Oxidatív stressz és atherosclerosis

Absztrakt Az atherosclerosis, ami a mai napig vezető halálok a fejlett országokban, genetikai hajlam és számos ismert környezeti rizikótényező hatására alakul ki. A legtöbb ilyen faktor oxidatív stressz keltése révén endothelialis működészavarhoz és egyéb proatherogen folyamatokhoz vezet. Az érelmeszesedés elsősorban az artériás rendszer tipikus helyein, az elágazásoknál és kanyarulatoknál alakul ki, ahol a szabályos lamináris áramlás zavart szenved. Emiatt fokozódik az endothelium permeabilitása a kis sűrűségű lipoprotein számára, ami így felhalmozódik az érfal intimarétegében és oxidálódik. Az oxidált kis sűrűségű lipoprotein számos úton hozzájárul az atherosclerosis kialakulásához: elősegíti a monocyták vándorlását az érfalba, a habossejt-képződést, a meszes plakk kialakulását, a plakkdestabilizációt és a thromboticus szövődményeket. Miután az oxidatív stressz az atherosclerosis patogenezisében számos ponton szerepet játszik, felmerül, hogy antioxidáns terápiával megelőzhető-e a betegség. Több klinikai vizsgálat szerint az antioxidánsok – mint az N-acetil-cisztein, C- és E-vitamin, folsav, ösztrogének – hatékonyak a coronariabetegség megelőzésében, de ezt randomizált klinikai vizsgálatok nem tudták bizonyítani. Orv. Hetil., 2015, 156(28), 1115–1119

Large-scale, high-density (up to 512 channels) recording of local circuits in behaving animals

Monitoring representative fractions of neurons from multiple brain circuits in behaving animals is necessary for understanding neuronal computation. Here we describe a system that allows high channel count recordings from a small volume of neuronal tissue using a lightweight signal multiplexing head-stage that permits free behavior of small rodents. The system integrates multi-shank, high-density recording silicon probes, ultra-flexible interconnects and a miniaturized microdrive. These improvements allowed for simultaneous recordings of local field potentials and unit activity from hundreds of sites without confining free movements of the animal. The advantages of large-scale recordings are illustrated by determining the electro-anatomical boundaries of layers and regions in the hippocampus and neocortex and constructing a circuit diagram of functional connections among neurons in real anatomical space. These methods will allow the investigation of circuit operations and behavior-dependent inter-regional interactions for testing hypotheses of neural networks and brain function

The effect of indomethacin, myeloperoxidase, and certain steroid hormones on bactericidal activity: an ex vivo and in vivo experimental study.

BACKGROUND: The role of myeloperoxidase (MPO) is essential in the killing of phagocytosed bacteria. Certain steroid hormones increase MPO plasma concentration. Our aim was to test the effect of MPO, its inhibitor indomethacin, and certain steroid hormones on bactericidal activity. METHODS: Human polymorphonuclear leukocytes (PMN) were incubated with opsonised Escherichia coli and either MPO, indomethacin, estradiol, or hydrocortisone. Intracellular killing capacity was evaluated with UV microscopy after treatment with fluorescent dye. Next, an in vivo experiment was performed with nine groups of rats: in the first phase of the study indomethacin treatment and Pasteurella multocida infection (Ii), indomethacin treatment without infection (I0), untreated control with infection (Mi) and untreated control without infection (M0); in the second phase of the study rats with infection and testosterone treatment (NT), castration, infection and testosterone treatment (CT), castration, infection and estradiol treatment (CE), non-castrated infected control (N0), and castrated infected control (C0). After treatment bacteria were reisolated from the liver and heart blood on agar plates, and laboratory parameters were analyzed. For the comparison of laboratory results ANOVA or Kruskal-Wallis test and LSD post hoc test was used. RESULTS: Indomethacin did not have a remarkable effect on the bacterial killing of PMNs, while the other compounds increased bacterial killing to various degrees. In the animal model indomethacin and infection caused a poor clinical state, a great number of reisolated bacteria, elevated white blood cell (WBC) count, decreased C-reactive protein (CRP) and serum albumin levels. Testosterone treatment resulted in less bacterial colony numbers in group NT, but not in group CT compared to respective controls (N0, C0). Estradiol treatment (CE) decreased colony numbers compared to control (C0). Hormone administration resulted in lower WBC counts, and in group CE, a decreased CRP. CONCLUSIONS: MPO, estradiol, and hydrocortisone improve bacterial killing activity of PMNs. Indomethacin treatment and castration weaken immune responses and clinical state of infected rats, while testosterone and estradiol have a beneficial effect

DNA cleavage site selection by Type III restriction enzymes provides evidence for head-on protein collisions following 1D bidirectional motion

DNA cleavage by the Type III Restriction–Modification enzymes requires communication in 1D between two distant indirectly-repeated recognitions sites, yet results in non-specific dsDNA cleavage close to only one of the two sites. To test a recently proposed ATP-triggered DNA sliding model, we addressed why one site is selected over another during cleavage. We examined the relative cleavage of a pair of identical sites on DNA substrates with different distances to a free or protein blocked end, and on a DNA substrate using different relative concentrations of protein. Under these conditions a bias can be induced in the cleavage of one site over the other. Monte-Carlo simulations based on the sliding model reproduce the experimentally observed behaviour. This suggests that cleavage site selection simply reflects the dynamics of the preceding stochastic enzyme events that are consistent with bidirectional motion in 1D and DNA cleavage following head-on protein collision

Miscellaneous. Folyóirat-referátumok

Folyóirat-referátumok. Esetismertetés Vérhányás, vérköpés vagy mindkettő? (Haematemesis, haemoptysis, or both?) O’Brien, J., Cowan, M., Patch, D. (Patch, D. = The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital and University College London, London, Egyesült Királyság): Lancet, 2013, 381, 346. | Kardiológia A revascularisatiót igénylő koszorúér többér-betegség stratégiája (perkután coronariaintervenció vs. coronaria-bypassműtét) cukorbetegségben: FREEDOM tanulmány (Strategies for multivessel revascularization in patients with diabetes) Farkouh, M. E., Domanski, M., Sleeper, I. A., et al., for the FREEDOM Trial Investigators. (Levelező szerző: Dr. V. Fuster, Mount Sinai School of Medicine, New York 10029, Amerikai Egyesült Államok; e-mail: valentin.fuster@ mssm.edu): N. Engl. J. Med., 2012, 367, 2375–2384. | Onkológia Az agresszív statinkezelés és a daganatos betegségek kockázata (Aggressive statin therapy and the risk of malignancy) Liao, J., Farmer, J. A. (Department of Medicine, Brigham & Women’s Hospital/ Harvard Medical School, Boston, MA, Amerikai Egyesült Államok; e-mail: [email protected]): Curr. Atheroscler. Rep., 2013, 15, 316. | Sportorvostan A nem szokásos edzésmódok hatása a teljesítményre: az irodalom áttekintése (The influence of nontraditional training modalities on physical performance: review of the literature) O ’ Hara, R. B., Serres, J., Traver, K. L., et al. (US Air Force School of Aerospace Medicine, Department of Aeromedical Research, P.O. Box 33505, Wright-Patterson AFB, OH 45433-0505, Amerikai Egyesült Államok; e-mail: reginald. [email protected]): Aviat. Space Environ. Med., 2012, 83, 985–990

The effect of selegiline on total scavenger capacity and liver fat content: a preliminary study in an animal model

Selegiline is a selective irreversible inhibitor of the B-type of monoamine oxidase (MAO-B). The spectrum of its pharmacological activity is wide, possesses antioxidant, antiapoptotic and neuroprotective properties and, additionally, we found it is effective on the total scavenger capacity (TSC), and the regulation of fat content in rat liver kept on lipid-rich diet. Our aim was to clarify whether the oral treatment with selegiline is protective on oxidative damage of Sprague-Dawley adult rats in vivo. Four groups of rats (five animals in a group) were examined: (1) lipid-rich diet, (2) normal rat food, (3) lipid-rich diet + selegiline and (4) normal rat food + selegiline. Selegiline solution (2.5 μg/ml) was supplied with the drinking water, which was freely available for the animals. Regarding the drinking habit of the rats (20-30 ml/day), the daily dose was roughly equal with that used in the human therapy (5-10 mg/day). TSC was determined both at the beginning (0 day) and at the end of the study (28 days), when the blood samples were taken for chemiluminometric assay. Fat content of the liver was determined in the freshly frozen tissue by Sudan staining. TSC was increased in both the selegiline-treated groups. Selegiline treatment prevented the increase of liver fat in the group fed with lipid-rich diet. Our results led us to the conclusion that prolonged selegiline administration can raise the antioxidant capacity of the animals and prevents the accumulation of fat in their livers. © 2011 Springer-Verlag