K. Mašek

Neuroendocrine immune interactions in health and disease.

The purpose of this paper is to review ways in which the neurohormonal system can interact with the immune system and to outline the main mechanisms which are involved in this interaction. Experimental as well as clinical evidence is presented to support the existence of a close interaction and bi-directional communication between the central nervous and immune systems. The role of major endocrine mechanisms and hormones is discussed. The evidences from experimental work to support the roles of the nervous system with neurotransmitters, the endocrine system with hormones, and the immune system with cytokines are presented. Aging, depression and cancer have a high degree of co-association and share mechanisms which result in cellular immune deficiency. Hormone therapy, zinc replenishment, antidepressants, immunomodulators like MDP act on these pathways to upregulate and improve cellular immunity. The authors believe that the central nervous system (CNS)-immune interaction is an important new frontier to be considered for new combination therapy in diseases with cellular immune deficiency such as cancer particularly in the aged with depression.

Inhibition of endotoxemia-induced nitric oxide synthase expression by cyclosporin A enhances hepatocyte injury in rats: amelioration by NO donors

Abstract The goals of the present study were to provide information into the controversy about nitric oxide (NO) status of the liver during endotoxemia and to assess the role of the phosphatase inhibitor cyclosporin A (CsA) during the insult. Rats were injected with saline, lipopolysaccharide (LPS, 10 mg/kg i.p.) or cyclosporin A (CsA, 5 mg/kg. i.p.)+LPS, S -nitroso- N -acetyl penicillamine (SNAP, 0.1 mM/kg)+CsA+LPS or molsidomine (molsid, 0.2 mg/kg)+CsA+LPS. Rat hepatocytes were isolated and tested for metabolic competence by the rate of urea synthesis and for lipid peroxidation. Hepatocytes were cultured under various treatments as LPS or cytokine mixture (CM, TNF-α 500 U/ml, INF-γ 100 U/ml, IL-1β 200 U/ml) with or without CsA and iNOS expression was evaluated by NO productivity and by RT-PCR. Twenty-four hours after LPS dosing in vivo, the mortality rate was 15%, while CsA pretreatment increased mortality rate to 30% and reduced hepatocyte viability, increased ALT leakage and reduced urea synthesis. SNAP and Molsid resulted in complete survival of rats, increased urea synthesis, increased cell viability and reduced alanine aminotransferase leakage. LPS or CM increased iNOS expression while CsA pretreatment reduced iNOS expression. There was no correlation between lipid peroxide levels in hepatocytes and functional status of hepatocytes under various treatments. This study demonstrates that NO produced during endotoxemia and under the present conditions is protective to the liver and may function as an adaptive mechanism and that the inhibition of iNOS by compounds like CsA produce unfavorable effects.

Mechanism of non-evaporable getter activation XPS and static SIMS study of Zr44V56 alloy

Abstract Thin films of Zr 44 V 56 alloy getter films were prepared on stainless-steel substrates by magnetron sputtering. The getter activation behaviour was investigated by X-ray photoelectron spectroscopy and static secondary ion mass spectroscopy (SSIMS). Both measurements reflect the disappearance of the superficial oxide layer covering air-exposed Zr–V surfaces via consecutive variation of the oxide stoichiometry, from stoichiometric to partially reduced oxides, during thermal activation. During the heating, hydrogen equilibrium concentration is established on the surface indicating enhancement of getter sorption activity. Although a detectable activation proceeds already at temperatures above 160°C, the activation process is reasonably fast (a few hours) at higher temperatures (above 200°C). In the Zr 44 V 56 alloy the reduction of the V oxide is faster than that of Zr oxide.

Interface termination and band alignment of epitaxially grown alumina films on Cu-Al alloy

Epitaxial ultrathin alumina films were grown on a Cu−9 at. % Al(111) substrate by selective oxidation of Al in the alloy in ultrahigh vacuum. The photoelectron spectra of Al 2p and valence band were measured in situ during oxidation. By analyzing multiple peaks of Al 2p, the interface atomic structure was discussed. The energy difference between the Fermi level of the substrate and the valence band maximum of alumina (band offset) was obtained. The relation between the interface atomic structure and the band offset was compared with the reported first-principles calculations. A novel method for controlling the band offset was proposed.

Nitric oxide synthase inhibitors modulate lipopolysaccharide-induced hepatocyte injury: dissociation between in vivo and in vitro effects

Effects of endotoxemia-induced NO production on rat liver and hepatocytes in culture were investigated. Rats were treated intraperitoneally with saline, lipopolysaccharide (LPS, 10 mg/kg), L-nitroarginine methyl ester (L-NAME)+LPS, aminoguanidine (AG)+LPS, FK 506+LPS, S-nitroso-N-acetyl penicillamine (SNAP)+L-NAME+LPS and SNAP+FK 506+LPS. Mortality, hepatocyte viability and liver function test were estimated. Liver morphology was observed by light and electron microscopy. Hepatocyte cultures were treated with LPS, cytokine mixture (CM) with or without FK 506, L-NAME or AG. Hepatocyte function and inducible form of NOS (iNOS) expression were evaluated. Twenty-four hours after treatments with saline, LPS, L-NAME+LPS, AG+LPS, FK 506+LPS, SNAP+L-NAME+LPS and SNAP+FK 506+LPS, rat mortalities were 0%, 10%, 48%, 8%, 20%, 38% and 0%, and hepatocyte viabilities were 93+/-3%, 80+/-3%, 52+/-8%, 88+/-1%, 70+/-3%, 80+/-4% and 82+/-3%, respectively. AG+LPS or L-NAME+LPS administration was followed by excessive vacuolization of hepatocytes with lesions in the intermediary lobule zone characterized by features of secondary necrosis as a continuation of apoptotic processes. SNAP+L-NAME+LPS resulted in a well-preserved structure of central vein lobules with sparse signs of apoptosis. Treatment with LPS or CM increased iNOS expression in hepatocyte culture, which was inhibited by L-NAME, FK 506 or AG. AG reduced LPS-induced rise in alanine aminotransferase leakage. LPS-induced NO exerts cytoprotective effects in vivo, while LPS-induced NO in vitro appears to be toxic. Based on the data of this report, one cannot use in vitro results to predict in vivo responses to LPS-induced NO production. The pharmacological modulation of iNOS expression or NO production in vivo or in vitro, therefore, by the development of specific NO donors or inhibitors is promising for improvement of hepatocyte functions under the two experimental conditions, respectively.

Miniature electron bombardment evaporation source: evaporation rate measurement

Miniature electron beam evaporation sources which operate on the principle of vaporization of source material, in the form of a tip, by electron bombardment are produced by several companies specialised in UHV equipment. These sources are used primarily for materials that are normally difficult to deposit due to their high evaporation temperature. They are appropriate for special applications, like heteroepitaxial thin films growth that require very low and well controlled deposition rate. We propose a simple and easily applicable method of evaporation rate control. The method is based on the measurement of ion current produced by electron bombardment of evaporated atoms. In order to be able to determine the ion current – evaporation flux calibration curves we measured the absolute values of evaporation flux by means of Bayard-Alpert ion gauge.

The analysis of post-tetanic potentiation in guinea-pig ileum longitudinal muscle strip

The effect of tetanus on the twitch responses of the longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum to electrical stimuli was investigated in the presence of naloxone and indomethacin. Naloxone was used to prevent post-tetanic twitch inhibition due to the release of endogenous opiate ligands, and indomethacin to diminish pretetanic twitch height. Twitch contractions following tetanus were potentiated in the presence of both drugs. The optimal stimulation parameters for the manifestation of post-tetanic potentiation (PTP) were determined; tetanic stimulation: 30 Hz for 25 s. supramaximal impulse intensity; twitches: 0.04 Hz, low impulse intensity. PTP was also obtained when indomethacin was replaced by noradrenaline or adenosine, i.e. by drugs whose mechanism of action also includes a presynaptic effect. Postsynaptic changes in contractility cannot fully account for the observed PTP of twitches judging from the smaller effect of tetanus on acetylcholine-evoked contractions. The hypothesis of a presynaptic origin of PTP at this muscarinic synapse was corroborated in the experiments where acetylcholine stores were labelled with [3H] choline and the release of the label was increased during PTP. Furthermore, a bioassay showed that the output of endogenous acetylcholine in the post-tetanic interval was increased in the presence of naloxone plus indomethacin but not in their absence. The fact that PTP was also observed in the absence of any drug, if the tetanic stimulation was short (10 s) and of low impulse intensity, suggested its possible physiological significance.

Interactions between the duration of stimulation and noradrenaline on cholinergic transmission in the myenteric plexus-smooth muscle preparation

Output of acetylcholine (ACh), electromyogram (EMG) recordings and contractions of myenteric plexus-longitudinal muscle strip preparations from the guinea-pig ileum were studied during stimulation by single impulses or by trains (30 Hz; 2 to 128 impulses) under control conditions and in the presence of noradrenaline (NA). During supramaximal stimulation NA (2.5 microM) inhibited both contractions of the smooth muscle and the release of ACh evoked by single impulses more effectively than those evoked by train stimulation so that in a train of 4 impulses the output of ACh per impulse after the 2nd to 4th impulses was 69 to 104% higher than the output after the 1st impulse. During submaximal stimulation, contractions and ACh release evoked by single impulses were almost completely inhibited by NA. The neurogenic EMG, a direct consequence of the localized action of released transmitter (ACh), was recorded in the longitudinal muscle 4 and 10 mm aborally from the focal stimulation site. The incidence of the neurogenic response was much higher at the proximal (4 mm) than at the distal (10 mm) site and was proportional to the number of impulses in a train (100 Hz). NA inhibited propagation of the neurogenic response evoked by single impulses whereas its effect during train stimulation was less. It is concluded that in the course of train stimulation, sites of transmission more distant from the stimulation focus was recruited, and consequently the secretion of ACh in succeeding impulses was enhanced. NA could interfere with this process; it might inhibit the invasion by action potentials of cholinergic nerve terminal varicosities, thereby reducing the release of ACh.

Oxidation of tungsten nanoclusters

Abstract The tungsten oxide nanoclusters were prepared by oxidation of epitaxialy grown tungsten thin film. The structure and morphology of tungsten and tungsten oxide nanoclusters were determined by RHEED (Reflection High-Energy Electron Diffraction) and AFM (Atomic Force Microscopy). The crystallographic structure and epitaxial relationships were evaluated. Annealing at the temperatures of 950 °C and 1150 °C gave rise to the tungsten clusters having (110) and (111) epitaxial planes, respectively. The two phases of tungsten oxide—WO 2 and WO 3 —were found in dependence of oxidation conditions. The oxide clusters were epitaxially oriented on the α-Al 2 O 3 substrate. The epitaxial orientations were deduced from the RHEED pattern and the surface distribution of clusters was characterised by AFM.

Rh particle growth on insulator substrates: RHEED study

Abstract Three-dimensional Rh particle catalysts were prepared by heteroepitaxial growth on α-Al 2 O 3 (0001), NaCl (001) and KCl (001) substrates. During the deposition, the particle structure and orientation were characterised by Reflection High Energy Electron Diffraction (RHEED). It was shown that at sufficiently high temperatures the Rh particles conserve the symmetry of the susubstrate (hexagonal in the case of α-Al 2 O 3 (0001) and cubic for (001) NaCl and (001) KCl substrates). At lower temperatures the layers are disordered or partially disordered.