The Influence of Methimazole and Its Putative Metabolites on Human Polymorphonuclear Leukocyte Function

An uncommon side effect of treatment with antithyroid drugs is agranulocytosis. These compounds are also known to be capable of modifying immune function in humans. The polymorphonuclear leukocytes are responsible for clearing invading foreign bodies from the bloodstream, and as such are the first line of defence against infection. The effect of methimazole, a thioureylene antithyroid drug commonly used in the treatment of hyperthyroidism, on selected parameters of polymorphonuclear leukocyte function, was investigated. Methimazole is metabolised by polymorphonuclear leukocytes, therefore the influence of some of its putative metabolites, namely 3-methylthiohydantoin, methylhydantoin and N-methylimidazole, was also assessed. The chemotactic, phagocytic and cidal capabilities of human polymorphonuclear leukocytes were examined. The ability of polymorphonuclear leukocytes to migrate under agarose towards the chemo-attractant, zymosan-stimulated serum, was found to be unaffected by methimazole, 3-methylthiohydantoin, methylhydantoin and methylimidazole at concentrations between 10-3 and 10-7 M. Phagocytosis of S, aureus, S. pyogenes, E. coli, L. casei and C. albicans proceded normally in the presence of 10-3 M methimazole, S. pyogenes and S. aureus, as representatives of hydrogen peroxide- and non-hydrogen peroxide producing bacteria respectively were the subject of further investigation which established that methimazole, 3-methylthiohydantoin, methylhydantoin and N- methyliraidazole did not significantly affect their ingestion at concentrations between 10-3 and 10-5M. Intracellular killing of all five pre-opsonised microorganisms by human polymorphonuclear leukocytes treated with 10-3M methimazole was stimulated by between ten and 40 per cent after 30 minutes co-incubation. Between 60 and 120 minutes there was no evidence of any significant stimulation. Further investigation with S. pyogenes and S. aureus revealed that methimazole, 3-methylthiohydantoin, methylhydantoin and N-methylimidazole exerted no significant effect on the killing of S. pyogenes, however dose-related inhibition was evident on treatment with between 10 and 10-5M methimazole and 3-methylthiohydantoin during phagocytosis of S. aureus. Methylhydantoin and N-methyl-imidazole produced no significant effects. The oxygen consumption of latex-stimulated polymorphonuclear leukocytes was found to be stimulated by 48 and 58 per cent respectively by methimazole and N-methylimidazole at 10 M, 3-methylthiohydantoin and methylhydantoin producing no significant change. The hexose monophosphate shunt activity of similarly stimulated polymorphonuclear leukocytes significantly increased by up to 20 per cent in the presence of methimazole, 3-methylthiohydantoin and N-methylinidazole. None of the compounds exerted any influence on the release of lysosomal enzymes by stimulated polymorphonuclear leukocytes, however methimazole, 3-methylthiohydantoin and N-methylimidazole inhibited myeloperoxidase activity by between 36 and 100 per cent at 10 14, this inhibition was dose-related at concentrations between 10-3 and 10-5M. Lysozyme and lactoferrin activity from the released lysosomal enzymes was unaffected by any of the four compounds, neither was the lysozyme activity of intact polymorphonuclear leukocytes. Alkaline phosphatase activity however was inhibited by around 50 per cent by methimazole and 3-methyl- thiohydantoin at concentrations of 10-3 M; again the inhibitory effect was significantly dose-related. Thus it would appear that methimazole acts, not by inhibiting the microbicidal oxidase system, as might have been expected, but by altering myeloperoxidase activity. (Abstract shortened by ProQuest.)

A calendar effect: weekend overreaction (and subsequent reversal) in spot FX rates

This paper investigates a calendar effect, namely the weekend overreaction, in spot foreign exchange markets of 8 major and 9 emerging currencies. We find that after a large price difference between Friday close and subsequent Monday open, most markets are likely to reverse in multiple horizons during the following week, which is consistent with the overreaction hypothesis. We develop a reversal trading strategy to exploit this effect which we show are robust to transaction costs and interest rates. In the out-of-sample test, the strategy is able to generate abnormal risk-adjusted returns, which suggests that these currency markets might be weak-form inefficient

Radio continuum emission from knots in the DG Tau jet

Context: HH 158, the jet from the young star DG Tau, is one of the few sources of its type where jet knots have been detected at optical and X-ray wavelengths. Aims: To search, using Very Large Array observations of this source, radio knots and if detected, compare them with the optical and X-ray knots. To model the emission from the radio knots. Methods: We analyzed archive data and also obtained new Very Large Array observations of this source, as well as an optical image, to measure the present position of the knots. We also modeled the radio emission from the knots in terms of shocks in a jet with intrinsically time-dependent ejection velocities. Results: We detected radio knots in the 1996.98 and 2009.62 VLA data. These radio knots are,within error, coincident with optical knots. We also modeled satisfactorily the observed radio flux densities as shock features from a jet with intrinsic variability. All the observed radio, optical, and X-ray knot positions can be intepreted as four successive knots, ejected with a period of 4.80 years and traveling away from the source with a velocity of 198 km s$^{-1}$ in the plane of the sky. Conclusions: The radio and optical knots are spatially correlated and our model can explain the observed radio flux densities. However, the X-ray knots do not appear to have optical or radio counterparts and their nature remains poorly understood.Comment: 8 pages, 8 figures, to appear in Astronomy & Astrophysic

First detection of acceleration and deceleration in protostellar Jets? Time variability in the Chamaeleontis II outflows

Context. Kinematical and time variability studies of protostellar jets are fundamental for understanding the dynamics and the physics of these objects. Such studies remain very sporadic, since they require long baselines before they can be accomplished. Alms. We present for the first time a multi-epoch (20 years baseline) kinematical investigation of HH 52, 53, and 54 at optical and near-IR wavelengths, along with medium (optical) and high resolution (NIR) spectroscopic analyses, probing the kinematical and physical time variability conditions of the gas along the flows. Methods. By means of multi-epoch and multi-wavelength narrow-band images, we derived proper motions (PMs), tangential velocities, velocity and flux variability of the knots. Radial velocities and physical parameters of the gas were derived from spectroscopy. Finally, spatial velocities and inclination of the flows were obtained by combining both imaging and spectroscopy. Results. The PM analysis reveals three distinct, partially overlapping outflows. Spatial velocities of the knots vary from 50 km s -1 to 120 km s-1. The inclinations of the three flows are 58 ± 3°, 84 ± 2°, and 67 ± 3° (HH 52, HH 53, and HH 54 flows, respectively). In 20 years, about 60% of the observed knots show some degree of flux variability. Our set of observations apparently indicates acceleration and deceleration in a variety of knots along the jets. For about 20% of the knots, mostly coincident with working surfaces or interacting knots along the flows, a relevant variability in both flux and velocity is observed. We argue that both variabilities are related and that all or part of the kinetic energy lost by the interacting knots is successively radiated. The physical parameters derived from the diagnostics are quite homogeneous along and among the three outflows. The analysis indicates the presence of very light (NH � 103 cm-3), ionised (Te,. � 0.2-0.6), and hot (Te � 14000-26000 K) flows, impacting a denser medium. Several knots are deflected, especially in the HH 52 flow. At least for a couple of them (HH 54 G and GO), the deflection originates from the collision of the two. For the more massive parts of the flow, the deflection is likely the result of the flow collision with a dense cloud or with clumps. Finally, we discuss the possible driving sources of the flows. ©ESO 2009

Issues of ideology in English language education worldwide: an overview

The relatively limited consideration of ideology in mainstream theory and research of teaching the English language to speakers of other languages has arguably prevented the problematization of many taken-for-granted perceptions and practices of the field. In this article I attempt to bring part of this marginalized body of scholarship on issues of ideology in the area of English language teaching (ELT) to highlight its potential insights for the field. The article sets out from a view of ideology as the most fundamental beliefs in any social practice, which may provide a less-formidable conception of the term and lessen the divergence among the minority of ELT researchers and professionals that do concern themselves with ideology. Then, after a brief sketch of the notion of ideology of language (education), I present an overview of aspects of this marginal but vibrant stream of thought on issues of ideology in ELT worldwide. Overall, the discussion is aimed to act as a call for the further understanding and embracement of sociopolitically-sensitive and ideologically-informed approaches to ELT theory, research, and practice

Stylized facts of intraday precious metals

This paper examines the stylized facts, correlation and interaction between volatility and returns at the 5-minute frequency for gold, silver, platinum and palladium from May 2000 to April 2015. We study the full sample period, as well as three subsamples to determine how high-frequency data of precious metals have developed over time. We find that over the full sample, the number of trades has increased substantially over time for each precious metal, while the bid-ask spread has narrowed over time, indicating an increase in liquidity and price efficiency. We also find strong evidence of periodicity in returns, volatility, volume and bid- ask spread. Returns and volume both experience strong intraday periodicity linked to the opening and closing of major markets around the world while the bid-ask spread is at its low- est when European markets are open. We also show a bilateral Granger causality between returns and volatility of each precious metal, which holds for the vast majority subsamples

The PAV trial: Does lactobacillus prevent post-antibiotic vulvovaginal candidiasis? Protocol of a randomised controlled trial [ISRCTN24141277]

BACKGROUND: Complementary and alternative medicines are used by many consumers, and increasingly are being incorporated into the general practitioner's armamentarium. Despite widespread usage, the evidence base for most complementary therapies is weak or non-existent. Post-antibiotic vulvovaginitis is a common problem in general practice, for which complementary therapies are often used. A recent study in Melbourne, Australia, found that 40% of women with a past history of vulvovaginitis had used probiotic Lactobacillus species to prevent or treat post-antibiotic vulvovaginitis. There is no evidence that this therapy is effective. This study aims to test whether oral or vaginal lactobacillus is effective in the prevention of post-antibiotic vulvovaginitis. METHODS/DESIGN: A randomised placebo-controlled blinded 2 × 2 factorial design is being used. General practitioners or pharmacists approach non-pregnant women, aged 18–50 years, who present with a non-genital infection requiring a short course of oral antibiotics, to participate in the study. Participants are randomised in a four group factorial design either to oral lactobacillus powder or placebo and either vaginal lactobacillus pessaries or placebo. These interventions are taken while on antibiotics and for four days afterwards or until symptoms of vaginitis develop. Women self collect a vaginal swab for culture of Candida species and complete a survey at baseline and again four days after completing their study medications. The sample size (a total of 496 – 124 in each factorial group) is calculated to identify a reduction of half in post-antibiotic vulvovaginitis from 23%, while allowing for a 25% drop-out. An independent Data Monitoring Committee is supervising the trial. Analysis will be intention-to-treat, with two pre-specified main comparisons: (i) oral lactobacillus versus placebo and (ii) vaginal lactobacillus versus placebo

Future directions in international financial integration research. A crowdsourced perspective

This paper is the result of a crowdsourced effort to surface perspectives on the present and future direction of international finance. The authors are researchers in financial economics who attended the INFINITI 2017 conference in the University of Valencia in June 2017 and who participated in the crowdsourcing via the Overleaf platform. This paper highlights the actual state of scientific knowledge in a multitude of fields in finance and proposes different directions for future research