bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effects of polyphenolics in red wine on diabetes associated oxidative/nitrative stress in streptozotocin‐diabetic rats
Authors: Drel Viktor R , Sybirna Nataliya
Published: July 2010

Increased accumulation of NT (3‐nitrotyrosine) and PARylated [poly(ADP‐ribosyl)ated] proteins in the tissues of diabetics are associated with diabetes complications (diabetes neuropathy, nephropathy and retinopathy). Red wine (its polyphenols are considered to be the main active components) can act as ROS (reactive oxygen species) scavengers, iron chelators and enzyme modulators. This study is novel in investigating the effect of red wine in preventing the accumulation of NT and PARylated proteins in the sciatic nerve, DRG (dorsal root ganglia), spinal cord, kidney and retina of diabetic animals. We have shown that during the experiment the body weight of control and diabetic groups of rats with consumption of red wine was significantly increased, by 52% and 19% accordingly. The significant increase in the content of NT in the sciatic nerve, DRG, spinal cord, kidney and retina, and PARylated proteins in the sciatic nerve, renal glomeruli and retinae of diabetic rats was partly or completely prevented by treatment with red wine. Red wine and its polyphenol preparations might be a promising option in the prevention and treatment of diabetic complications.
Immunoneutralization of procalcitonin or its component peptides: a promising treatment of sepsis
Authors: Becker Kenneth L.
Published: July 2010

Sepsis and the severe systemic response syndrome are very common illnesses that are responsible for a great amount of morbidity and death. These closely related conditions are characterized by a remarkable increase in the prohormone ProCT (procalcitonin). ProCT is both a marker of sepsis and a harmful mediator of the disease. In the present issue of Clinical Science, in a study in rats with endotoxin shock, Tavares and Miñano used an antibody to a segment of N-ProCT (aminoprocalcitonin) that is part of the ProCT molecule, and confirmed that immunoneutralization of ProCT saves the animals from this severe illness. Furthermore, they extensively studied the epiphenomena associated with this immunoneutralization.
Semantically Related Reading Issues for Children From Low Income Environments
Authors: Ziolkowski Robyn A. , Goldstein Howard
Published: July 2010

In this article, the authors discuss research that addresses semantically related reading issues for children in poverty. In addition to providing a theoretical framework, the authors provide research-based intervention strategies and suggestions for speech-language pathologists to use to improve remediation efforts on vocabulary development, particularly in the area of semantic representation, for children who are at risk for developing reading disabilities.
On Designing Effective Caregiver Training Programs for Low Income Families
Authors: Oetting Janna B. , Pruitt Sonja L. , Farho Shannon L.
Published: July 2010

In this article, we describe Tips About Talk, a group-based prevention program we created to increase low-income caregivers' knowledge and use of positive talking strategies to facilitate their children’s speech, language, and literacy skills. Following this, we present findings from a study that evaluated the effectiveness of the program and describe the changes we have made to our services based on these findings.
A mechanical memory with a dc modulation of nonlinear resonance
Authors: Noh Hyunho , Shim Seung-Bo , Jung Minkyung , Khim Zheong G. , Kim Jinhee
Published: July 2010

We present a mechanical memory device based on dynamic motion of a nanoelectromechanical (NEM) resonator. The NEM resonator exhibits clear nonlinear resonance characteristics which can be controlled by the dc bias voltage. For memory operations, the NEM resonator is driven to the nonlinear resonance region, and binary values are assigned to the two allowed states on the bifurcation branch. The transition between memory states is achieved by modulating the nonlinear resonance characteristics with dc bias voltage. Our device works at room temperature and modest vacuum conditions with a maximum operation frequency of about 5 kHz.
Analyzing molecular static linear response properties with perturbed localized orbitals
Authors: Autschbach Jochen , King Harry F.
Published: July 2010

Perturbed localized molecular orbitals (LMOs), correct to first order in an applied static perturbation and consistent with a chosen localization functional, are calculated using analytic derivative techniques. The formalism is outlined for a general static perturbation and variational localization functionals. Iterative and (formally) single-step approaches are compared. The implementation employs an iterative sequence of 2×2 orbital rotations. The procedure is verified by calculations of molecular electric-field perturbations. Boys LMO contributions to the electronic static polarizability and the electric-field perturbation of the ⟨r2⟩ expectation value are calculated and analyzed for ethene, ethyne, and fluoroethene (H2CCHF). For ethene, a comparison is made with results from a Pipek–Mezey localization. The calculations show that a chemically intuitive decomposition of the calculated properties is possible with the help of the LMO contributions and that the polarizability contributions in similar molecules are approximately transferable.
Vibrationally resolved photoelectron imaging of gold hydride cluster anions: AuH− and Au2H−
Authors: Wu Xia , Qin Zhengbo , Xie Hua , Cong Ran , Wu Xiaohu , Tang Zichao , Fan Hongjun
Published: July 2010

Photoelectron spectra and angular distributions in photodetachment of gold hydride anions AuH− and Au2H− have been obtained using photoelectron velocity-map imaging. Both the images exhibit vibrationally resolved ground state transitions. The adiabatic electron affinities of AuH and Au2H are measured to be 0.758(20) and 3.437(3) eV, respectively. Franck–Condon analyses of the AuH spectra determined that the equilibrium bond length of the ground state of AuH− is 1.597(6) Ǻ. The photoelectron images of Au2H− show a vibrational progression of 148(4) cm−1 assigned to the Au–Au stretching mode at the ground state. Ab initio calculation results are in excellent agreement with the experimental results. For the ground state of Au2H, a new bent Au–Au–H structure with the angle of 131° is suggested. Moreover, energy-dependent photoelectron anisotropy parameters are also reported and discussed.
Solid-liquid surface free energy of Lennard-Jones liquid on smooth and rough surfaces computed by molecular dynamics using the phantom-wall method
Authors: Leroy Frédéric , Müller-Plathe Florian
Published: July 2010

Different model Lennard-Jones solid-liquid interfaces have been considered. In the systems, either the interaction strength between solid and liquid was varied, or the topography of the solid surface was modified. In all situations, the solid-liquid interfacial free energy variations with respect to a reference solid-liquid interface were quantified by means of a thermodynamic integration method [F. Leroy et al., Macromol. Rapid Commun. 30, 864 (2009)], referred to as the phantom-wall method. Additionally, the liquid-vapor surface free energy was determined. This result was combined with Young’s equation for contact angle calculations of cylindrical liquid droplets. It allowed us to show that the change in contact angle of a droplet placed on smooth solid surfaces with respect to solid-liquid interaction strength could be obtained by neglecting the solid-vapor surface free energy contribution when the solid-liquid interaction was weak. We also showed that the implementation of roughness by means of parallel grooves whose the density was varied could yield either higher or lower solid-liquid surface free energy, depending on the solid-liquid surface free energy of the smooth interface. Roughness led to lower surface free energy when the smooth surface had favorable interaction with the liquid, while it led to a higher surface free energy when the smooth surface had loose interactions with the liquid, though the effect was found to be weak. The consistency of the whole set of results, as well as agreement with the existing results on similar systems, shows the ability of the thermodynamic integration method employed here to capture the variation of interfacial thermodynamic quantities when modifying either the chemical nature or the topography of a solid surface in contact with a given liquid phase.
Adsorption and switching properties of a N-benzylideneaniline based molecular switch on a Au(111) surface
Authors: Óvári László , Luo Ying , Leyssner Felix , Haag Rainer , Wolf Martin , Tegeder Petra
Published: July 2010

High resolution electron energy loss spectroscopy has been employed to analyze the adsorption geometry and the photoisomerization ability of the molecular switch carboxy-benzylideneaniline (CBA) adsorbed on Au(111). CBA on Au(111) adopts a planar (trans) configuration in the first monolayer (ML) as well as for higher coverages (up to 6 ML), in contrast to the strongly nonplanar geometry of the molecule in solution. Illumination with UV light of CBA in direct contact with the Au(111) surface (≤1 ML) caused no changes in the vibrational structure, whereas at higher coverages (>1 ML) pronounced modifications of vibrational features were observed, which we assign to a trans→cis isomerization. Thermal activation induced the back reaction to trans-CBA. We propose that the photoisomerization is driven by a direct (intramolecular) electronic excitation of the adsorbed CBA molecules in the second ML (and above) analogous to CBA in the liquid phase.
A computational study of ultrafast acid dissociation and acid-base neutralization reactions. I. The model
Authors: Maurer Patrick , Thomas Vibin , Rivard Ugo , Iftimie Radu
Published: July 2010

Ultrafast, time-resolved investigations of acid-base neutralization reactions have recently been performed using systems containing the photoacid 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) and various Brønsted bases. Two conflicting neutralization mechanisms have been formulated by Mohammed et al. [Science 310, 83 (2005)] and Siwick et al. [J. Am. Chem. Soc. 129, 13412 (2007)] for the same acid-base system. Herein an ab initio molecular dynamics based computational model is formulated, which is able to investigate the validity of the proposed mechanisms in the general context of ground-state acid-base neutralization reactions. Our approach consists of using 2,4,6-tricyanophenol (exp. pKa≅1) as a model for excited-state HPTS∗ (pKa≅1.4) and carboxylate ions for the accepting base. We employ our recently proposed dipole-field/quantum mechanics (QM) treatment [P. Maurer and R. Iftimie, J. Chem. Phys. 132, 074112 (2010)] of the proton donor and acceptor molecules. This approach allows one to tune the free energy of neutralization to any desired value as well as model initial nonequilibrium hydration effects caused by a sudden increase in acidity, making it possible to achieve a more realistic comparison with experimental data than could be obtained via a full-QM treatment of the entire system. It is demonstrated that the dipole-field/QM model reproduces correctly key properties of the 2,4,6-tricyanophenol acid molecule including gas-phase proton dissociation energies and dipole moments, and condensed-phase hydration structure and pKa values.
Quantifying chaos for ecological stoichiometry
Authors: Duarte Jorge , Januário Cristina , Martins Nuno , Sardanyés Josep
Published: July 2010

The theory of ecological stoichiometry considers ecological interactions among species with different chemical compositions. Both experimental and theoretical investigations have shown the importance of species composition in the outcome of the population dynamics. A recent study of a theoretical three-species food chain model considering stoichiometry [B. Deng and I. Loladze, Chaos 17, 033108 (2007)] shows that coexistence between two consumers predating on the same prey is possible via chaos. In this work we study the topological and dynamical measures of the chaotic attractors found in such a model under ecological relevant parameters. By using the theory of symbolic dynamics, we first compute the topological entropy associated with unimodal Poincaré return maps obtained by Deng and Loladze from a dimension reduction. With this measure we numerically prove chaotic competitive coexistence, which is characterized by positive topological entropy and positive Lyapunov exponents, achieved when the first predator reduces its maximum growth rate, as happens at increasing δ1. However, for higher values of δ1 the dynamics become again stable due to an asymmetric bubble-like bifurcation scenario. We also show that a decrease in the efficiency of the predator sensitive to prey’s quality (increasing parameter ζ) stabilizes the dynamics. Finally, we estimate the fractal dimension of the chaotic attractors for the stoichiometric ecological model.
Band lineup between silicon and transparent conducting oxides
Authors: Höffling B. , Schleife A. , Fuchs F. , Rödl C. , Bechstedt F.
Published: July 2010

Modern quasiparticle calculations based on hybrid functionals are used to predict natural band discontinuities between silicon and In2O3, ZnO, and SnO2 by two alignment methods, a modified Tersoff method for the branch-point energy and the Shockley–Anderson model via the electron affinity rule. The results of both methods are found to be in good agreement. A tendency for misaligned type-II heterostructures is predicted, indicating efficient electron-hole separation at the Si-oxide interfaces.
Unusual resistance hysteresis in n-layer graphene field effect transistors fabricated on ferroelectric Pb(Zr0.2Ti0.8)O3
Authors: Hong X. , Hoffman J. , Posadas A. , Zou K. , Ahn C. H. , Zhu J.
Published: July 2010

We have fabricated n-layer graphene field effect transistors on epitaxial ferroelectric Pb(Zr0.2Ti0.8)O3 (PZT) thin films. At low gate voltages, PZT behaves as a high-κ dielectric with κ up to 100. An unusual resistance hysteresis occurs in gate sweeps at high voltages, with its direction opposite to that expected from the polarization switching of PZT. The relaxation of the metastable state is thermally activated, with an activation barrier of 50–110 meV and a time constant of 6 h at 300 K. We attribute its origin to the slow dissociation/recombination dynamics of water molecules adsorbed at the graphene-PZT interface. This robust hysteresis can potentially be used to construct graphene-ferroelectric hybrid memory devices.
Controllable chirality switching of a moving domain wall by oblique magnetic field
Authors: Seo Soo-Man , Lee Kyung-Jin , Jung Soon-Wook , Lee Hyun-Woo
Published: July 2010

A full micromagnetic model and a simplified one-dimensional analytical model are used to investigate the domain wall dynamics driven by an oblique magnetic field. Both models show that the Walker breakdown [N. L. Schryer and L. R. Walker, J. Appl. Phys. 45, 5406 (1974)] can occur at two distinct field strengths. However, the two models exhibit an important discrepancy due to the antivortex injection at the Walker field, which is not taken into account in the analytical model. The chirality of the domain wall is switched controllably when the field strength is in the range between the two Walker fields. The field window for controllable switching becomes broader with increasing oblique field angle or damping constant.
Charge conversion effects of carbon nanotube network transistors by temperature for Al2O3 gate dielectric formation
Authors: Kim Un Jeong , Son Hyung Bin , Lee Eun Hong , Kim Jong Min , Min Shin Chul , Park Wanjun
Published: July 2010

We report on the observation of the electrical characteristics for field effect transistors with random networks of single-walled carbon nanotubes induced by thermal contribution on gate dielectric formation. For the Al2O3 gate dielectric, only the deposition temperature gradually changes the electrical polarity from p-type to n-type. Competition between the electron transfer from the Al2O3 layers to the nanotube surface and the electron capture by the oxygen molecules adsorbed on the tube wall is critical for transport depending on the deposition temperature.
KCNJ10 gene mutations causing EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) disrupt channel function
Authors: Reichold Markus , Zdebik Anselm A. , Lieberer Evelyn , Rapedius Markus , Schmidt Katharina , Bandulik Sascha , Sterner Christina , Tegtmeier Ines , Penton David , Baukrowitz Thomas , Hulton Sally-Anne , Witzgall Ralph , Ben-Zeev Bruria , Howie Alexander J. , Kleta Robert , Bockenhauer Detlef , Warth Richard
Published: July 2010

Mutations of the
KCNJ10
(
Kir4.1
) K
+
channel underlie autosomal recessive epilepsy, ataxia, sensorineural deafness, and (a salt-wasting) renal tubulopathy (EAST) syndrome. We investigated the localization of KCNJ10 and the homologous KCNJ16 in kidney and the functional consequences of
KCNJ10
mutations found in our patients with EAST syndrome. Kcnj10 and Kcnj16 were found in the basolateral membrane of mouse distal convoluted tubules, connecting tubules, and cortical collecting ducts. In the human kidney, KCNJ10 staining was additionally observed in the basolateral membrane of the cortical thick ascending limb of Henle's loop. EM of distal tubular cells of a patient with EAST syndrome showed reduced basal infoldings in this nephron segment, which likely reflects the morphological consequences of the impaired salt reabsorption capacity. When expressed in CHO and HEK293 cells, the KCNJ10 mutations R65P, G77R, and R175Q caused a marked impairment of channel function. R199X showed complete loss of function. Single-channel analysis revealed a strongly reduced mean open time. Qualitatively similar results were obtained with coexpression of KCNJ10/KCNJ16, suggesting a dominance of KCNJ10 function in native renal KCNJ10/KCNJ16 heteromers. The decrease in the current of R65P and R175Q was mainly caused by a remarkable shift of pH sensitivity to the alkaline range. In summary, EAST mutations of KCNJ10 lead to impaired channel function and structural changes in distal convoluted tubules. Intriguingly, the metabolic alkalosis present in patients carrying the R65P mutation possibly improves residual function of KCNJ10, which shows higher activity at alkaline pH.
The female political leader
Authors: Ponton Douglas M.
Published: July 2010

This work examines the linguistic construction of gender identity in the discourse of Margaret Thatcher. Identity is defined in the terms of Bucholtz and Hall (2005) as an ‘emergent’ phenomenon, depending on local contexts of interaction. In analysing the contributions by media figures to processes of identity construction recourse is made to the theories of Turner and Oakes (e.g. 1989) in the field of social identity theory. Interviewers’ questions are examined for what they reveal about identity presuppositions. Mrs Thatcher at times plays along with these presuppositions, ignores them, or objects to them. Her answers tell us something about the identity she wishes to construct. The work focuses on Thatcher’s first major political breakthrough; her conquest of the Conservative leadership in 1975. The toolkit for examining identity in discourse proposed by Bucholtz and Hall (2005) is adopted, and Corpus Linguistics and the Appraisal Framework of Martin and White (2005) are used in support of the selected tools.
Governing ‘others’
Authors: Panu Mihnea
Published: July 2010

This paper argues that for contemporary liberalism to govern legitimately, governmental discourses have to create certain identities as ‘other’, that is, as the polar opposite of the good, normal citizen. To fix those identities as a-relational ‘substances’ in the universal language of law and science. And to use those ‘substances’ in games of inclusion/exclusion that simulate non-intervention while safeguarding the liberal ‘will to govern’. Centrally, the identities posited as ‘other’ are those the contemporary governmental discourses also posit as ‘particular’: the poor, the racialised and the gendered. Thus, it is argued that those governmental practices depend in equal measures on the simultaneously individualizing and totalising nature of governmental bio-power, on the particular/universal liberal tension and on the essentialising nature of scientific truths. Those points are illustrated by the US national family planning strategy’s construction of reality in terms of a ‘pathological mother’, a (m)other.
Inside the experience of anorexia nervosa: A narrative thematic analysis
Authors: Ross James Alistair , Green Charlotte
Published: July 2010

Aim: This study considers the question of whether inpatient admission for anorexia nervosa was a therapeutic experience for two women with chronic anorexia nervosa. The question of whether inpatient admission for anorexia nervosa can be therapeutic is not answerable through existing research evidence. Method: The women were interviewed about their experience of having anorexia, its impact on their lives and the treatment they received. The interviews involved learning about the women's experiences by listening to their stories rather than asking them direct questions about what has been therapeutic about their treatment. Analysis: Their narratives were used to develop understanding grounded in experience and were analysed using a narrative thematic analysis. Ideas, themes and connections were noted but not coded as found in some forms of thematic analysis. Discussion: Consideration is given to the therapeutic qualities of the treatments the women received and the place of therapeutic inpatient admission. The central theme of this research was ‘relationships’ which indicates the use of therapeutic approaches that emphasise the importance of the therapeutic relationship in the treatment of chronic anorexia nervosa. It is suggested that psychodynamic and attachment theories should be used to inform overall treatment models. Some important issues for service provision and areas for further research are identified.
Involvement of the P1 Cistron in Overcoming eIF4E-Mediated Recessive Resistance Against Clover yellow vein virus in Pea
Authors: Nakahara Kenji S. , Shimada Ryoko , Choi Sun-Hee , Yamamoto Haruko , Shao Jun , Uyeda Ichiro
Published: July 2010

Two recessive genes (cyv1 and cyv2) are known to confer resistance against Clover yellow vein virus (ClYVV) in pea. cyv2 has recently been revealed to encode eukaryotic translation initiation factor 4E (eIF4E) and is the same allele as sbm1 and wlm against other potyviruses. Although mechanical inoculation with crude sap is rarely able to cause infection of a cyv2 pea, biolistic inoculation of the infectious ClYVV cDNA clone does. At the infection foci, the breaking virus frequently emerges, resulting in systemic infection. Here, a derived cleaved-amplified polymorphic sequence analysis showed that the breakings were associated with a single nonsynonymous mutation on the ClYVV genome, corresponding to an amino-acid substitution at position 24 (isoleucine to valine) on the P1 cistron. ClYVV with the point mutation was able to break the resistance. This is a first report demonstrating that P1 is involved in eIF4E-mediated recessive resistance.
Information Asymmetry and the Bid‐Ask Spread: Evidence From the UK
Authors: Gregoriou Andros , Ioannidis Christos , Skerratt Len
Published: July 2010

Abstract: The generally accepted factors that determine the bid‐ask spread are volatility, trading volume and market value (Atkins and Dyl, 1997;Glosten and Harris, 1988; andMenyah and Paudyal, 2000). FollowingKim and Verrecchia (1994)we include a measure of the disagreement in analysts’ earnings forecasts in our model of the bid ask spread. This measure serves as a proxy for the informational disadvantage of market makers with respect to informed traders. Market makers respond to the additional risk by increasing the bid‐ask spread. We find that the disagreement amongst analysts is significant for horizons up to and including six months (and with the hypothesised sign) in explaining FTSE 100 company spreads, rendering strong empirical support for our model.
Transformation of Polishing Grooves into Ridges on the Worn Surface of Alumina
Authors: Ravikiran A.
Published: July 2010

Wear experiments were conducted on self‐mated alumina, in a pin on disk configuration. Worn surfaces contained pits in the size and shape of grains with a depth that varied up to 150 nm. Original polishing grooves present before the wear test and the wear grooves generated during sliding on the surface bulged and transformed into ridges within some of the pits. The height of the bulge was about 100 nm within a pit 126 nm deep. Pits also contained bulged spots and short parallel ridges.
Toughening of an Alumina—Mullite Composite by Unbroken Bridging Elements
Authors: Khan Ajmal , Chan Helen M. , Harmer Martin P. , Cook Robert F.
Published: July 2010

The toughness‐curve (T‐curve) behavior of a composite that is composed of 30 vol% spherical, polycrystalline, fine‐grained alumina agglomerates dispersed throughout a constant‐toughness 50‐vol%‐alumina—50‐vol%‐mullite matrix was compared to that for a coarse‐grained agglomerate version of the composite, with the intent of identifying the operative toughening mechanisms in the latter. The T‐curve behavior was evaluated using the indentation‐strength method, and the underlying T‐curves were deconvoluted from experimental data using an indentation‐fracture‐mechanics model. Compared to the T‐curve of the coarse‐grained composite, the toughness of the “fine‐grained” composite increased from a similar initial toughness and over a similar crack‐length range but to a lower saturation value. The T‐curve of the fine‐grained composite can be explained as being derived predominantly from unbroken bridging elements in the crack wake, set up by agglomerate‐induced crack‐path deflections in the matrix. This mechanism is proposed to function to the same degree and account for the majority of the observed toughening in the coarse‐grained composite, with the remaining toughening increment being derived from intra‐agglomerate grain bridging. Calculations suggest that unbroken bridging elements do not behave as simple elastic cantilevered beams that bend uniaxially with increasing crack‐opening displacement.
Fine Strontium Ferrite Powders from an Ethanol‐Based Microemulsion
Authors: Fang Jiye , Wang John , Gan Leong‐Ming , Ng Ser‐Choon , Ding Jun , Liu Xiangyuan
Published: July 2010

A fine strontium ferrite powder with high coercivity was successfully prepared by forming hydroxide precursor particles in the continuous ethanol‐based phase of a microemulsion consisting of iso‐octane, NP9, and an ethanol solution containing Sr2+ and Fe3+ cations at a molar ratio of 1:12. The microemulsion‐derived hydroxide precursor was calcined at various temperatures, ranging from 600° to 1100°C, to develop the hexagonal strontium ferrite phase. X‐ray diffractometry and infrared characterizations revealed that the formation mechanisms of strontium ferrite in the microemulsion‐derived precursor differed from those of the precursor derived by conventional coprecipitation. The microemulsion resulted in a strontium ferrite of finer particle size and better magnetic properties than those of the conventionally coprecipitated strontium ferrite. The microemulsion‐derived strontium ferrite exhibited an intrinsic coercivity of 6195 Oe and a saturation magnetization of 58.28 emu/g when calcined at 900oC. The saturation magnetization increased further, to 69.75 emu/g, when the microemulsion‐derived precursor was calcined at 1100oC.
Natural variation in priming of basal resistance: from evolutionary origin to agricultural exploitation
Authors: AHMAD SHAKOOR , GORDON‐WEEKS RUTH , PICKETT JOHN , TON JURRIAAN
Published: July 2010

Biotic stress has a major impact on the process of natural selection in plants. As plants have evolved under variable environmental conditions, they have acquired a diverse spectrum of defensive strategies against pathogens and herbivores. Genetic variation in the expression of plant defence offers valuable insights into the evolution of these strategies. The ‘zigzag’ model, which describes an ongoing arms race between inducible plant defences and their suppression by pathogens, is now a commonly accepted model of plant defence evolution. This review explores additional strategies by which plants have evolved to cope with biotic stress under different selective circumstances. Apart from interactions with plant‐beneficial micro‐organisms that can antagonize pathogens directly, plants have the ability to prime their immune system in response to selected environmental signals. This defence priming offers disease protection that is effective against a broad spectrum of virulent pathogens, as long as the augmented defence reaction is expressed before the invading pathogen has the opportunity to suppress host defences. Furthermore, priming has been shown to be a cost‐efficient defence strategy under relatively hostile environmental conditions. Accordingly, it is possible that selected plant varieties have evolved a constitutively primed immune system to adapt to levels of disease pressure. Here, we examine this hypothesis further by evaluating the evidence for natural variation in the responsiveness of basal defence mechanisms, and discuss how this genetic variation can be exploited in breeding programmes to provide sustainable crop protection against pests and diseases.
Replacing the acetyl linkage in aspirin with choline and magnesium moieties reduces the occurrence of gastric mucosal injury
Authors: DANESH B. J. Z. , NELSON L. M. , RUSSELL R. I. , DOCHERTY C.
Published: July 2010

The acetyl moiety in aspirin (acetyl salicylic acid: ASA) is considered to play a major part in the pathogenesis of ASA‐induced mucosal injury. At equivalent salicylate doses and pH values, the induction of acute gastric mucosal haemorrhagic erosions in rats by ASA and choline magnesium trisalicylate (CMT), a new non‐acetylated salicylate, with and without the potentiating damaging effect of taurodeoxycholic acid (TDCA) were compared. Test solutions were administered byper oralintubation to five groups of fasting Sprague–Dawley rats (n= 24). Gastric mucosa were examined after 4 hours and mucosal injury assessed by a lesion‐scoring system. The incidence and severity (median lesion scores with quartiles) of the lesions were 83% and 13 (7:20) respectively for ASA (128 mg kg−1) compared with 17% and 0 (0:0) for CMT (128 mg kg−1) (P< 0.001 andP< 0.001). TDCA increased mucosal damage to 100% and 29 (20:34) for ASA compared with 30% and 0 (0:4) for CMT (P < 0.001) and P < 0.001). Serum salicylate levels (median values of 1.4 for ASA and 1.5 mmol litre−1for CMT) were not significantly different. It is concluded that replacing the acetyl moiety in ASA with choline and magnesium moieties reduces the ASA‐induced mucosal injury, without affecting blood salicylate concentrations.
The effects of intravenous famotidine on pentagastrin‐stimulated gastric secretion in man
Authors: DE GARA C. J. , BURGET D. W. , CHREMOS A. N. , SILLETTI G , HUNT R. H.
Published: July 2010

Eight healthy male volunteers were each studied on four occasions in a 7 hour double‐blind, placebo‐controlled experiment. Three continuous 6 hour intravenous (i.v.) infusion rates of famotidine, calculated to achieve steady‐state plasma concentrations of 10, 30 and 90 ng ml−1, were compared to placebo. Commencing at the third study hour, hourly incremental step‐up i.v. infusions of pentagastrin 0.1, 0.2, 0.5, 1.0 and 2.0 μg kg−1. hour were administered on each of the four study days. Hourly blood samples were taken for the subsequent determination of plasma famotidine concentration. The three famotidine infusion rates inhibited basal gastric secretion. Pentagastrin‐stimulated secretion was inhibited in a dose‐dependent manner. The highest dose of famotidine (38.7 μg kg−1 hour) inhibited each infusion rate of pentagastrin‐stimulated gastric secretion between 92 and 96 %. The lowest dose of famotidine (4.3 μg kg−1, hour) inhibited pentagastrin 0.1 μg kg−1. hour stimulated secretion by 50% but, when stimulated with pentagastrin 2.0 μg kg−1.hour, gastric secretion was inhibited by only 25%. This study indicates that the intravenous preparation of famotidine is a potent inhibitor of pentagastrin‐stimulated gastric acid secretion.
Review; post‐marketing surveillance of the safety of cimetidine—the problems of data interpretation
Authors: JONES D. G. COLIN , LANGMAN M. J. S. , LAWSON D. H. , VESSEY M P.
Published: July 2010

Experience obtained during post‐marketing surveillance of the safety of cimetidine emphasizes the difficulties in interpretation posed by the high background frequency of disease of all types in drug takers. The multiple sources of confounding factors, and their high prevalence, make it impossible to detect adverse events which mimic ordinary disease, particularly when a consistent relationship between adverse event and drug exposure is not observed. The inclusion of controls emphasizes the difficulties but does not ease interpretation.
Prednisolone absorption in inflammatory bowel disease: correlation with anatomical site and extent
Authors: RODRIGUES C. A. , NABI E. M. , SPILIADIS C , MCINTYRE P. B. , PHONGSATHORN V. , LENNARD‐JONES J. E. , ROSEN A. , WILLOUGHBY J. M. T.
Published: July 2010

Prednisolone absorption was studied in 13 normal subjects, eight patients with ulcerative colitis and 21 patients with Crohn's disease, by measuring plasma levels after a single oral dose. Absorption of the drug was delayed in all patient groups. The peak plasma level of the drug was lower in patients with extensive small bowel Crohn's disease. Patients in this category may need higher doses of oral prednisolone than other patients with inflammatory bowel disease.
Effect of two potent calmodulin antagonists on calcium transport of brush border and basolateral vesicles from human duodenum
Authors: STOLL R. , STERN H. , RUPPIN H. , DOMSCHKE W.
Published: July 2010

In the present in‐vitro study we investigated the possible role of the calmodulin‐antagonistic drugs loperamide and calmidazolium in the regulation of transepithelial Ca2+ transport of human duodenum. Brush border membrane vesicles and basolateral membrane vesicles were simultaneously prepared from surgically resected pieces of morphologically intact human duodenum with a modified Percoll‐gradient centrifugation method. Brush border and basolateral membrane vesicles were characterized using enzyme marker analysis and electron microscopy: alkaline phosphatase was enriched 20‐fold in brush border membrane vesicles, whereas [Na++ K+]‐stimulated adenosine triphosphatase was enriched 15‐fold in basolateral membrane vesicles. Calmodulin activity was determined by a specific radioimmunoassay after solubilizing brush border and basolateral membrane vesicles in 1% Triton X‐100. In basolateral membrane vesicles, we found no calmodulin activity. In brush border membrane vesicles calmodulin activity was impaired by 50% after pre‐incubation with loperamide or calmidazolium. We measured calcium, sodium, d‐glucose and d‐mannitol uptake with a rapid filtration technique. Before the transport experiments, brush border and basolateral membrane vesicles were pre‐incubated with 5 μM loperamide or 5 μM calmidazolium for 60 min at 5 °C. In drug‐pretreated, brush border membrane vesicles calcium uptake was signficantly reduced after 1 min incubation (– 25%±5%, P < 0.05); this effect was completely reversed in the presence of 5 μM calmodulin. In basolateral membrane vesicles, we found two Ca2+ transport systems: (1) Na+/Ca2+ exchange and (2) ATP‐dependent Ca2+ transport. In basolateral membrane vesicles loperamide had no effect. Calmidazolium had no effect on Na+/Ca2+ exchange, but significantly inhibited ATP‐dependent Ca2+ transport. This effect could not be reversed by calmodulin.
Review: acute human models of gastric mucosal injury
Authors: HAWKEY C. J.
Published: July 2010

The use of acute human models of gastric mucosal injury has been stimulated by a need to understand more fully the problems of non‐steroidal anti‐inflammatory drugs but such models have other applications. None is ideal and they all share certain drawbacks. For none of them has a precise relationship to clinical events been established and they have all tended to be employed on a population of young healthy subjects who are not those at greatest clinical risk. Of individual methods mucosal potential difference is an indirect measure which is too often affected by other influences to be acceptable as a measure of mucosal injury when used alone, although it has some value as an adjunct to other measurements. Assay of DNA in gastric washings is a suitable technique for quantifying desquamation of gastric epithelial cells occurring in response to acute injury; on present evidence its significance is much more difficult to assess in the context of continuing challenge over several days. By contrast, measurement of microbleeding is more suitable for quantifying injury over several days of NSAID ingestion; little bleeding is recorded with a single acute challenge. Endoscopy can demonstrate macroscopic lesions which result from mucosal injury—injury which is quantified more easily and sensitively by measurements of cellular exfoliation or bleeding. Paradoxically, endoscopy's strength has been to underline the scientific weakness of acute models because it shows that it is rare for ulcers, which are the lesions of clinical concern to develop in these studies.
Does Caved‐S decrease the gastric ulcer relapse rate during maintenance treatment with ranitidine?
Authors: MORGAN A. G. , PACSOO C. , TAYLOR P. , McADAM W. A. F.
Published: July 2010

Ninety‐five patients with healed gastric ulcers were treated with ranitidine 150 mg at night plus either Caved‐S two tablets twice daily, or an identical placebo preparation. Treatment was continued for 2 years: the recurrence rate after 1 year was 12.5% for single therapy and 19% for combined therapy, and 30 and 40% respectively after 2 years (differences not significant). No serious side‐effects were encountered, but patients found the combination therapy difficult to take, and it conferred no clinical advantage. In a 3 month follow‐up after stopping maintenance therapy, 11% of the patients had a symptomatic ulcer recurrence. It is therefore recommended that elderly patients with gastric ulceration should remain on maintenance therapy for life.
Effect of nicardipine on gastric acid secretion in man
Authors: PRIOR A. , WHORWELL P. J.
Published: July 2010

The effect of nicardipine on basal and pentagastrin‐stimulated gastric acid secretion in normal volunteers was investigated. When compared with saline, an intravenous infusion of nicardipine caused a significant decrease in peak acid output (from 37.8 mmol hour−1 to 28.8 mmol hour−1; P= 0.04) and a small reduction in aspirate volume. Nicardipine had no significant action on basal acid output or volume of aspirate. Proteolytic activity in both the basal and stimulated periods was unaffected by nicardipine as were serum gastrin concentrations. Although calcium channel blocking agents are theoretically antisecretory the present study suggests they are unlikely to have clinically useful therapeutic actions.
What is an intractable duodenal ulcer and how should it be managed?
Authors: POUNDER R. E.
Published: July 2010

An intractable duodenal ulcer is an ulcer that has not healed after 8 weeks of full‐dose treatment with a modern antiulcer drug. Such ulcers are relatively rare ‐ perhaps five in 100 patients will have intractable duodenal ulceration. The differential diagnosis includes non‐compliance as a cause of continuing ulceration, hypersecretion of gastric acid or other rare causes of ulcers in the duodenum. Investigations should include biopsy of the continuing ulceration at endoscopy, measurement of fasting plasma gastrin and routine haematology and biochemistry profiles. An intractable duodenal ulcer can be treated either by using a powerful antisecretory regimen (high doses of ranitidine or famotidine or a conventional dose of omeprazole), by changing to tripotassium dicitrato bismuthate or, in exceptional circumstances, by extremely careful surgical intervention.
What are the differences between the H2‐receptor antagonists?
Authors: SCHUNACK W.
Published: July 2010

The H2‐receptor antagonists which are used for ulcer therapy fall into four main structural classes. Cimetidine is an imidazole derivative; ranitidine belongs to the basically substituted furans, famotidine is a member of the guanidinothiazole group; and roxatidine belongs to the aminoalkylphenoxy series. Famotidine is the most potent, selective H2‐receptor antagonist yet available for ulcer therapy. On a weight basis, famotidine is approximately eight times more potent than ranitidine and 40 times more potent than cimetidine. Cimetidine, ranitidine and famotidine are competitive antagonists, while the long‐acting H2‐receptor antagonists, e.g. loxtidine and lamitidine, are insurmountable H2‐receptor blockers. Famotidine has a longer duration of action than either ranitidine or cimetidine. Because famotidine does not interact with cytochrome P‐450 of the hepatic enzyme system, it does not appear to affect the metabolism of drugs metabolized by this system. The overall number of side‐effects of the H2‐receptor antagonists is in the range of 2–3% and no irreversible adverse effects are known. Famotidine has been found to be generally well tolerated. In a first post‐marketing study, the number of patients with side‐effects was only 0.43%. Side‐effects such as headache, dizziness, constipation and diarrhoea have been observed only occasionally. Thus, famotidine is a safe and potent H2‐receptor blocker of acid secretion.
Lessons from prolonged gastric pH monitoring
Authors: BUMM R. , BLUM A. L.
Published: July 2010

Intragastric pH monitoring has shown that the distribution of acidity within the stomach is not homogeneous. Not only is it affected by meals but it also has a circadian rhythm in which nocturnal pH falls to very acid levels in normal subjects. Although results of pH monitoring are highly reproducible within individuals, considerable inter‐individual variation has been shown. Duodenal ulcer patients do not appear to possess the normal buffering reaction to meals, but their night‐time acidity is within the normal range. In these patients, antacids and pirenzepine have a small acid‐neutralizing effect in the stomach; cimetidine is less potent than ranitidine and famotidine. Clinicians can choose between a single dose of either ranitidine or famotidine in the evening with dinner and a twice‐daily regimen.
Why are non‐steroidal anti‐inflammatory drugs important in peptic ulceration?
Authors: PORRO G. BIANCHI , PACE F. , CARUSO I.
Published: July 2010

The pathogenetic role of non‐steroidal anti‐inflammatory drugs (NSAIDs) in peptic ulcer disease is reviewed, on the basis of available experimental and epidemiological knowledge. In addition, original clinical data are provided concerning the prophylactic and therapeutic role of the H2‐receptor antagonists ranitidine and cimetidine, and colloidal bismuth subcitrate, in the treatment of NSAID‐associated peptic lesions in rheumatic patients.
A comparison of two ranitidine intravenous infusion regimens in critically ill patients
Authors: MARCHANT J. , SUMMERS K. , McISAAC R. L. , WOOD J. R.
Published: July 2010

The effect of two ranitidine intravenous infusion regimens on intragastric pH was studied in 134 critically ill patients admitted to 15 intensive care units. Intragastric pH was determined hourly for 30 hours. Those patients whose intragastric acidity fell below pH 4.0 for 3 or more of the first 6 hours were considered ‘at risk’ of developing stress‐related gastric lesions and randomized to receive a 50 mg bolus of ranitidine together with a continuous intravenous infusion of either 0.125 or 0.25 mg kg—1 h—1 ranitidine for 24 hours. The maximal elevation in intragastric pH was achieved within 12 hours. The median intragastric pH for the last 20 hours of the infusion period was 5.9 for the higher dose group and 5.6 for the lower dose group. The increase in intragastric pH achieved by the two dosage regimens did not differ significantly throughout the 24 hour period. Patients having two or more of five major risk factors (head injury, major trauma, sepsis, respiratory failure/insufficiency and major surgery) had better overall control of intragastric pH on the higher dose of ranitidine than those receiving the lower dose. The majority of intensive care patients are likely to receive satisfactory treatment with the lower dosage regimen that was tested (0.125 mg kg—1 h—1). Those with multiple risk factors may, however, require treatment with higher doses of ranitidine (0.25 mg kg—1 h—1).
Effect of enprostil on basal and meal‐stimulated gastric acid and pepsin secretion, serum gastrin and gastric emptying in healthy persons
Authors: BERSTAD K. , MASSEY H. , BERSTAD A.
Published: July 2010

Ten healthy volunteers took part in a double‐blind, randomized, crossover study of the effect of single doses of enprostil (70 μg) and placebo on basal and meal‐stimulated gastric acid, pepsin secretion and serum gastrin. Meal‐stimulation was induced by modified sham feeding combined with repeated gastric instillation and withdrawal of meat soup. When studied between 1 and 2.5 hours after oral administration of the drug, enprostil decreased basal acid output by 92% (P < 0.001) and stimulated acid output by 70% (P < 0.001). Basal and stimulated volumes of gastric juice were decreased by 50% (P < 0.02) and 35% (P < 0.002), respectively. Enprostil decreased stimulated pepsin output by 34% (P < 0.05), but had no effect on the concentration of pepsin. Neither basal nor stimulated serum gastrin concentrations were affected by enprostil. Percent recovery of the meal was measured by an unabsorbable marker, polyethylene glycol, instilled into the stomach mixed with the soup. Polyethylene glycol recovery decreased from 89% with placebo to 67% with enprostil (P < 0.01), indicating an enhanced gastric emptying rate with enprostil.
Pharmacological response to cimetidine and healing of duodenal ulceration: effects of highdose cimetidine and combination of cimetidine with pirenzepine
Authors: DEAKIN M. , COLIN‐JONES D. G. , WILLIAMS J. G.
Published: July 2010

Overnight gastric secretion was studied in 32 patients with acute duodenal ulcers before treatment and whilst taking cimetidine 400 mg b.d. After 6 weeks of treatment with cimetidine 400 mg b.d. 13 patients had healed ulcers, seven patients had healed ulcers but a persistent erosive duodenitis, and 12 patients had persisting ulceration. Inhibition of nocturnal gastric secretion by cimetidine 400 mg b.d. was most profound in patients who healed their ulcers completely; a less profound inhibition of nocturnal gastric secretion was seen in the non‐healing and duodentis groups. In patients with persisting ulcers and poor inhibition of nocturnal gastric secretion by cimetidine, gastric secretion could be suppressed by either cimetidine 400 mg b.d. in combination with pirenzepine 50 mg b.d., or by cimetidine 1600 mg nocte, but suppression of nocturnal gastric secretion was more effective with cimetidine 1600 mg than cimetidine with pirenzepine.
Review: interactions between H2‐antagonists and non‐steroidal anti‐inflammatory drugs
Authors: HOWDEN C. W.
Published: July 2010

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are being prescribed increasingly with an H2‐antagonist. This article reviews those published studies which have examined the potential for pharmacokinetic and, where appropriate, pharmacodynamic interactions between these classes of drugs. Studies involving the administration of a single dose of a NSAID to young healthy volunteers are of limited relevance in establishing the likely effect of an H2‐antagonist on the blood concentrations of an NSAID in patients. Appropriate studies are those which will examine the effects of H2‐antagonists on the steady‐state pharmacokinetics of NSAIDs in patients with inflammatory joint diseases. More of such studies are required, particularly involving elderly patients.