Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure

COENZYME Q10 IN PHYSICAL EXERCISE. We identified eleven studies in which CoQ10 was tested for an effect on exercise capacity, six showed a modest improvement in exercise capacity with CoQ10 supplementation but five showed no effect. CoQ10 IN HYPERTENSION. We identified eight published trials of CoQ10 in hypertension. Altogether in the eight studies the mean decrease in systolic blood pressure was 16 mm Hg and in diastolic blood pressure, 10 mm Hg. Being devoid of significant side effects CoQ10 may have a role as an adjunct or alternative to conventional agents in the treatment of hypertension. CoQ10 IN HEART FAILURE. We performed a randomised double blind placebo-controlled pilot trial of CoQ10 therapy in 35 patients with heart failure. Over 3 months, in the CoQ10 patients but not in the placebo patients there were significant improvements in symptom class and a trend towards improvements in exercise time. META-ANALYSIS OF RANDOMISED TRIALS OF COENZYME Q10 IN HEART FAILURE. In nine randomised trials of CoQ10 in heart failure published up to 2003 there were non-significant trends towards increased ejection fraction and reduced mortality. There were insufficient numbers of patients for meaningful results. To make more definitive conclusions regarding the effect of CoQ10 in cardiac failure we recommend a prospective, randomised trial with 200-300 patients per study group. Further trials of CoQ10 in physical exercise and in hypertension are recommended.     

Mapping of a restriction fragment length polymorphism within the human aldolase B gene

Summary Peripheral blood DNA was hybridized to the full-length cDNA and the cloned structural gene of human aldolase B. With PvuII endonuclease a restriction fragment length polymorphism was detected that was present in the heterozygous state in about 21% of the individuals tested. A map of the human aldolase gene was constructed for the two groups of individuals found to produce different fragments after PvuII digestion. This allowed the localization of the polymorphic site within the gene, which was found to be due to the loss of a PvuII site in the last intron upstream from the 3 end. This polymorphism may be used as a genetic marker to study individuals affected by hereditary fructose intolerance.     

Electronic and vibrational polarizabilities of the twenty naturally occurring amino acids

The geometries, relative energies, gas-phase static and dynamic dipole polarizabilities of the two most stable neutral forms and of the zwitterionic form of the twenty naturally occurring amino acids have been obtained by Density Functional and conventional ab initio Hatree-Fock theories using correlation consistent basis sets. Mean electronic polarizabilities (s) are encompassed in the 40-160 a.u. range and are little dependent on the amino acid framework conformation and structure. The relation between and the number of electrons in the molecule makes to classify the amino acids as one of the most polarizable family of compounds. Calculated values of the neutral forms linearly relate to the molecular volume and molecular hardness as well as, rather unexpectedly, with the experimental values in water solution, where amino acids are known to be in a zwitterionic form. Vibrational polarizabilities amount to 15-45 a.u.. They come essentially from the low-frequency angular deformation modes of the -OH and -NH(2) groups.     

Differential distribution of aldolase A and C in the human central nervous system

We have analyzed the distribution of aldolase A and C mRNAs and proteins in various areas of the human brain using Northern blot analyses and immunohistochemistry. Aldolase A mRNA expression was higher than aldolase C mRNA expression in all areas of the brain examined. Aldolase C mRNA expression was highest in the cerebellum. Aldolase C protein was present in well-delimited regions of the CNS, and was distributed in stripes in the Purkinje cell layer of the cerebellum, in the inferior olives and in the sensory neurons of the posterior horn of the spinal cord. The novel finding of aldolase C in well-delimited cell compartments of the human cerebellum and in several other areas of the CNS lends weight to the hypothesis that this protein exerts other functions (e.g. sensory transmission) besides those characteristic of a glycolytic enzyme.     

Low-frequency vibrational modes in proteins: a neutron scattering investigation

The low-frequency dynamics of plastocyanin, an electron transfer copper protein, has been investigated by incoherent neutron scattering at different temperatures. The contribution to the dynamic structure factor arising from H/D exchangeable and non-exchangeable protein protons has been evaluated by analyzing two differently exchanged protein samples. The dynamic structure factor of a hydrated plastocyanin sample with all the exchangeable hydrogens (about 150) replaced by deuterium exhibits an excess of vibrational modes, at about 3.5 meV, reminiscent of the boson peak found in other proteins and glassy systems. When only fast exchangeable hydrogens (about 50) are substituted by deuterium, the protein, besides the above-mentioned peak, shows an additional peak at about 1 meV. These vibrational peaks are discussed in connection with the topological disorder of the systems and the fluctuations of the intramolecular hydrogen bonds.     

Spectral analysis of Delayed Luminescence from human skin as a possible non-invasive diagnostic tool

In vivo measurements of Delayed Luminescence (DL), the low-level photo-induced emission which lasts for a longer time after switching off the excitation light, have been performed on human skin, with the aim to develop a technique for optical biopsy. Preliminary tests have been performed on healthy volunteers, measuring the time decays of the spectral components (λ_emiss = 400–800 nm) starting 10 μs after switching off the excitation (λ_exc = 337 nm). Significant differences in the decay trends of DL from different subjects were revealed and quite a good reproducibility for the same subject was observed. The modeling of experimental data has been examined in detail in order to get parameters, characterizing the theoretical fit, whose changes may be correlated with age differences and seasonal variations. Proceedings of the XVIII Congress of the Italian Society of Pure and Applied Biophysics (SIBPA), Palermo, Sicily, September 2006.     

Denitrosylate and live longer: how ADH5/GSNOR links mitophagy to aging

Mitochondrial dynamics is required to adapt the manifold functions of mitochondria to cell needs and regulate their turnover by mitophagy. Actually, only if fragmented, mitochondria are engulfed by phagophores, the precursors to autophagosomes, and subsequently degraded. This process is essential to maintain a correct and healthy number of mitochondria that, otherwise, might be harmful. They, indeed, represent the main source of reactive oxygen species that – according to the mitochondrial free radical theory of aging – can cause aging when chronically overproduced. In a recent study, we demonstrated that S-nitrosylation, the reversible modification of cysteine residues by nitric oxide (NO), hyperactivates mitochondrial fragmentation by targeting DNM1L/Drp1 (dynamin 1-like) at Cys644, but inhibits mitophagy, the concomitant occurrence of these conditions driving cell senescence. We demonstrated that cell senescence, as well as mouse and human aging are characterized by an epigenetically-driven decrease in ADH5/GSNOR (alcohol dehydrogenase 5 [class III], chi polypeptide), suggesting that ADH5 may act as new longevity gene.     

A mechanistic model on the role of “radially-running” collagen fibers on dissection properties of human ascending thoracic aorta

Aortic dissection (AoD) is a common condition that often leads to life-threatening cardiovascular emergency. From a biomechanics viewpoint, AoD involves failure of load-bearing microstructural components of the aortic wall, mainly elastin and collagen fibers. Delamination strength of the aortic wall depends on the load-bearing capacity and local micro-architecture of these fibers, which may vary with age, disease and aortic location. Therefore, quantifying the role of fiber micro-architecture on the delamination strength of the aortic wall may lead to improved understanding of AoD. We present an experimentally-driven modeling paradigm towards this goal. Specifically, we utilize collagen fiber micro-architecture, obtained in a parallel study from multi-photon microscopy, in a predictive mechanistic framework to characterize the delamination strength. We then validate our model against peel test experiments on human aortic strips and utilize the model to predict the delamination strength of separate aortic strips and compare with experimental findings. We observe that the number density and failure energy of the radially-running collagen fibers control the peel strength. Furthermore, our model suggests that the lower delamination strength previously found for the circumferential direction in human aorta is related to a lower number density of radially-running collagen fibers in that direction. Our model sets the stage for an expanded future study that could predict AoD propagation in patient-specific aortic geometries and better understand factors that may influence propensity for occurrence.     

The biosynthetic pathway of new polyamines in Caldariella acidophila

A spontaneous mutant of Escherichia coli (strain AB2847), selected for resistance to the aminoglycoside antibiotic neamine, shows severe restriction of amber suppressors in vivo. Ribosomes isolated from the mutant exhibit only low misreading in vitro in the presence of the antibiotic. Genetic and biochemical analyses indicate that the neamine-resistant phenotype is the result of two distinct mutations. The first, res3128, appears to affect the gene (strA) coding for the ribosomal protein S12. Although it leads to a restrictive phenotype it does not, however, confer resistance to streptomycin. The second mutation, X3128, is located between the sirA and AROB loci and is lethal when segregated from the res3128 mutation. It may affect the ribosome at the level of a post-translational modification.