Varenicline, an alpha-4 beta-2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking

Abstract Alcohol dependence is a disease that impacts millions of individuals worldwide. There has been some progress with pharmacotherapy for alcohol-dependent individuals; however, there remains a critical need for the development of novel and additional therapeutic approaches. Alcohol and nicotine are commonly abused together, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, reduces nicotine intake and was recently approved as a smoking cessation aid. We have investigated the role of varenicline in the modulation of ethanol consumption and seeking using three different animal models of drinking. We show that acute administration of varenicline, in doses reported to reduce nicotine reward, selectively reduced ethanol but not sucrose seeking using an operant self-administration drinking paradigm and also decreased voluntary ethanol but not water consumption in animals chronically exposed to ethanol for 2 months before varenicline treatment. Furthermore, chronic varenicline administration decreased ethanol consumption, which did not result in a rebound increase in ethanol intake when the varenicline was no longer administered. The data suggest that the alpha4beta2 nAChRs may play a role in ethanol-seeking behaviors in animals chronically exposed to ethanol. The selectivity of varenicline in decreasing ethanol consumption combined with its reported safety profile and mild side effects in humans suggest that varenicline may prove to be a treatment for alcohol dependence.

Mutations in exon 3 of the beta-catenin gene are rare in melanoma cell lines

Mutations in exon 3 of the CTNNB1 gene encoding beta-catenin have been reported in colorectal cancer cell lines and tumours. Although one study reported mutations or deletions affecting beta-catenin in 20% of melanoma cell lines, subsequent reports detected a much lower frequency of aberrations in uncultured melanomas. To determine whether this difference in mutation frequency reflected an in vitro culturing artefact, exon 3 of CTNNB1 was screened in a panel of 62 melanoma cell lines. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect intragenic deletions affecting exon 3. One out of 62 (1.6%) cell lines was found to carry a mutation, indicating that aberration of the Wnt-1/wingless pathway through activation of beta-catenin is a rare event, even in melanoma cell lines.

A hydrogen gas sensor based on Pt/nanostructured WO3/SiC Schottky diode

Pt/nanostructured WO3/SiC Schottky diodes were fabricated and applied for hydrogen gas sensing applications. The nanostructured WO3 films were synthesized from tungsten coated SiC substrates via an acid-etching method using a 1.5 M HNO3 solution for 1 hr, 2 hrs and 3 hrs duration. Scanning electron microscopy of the developed films revealed platelet crystals with thicknesses in the order of 20-60 nm and lengths between 100-700 nm. X-ray diffraction analysis revealed that the rate of oxidation of tungsten increases as the duration of acid-etching increases. The devices were tested towards hydrogen gas balanced in air at different temperatures from 25°C to 200°C. At 200°C, voltage shifts of 0.45 V, 0.93 V and 2.37 V were recorded for devices acid-etched for 1 hr, 2 hrs and 3 hrs duration, respectively upon exposure to 1% hydrogen, under a constant forward bias current of 500 µA.

Hydrogen gas sensing properties of Pt/Ta2O5 Schottky diodes based on Si and SiC substrates

In this paper, we fabricated Pt/tantalum oxide (Ta2O5) Schottky diodes for hydrogen sensing applications. Thin (4 nm) layer of Ta2O5 was deposited on silicon (Si) and silicon carbide (SiC) substrates by radio frequency (RF) sputtering technique. We compared the performance of these sensors at different elevated temperatures of 100 ∘C and 150 ∘C. At these temperatures, the sensor based on SiC exhibited a larger sensitivity while the sensor based on Si exhibited a faster response toward hydrogen gas. We discussed herein, the responses exhibited by the Pt/Ta2O5 based Schottky diodes demonstrated a promising potential for hydrogen sensing applications.

Hydrogen gas sensing performance of a Pt/graphene/SiC device

In this work, we present the development of a Pt/graphene/SiC device for hydrogen gas sensing. A single layer of graphene was deposited on 6H-SiC via chemical vapor deposition. The presence of graphene C-C bonds was observed via X-ray photoelectron spectroscopy analysis. Current-voltage characteristics of the device were measured at the presence of hydrogen at different temperatures, from 25°C to 170°C. The dynamic response of the device was recorded towards hydrogen gas at an optimum temperature of 130°C. A voltage shift of 191 mV was recorded towards 1% hydrogen at −1 mA constant current.

The asthmatic athlete, inhaled beta agonists, and performance

INTRODUCTION: The large increase in the number of athletes who apply to use inhaled beta agonists (IBAs) at the Olympic Games is a concern to the medical community. This review will examine the use of IBAs in the asthmatic athlete, the variability that exists between countries and sport, and outline a plan to justify the use of these medications. DATA SOURCES: Much of this article is a result of an International Olympic Committee (IOC) Medical Commission-sponsored meeting that took place in May 2001. Records of the use of IBAs at previous Olympics were reviewed. MEDLINE Searches (PubMed interface) were performed using key words to locate published work relating to asthma, elite athletes, performance, treatment, and ergogenic aids. MAIN RESULTS: Since 1984 there have been significant increases in the use of IBAs at the Olympic Games as well as marked geographical differences in the percentage of athletes requesting the use of IBAs. There are large differences in the incidence of IBA use between sports with a trend towards increased use in endurance sports. There are no ergogenic effects of any IOC-approved IBA given in a therapeutic dose. CONCLUSIONS: In many cases, the prescription of IBAs to this population has been made on empirical grounds. Beginning with the 2002 Winter Games, athletes will be required to submit to the IOC Medical Commission clinical and laboratory evidence that justifies the use of this medication. The eucapnic voluntary hyperpnea test will be used to assess individuals who have not satisfied an independent medical panel of the need to use an IBA.

Cytokine synthesis by intestinal intraepithelial lymphocytes. Both gamma/delta T cell receptor-positive and alpha/beta T cell receptor-positive T cells in the G1 phase of cell cycle produce IFN-gamma and IL-5

Murine intestinal intraepithelial lymphocytes (IEL) have been shown to contain subsets of alpha/beta TCR+ and gamma/delta TCR+ T cells that spontaneously produce cytokines such as IFN-gamma and IL-5. We have now determined the nature and cell cycle stage of these cytokine-producing T lymphocytes in EIL by using IFN-gamma- and IL-5-specific ELISPOT assay, cytokine-specific mRNA-cDNA dot-blot hybridization and polymerase chain reaction, and flow cytometry (FACS) for DNA analysis. When CD3+ T cells from IEL of normal C3H/HeN mice were separated into low and high density fractions by discontinuous Percoll gradients, IFN-gamma and IL-5 spot-forming cells were only found in the former population. Analysis of mRNA for these cytokines by both IFN-gamma- and IL-5-specific dot-blot hybridization and polymerase chain reaction revealed that higher levels of message for IFN-gamma and IL-5 were also seen in the low density fraction. However, cell cycle analysis of these two fractions by FACS using propidium iodide showed a similar pattern of cell cycle stages in both low and high density populations (G0 + G1 approximately 96 to 98% and S/G2 + M approximately 2 to 4%). Finally, mRNA from gamma/delta TCR+ and alpha/beta TCR+ T cells in both low and high density fractions of IEL were analyzed for IFN-gamma and IL-5 message by polymerase chain reaction. After 35 cycles of amplification, both gamma/delta TCR+ and alpha/beta TCR+ T cells in the low density fraction expressed higher levels of message for these two cytokines when compared with the high density population. These results have now shown that both gamma/delta and alpha/beta TCR+ IEL can be separated into low and high density subsets and both fractions possess a similar stage of cell cycle. However, only the low density cells (in G1 phase) of both gamma/delta and alpha/beta TCR types possess increased cytokine-specific mRNA and produce the cytokines IFN-gamma and IL-5. Our results suggest that alpha/beta TCR+ and gamma/delta TCR+ IEL can produce cytokines without cell proliferation.

Pt/Nanostructured RuO2/SiC Schottky Diode based hydrogen gas sensors

In this paper, we report the development of novel Pt/nanostructured RuO2/SiC Schottky diode based sensors for hydrogen gas applications. The nanostructured ruthenium oxide thin films were deposited on SiC substrates using radio frequency sputtering technique. Scanning electron microscopy revealed the sputtered RuO2 layer consists of nano-cubular structures with dimensions ranging between 10 and 50 nm. X-ray diffraction confirmed the presence of tetragonal ruthenium (IV) oxide, with preferred orientation along the (101) lattice plane. The current-voltage characteristics of the sensors were investigated towards hydrogen gas in synthetic air at different temperatures from 25 °C to 240 °C. The dynamic responses of the sensors were studied at an optimum temperature of 240 °C and a voltage shift of 304 mV was recorded toward 1% hydrogen gas.

Pt/Nanograined ZnO/SiC Schottky diode based hydrogen and propene sensor

A nanostructured Schottky diode was fabricated to sense hydrogen and propene gases in the concentration range of 0.06% to 1%. The ZnO sensitive layer was deposited on SiC substrate by pulse laser deposition technique. Scanning electron microscopy and X-ray diffraction characterisations revealed presence of wurtzite structured ZnO nanograins grown in the direction of (002) and (004). The nanostructured diode was investigated at optimum operating temperature of 260 °C. At a constant reverse current of 1 mA, the voltage shifts towards 1% hydrogen and 1% propene were measured as 173.3 mV and 191.8 mV, respectively.

Hydrogen gas sensing performance of Pt/SnO2 nanowires/SiC MOS devices

This paper presents material and gas sensing properties of Pt/SnO2 nanowires/SiC metal oxide semiconductor devices towards hydrogen. The SnO2 nanowires were deposited onto the SiC substrates by vapour-liquid-solid growth mechanism. The material properties of the sensors were investigated using scanning electron microscopy, transmission electron microscopy and X-ray photoelectron spectroscopy. The current-voltage characteristics have been analysed. The effective change in the barrier height for 1% hydrogen was found to be 142.91 meV. The dynamic response of the sensors towards hydrogen at different temperatures has also been studied. At 530°C, voltage shift of 310 mV for 1% hydrogen was observed.

Hydrogen sensing properties of Pt/Lanthanum oxide- molybdenum oxide nanoplatelet/SiC based Schottky diode

An investigation of the electrical and hydrogen sensing properties of a novel Schottky diode based on a nanostructured lanthanum oxide-molybdenum oxide compound is presented herein. Molybdenum oxide (MoO3) nanoplatelets were grown on SiC substrates via thermal evaporation which was then subsequently coated with lanthanum oxide (La2O3) by RF sputtering. The current-voltage characteristics and hydrogen sensing performance (change in barrier height and sensitivity as well as the dynamic response) were examined from 25 to 300°C. At 180°C, a voltage shift of 2.23V was measured from the sensor while exposed to 1% hydrogen gas under a 100 μA constant reverse bias current. The results indicate that the presence of a La2O3 thin layer substantially improves the hydrogen sensitivity of the MoO3 nanoplatelets.

Pt/TiO2 nanotubes/SiC schottky diodes for hydrogen gas sensing applications

Titanium oxide nanotubes Schottky diodes were fabricated for hydrogen gas sensing applications. The TiO2 nanotubes were synthesized via anodization of RF sputtered titanium films on SiC substrates. Two anodization potentials of 5 V and 20 V were used. Scanning electron microscopy of the synthesized films revealed nanotubes with avarage diameters of 20 nm and 75 nm. X-ray diffraction analysis revealed that the composition of the oxide varied with the anodization potential. TiO2 (anatase) being formed preferentially at 5 V and TiO (no anatase) at 20 V. Current-voltage characteristics of the diodes were studied towards hydrogen at temperatures from 25°C to 250°C. At constant current bias of −500 μA and 250°C, the lateral voltage shifts of 800 mV and 520 mV were recorded towards 1% hydrogen for the 5 V and 20 V anodized nanotubes, respectively.

Pt/MoO3 nano-flower/SiC Schottky diode based hydrogen gas sensor

In this paper, we report the development of a novel Pt/MoO3 nano-flower/SiC Schottky diode based device for hydrogen gas sensing applications. The MoO3 nanostructured thin films were deposited on SiC substrates via thermal evaporation. Morphological characterization of the nanostructured MoO3 by scanning electron microscopy revealed randomly orientated thin nanoplatelets in a densely packed formation of nano-flowers with dimensions ranging from 250 nm to 1 μm. Current-voltage characteristics of the sensor were measured at temperatures from 25°C to 250°C. The sensor showed greater sensitivity in a reverse bias condition than in forward bias. Dynamic response of the sensor was investigated towards different concentrations of hydrogen gas in a synthetic air mixture at 250°C and a large voltage shift of 5.7 V was recorded upon exposure to 1% hydrogen.