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Saccharomyces cerevisiae Coq8 is a member of the ancient UbiB atypical protein kinase family. Coq8, and its orthologs UbiB, ABC1, ADCK3, and ADCK4, are required for the biosynthesis of coenzyme Q in yeast, E. coli, A. thaliana, and humans. Each Coq8 ortholog retains nine highly conserved protein kinase-like motifs, yet its functional role in coenzyme Q biosynthesis remains mysterious. Coq8 may function as an ATPase whose activity is stimulated by coenzyme Q intermediates and phospholipids. A key yeast point mutant expressing Coq8-A197V was previously shown to result in a coenzyme Q-less, respiratory deficient phenotype. The A197V substitution occurs in the crucial Ala-rich protein kinase-like motif I of yeast Coq8. Here we show that long-term cultures of mutants expressing Coq8-A197V produce spontaneous revertants with the ability to grow on medium containing a non-fermentable carbon source. Each revertant is shown to harbor a secondary intragenic suppressor mutation within the COQ8 gene. The intragenic suppressors restore the synthesis of coenzyme Q. One class of the suppressors fully restores the levels of coenzyme Q and key Coq polypeptides necessary for the maintenance and integrity of the high-molecular mass CoQ synthome (also termed complex Q), while the other class provides only a partial rescue. Mutants harboring the first class of suppressors grow robustly under respiratory conditions, while mutants containing the second class grow more slowly under these conditions. Our work provides insight into the function of this important yet still enigmatic Coq8 family.

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Coenzyme Q (CoQ or ubiquinone) serves as an essential redox-active lipid in respiratory electron and proton transport during cellular energy metabolism. CoQ also functions as a membrane-localized antioxidant protecting cells against lipid peroxidation. CoQ deficiency is associated with multiple human diseases; CoQ10 supplementation in particular has noted cardioprotective benefits. In Saccharomyces cerevisiae, Coq10, a putative START domain protein, is believed to chaperone CoQ to sites where it functions. Yeast coq10 deletion mutants (coq10Δ) synthesize CoQ inefficiently during log phase growth and are respiratory defective and sensitive to oxidative stress. Humans have two orthologs of yeast COQ10, COQ10A and COQ10B Here, we tested the human co-orthologs for their ability to rescue the yeast mutant. We showed that expression of either human ortholog, COQ10A or COQ10B, rescues yeast coq10Δ mutant phenotypes, restoring the function of respiratory-dependent growth on a nonfermentable carbon source and sensitivity to oxidative stress induced by treatment with PUFAs. These effects indicate a strong functional conservation of Coq10 across different organisms. However, neither COQ10A nor COQ10B restored CoQ biosynthesis when expressed in the yeast coq10Δ mutant. The involvement of yeast Coq10 in CoQ biosynthesis may rely on its interactions with another protein, possibly Coq11, which is not found in humans. Coexpression analyses of yeast COQ10 and human COQ10A and COQ10B provide additional insights to functions of these START domain proteins and their potential roles in other biologic pathways.

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OBJECTIVES: This monocentric, observational and retrospective survey was performed to check the appropriateness between aminoglycoside prescriptions and inhibitor quotient to be reached, in Intensive Care Unit (ICU) patients. We identified variability factors for aminoglycoside plasmatic concentrations at peak such as standardized index of gravity (IGS2 scale), age, sex, weight, and severity of sepsis. PATIENTS AND METHOD: Eighty-seven ICU patients received an antibiotic combination mandatorily including an aminoglycoside (amikacin or gentamicin) as curative treatment for a severe infection. Prescribed dosages were 15mg/kg for amikacin and 5mg/kg for gentamicin. The maximal concentration (Cmax) and minimal inhibiting concentration (MIC) of involved bacteria were recorded. The aminoglycoside ratio Cmax/MIC, called inhibitor quotient, was determined. The inhibitor quotient was considered efficient when superior to 10. The Cmax for aminoglycoside first peak was also compared with the theoretical Cmax to be reached. RESULTS: In the aminoglycoside Cmax, 50.3% were efficient (59.6% for amikacin Cmax and 38.9% for gentamicin Cmax). In 46% of the cases, the inhibitor quotient was efficient; 12.6% of Cmax reached the theoretical Cmax. Factors identified as negatively interacting with biological efficiency were: Gram-positive bacteria or anaerobic bacteria infections and planned surgery. CONCLUSION: In the inhibitor quotients, 49.7% were at inefficient rates, even when the recommended aminoglycoside dosage for was given. Therefore, dose and administration should be updated.

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A characteristic feature of Helicobacterpylori infection in developing countries is early acquisition of the bacteria during childhood. Recent study has documented the frequency of transient infection in young children in particular during the first year following eradication therapy. Children living in developing countries present several risk factors for acquisition including crowding, young age, and recurrent gastroenteritis. The risk of infection increases significantly in function of the number of infected persons in a child's family. Using molecular biology techniques based on gene sequencing, we have shown that strains in different members of the same family were identical not only between parents and children but also between siblings. The relationship between chronic diarrhoea, retarded growth, iron-deficient anaemia, and Helicobacter pylori infection in children especially from developing countries remains controversial. Gram staining of biopsy smears to detect Helicobacter pylori is an efficient diagnostic method and can be a good alternative when culture is unfeasible. Respiratory testing and detection of antigens in stools are effective and appear to be well suited to diagnosis of Helicobacter pylori infection. In developing countries Helicobacter pylori is a common infectious agent warranting further study to gain insight into clinical presentation, epidemiological features, and treatment requirements including sensitivity to antibiotics

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In order to determine whether the decrease in taurine concentration in the placenta during pregnancy could affect fetal development, as has been observed in animals, we measured the concentration of taurine in placentas obtained after vaginal expulsion. 31 placentas from women with normal pregnancies of over 37 weeks who have given birth to infants of normal weight (3,200 +/- 310 g) were included in the study. In addition, 26 placentas of infants considered to be hypotrophic were also included (gestation over 37 weeks, birth weight: 2,260 +/- 230 g). The taurine was assayed using gaz-liquid chromatography. The concentration of taurine in the placenta was 2.80 +/- 0.56 mumol/g for the placentas of normal birth weight infants and 2.40 +/- 0.64 mumol/g for the placentas of hypotrophic infants (p less than 0.02). There is no significant correlation in normal and hypotrophic newborns between the gestation period, the weight and height at birth, the weight of the placenta, and the taurine concentration in the placenta. The taurine concentration in placentas of hypotrophic born infants is significantly reduced compared to the placentas from normal infants.

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In order to evaluate tissue taurine storage during pregnancy, we determined the taurine concentration of a skeletal muscle (abdominal wall), the brain (left parietal lobe), and the liver (right lobe) in 41 children aged 1-10 days, born after 24-41 weeks gestation. Samples were obtained during autopsy. Taurine dosage was carried out by gas chromatography. Muscle and liver taurine concentrations decreased with the duration of gestation. For a given duration of pregnancy, there was no correlation between birth weight and these three tissue concentrations. From these results, we estimate that the fetus accumulates 35-40 mumol/24 h of taurine during the last 3 months of gestation.

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Taurine may function in brain as a neuroinhibitor, and intracerebroventricular taurine has the capacity to induce hypothermia. Its antiepileptic properties have been observed in animals and humans. On the basis of these data, we studied taurine concentration in the cerebrospinal fluid of 32 children with simple febrile convulsions (16 +/- 6 months) and of 25 children with acute hyperthermia without neurologic signs (13 +/- 8 months). Taurine concentration in cerebrospinal fluid was similar in febrile convulsion children (8 +/- 4 mumol/l) compared to a control group (7.8 +/- 3 mumol/l).

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Lean body mass was estimated in 15 adequately nourished and afebrile children, aged 1 to 24 months, receiving parenteral and/or enteral nutrition with anthropometric measurements (30 analyses). At the same time, muscle mass was evaluated from the 24 hour-urinary excretion of creatinine and 3-methylhistidine. Statistical computations showed and excellent correlation between the results obtained by both methods. The stable conditions for these children receiving artificial nutrition (normal nitrogen, carbohydrate and fat intakes, excluding exogenous creatinine and 3-methylhistidine) allow the use of these two biological measurements as markers of muscle mass and provide a control for the validity of the results of anthropometric measurements. Urinary excretion of 3-methyl-histidine not correlated with that of creatinine or with anthropometric data should suggest an increase in myofibrillary catabolism. These 3 simple, non invasive tests may be particularly useful in patients receiving artificial nutrition, to study the short- and long-term efficacy of the methods of artificial feeding used and to modulate the intake of nitrogen, carbohydrates and fat.

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