bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular effects of anandamide and N‐acylvanillylamines in the human forearm and skin microcirculation
Authors: Movahed Pouya , Evilevitch Vladimir , Andersson Tomas L G , Jönsson Bo A G , Wollmer Per , Zygmunt Peter M , Högestätt Edward D
Published: July 2005

The endocannabinoid anandamide is an emerging potential signalling molecule in the cardiovascular system. Anandamide causes vasodilatation, bradycardia and hypotension in animals and has been implicated in the pathophysiology of endotoxic, haemorrhagic and cardiogenic shock, but its vascular effects have not been studied in man.

Human forearm blood flow and skin microcirculatory flow were recorded using venous occlusion plethysmography and laser‐Doppler perfusion imaging (LDPI), respectively. Each test drug was infused into the brachial artery or applied topically on the skin followed by a standardized pin‐prick to disrupt the epidermal barrier.

Anandamide failed to affect forearm blood flow when administered intra‐arterially at infusion rates of 0.3–300 nmol min−1. The highest infusion rate led to an anandamide concentration of approximately 1 μM in venous blood as measured by mass spectrometry.

Dermal application of anandamide significantly increased skin microcirculatory flow and coapplication of the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine inhibited this effect. The TRPV1 agonists capsaicin, olvanil and arvanil all induced concentration‐dependent increases in skin blood flow and burning pain when administered dermally. Coapplication of capsazepine inhibited blood flow and pain responses to all three TRPV1 agonists.

This study shows that locally applied anandamide is a vasodilator in the human skin microcirculation. The results are consistent with this lipid being an activator of TRPV1 on primary sensory nerves, but do not support a role for anandamide as a circulating vasoactive hormone in the human forearm vascular bed.

British Journal of Pharmacology (2005) 146, 171–179. doi:10.1038/sj.bjp.0706313
Dexamethasone and cardiac potassium currents in the diabetic rat
Authors: Shimoni Yakhin
Published: July 2005

Experiments were designed to compare effects of dexamethasone on transient (Ipeak) and sustained (Isus) K+ currents in control and diabetic rat myocytes. Ventricular myocytes were isolated from control or type 1 streptozotocin (STZ)‐induced diabetic male and female rats. Currents were measured using whole‐cell voltage‐clamp methods.

Incubation of cells from control males or females with 100 nM dexamethasone (5–9 h) significantly (P<0.005) augmented Isus (by 28–31%). Ipeak was unchanged. Isus augmentation was abolished by cycloheximide or cytochalasin D, but not by inhibition of protein kinases A or C. Inhibition of tyrosine kinases by genistein (but not its inactive analog genistin) prevented the increase of Isus by dexamethasone. In marked contrast, dexamethasone had a significantly (P<0.015) smaller effect on Isus (11% increase) in cells from male STZ‐diabetic rats, as compared to control cells. However, Isus augmentation in cells from female STZ‐diabetic rats was normal (31% increase). In ovariectomized‐diabetic rats, Isus was unchanged by dexamethasone. The reduced effect in diabetic males might be due to preactivation of tyrosine kinases linking dexamethasone to current modulation.

In conclusion, type I diabetes is associated with gender‐specific changes in sensitivity of K+ currents to glucocorticoids, linked to alterations in tyrosine‐phosphorylated proteins.

British Journal of Pharmacology (2005) 146, 280–287. doi:10.1038/sj.bjp.0706314
Studies on the effect of MDMA (‘ecstasy’) on the body temperature of rats housed at different ambient room temperatures
Authors: Green A Richard , O'Shea Esther , Saadat Kathryn S , Elliott J Martin , Colado M Isabel
Published: July 2005

3,4‐Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) administration to rats produces hyperthermia if they are housed in normal or warm ambient room temperature (Ta) conditions (20°C), but hypothermia when in cool conditions (Ta17°C). We have now investigated some of the mechanisms involved.

MDMA (5 mg kg−1 i.p.) produced a rapid decrease in rectal temperature in rats at Ta 15°C. This response was blocked by pretreatment with the dopamine D2 receptor antagonist remoxipride (10 mg kg−1 i.p.), but unaltered by pretreatment with the D1 antagonist SCH23390 (1.1 mg kg−1 i.p.).

MDMA (5 mg kg−1) did not alter the tail temperature of rats at Ta 15°C, but decreased the tail temperature of rats at Ta 30°C.

A neurotoxic dose of MDMA (three doses of 5 mg kg−1 given 3 h apart) decreased cortical and hippocampal 5‐HT content by approximately 30% 7 days later. This lesion did not influence the rise in tail temperature when rats were moved from Ta 20°C to 30°C compared to nonlesioned controls, but did result in a lower tail temperature than that of controls when they were returned to Ta 24°C.

Acute administration of MDMA (5 mg kg−1) to MDMA‐lesioned rats produced a sustained decrease in tail temperature in rats housed at Ta 30°C compared to nonlesioned controls.

These data suggest that the thermoregulatory problems previously observed in MDMA‐lesioned rats housed at Ta 30°C result, partially, from their inability to lose heat by vasodilation of the tail, a major heat‐loss organ in this species.

British Journal of Pharmacology (2005) 146, 306–312. doi:10.1038/sj.bjp.0706318
Induction of cytochrome P450 1A by cow milk‐based formula: a comparative study between human milk and formula
Authors: Xu Haibo , Rajesan Ratheishan , Harper Patricia , Kim Richard B , Lonnerdal Bo , Yang Mingdong , Uematsu Satoko , Hutson Janine , Watson‐MacDonell Jo , Ito Shinya
Published: July 2005

During the treatment of neonatal apnea, formula‐fed infants, compared to breastfed infants, show nearly three‐fold increase in clearance of caffeine, a substrate of cytochrome P450 1A (CYP1A) and in part CYP3A4. However, human milk is known to contain higher concentrations of environmental pollutants than infant formula, which are potent CYP1A inducers. To gain insight into the mechanism underlying this apparent contradiction, we characterized CYP1A and CYP3A4 induction by human milk and cow milk‐based infant formula.

The mRNA and protein expression of CYP1A1/1A2 were significantly induced by cow milk‐based formula, but not by human milk, in HepG2 cells.

Luciferase reporter assay demonstrated that cow milk‐based formula but not human milk activated aryl hydrocarbon receptor (AhR) significantly. The cotreatment of 3,4‐dimethoxyflavone, an AhR antagonist, abolished the formula‐induced CYP1A expression. In addition, AhR activation by dibenzo[a,h]anthracene, a potent AhR agonist, was significantly suppressed by infant formula and even more by human milk.

In contrast, CYP3A4 mRNA expression was only mildly induced by formula and human milk. Consistently, neither formula nor human milk substantially activated pregnane X receptor (PXR).

Effects of whey and soy protein‐based formulas on the AhR–CYP1A and the PXR–CYP3A4 pathways were similar to those of cow milk‐based formula.

In conclusion, infant formula, but not human milk, enhances in vitro CYP1A expression via an AhR‐mediated pathway, providing a potential mechanistic basis for the increased caffeine elimination in formula‐fed infants.

British Journal of Pharmacology (2005) 146, 296–305. doi:10.1038/sj.bjp.0706319
Worldwide Genetic Variation at the 3′‐UTR Region of theLDLRGene: Possible Influence of Natural Selection
Authors: Fagundes N. J. R. , Salzano F. M. , Batzer M. A. , Deininger P. L. , Bonatto S. L.
Published: July 2005

The low density lipoprotein receptor gene (LDLR) contains manyAluinsertions, and is especiallyAlu‐rich at its 3′‐untranslated region (3′‐UTR). Previous studies suggested that theLDLR3′‐UTR could regulate gene expression by the stabilization of its mRNA. Given the fasterAluevolutionary rate, and wondering about its consequences in a possibly regulatory locus, we have studied ∼800 bp of 222 chromosomes from individuals of African, Asian, Caucasian and Amerind ancestry, to better understand the evolution of the worldwide genetic diversity at this locus. Twenty‐one polymorphic sites, distributed in 15 haplotypes, were found. High genetic diversity was observed, concentrated in oneAluinsertion (AluU), which also shows a fast evolutionary rate. Genetic diversity is similar in all populations except Amerinds, suggesting a bottleneck during the peopling of the American continent. Three haplotype clusters (A, B, C) are distinguished, cluster A being the most recently formed (∼500,000 years ago). No clear geographic structure emerges from the haplotype network, the globalFst(0.079) being lower than the average for the human genome. When ancestral population growth is taken into account, neutrality statistics are higher than expected, possibly suggesting the action of balancing selection worldwide.
Family‐Based Association Tests for Different Family Structures Using Pooled DNA
Authors: Zou Guohua , Zhao Hongyu
Published: July 2005

DNA pooling is a cost‐effective strategy for genomewise association studies to identify disease genes. In the context of family‐based association studies, Risch & Teng (1998) mainly considered families of identical structures to detect associations between genetic markers and disease, and suggested possible approaches to incorporating different family types without a thorough study of their properties. However, families collected in real genetic studies often have different structures and, more importantly, the informativeness of each family structure depends on the disease model which is generally unknown. So there is a need to develop and investigate statistical methods to combine information from diverse family types. In this article, we propose a general strategy to incorporate different family types by assigning each family an “optimal” weight in association tests. In addition, we consider measurement errors in our analysis. When we evaluate our approach under different disease models and measurement errors, we find that our weighting scheme may lead to a substantial reduction in sample size required over the approach suggested by Risch & Teng (1998), and measurement errors may have significant impact on the required sample size when the error rates are not negligible.
Genetic Polymorphisms and Haplotypes of the Human Cardiac Sodium Channel α Subunit Gene (SCN5A) in Japanese and their Association with Arrhythmia
Authors: Maekawa K. , Saito Y. , Ozawa S. , Adachi‐Akahane S. , Kawamoto M. , Komamura K. , Shimizu W. , Ueno K. , Kamakura S. , Kamatani N. , Kitakaze M. , Sawada J.
Published: July 2005

Genetic variations in cardiac ion channels have been implicated not only as the causes of inherited arrhythmic syndromes, but also as genetic risk factors for some acquired arrhythmias. To elucidate the potential roles of genetic polymorphisms of the α subunit of the voltage‐gated sodium channel type V (SCN5A) in cardiac rhythm disturbance, the entire SCN5A coding exons and their flanking introns were sequenced in 166 Japanese arrhythmic patients and 232 healthy controls. We detected 69 genetic variations, including 54 novel ones. Out of the 12 novel nonsynonymous single nucleotide polymorphisms (SNPs), p.Leu1988Arg was found at a frequency of 0.015. The other 11 SNPs were rare (0.001), with 6 found in arrhythmic patients and 5 in healthy controls. The frequency of a novel intronic SNP, c.703+130G>A, was significantly higher in the patients than in the controls, suggesting this SNP is associated with an unknown risk factor for arrhythmia. Following linkage disequilibrium analysis, the haplotype structure of SCN5A was inferred using high‐frequency SNPs. The frequency of the haplotype harbouring both p.Leu1988Arg and the common SNP p.His558Arg (haplotype GG) was significantly lower in the patients than in the controls. This finding suggests that this haplotype (GG) might have been positively selected in the controls because of its protective effect against arrhythmias. This study provides fundamental information necessary to elucidate the effect of genetic variations in SCN5A on channel function and cardiac rhythm in Japanese, and probably in the Asian population.
Score Statistic to Test for Genetic Correlation for Proband‐Family Design
Authors: El Galta R. , Van Duijn C. M. , Van Houwelingen J. C. , Houwing‐Duistermaat J. J.
Published: July 2005

In genetic epidemiological studies informative families are often oversampled to increase the power of a study. For a proband‐family design, where relatives of probands are sampled, we derive the score statistic to test for clustering of binary and quantitative traits within families due to genetic factors. The derived score statistic is robust to ascertainment scheme. We considered correlation due to unspecified genetic effects and/or due to sharing alleles identical by descent (IBD) at observed marker locations in a candidate region. A simulation study was carried out to study the distribution of the statistic under the null hypothesis in small data‐sets. To illustrate the score statistic, data from 33 families with type 2 diabetes mellitus (DM2) were analyzed. In addition to the binary outcome DM2 we also analyzed the quantitative outcome, body mass index (BMI). For both traits familial aggregation was highly significant. For DM2, also including IBD sharing at marker D3S3681 as a cause of correlation gave an even more significant result, which suggests the presence of a trait gene linked to this marker. We conclude that for the proband‐family design the score statistic is a powerful and robust tool for detecting clustering of outcomes.
Polymorphic Alu Insertions and their Associations with MHC Class I Alleles and Haplotypes in the Northeastern Thais
Authors: Dunn D. S. , Romphruk A. V. , Leelayuwat C. , Bellgard M. , Kulski J. K.
Published: July 2005

Polymorphic Alu insertions (POALINs) are known to contribute to the strong polymorphic nature of the Major Histocompatibility Complex (MHC). Previous population studies on MHC POALINs were limited to only Australian Caucasians and Japanese. Here, we report on the individual insertion frequency of the five POALINs within the MHC class I region, their HLA‐A and ‐B associations, and the three and four locus alpha block POALIN haplotype frequencies in the Northeastern (NE) Thai population. Of the five POALINs, the lowest frequency was 0.018 for AluyHF and the highest frequency was 0.292 for AluyHJ and AluyHG. The strongest positive associations between the POALINs and HLA class I alleles was between AluyMICB and HLA‐B*57, AluyHJ and HLA‐A*24 and HLA‐A*01, and AluyHG and HLA‐A*02, supporting previous findings in Caucasians and Japanese. Single POALIN haplotypes were found more frequently than multiple POALIN haplotypes. However, of the seven different POALIN haplotypes within the MHC alpha block, there were only two significant differences between the NE Thais, Caucasians and Japanese. This study confirms that the MHC POALINs are in linkage disequilibrium with HLA‐A and –B alleles and that there are significant frequency differences for some of the POALINs when compared between NE Thai, Caucasians and Japanese.
Reparation or Retribution: An Investigation into Regulatory Compliance in Planning
Authors: McKay Stephen , Ellis Geraint
Published: July 2005

It is an axiom of good planning practice that procedure is informed by up-to-date research. Consequently, it is surprising to discover that there remains a dearth of specialised planning-enforcement literature relating to theory and implementation. In this paper an evaluation is given of the effectiveness of planning enforcement in Britain by reviewing existing legislative mechanisms and strategies employed by officials. Theoretical perspectives are drawn upon to suggest how the system might be improved through attention to the structural factors underpinning it.
Spatial Proximity Effects and Regional Equity Gaps in the Venture Capital Market: Evidence from Germany and the United Kingdom
Authors: Martin Ron , Berndt Christian , Klagge Britta , Sunley Peter
Published: July 2005

The issue of ‘equity gaps’ has loomed large in recent discussions of enterprise formation and development, both in the United Kingdom and in Germany. One particularly intriguing, but highly elusive, aspect of this issue is the question of whether equity gaps have a regional dimension: are certain regions at a systematic disadvantage with respect to the provision of equity capital? In this paper, we explore this question in the context of the UK and German venture capital industries, drawing both on unpublished industry data and on information obtained from original surveys of venture capital firms in the two countries. We report clear evidence that the venture industries in both countries are spatially constituted. Despite important national differences, venture capital firms tend to be concentrated in identifiable clusters and their investment outcomes show clear evidence of spatial proximity effects; investment is disproportionately concentrated in those regions that also contain the major clusters of venture capital firms. However, how far this spatial form produces regional equity gaps is hard to determine. Venture capitalists themselves argue that they do not intentionally discriminate between regions in their decisionmaking, and many acknowledge the existence of funding and deal-size gaps but not regional gaps per se. But their perception of project risk is, nevertheless, regionally sensitive. We argue that the notion of a simple supply gap overlooks the way in which the localised form of the industry is based on a dynamic learning process in which demand and supply processes combine with their embeddedness in social networks and individual perceptions in a mutually reinforcing way. Less-favoured regions, with low investment rates, few local venture capital firms, and a dearth of experienced specialist intermediaries, may thus be trapped in a situation of both depressed demand for and supply of venture capital investment.
‘I Think it's Just Natural’: The Spatiality of Racial Segregation at a US High School
Authors: Thomas Mary E
Published: July 2005

In this paper I consider the performativity of racial identities and difference at a southern US high school. I utilize Butler's performativity theory along with geographic theories of race, racial difference, and racism to argue that teenage girls reinstate racial difference through their everyday spatial practices. The paper has two substantive sections in addition to the introduction and the conclusion. The first explores the segregated high school lunchroom. Here I examine two girls' narratives and suggest that these girls encounter the spatiality of racial difference in the lunchroom and repeat the practices of segregated sitting. Thus, they reinscribe racialized difference and identity through their spatial practices of sitting with same-race friends. The second substantive section focuses on girls' practices of identifying others' racial identities. In this section I argue that these identifications are spatialized and that racial difference and categorization are achieved through spatial policing and boundary making. Throughout the paper I argue that racial identity and racial difference are performative, but that performativity must account for the normative spatiality of social and racial practice.
New-Build ‘Gentrification’ and London's Riverside Renaissance
Authors: Davidson Mark , Lees Loretta
Published: July 2005

In a recent conference paper Lambert and Boddy (2002) questioned whether new-build residential developments in UK city centres were examples of gentrification. They concluded that this stretched the term too far and coined ‘residentialisation’ as an alternative term. In contrast, we argue in this paper that new-build residential developments in city centres are examples of gentrification. We argue that new-build gentrification is part and parcel of the maturation and mutation of the gentrification process during the post-recession era. We outline the conceptual cases for and against new-build ‘gentrification‘, then, using the case of London's riverside renaissance, we find in favour of the case for.
Falling through the Cracks: Limits to an Instrumental Rational Role for Environmental Information in Planning
Authors: Hills Sarah
Published: July 2005

This paper explores the potential for environmental information to play an instrumental rational role in planning through an empirical investigation of regional planning processes in the German federal state of Brandenburg. The findings show that environmental information is used in only a limited number of policy issues and processes and that where it plays a role in choice making, its function is procedural rather than instrumental. The author concludes that the influence of the regulatory framework on the decisionmaking jurisdiction of regional planning and the disappearance of environmental information in decisions of great economic importance are key constraints on a rational instrumental role for environmental information.
Electoral Participation and Political Context: The Turnout–Marginality Paradox at the 2001 British General Election
Authors: Pattie Charles J , Johnston Ron J
Published: July 2005

Constituency-level analyses of electoral turnout commonly uncover a correlation between the marginality of a seat and the level of electoral participation in the seat: the closer the local contest, the greater the rate of participation in the election. However, repeated efforts to assess the impact of constituency marginality on the propensity of individual electors to participate have met with failure. The 2001 British General Election was no exception to either result. This presence of an ecological aggregate-level relationship which is not replicated at the level of individual voters is paradoxical. However, the paradox can be resolved when two analytical steps are combined. First, nonvoters are classified into two groups according to their reasons for abstention: those who abstain on purpose (‘voluntary abstainers’), and those who fail to vote for reasons largely beyond their control (‘involuntary abstainers’). Second, attention is paid not only to actual marginality but also to perceived marginality. Individuals who think their constituency is competitive are less likely to abstain deliberately than individuals who think their constituency is safe.
Corporate Strategy and the Management of Ethical Trade: The Case of the UK Food and Clothing Retailers
Authors: Hughes Alex
Published: July 2005

Ethical trade, involving codes of conduct for worker welfare, has recently emerged as a form of corporate self-regulation for global commodity chains in the context of a neoliberal trading environment. I present a particular critique of ethical trade based on its embeddedness in corporate strategies and management systems. The ethical trading strategies of leading UK food and clothing retailers form the empirical focus of inquiry, and theories found in the literature on economic geography concerning corporate strategy and interfirm organisation are used to gain critical insight into the management systems used by these retailers when they attempt to put ethical trading principles into practice in their global supply chains. Variations are observed between retailers in terms of their commitment to ethical trade, which are shaped by issues of corporate culture, financial management, and corporate restructuring. Varying levels of commitment to ethical trading strategy are argued in turn to influence organisational approaches to social auditing in the supply chain. Three contrasting modes of organisation for ethical monitoring are suggested to be used by retail companies—the arm's-length approach, the coordinated approach, and the developmental approach—each of which holds contrasting implications for suppliers and workers at production sites. I argue that corporate approaches to ethical trade vary markedly and that these variations have the capacity to shape the regulation of labour conditions at sites of export production.
The role of dendritic cells in shaping the immune response
Authors: Howard C. J. , Charleston B. , Stephens S. A. , Sopp P. , Hope J. C.
Published: July 2005

Dendritic cells are central to the initiation of primary immune responses. They are the only antigen-presenting cell capable of stimulating naive T cells, and hence they are pivotal in the generation of adaptive immunity. Dendritic cells also interact with and influence the response of cells of the innate immune system. The manner in which dendritic cells influence the responses in cells of both the innate and adaptive immune systems has consequences for the bias of the adaptive response that mediates immunity to infection after vaccination or infection. It also provides an opportunity to intervene and to influence the response, allowing ways of developing appropriate vaccination strategies. Mouse and human studies have identified myeloid, lymphoid and plasmacytoid dendritic cells. Studies in domesticated animals with agents of specific infectious diseases have confirmed the applicability of certain of the generic models developed from mice or fromin vitrostudies on human cells.In vivoandex vivostudies in cattle have demonstrated the existence of a number of subpopulations of myeloid dendritic cells. These cells differ in their ability to stimulate T cells and in the cytokines that they produce, observations clearly having important implications for the bias of the T-cell response. Dendritic cells also interact with the innate immune system, inducing responses that potentially bias the subsequent adaptive response.
Genetic variation and responses to vaccines
Authors: Glass Elizabeth J.
Published: July 2005

Disease is a major source of economic loss to the livestock industry. Understanding the role of genetic factors in immune responsiveness and disease resistance should provide new approaches to the control of disease through development of safe synthetic subunit vaccines and breeding for disease resistance. The major histocompatibility complex (MHC) has been an important candidate locus for immune responsiveness studies. However, it is clear that other loci play an important role. Identifying these and quantifying the relative importance of MHC and non-MHC genes should result in new insights into host–pathogen interactions, and information that can be exploited by vaccine designers. The rapidly increasing information available about the bovine genome and the identification of polymorphisms in immune-related genes will offer potential candidates that control immune responses to vaccines. The bovine MHC,BoLA, encodes two distinct isotypes of class II molecules, DR and DQ, and in about half the common haplotypes theDQgenes are duplicated and expressed. DQ molecules are composed of two polymorphic chains whereas DR consists of one polymorphic and one non-polymorphic chain. Although, it is clear that MHC polymorphism is related to immune responsiveness, it is less clear how different allelic and locus products influence the outcome of an immune response in terms of generating protective immunity in outbred animals. A peptide derived from foot-and-mouth disease virus (FMDV) was used as a probe for BoLA class II function. Both DR and DQ are involved in antigen presentation. In an analysis of T-cell clones specific for the peptide, distinct biases to particular restriction elements were observed. In addition inter-haplotype pairings of DQA and DQB molecules produced functional molecules, which greatly increases the numbers of possible restriction elements, compared with the number of genes, particularly in cattle with duplicatedDQgenes. In a vaccine trial with several peptides derived from FMDV,BoLAclass IIDRB3polymorphisms were correlated with both protection and non-protection. Although variation in immune responsiveness to the FMDV peptide between different individuals is partly explainable byBoLAclass II alleles, other genetic factors play an important role. In a quantitative trait locus project, employing a second-generation cross between Charolais and Holstein cattle, significant sire and breed effects were also observed in T-cell, cytokine and antibody responses to the FMDV peptide. These results suggest that both MHC and non-MHC genes play a role in regulating bovine immune traits of relevance to vaccine design. Identifying these genes and quantifying their relative contributions is the subject of further studies.
Advances in mucosal vaccination
Authors: Meeusen Els N. T. , Scheerlinck Jean-Pierre Y. , Wattegedera Sean , Entrican Gary
Published: July 2005

Pathogens that enter the body via mucosal surfaces face unique defense mechanisms that combine the innate barrier provided by the mucus layer with an adaptive response typified by the production and transepithelial secretion of pathogen-specific IgA. Both the measurement and induction of mucosal responses pose significant challenges for experimental and practical application and may need to be adapted to the species under study. In particular, for livestock, immunization procedures developed in small rodent models are not always effective in large animals or compatible with management practices. This paper reviews the latest advances in our understanding of the processes that lead to secretory IgA responses and how this relates to the development of mucosal immunization procedures and adjuvants for veterinary vaccines. In addition, it highlights the complex interactions that can take place between the pathogen and the host's immune response, with specific reference toChlamydia/Chlamydophilainfections in sheep.
Vaccination against classical swine fever virus: limitations and new strategies
Authors: Greiser-Wilke Irene , Moennig Volker
Published: July 2005

The most widely used vaccines for the control of classical swine fever (CSF) in countries where it is endemic are live attenuated virus strains, which are highly efficacious, inducing virtually complete protection against challenge with pathogenic virus. In the European Union (EU), the combination of prophylactic mass vaccination and culling of infected pigs in endemic regions has made it possible to almost eradicate the disease. However, it is not possible to discriminate between infected and vaccinated animals, thus hampering disease control measures that rely on serology. Therefore, vaccination was banned at the end of 1990 before the internal common market was established in the EU. Vaccination is allowed only in severe emergencies. In addition, there are strict restrictions on the international trade in pig products from countries using vaccination. To circumvent these problems, marker vaccines which allow differentiation of infected from vaccinated animals (DIVA) have been developed. There are several approaches, ranging from protective peptides, single expressed proteins, naked DNA and chimeric viruses. To date, two subunit vaccines based on the E2 glycoprotein are commercially available and have been tested extensively for their efficacy. The accompanying discriminatory tests are based on an ELISA detecting another viral glycoprotein, the Erns. The subunit vaccines were found to be less efficacious than live attenuated vaccines. In addition, the currently available discriminatory tests do not provide high enough specificity and sensitivity. Although there is an urgent need for more advanced marker vaccines and better discriminatory tests, the development of new DIVA vaccines against CSF is hampered by the small market potential for these products.
Complexities of the pathogenesis ofMannheimia haemolyticaandHaemophilus somnusinfections: challenges and potential opportunities for prevention?
Authors: Czuprynski Charles J. , Leite Fabio , Sylte Matt , Kuckleburg C. , Schultz Ron , Inzana Tom , Behling-Kelly Erica , Corbeil Lynette
Published: July 2005

Progress in producing improved vaccines against bacterial diseases of cattle is limited by an incomplete understanding of the pathogenesis of these agents. Our group has been involved in investigations of two members of the family Pasteurellaceae,Mannheimia haemolyticaandHaemophilus somnus, which illustrate some of the complexities that must be confronted. Susceptibility toM. haemolyticais greatly increased during active viral respiratory infection, resulting in rapid onset of a severe and even lethal pleuropneumonia. Despite years of investigation, understanding of the mechanisms underlying this viral–bacterial synergism is incomplete. We have investigated the hypothesis that active viral infection increases the susceptibility of bovine leukocytes to theM. haemolyticaleukotoxin by increasing the expression of or activating the β2integrin CD11a/CD18 (LFA-1) on the leukocyte surface.In vitroexposure to proinflammatory cytokines (i.e. interleukin-1β, tumor necrosis factor-α and interferon-γ) increases LFA-1 expression on bovine leukocytes, which in turn correlates with increased binding and responsiveness to the leukotoxin. Alveolar macrophages and peripheral blood leukocytes from cattle with active bovine herpesvirus-1 (BVH-1) infection are more susceptible to the lethal effects of the leukotoxinex vivothan leukocytes from uninfected cattle. Likewise,in vitroincubation of bovine leukocytes with bovine herpesvirus 1 (BHV-1) potentiates LFA-1 expression and makes the cells more responsive to leukotoxin. A striking characteristic ofH. somnusinfection is its propensity to cause vasculitis. We have shown thatH. somnusand its lipo-oligosaccharide (LOS) trigger caspase activation and apoptosis in bovine endothelial cellsin vitro. This effect is associated with the production of reactive oxygen and nitrogen intermediates, and is amplified in the presence of platelets. The adverse effects ofH. somnusLOS are mediated in part by activation of endothelial cell purinergic receptors such as P2X7. Further dissection of the pathways that lead to endothelial cell damage in response toH. somnusmight help in the development of new preventive or therapeutic regimens. A more thorough understanding ofM. haemolyticaandH. somnusvirulence factors and their interactions with the host might identify new targets for prevention of bovine respiratory disease.
Warmwater fish vaccinology in catfish production
Authors: Klesius Phillip H. , Evans Joyce J. , Shoemaker Craig A.
Published: July 2005

The ability of the fish industry to provide a continuous supply of fish protein depends on both proper biosecurity and strategies to significantly reduce the risk of infectious diseases. Vaccination is a safe and effective means to prevent disease and to increase the productivity and profitability of farmed fish. Vaccines are likely to be the prime prophylactic measure of the future because of rapidly developing advances in fish vaccine technology and producer acceptance. The efficacy of a vaccine is influenced by a variety of factors that must be considered in the development of vaccination strategies for fish. This review highlights some of these factors. The response to a modified live vaccine againstEdwardsiella ictaluriis used for illustration.
Recent trends in the molecular diagnosis of infectious bursal disease viruses
Authors: Jackwood Daral J.
Published: July 2005

Infectious bursal disease virus (IBDV) causes an immunosuppressive disease in young chickens. Two serotypes of this double-stranded RNA virus exist but only serotype 1 viruses cause disease in chickens. Detection and strain identification of IBDV is important because antigenic subtypes found within serotype 1 make it necessary to tailor vaccination programs to the antigenic type found in the bird's environment. Because conventional virus isolation and characterization are not practical for routine diagnosis of IBDV, antigen-capture enzyme-linked immunosorbent assay (ELISA) and molecular assays based on reverse transcription–polymerase chain reaction (RT-PCR) technology were developed. Compared with antigen-capture ELISA, RT-PCR assays have greater versatility and are more sensitive and specific. Strain identification has been accomplished using a variety of post-RT-PCR assays, including restriction enzyme digestion of the RT-PCR products. The resulting restriction fragment length polymorphisms (RFLP) are used to differentiate viruses into molecular groups that correlate with antigenic and pathogenic types. Recently, two types of real-time RT-PCR have been used to identify and differentiate strains of IBDV. Both methods use distance-dependent interaction between two dye molecules, known as fluorescence resonance energy transfer (FRET). The dye molecules are attached to one or more nucleotide probes that detect specific nucleotide sequences of the virus. Our laboratory has used a two-probe assay to identify single-nucleotide mutations among IBDV strains. A mutation probe is used in this assay to detect substitution mutations in a region of the viral genome that encodes a neutralizing epitope of the virus. These assays are accurate, reliable and inexpensive compared with conventional RT-PCR because they do not require RFLP or other labor-intensive post-RT-PCR assays to distinguish viral strains.
Diagnosis ofMycoplasma hyopneumoniae
Authors: Thacker Eileen L.
Published: July 2005

Mycoplasma hyopneumoniae, the cause of enzootic pneumonia, remains an important pathogen in the swine industry. This small, complex organism colonizes the ciliated cells of the respiratory tract, resulting in little exposure to the immune system. Confirming the presence ofM. hyopneumoniae, as well as identifying its role in respiratory disease and pneumonia, remains challenging to the veterinary profession. While culture of the organism remains the gold standard for identification, the use of serology, the polymerase chain reaction and various assays to detect the presence ofM. hyopneumoniaein tissue is common in diagnostic laboratories. Because of the roleM. hyopneumoniaeplays in increasing the severity of pneumonia associated with concurrent bacterial and viral infections, understanding the pathogenesis and diagnostic assays available is critical for developing effective intervention strategies to control respiratory disease on a herd basis.
The emergence ofClostridium difficileas a pathogen of food animals
Authors: Songer J. Glenn
Published: July 2005

Clostridium difficilecauses pseudomembranous colitis in humans, usually after disruption of the bowel flora by antibiotic therapy. Factors mediating the frank disease include the dose and toxigenicity of the colonizing strain, its ability to adhere to colonic epithelium, the concurrent presence of organisms that affect multiplication and toxin production or activity, and the susceptibility of the host. Toxins A (an enterotoxin) and B (a cytotoxin) play the major role in pathogenesis and the detection of toxins in gut contents is the gold standard for diagnosis. Disease in horses takes the form of often-fatal foal hemorrhagic enteritis. Nosocomial, antibiotic-associated, disease is increasingly common in adult horses. Enteric clinical signs are reported in ostriches, companion animals and recently calves.Clostridium difficilecolitis is now a common diagnosis in neonatal pigs in the USA and elsewhere. Clinical features include onset at 1–5 days of age, sometimes with dyspnea, mild abdominal distension and scrotal edema, and commonly with yellow, pasty diarrhea. There is mesocolonic edema grossly, with microscopic diffuse colitis, mucosal edema, crypt distension, epithelial necrosis and superficial mucosal erosion. Neutrophil infiltration of the lamina propria is common, and fibrin and numerous rod-shaped bacteria are observed on the surface. About two-thirds of litters and one-third of piglets will be affected (based upon positive toxin tests), although this appears to vary with the season. The case fatality rate is probably low if considering only direct effects ofC. difficileinfection. The significance of toxin-positive non-diarrheic pigs and the nature of the interaction of toxins A and B with enterocytes are unknown. Given the widespread occurrence of the disease, there is substantial effort to develop immunoprophylactic products.
Hepatitis E viruses in humans and animals
Authors: Goens S. Denise , Perdue Michael L.
Published: July 2005

Hepatitis E virus (HEV) is an emerging pathogen belonging to a newly recognized family of RNA viruses (Hepeviridae). HEV is an important enterically transmitted human pathogen with a worldwide distribution. It can cause sporadic cases as well as large epidemics of acute hepatitis. Epidemics are primarily waterborne in areas where water supplies are contaminated with HEV of human origin. There is increasing evidence, however, that many animal species are infected with an antigenically similar virus. A recently isolated swine virus is the best candidate for causing a zoonotic form of hepatitis E. The virus is serologically cross-reactive with human HEV and genetically very similar, and the human and swine strains seem to be cross-infective. Very recent evidence has also shown that swine HEV, and possibly a deer strain of HEV, can be transmitted to humans by consumption of contaminated meat. In this review, we discuss the prevalence, pathogenicity, diagnosis and control of human HEV, swine HEV, the related avian HEV and HEV in other hosts and potential reservoirs.
The use of nuclear ribosomal DNA markers for the identification of bursate nematodes (order Strongylida) and for the diagnosis of infections
Authors: Chilton Neil B.
Published: July 2005

Many bursate nematodes are of major importance to animal health. Animals are often parasitized by multiple species that differ in their prevalence, relative abundance and/or pathogenicity. Implementation of effective management strategies for these parasites requires reliable methods for their detection in hosts, identification to the species level and measurement of intensity of infection. One major problem is the difficulty of accurately identifying and distinguishing many species of bursate nematode because of the remarkable morphological similarity of their eggs and larvae. The inability to identify, with confidence, individual nematodes (irrespective of their life-cycle stage) to the species level by morphological methods has often led to a search for species-specific genetic markers. Studies over the past 15 years have shown that sequences of the internal transcribed spacers of ribosomal DNA provide useful genetic markers, providing the basis for the development of PCR-based diagnostic tools. Such molecular methods represent powerful tools for studying the systematics, epidemiology and ecology of bursate nematodes and, importantly, for the specific diagnosis of infections in animals and humans, thus contributing to improved control and prevention strategies for these parasites.
Potential nutritional and physiological functions of betaine in livestock
Authors: Eklund M. , Bauer E. , Wamatu J. , Mosenthin R.
Published: July 2005

The present review summarises the potential nutritional and physiological functions of betaine as a feed additive in relation to performance criteria in livestock production. Betaine, the trimethyl derivative of the amino acid glycine, is a metabolite of plant and animal tissues. In plants, betaine is particularly synthesised and accumulated as an osmoprotectant against salt and temperature stress. In animals, betaine is the product of choline oxidation or it originates from nutritional sources. Over the past decades, numerous studies have been carried out to investigate the potential effects of betaine supplementation on animal performance. Due to its chemical structure, betaine shows the characteristics of a dipolar zwitterion resulting in osmoprotective properties. Promoting effects on the intestinal tract against osmotic stress occurring during diarrhoea or coccidiosis have been reported following betaine supplementation in pigs and poultry. There is also some evidence that dietary betaine may improve the digestibility of specific nutrients. As a product of choline oxidation, betaine is involved in transmethylation reactions of the organism. Betaine as a methyl donor provides its labile methyl groups for the synthesis of several metabolically active substances such as creatine and carnitine. Supplementation with betaine may decrease the requirement for other methyl donors such as methionine and choline. There is also some evidence for enhanced methionine availability after dietary supplementation of betaine resulting in improved animal performance. Alterations in the distribution pattern of protein and fat in the body have been reported following betaine supplementation. A more efficient use of dietary protein may result from a methionine-sparing effect of betaine, but also direct interactions of betaine with metabolism-regulating factors have to be considered. Though the mode of action of betaine as a carcass modifier remains open, there is, however, growing evidence that betaine could have a positive impact both on animal performance and carcass quality.
The phenolic compounds of olive oil: structure, biological activity and beneficial effects on human health
Authors: Tripoli Elisa , Giammanco Marco , Tabacchi Garden , Di Majo Danila , Giammanco Santo , La Guardia Maurizio
Published: July 2005

The Mediterranean diet is rich in vegetables, cereals, fruit, fish, milk, wine and olive oil and has salutary biological functions. Epidemiological studies have shown a lower incidence of atherosclerosis, cardiovascular diseases and certain kinds of cancer in the Mediterranean area. Olive oil is the main source of fat, and the Mediterranean diet's healthy effects can in particular be attributed not only to the high relationship between unsaturated and saturated fatty acids in olive oil but also to the antioxidant property of its phenolic compounds. The main phenolic compounds, hydroxytyrosol and oleuropein, which give extra-virgin olive oil its bitter, pungent taste, have powerful antioxidant activity bothin vivoandin vitro. The present review focuses on recent works analysing the relationship between the structure of olive oil polyphenolic compounds and their antioxidant activity. These compounds' possible beneficial effects are due to their antioxidant activity, which is related to the development of atherosclerosis and cancer, and to anti-inflammatory and antimicrobial activity.
The impact of long-chainn-3 polyunsaturated fatty acids on human health
Authors: Ruxton C. H. S. , Calder P. C. , Reed S. C. , Simpson M. J. A.
Published: July 2005

A considerable literature has been published on the health benefits of fish, oil-rich fish and fish oils and their constituent long-chain (LC)n-3 PUFA. Evidence from epidemiological studies highlights the cardioprotective attributes of diets rich in fish, especially oil-rich fish. Data from intervention trials are consistent in suggesting that LCn-3 PUFA lower the risk of CVD, probably by the multiple mechanisms of lowering serum triacylglycerols, improving the LDL:HDL ratio, anti-arrhythmic effects on heart muscle, improved plaque stability, anti-thrombotic effects and reduced endothelial activation. Research indicates LCn-3 PUFA provision has an impact during development, and there is preliminary evidence that docosahexaenoic acid supplementation during pregnancy could optimise brain and retina development in the infant. LCn-3 PUFA are also postulated to ameliorate behavioural and mental health disturbances such as depression, schizophrenia, dementia and attention deficit hyperactivity disorder. However, despite some positive evidence in each of these areas, use of LCn-3 PUFA in these conditions remains at the experimental stage. In the case of immune function, there is little doubt that LCn-3 PUFA have a positive effect. Although intervention trials in rheumatoid arthritis show strong evidence of benefit, evidence for efficacy in other inflammatory conditions, including Crohn's disease, ulcerative colitis, psoriasis, lupus, multiple sclerosis, cystic fibrosis and asthma, is inconsistent or inadequate. More promising evidence in some conditions may come from studies which attempt to modify the fetal environment using LCn-3 PUFA supplementation during pregnancy.