondrial DNA ( mtDNA) copy number, increased steady-state OxPhos protein levels and decreased mitochondrial membrane potential with respect to isogenic wild-type cybrids; (4) this change was not observed in 2959 human mtDNAs from different mitochondrial haplogroups; (5) the affected amino acid was conserved in all the ATP6 sequences analyzed; and (6) using in silico prediction, the mutation was classified as 'probably damaging'. However, measurement of ATP synthesis showed no differences between wild-type and mutated cybrids. Thus, we suggest that m. 8839G>C may lower the efficiency between proton translocation within F0 and F1 rotation, required for ATP synthesis. Further experiments are needed to fully characterize the molecular mechanisms involved in m. 8839G>C pathogenicity. [ABSTRACT FROM AUTHOR]

Background:The metabolic response to surgery includes alterations in protein metabolism, resulting in a net loss of proteins. Protein hypercatabolism is considered an unavoidable consequence of injury, and an important source of morbidity and mortality. Our purpose was to determine the effect of nutrition on protein metabolism following gastrointestinal surgery, and to elucidate whether postoperative protein loss can be prevented with adequate nutritional support.Methods:Patients who had undergone gastrointestinal surgery were given four different parenteral nutritions with increasing glucose, lipid and amino acid content during the 7 days following surgery. Nitrogen balance, protein synthesis and protein breakdown were determined using in vivo stable isotope labelling. Other metabolites (3-methylhistidine, creatinine, urea, cortisol, glucose, insulin, amino acids and C-reactive protein) were measured.Results:A nutrition-dependent alteration of protein metabolism was found in response to surgical injury. Nutrition modified nitrogen balance, whole-body protein breakdown and, to a lesser extent, whole-body protein synthesis and muscle protein breakdown. The low-energy parenteral nutrition without amino acids produced a negative nitrogen balance (postoperative day 7=−0.381 g protein kg−1day−1) and important alterations in postoperative protein metabolism that did not normalize during the study period (day 7 protein synthesis=239% and protein breakdown 217% vs preoperative). Patients receiving the two low energy parenteral nutritions containing amino acids had a less negative nitrogen balance (day 7=−0.011 and −0.133 g protein kg−1day−1) and a transient increase in protein metabolism. The complete parenteral nutrition maintained, during all studied days, protein metabolism parameters within the preoperative reference range (synthesis day 2=92%, day 4=110% day 7=79%; breakdown day 2=85%, day 4=80%, day 7=76% vs preoperative) and a positive nitrogen balance (day 2=+0.0387, day 4=+0.578 and day 7=+0.227 g protein kg−1day−1).Conclusion:Complete nutritional support can prevent protein loss after gastrointestinal surgery and maintain protein metabolism without alterations.European Journal of Clinical Nutrition (2008) 62, 254–262; doi:10.1038/sj.ejcn.1602732; published online 21 March 2007 [ABSTRACT FROM AUTHOR]

Background: Intravitreal triamcinolone has increasingly been used for the treatment of oedematous and neovascular diseases and purification of triamcinolone suspension may be important in order to avoid the potential toxic effects of the vehicle. The aim was to evaluate different techniques used to reduce the solvent agent benzyl alcohol (9.9 mg/ml) from a commercially prepared triamcinolone acetonide suspension. Methods: Different techniques were used to reduce the solvent agent benzyl alcohol: filter techniques using 0.22 μm or 5 μm pore size, and non-filter techniques using sedimentation or centrifugation. Quantification of triamcinolone acetonide and benzyl alcohol was performed by high pressure liquid chromatography (HPLC). Results: Benzyl alcohol concentration was decreased significantly in all the techniques used compared with the original commercial suspension (p<0.05), with no significant differences among them. The reduction was approximately one tenth of its original concentration. However, triamcinolone acetonide concentration differed significantly depending on the method used. Centrifugation method showed no differences versus the original commercial solution; sedimentation technique reduced the expected dose only 25%; the filter technique using a 5 μm pore size membrane reduced the expected dose to one fourth, while the filter technique using a 0.22 μm pore size membrane reduced the expected dose to 45%. Conclusions: All the different techniques employed effectively reduced the concentration of benzyl alcohol. However, the final concentration of triamcinolone was much lower than expected using the filter techniques. The pore size membrane inversely influenced the final concentration, with part of the triamcinolone crystals probably being entrapped in the filter. Centrifugation is recommended as the best way of administering the drug. [ABSTRACT FROM AUTHOR]