Respiratory inhibition of isolated mammalian mitochondria by salivary antifungal peptide histatin-5

Histatin-5 is a peptide secreted in the human saliva, which possesses powerful antifungal activity. Previous studies have shown that this peptide exerts its candidacidal activity, through the inhibition of both mitochondrial respiration and the formation of reactive oxygen species. The purpose of the present study was to investigate the biological consequences of histatin-5 action on mammalian mitochondria to verify if the toxic mechanism exerted on mitochondria from Candida albicans is an exclusive for fungal cells. Moreover, hypothesising that the damage exerted on mitochondria may induce programmed cellular death pathways, we evaluated two main markers of apoptosis: the mitochondrial membrane potential (DeltaPsi) and the release of cytochrome c. The results obtained show that exposure of isolated mammalian mitochondria to histatin-5 determines: (i) a large inhibition of the respiratory chain at the level of complex 1, (ii) a slight decrease in the mitochondrial membrane potential, and (iii) no release of cytochrome c. (C) 2003 Elsevier Inc. All rights reserved

Serum Compounds of Energy Metabolism Impairment Are Related to Disability, Disease Course and Neuroimaging in Multiple Sclerosis

Multiple sclerosis (MS) is characterized by primary inflammation, demyelination, and progressive neurodegeneration. A biochemical MS feature is neuronal mitochondrial dysfunction, compensated by anaerobic metabolism increase, likely aggravating progression of neurodegeneration. Here, we characterized a pragmatic serum profile of compounds related to mitochondrial energy metabolism of potential clinical use. Blood samples of 518 well characterized (disability, disease course) MS patients and 167 healthy controls were analyzed for serum purines, pyrimidines, creatinine, and lactate. Nine of the 15 compounds assayed, hypoxanthine, xanthine, uric acid, inosine, uracil, β-pseudouridine, uridine, creatinine, and lactate, differed significantly between MS patients and controls (p < 0.0001). Using these nine compounds, a unifying Biomarker Score was calculated. Controls and MS patients had mean Biomarker Scores of 0.4 ± 0.7 and 4.4 ± 1.9, respectively (p < 0.00001). The Biomarker Score was higher in patients with progressive (6.0 ± 1.8 than with relapsing remitting disease course (3.6 ± 1.5, p < 0.00001). High association between the Biomarker Score and increase in disability (EDSS) was also observed. Additionally, in 50 patients who underwent magnetic resonance imaging (MRI), increase in the Biomarker Score correlated to neuroanatomical alterations. These results, obtained in a large cohort of MS patients evaluated for serum metabolic compounds connected to energy metabolism, demonstrated that the Biomarker Score might represent a pragmatic, resource saving, easy to obtain, laboratory tool useful to monitor MS patients and predict at an early stage who will switch from an RR to a progressive disease course. For the first time, it was also clearly shown a link between mitochondrial dysfunction and MRI lesions characteristic of MS

Level Statistics of XXZ Spin Chains with Discrete Symmetries: Analysis through Finite-size Effects

Level statistics is discussed for XXZ spin chains with discrete symmetries for some values of the next-nearest-neighbor (NNN) coupling parameter. We show how the level statistics of the finite-size systems depends on the NNN coupling and the XXZ anisotropy, which should reflect competition among quantum chaos, integrability and finite-size effects. Here discrete symmetries play a central role in our analysis. Evaluating the level-spacing distribution, the spectral rigidity and the number variance, we confirm the correspondence between non-integrability and Wigner behavior in the spectrum. We also show that non-Wigner behavior appears due to mixed symmetries and finite-size effects in some nonintegrable cases.Comment: 19 pages, 6 figure

Electronic States and Superconductivity in Multi-layer High-Tc Cuprates

We study electronic states of multilayer cuprates in the normal phases as functions of the number of CuO_2 planes and the doping rate. The resonating valence bond wave function and the Gutzwiller approximation are used for a two-dimensional multilayer t-t'-t''-J model. We calculate the electron-removal spectral functions at (\pi,0) in the CuO_2 plane next to the surface to understand the angle-resolved photoemission spectroscopy (ARPES) spectra. We find that the trilayer spectrum is narrower than the bilayer spectrum but is wider than the monolayer spectrum. In the tri- and tetralayer systems, the outer CuO_2 plane has different superconducting amplitude from the inner CuO_2 plane, while each layer in the bilayer systems has same amplitude. The recent ARPES and NMR experiments are discussed in the light of the present theory.Comment: 7 pages, 7 figure

Extended Aharonov-Bohm period analysis of strongly correlated electron systems

The `extended Aharonov-Bohm (AB) period' recently proposed by Kusakabe and Aoki [J. Phys. Soc. Jpn (65), 2772 (1996)] is extensively studied numerically for finite size systems of strongly correlated electrons. While the extended AB period is the system length times the flux quantum for noninteracting systems, we have found the existence of the boundary across which the period is halved or another boundary into an even shorter period on the phase diagram for these models. If we compare this result with the phase diagram predicted from the Tomonaga-Luttinger theory, devised for low-energy physics, the halved period (or shorter periods) has a one-to-one correspondence to the existence of the pairing (phase separation or metal-insulator transition) in these models. We have also found for the t-J model that the extended AB period does not change across the integrable-nonintegrable boundary despite the totally different level statistics.Comment: 26 pages, RevTex, 16 figures available on request from [email protected], to be published in J. Phys. Soc. Jpn 66 No. 7(1997), We disscus the extended AB period of strongly correlated systems more systematically by performing numerical calculation for the t-J-J' model and the extended Hubbard model in addition to the 1D t-J model and the t-J ladde