bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of oestrogenic potency of chemicals used as growth promoter by in‐vitro methods
Authors: Guevel Rémy Le , Pakdel Farzad
Published: October 2011

Three in‐vitro bioassays were used to compare the oestrogenic potency of chemicals used as growth promoter in beef cattle in certain non‐European Union countries (17β‐oestradiol, α‐zearalanol, testosterone, trenbolone, trenbolone acetate, melengestrol acetate) or found as food contaminant such as the mycotoxin zearalenone and some of their metabolites (17α‐oestradiol, oestrone, 17α‐epitestosterone, 19‐nortestosterone, androstendione, zearalanone, α‐zearalanol, β‐zearalanol, α‐zearalenol, β‐zearalenol). The strong oestrogens 17α‐ethinyl oestradiol and diethylstilboestrol were used as standards. The first bioassay was based on the activation of a reporter gene by oestrogens in recombinant yeast expressing human or rainbow trout oestrogen receptor. In the second bioassay, the vitellogenin gene induction of rainbow trout hepatocyte cultures was used as a biomarker for the exposure to oestrogens. The third bioassay was based on the alkaline phosphatase gene induction by oestrogens in the human endometrial Ishikawa cell line. The assessment of oestrogenic potency of these chemicals clearly demonstrates the strong oestrogenicity of the mycotoxin zearalenone and its metabolites and particularly α‐zearalenol which was as potent as ethinyl oestradiol and diethylstilboestrol in the human endometrial Ishikawa cell line.
Neonatal exposure to potent and environmental oestrogens and abnormalities of the male reproductive system in the rat: evidence for importance of the androgen‐oestrogen balance and assessment of the relevance to man
Authors: Williams K. , McKinnell C. , Saunders P.T.K. , Walker M. , Fisher J.S. , Turner K.J. , Atanassova N. , Sharpe R.M.
Published: October 2011

The effects on reproductive tract development in male rats, of neonatal exposure to potent (reference) oestrogens, diethylstilboestrol (DES) and ethinyl oestradiol (EE), with those of two environmental oestrogens, octylphenol and bisphenol A were systematically compared. Other treatments, such as administration of a gonadotrophin‐releasing hormone antagonist (GnRHa) or the anti‐oestrogen tamoxifen or the anti‐androgen flutamide, were used to aid interpretation of the pathways involved. All treatments were administered in the neonatal period before onset of puberty. The cellular sites of expression of androgen receptors (AR) and of oestrogen receptor‐α (ERα) and ERβ were also established throughout development of the reproductive system. The main findings were as follows: (i) all cell types that express AR also express one or both ERs at all stages of development; (ii) Sertoli cell expression of ERβ occurs considerably earlier in development than does expression of AR; (iii) most germ cells, including fetal gonocytes, express ERβ but not AR; (iv) treatment with high, but not low, doses of potent oestrogens such as DES and EE, induces widespread structural and cellular abnormalities of the testis and reproductive tract before puberty; (v) the latter changes are associated with loss of immunoexpression of AR in all affected tissues and a reduction in Leydig cell volume per testis; (vi) none of the effects in (iv) and (v) can be duplicated by treating with high‐dose octylphenol or bisphenol A; (vi) none of the reproductive tract changes in (iv) and (v) can be induced by simply suppressing androgen production (GnRHa treatment) or action (flutamide treatment); and (vii) the adverse changes induced by high‐dose DES (iv and v) can be largely prevented by co‐administration of testosterone. Thus, it is suggested that many of the adverse changes to the testis and reproductive tract induced by exposure to oestrogens result from a combination of high oestrogen and low androgen action. High oestrogen action or low androgen action on their own are unable to induce the same changes.
Tissue‐specific expression pattern of estrogen receptors (ER): Quantification of ERα and ERβ mRNA with real‐time RT‐PCR
Authors: PFAFFL M. W. , LANGE I. G. , DAXENBERGER A. , MEYER H. H. D.
Published: October 2011

We have examined the tissue‐specific mRNA expression of ERα and ERβ in various bovine tissues using real‐time RT‐PCR. The goal of this study was to evaluate the deviating tissue sensitivities and the influence of the estrogenic active preparation RALGRO on the tissue‐specific expression and regulation of both ER subtypes. RALGRO contains Zeranol (α‐Zearalanol), a derivative of the mycotoxin Zearalenon, shows strong estrogenic and anabolic effects, and exhibits all symptoms of hyperestrogenism, in particular reproductive and developmental disorders. Eight heifers were treated over 8 weeks with multiple‐dose implantations (0X, 1X, 3X, 10X) of Zeranol. Plasma Zeranol concentration, measured by enzyme immunoassay, of multiple treated heifers was elevated. To quantify ERα and ERβ transcripts also in low‐abundant tissues, sensitive and reliable real‐time RT‐PCR quantification methods were developed and validated on the LightCycler. Expression results indicate the existence of both ER subtypes in all 15 investigated tissues. All tissues exhibited a specific ERα and ERβ expression pattern and regulation. With increasing Zeranol concentrations, a significant downregulation of ERα mRNA expression could be observed in jejunum (p<0.001) and kidney medulla (p<0.05). These data support the hypothesis that ERβ may have different biological functions than ERα, especially in kidney and jejunum.
The role of environmental factors in the pathogenesis of breast cancer
Authors: HUFF JAMES
Published: October 2011

Breast cancer amongst women is the most common malignancy in the world, especially in the United States and Western Europe. In 1999, upwards of 175,000 women in the United States and 800,000 women worldwide are estimated to develop cancer of the breast; nearly 30% of cancers in women in the US and 21% of cancers worldwide are of the breast. The rate of breast cancer in the US has steadily increased from roughly 80/100,000 population in 1973 to nearly 115/100,000 in 1995. However, mortality from breast cancer in the US seems to have flattened and slightly decreased in the 1990s, especially among younger women. These decreases are probably the result of earlier detection and improved treatment. Nonetheless, each year more than 43,000 women in the US and 314,000 worldwide will die of breast cancer. The cause or causes for the overwhelming majority of breast and other cancers remain largely unknown. In this commentary, we suggest the influence of environmental chemicals on the occurrence of breast cancer, and the need to consider chemicals in epidemiology investigations. The current emphasis seems to center on pesticides, especially those that are biologically persistent and that mimic natural hormones. The concentration of epidemiologic effort on these chemicals ‐ most often DDT and metabolites and PCBs ‐ may in fact be missing other potential carcinogenic or co‐carcinogenic effects of many other environmental factors that may influence the occurrence of breast cancer. Clearly there are hundreds of chemicals in our environment ‐ workplaces, consumer products, schools, homes, restaurants, taverns, foods, water, air, soil, pollution, contaminants ‐ that we are constantly and routinely being exposed. In some cases we are exposed to certain chemicals in relatively large amounts, especially in workplaces, occupations, avocations, or hobbies. In the absence of epidemiological evidence, long‐term bioassays using laboratory animals continue to be the most common, reliable, and accepted method for identifying carcinogens. Most often epidemiological data are not available on chemicals and cancer, or in many cases if they are available the findings are frequently inconclusive. Hence for public health and regulatory actions one must typically rely on a blending of epidemiological results and animal data, or on experimental chemical carcinogenesis data alone. Biologically and mechanistically we have little scientific evidence to suggest that chemicals causing cancer in animals will not likewise cause cancer in humans Consequently, by reducing exposures to chemicals, the incidence, suffering, and mortality of environmentally associated diseases will be reduced or eliminated. And this is an attainable and befitting goal we must continue to strive.
Carcinogenicity of estrogens in human breast epithelial cells1
Authors: RUSSO JOSE , HU YUN FU , TAHIN QUIVO , MIHAILA DANA , SLATER CAROLYN , LAREEF M. HASAN , RUSSO IRMA H.
Published: October 2011

Epidemiological and clinical evidences indicate that breast cancer risk is associated with prolonged ovarian function that results in elevated circulating levels of steroid hormones. Principal among these is estrogen, which is associated with two important risk factors, early onset of menarche and late menopause. However, up to now there is no direct experimental evidence that estrogens are responsible of the initiation of human breast cancer. We postulate that if estrogens are causative agents of this disease, they should elicit in human breast epithelial cells (HBEC) genomic alterations similar to those exhibited by human breast cancers, such as DNA amplification and loss of genetic material representing tumor suppressor genes. These effects could result from binding of the hormone to its nuclear receptors (ER) or from its metabolic activation to reactive metabolites. This hypothesis was tested by treating with the natural estrogen 17β‐estradiol (E2) and the synthetic steroid diethylstilbestrol (DES) MCF‐10F cells, a HBEC line that is negative for ER. Cells treated with the chemical carcinogen benzo (a) pyrene (BP) served as a positive control of cell transformation. BP‐, E2‐, and DES‐treated MCF‐10F cells showed increases in survival efficiency and colony efficiency in agar methocel, and loss of ductulogenic capacity in collagen gel. The largest colonies were formed by BP‐treated cells, becoming progressively smaller in DES‐ and E2‐treated cells. The loss of ductulogenic capacity was maximal in BP‐, and less prominent in E2‐ and DES‐treated cells. Genomic analysis revealed that E2‐ and DES‐treated cells exhibited loss of heterozygosity in chromosomes 3 and 11, at 3p21, 3p21‐21.2, 3p21.1–14.2, and 3p14.2–14.1, and at 11q23.3 and 11q23.1–25 regions, respectively. It is noteworthy that these loci are also affected in breast lesions, such as ductal hyperplasia, carcinoma in situ, and invasive carcinoma. Our data are the first ones to demonstrate that estrogens induce in HBEC phenotypic changes indicative of cell transformation and that those changes are associated with significant genomic alterations that might unravel new pathways in the initiation of breast cancer.
Alzheimer’s disease: pathological mechanisms and the beneficial role of melatonin
Authors: Rosales‐Corral Sergio A. , Acuña‐Castroviejo Dario , Coto‐Montes Ana , Boga Jose A. , Manchester Lucien C. , Fuentes‐Broto Lorena , Korkmaz Ahmet , Ma Shuran , Tan Dun‐ Xian , Reiter Russel J.
Published: October 2011

Abstract:  Alzheimer’s disease (AD) is a highly complex neurodegenerative disorder of the aged that has multiple factors which contribute to its etiology in terms of initiation and progression. This review summarizes these diverse aspects of this form of dementia. Several hypotheses, often with overlapping features, have been formulated to explain this debilitating condition. Perhaps the best‐known hypothesis to explain AD is that which involves the role of the accumulation of amyloid‐β peptide in the brain. Other theories that have been invoked to explain AD and summarized in this review include the cholinergic hypothesis, the role of neuroinflammation, the calcium hypothesis, the insulin resistance hypothesis, and the association of AD with peroxidation of brain lipids. In addition to summarizing each of the theories that have been used to explain the structural neural changes and the pathophysiology of AD, the potential role of melatonin in influencing each of the theoretical processes involved is discussed. Melatonin is an endogenously produced and multifunctioning molecule that could theoretically intervene at any of a number of sites to abate the changes associated with the development of AD. Production of this indoleamine diminishes with increasing age, coincident with the onset of AD. In addition to its potent antioxidant and anti‐inflammatory activities, melatonin has a multitude of other functions that could assist in explaining each of the hypotheses summarized above. The intent of this review is to stimulate interest in melatonin as a potentially useful agent in attenuating and/or delaying AD.
EFFECT OF ACQUISITION TIME AND CHEMICAL FAT SUPPRESSION ON MENINGEAL ENHANCEMENT ON MR IMAGING IN DOGS
Authors: d'Anjou Marc‐André , Carmel Éric Norman , Blond Laurent , Beauchamp Guy , Parent Joane
Published: October 2011

Our purpose was to characterize meningeal gadolinium enhancement on magnetic resonance (MR) imaging in dogs with inflammatory and neoplastic diseases, and to assess interobserver variability and the impact of delayed acquisition and chemical fat saturation on its conspicuity. Transverse T1‐weighted FLAIR images were acquired prior to, and immediately following gadolinium injection (T0), and at 5 (T5) and 15–20 min delay (TD), with and without fat suppression, in 155 consecutive dogs imaged for suspected brain disease. The agreement on meningeal enhancement was globally substantial (κ = 0.61) and the likelihood of obtaining a definite diagnosis was significantly increased with the use of fat suppression (P ≤ 0.004). Meningeal enhancement was judged definitively present by consensus in 46 of 155 (30%) dogs. Of these, meningeal enhancement was characterized qualitatively and quantitatively in 30 dogs with a clinical diagnosis (18 inflammatory, 11 neoplastic, 1 infarct), and image sequences were compared. Meningeal enhancement was more often diffuse and leptomeningeal in animals with inflammation versus neoplasia (50% vs. 42%, and 69% vs. 48%, respectively), but significant associations were not found. Meningeal thickness and contrast ratio were higher with neoplasia (P ≤ 0.02), but results did not vary significantly between series for either group. Yet, images with fat suppression were most useful 50% of the time for definite diagnosis and/or characterization of meningeal enhancement. While delayed image acquisition following gadolinium injection does not improve characterization of meningeal enhancement in dogs, fat suppression is beneficial qualitatively.
“I am, personally, the Fall of the West”: Postmodernism and the Critical Reception (and Legacy) of Barry Hannah’s Fiction
Authors: Graybill Mark S.
Published: October 2011

While relatively few of the remembrances of Barry Hannah in the popular press mention the adjective ‘postmodern’ to describe Hannah’s work, and while Hannah himself was skeptical of the concept, it has largely shaped the trajectory of critical discourse on Hannah’s aesthetic among his academic readers. Indeed, as his reputation among literary scholars has grown, so has the strength of his association with postmodernism. Fred Hobson wrote nearly two decades ago of Hannah’s celebrated novel, Ray (1980), that “for once, the southern writer inhabiting the postmodern world is close to being a postmodern writer himself” (37). Hobson cannot bring himself to make a more definitive declaration (Hannah is only ‘close to being’ a postmodernist), because he wants to like Hannah’s work, but ultimately values more a southern writer who “essentially accepts, rather than invents, his world, is not given to fantasy, does not in his fiction question the whole assumed relationship between narrator and narrative, does not question the nature of fiction itself”– in other words, one who “plays by the old rules of the game” (9). Subsequent critics, however, have worked steadily toward an understanding of Hannah’s work as prototypically postmodern. This essay discusses those works that have contributed most significantly to that understanding and considers briefly the future criticism on Hannah’s work.
Victorian Sexualities
Authors: Furneaux Holly
Published: October 2011

The popular stereotype of the prudish Victorians has persisted for too long. This article charts the rethinking of Victorian sexuality in the academy and beyond. It presents a detailed examination of the effects of sexological categorisation, looking at the legacy of the invention of homosexuality and heterosexuality for approaches to the period. In particular it explores the ramifications of Michel Foucault’s discursive thesis, under which the homosexual became a species. In a final section the essay traces recent developments in the field, unrestricted by the binary opposition of the homo and hetero, enabled by queer theory and the turn to affect. Such approaches have given rise to fuller accounts of the varieties of Victorian emotional and erotic experience, work that can counter far right misappropriations of the period as a type of heterosexual gold‐standard.
Stimulatory effect of α‐synuclein on the tau‐phosphorylation by GSK‐3β
Authors: Kawakami Fumitaka , Suzuki Minori , Shimada Naoki , Kagiya Go , Ohta Etsuro , Tamura Kei , Maruyama Hiroko , Ichikawa Takafumi
Published: October 2011

Hyperphosphorylation of tau protein (tau) causes neurodegenerative diseases such as Alzheimer’s disease (AD). Recent studies of the physiological correlation between tau and α‐synuclein (α‐SN) have demonstrated that: (a) phosphorylated tau is also present in Lewy bodies, which are cytoplasmic inclusions formed by abnormal aggregation of α‐SN; and (b) the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) increases the phosphorylation of tau as well as the protein level of α‐SN in cultured neuronal cells, and also in mice. However, the molecular mechanism responsible for the α‐SN‐mediated hyperphosphorylation of tau remains to be elucidated. In this in vitro study, we found that: (a) α‐SN directly stimulates the phosphorylation of tau by glycogen synthase kinase‐3β (GSK‐3β), (b) α‐SN forms a heterotrimeric complex with tau and GSK‐3β, and (c) the nonamyloid beta component (NAC) domain and an acidic region of α‐SN are responsible for the stimulation of GSK‐3β‐mediated tau phosphorylation. Thus, it is concluded that α‐SN functions as a connecting mediator for tau and GSK‐3β, resulting in GSK‐3β‐mediated tau phosphorylation. Because the expression of α‐SN is promoted by oxidative stress, the accumulation of α‐SN induced by such stress may directly induce the hyperphosphorylation of tau by GSK‐3β. Furthermore, we found that heat shock protein 70 (Hsp70) suppresses the α‐SN‐induced phosphorylation of tau by GSK‐3β through its direct binding to α‐SN, suggesting that Hsp70 acts as a physiological suppressor of α‐SN‐mediated tau hyperphosphorylation. These results suggest that the cellular level of Hsp70 may be a novel therapeutic target to counteract α‐SN‐mediated tau phosphorylation in the initial stage of neurodegenerative disease.

Structured digital abstract

 GSK3Bphosphorylates GSK3B by protein kinase assay (View interaction)

 TAU binds to ‐SN by pull down (View interaction)

 GSK3Bphosphorylates TAU by protein kinase assay (View Interaction: 1, 2, 3, 4)

 TAU physically interacts with ‐SN and HSP70 by pull down (View interaction)

 TAU physically interacts with ‐SN and GSK3Bby pull down (View interaction)

 GSK3Bbinds to ‐SN by pull down (View interaction)

 GSK3B physically interacts with ‐SN and HSP70 by pull down (View interaction)

 HSP70 binds to ‐SN by pull down (View interaction)

 GSK3Bphosphorylates Gs by protein kinase assay (View interaction)
Effective use of negative pressure wound therapy provides quick wound‐bed preparation and complete graft take in the management of chronic venous ulcers
Authors: Egemen Onur , Ozkaya Ozay , Ozturk Muhammed Besir , Aksan Tolga , Orman Çağdaş , Akan Mithat
Published: October 2011

Venous ulcers are characterised by longstanding and recurrent loss of skin integrity. Once occurred, healing is slow and recurrence is high because of inappropriate conditions of the wound bed. This study involves 20 patients with chronic venous ulcers at least 6 weeks of duration treated with negative pressure wound therapy (NPWT). Patients underwent a radical debridement of all devitalised tissues in the first operation. After adequate haemostasis, silver‐impregnated polyurethane foam was applied. Once the wounds were determined to be clean and adequate granulation tissue formation was achieved, split‐thickness skin grafts were applied. Black polyurethane foam was applied over them. All wounds completely healed without the need for further debridement or regrafting. The mean number of silver‐impregnated foam dressing changes prior to grafting was 2·9 (one to eight changes). The mean number of NPWT foam changes was 2·6 after skin grafting (two to five changes). Two patients who did not use conservative treatments for chronic venous insufficiency (CVI) after discharge from the hospital had recurrence of venous ulcers in the follow‐up period. Application of NPWT provides quick wound‐bed preparation and complete graft take in venous ulcer treatment.
Cognitive Science and Religious Belief
Authors: Wood Graham
Published: October 2011

The cognitive science of religion draws on insights from evolutionary psychology, and offers explanations of religious belief based on natural cognitive processes. This article examines a number of competing explanations of religious belief by considering it as a solution to the challenge of cooperation. The challenge of stopping individuals cheating within a cooperative group has been a problem throughout humanity’s evolutionary history. Empirical evidence drawn from fields such as anthropology and psychology suggests that religious beliefs are part of an evolved cognitive system that motivates individuals to cooperate with other members of their group. Three possible evolutionary accounts, the memetic, by‐product, and adaptation accounts, are considered as evolved solutions to the challenge of cooperation.
Social Intuitionism and the Psychology of Moral Reasoning
Authors: Sauer Hanno
Published: October 2011

Rationalism about the psychology of moral judgment holds, among other things, that the justifying moral reasons we have for our judgments are also the causally effective reasons for why we make those judgments. This can be called the ‘effectiveness’‐thesis regarding moral reasoning. The theory that best exemplifies the thesis is the traditional conscious reasoning‐paradigm. Current empirical moral psychology, however, poses a serious challenge to this thesis: it argues that in fact, emotional reactions are necessary and sufficient to account for moral judgment, and that typically, moral reasoning is a matter of mere confabulation. In this survey, the empirical challenge to this thesis made by the ‘social intuitionist’ model of moral judgment and reasoning is discussed. The model claims that moral reasoning is essentially ineffective and, psychologically speaking, a matter of mere post hoc‐rationalizations of cognitively impenetratable gut reactions. Several interpretations of this evidence are discussed and it is shown that there is room for a psychology of moral reasoning that can account for the available empirical evidence and yet does not have to give up the most central elements of a normative picture of moral reasoning.
Sympathy and Perspective‐Taking in Confucian Ethics
Authors: Tiwald Justin
Published: October 2011

This article spells out a forgotten debate in Confucian ethics that concerns the finer points of empathy, sympathy, and perspective‐taking (sometimes called ‘role‐taking’). The debate’s central question is whether sympathy is more virtuous when it is automatic and other‐focused – that is, when we engage in perspective‐taking without conscious effort and sympathize without significant reference to our selves or our own feelings. The seeds of this debate can be found in classical Confucianism, but the relevant issues come in for more explicit and nuanced analysis in neo‐Confucianism broadly construed, especially in the thought of Zhu Xi and Dai Zhen. I unpack the technical distinctions and psychological presuppositions that underlie three of Zhu’s critiques of non‐automatic and self‐focused perspective‐taking, and then reconstruct Dai’s responses to these critiques.
Preserved and impaired task‐switching abilities in non‐demented patients with Parkinson's disease
Authors: Crescentini Cristiano , Mondolo Federica , Biasutti Emanuele , Shallice Tim
Published: October 2011

Existing studies on task switching in Parkinson's disease (PD) patients have led to somewhat different results. In particular, it is unclear whether PD patients have a deficit in attentional control. In this study, we assessed task‐switching abilities in samples of non‐demented PD patients and elderly controls. We used a paradigm in which there was a random task sequence and the task was cued in every trial. This allowed the investigation of both task‐set reconfiguration and task‐set dissipation. In terms of the proportion of errors made, the patients showed increased switch cost and congruency effects. For reaction times, PD patients showed enlarged congruency effects on switch trials, specifically in the condition in which we used a short constant response‐cue interval (RCI). Nevertheless, in a similar fashion to older controls, the patients showed reductions in reaction time switch cost from a short to a long cue‐target interval (CTI) and from a short to a long RCI. While these latter findings, respectively, suggest unimpaired task preparation and task dissipation on correct trials in the PD patients, the overall results show that they have a deficit in biasing and selecting currently relevant task sets and more generally argue in favour of a failure of attentional control in PD.
Language Contact and New Dialect Formation: Evidence from German in North America
Authors: Nützel Daniel , Salmons Joseph
Published: October 2011

When viewing language and dialect contact through the lens of the social settings of variation and acquisition, it becomes apparent that the types and degrees of conservatism in colonial dialects of German are tightly tied to the varieties learned and the patterns of acquisition in the community. Working within the framework of recent theories on stability in language contact and new dialect (koine) formation, the authors explore what the basic social settings of some German‐American immigrant communities in Indiana and Wisconsin reveal about the structural consequences of language and dialect contact.
MFT Doctoral Dissertations: A Brief Report
Authors: Morris James
Published: October 2011

This brief report responds to the relative dearth of information available about MFT doctoral dissertations. A preliminary analysis of one COAMFTE program is detailed. Suggestions for future action are offered.
In vivo vitiligo induction and therapy model: double‐blind, randomized clinical trial
Authors: van Geel Nanja , Speeckaert Reinhart , Mollet Ilse , De Schepper Sofie , De Wolf Julie , Tjin Esther P.M. , Luiten Rosalie M. , Lambert Jo , Brochez Lieve
Published: October 2011

In this study, we developed an in vivo vitiligo induction model to explore the underlying mechanisms leading to Koebner’s phenomenon and to evaluate the efficacy of therapeutic strategies. The model consisted of 12 pigmented test regions on the back of generalized vitiligo patients that were exposed to three Koebner induction methods: cryotherapy, 755 nm laser therapy, and epidermal abrasion. In addition, four cream treatments (pimecrolimus, tacrolimus, steroid and placebo) were randomly applied. Koebnerization was efficiently induced by all three induction methods. In general, cryotherapy was the best method of Koebner induction, followed by 755 nm laser therapy and epidermal abrasion. Reproducible results were obtained, which showed enhanced depigmented surface areas and higher amounts of T lymphocytes in placebo‐treated test zones compared to active treated areas. Tacrolimus and local steroids were better inhibitors of Koebner’s process (P < 0.05) compared to pimecrolimus. Our in vivo vitiligo induction model is very informative to investigate vitiligo induction and to determine the efficacy of topical treatments in vitiligo. This proof of concept confirms the efficient comparison of head‐to‐head therapeutic strategies intra‐individually in a standardized, specific and better timed way.
Modelling melanoma in mice
Authors: Walker Graeme J. , Soyer H. P. , Terzian Tamara , Box Neil F.
Published: October 2011

Phenotypic and molecular heterogeneity in human melanoma has impaired efforts to explain many of the clinically important features of melanoma. For example, many of the underlying mechanisms that might predict age‐of‐onset, time to metastasis and other key elements in melanoma progression remain unknown. Furthermore, melanoma staging used to predict outcome and treatment has not yet moved beyond a basic phenotypic classification. While molecularly targeted therapies show great promise for melanoma patients, establishing accurate animal models that recapitulate human cutaneous melanoma progression remains a priority. We examine the relevance of mice as models for human melanoma progression and for key molecular and histopathologic variants of melanoma. These mice may be used as preclinical models to probe the relationships between causative mutations, disease progression and outcome for molecularly targeted therapeutics. We ask how new mouse models, or more detailed histopathologic and molecular analyses of existing mouse models, may be used to advance our understanding of genotype–phenotype correlations in this tumour type. This necessarily involves a consideration of the utility of mice as models for ultraviolet radiation‐induced melanoma, and how this might be improved.
Japanese herbal medicine, inchinkoto, inhibits inducible nitric oxide synthase induction in interleukin‐1β‐stimulated hepatocytes
Authors: Matsuura Takashi , Kaibori Masaki , Araki Yoshiro , Matsumiya Miho , Yamamoto Yuka , Ikeya Yukinobu , Nishizawa Mikio , Okumura Tadayoshi , Kwon A‐Hon
Published: October 2011

Aim:  A herbal medicine, kampo inchinkoto (TJ‐135), is used to treat jaundice and liver fibrosis in patients with cirrhosis. In the inflamed liver, proinflammatory cytokines stimulate the induction of inducible nitric oxide synthase (iNOS) gene expression. Over‐production of nitric oxide (NO) by iNOS has been implicated as a factor in liver injury. We examined interleukin (IL)‐1β‐stimulated hepatocytes as a simple in vitro injury model to determine liver‐protective effects of TJ‐135. The objective was to investigate whether TJ‐135 influences iNOS induction and to determine its mechanism.

Methods:  Primary cultured rat hepatocytes were treated with IL‐1β in the presence or absence of TJ‐135. The induction of iNOS and its signaling pathway were analyzed.

Results:  IL‐1β produced increased levels of NO. This effect was inhibited by TJ‐135, which exerted its maximal effects at 3 mg/mL. TJ‐135 decreased the levels of iNOS protein and its mRNA expression. Experiments with nuclear extracts revealed that TJ‐135 inhibited the translocation of nuclear factor‐κB (NF‐κB) to the nucleus and its DNA binding. TJ‐135 also inhibited the activation of Akt, resulting in the reduction of type I IL‐1 receptor mRNA and protein expression. Transfection experiments with iNOS promoter‐luciferase constructs demonstrated that TJ‐135 suppressed iNOS induction by inhibition of promoter transactivation and mRNA stabilization. TJ‐135 reduced the expression of an iNOS gene antisense‐transcript. Delayed administration or withdrawal of TJ‐135 after IL‐1β addition also inhibited iNOS induction.

Conclusions:  Results indicate that TJ‐135 inhibits the induction of iNOS at both transcriptional and post‐transcriptional steps, leading to the prevention of NO production. TJ‐135 may have therapeutic potential for various liver injuries through the suppression of iNOS induction.
Randomized, Blinded Comparison of Epinephrine and Vasopressin for Treatment of Naturally Occurring Cardiopulmonary Arrest in Dogs
Authors: Buckley G.J. , Rozanski E.A. , Rush J.E.
Published: October 2011

Background

Administration of epinephrine duringCPRis recommended for treatment of cardiopulmonary arrest (CPA) in dogs. Administration of epinephrine duringCPRmight be associated with deleterious adverse effects. Vasopressin has been studied for use inCPRas an alternative.

Hypothesis

That administration of vasopressin instead of epinephrine with standardCPRtechniques will result in improved outcome.

Animals

Seventy‐seven client‐owned dogs identified in theER/ICUwithCPAwere eligible for inclusion.

Methods

Randomized, prospective clinical study. Dogs were randomized to receive epinephrine (0.01–0.02mg/kg) or vasopressin (0.5–1 U/kg) in a blinded fashion. Attending veterinarians were asked to adhere to standardizedCPRprotocol for the 1st 6 minutes ofCPR, during which time doses of the study drug were administered at 3‐minute intervals.

Results

A total of 60 dogs completed this study with 31 receiving epinephrine and 29 receiving vasopressin. Overall rate of return of spontaneous circulation (ROSC) was 60% (36/60), 32% (19/60) of dogs survived to 20 minutes, 18% (11/60) survived to 1 hour. No difference was seen in rates ofROSCbetween the 2 groups (P = .20). Dogs receiving epinephrine were more likely to survive to 1 hour (odds ratio 5.86; 95%CI: 1.19–28.95) than those receiving vasopressin (P = .027).

Conclusions and Clinical Importance

ROSCwas similar in dogs receiving epinephrine or vasopressin. In this study, a survival advantage at 1 hour was seen in those animals receiving epinephrine. No advantage of routine use of vasopressin over epinephrine was detected. Further studies are required to examine subgroups of dogs that might benefit from specific interventions.
Characteristics of neuropsychological functions in inpatients with poorly‐controlled type 2 diabetes mellitus
Authors: Takeuchi Ai , Matsushima Eisuke , Kato Motoichiro , Konishi Mika , Izumiyama Hajime , Murata Yuji , Hirata Yukio
Published: October 2011

Aims/Introduction:  It has been suggested that type 2 diabetes is associated with cognitive impairment. We investigated the neuropsychological profile of inpatients with poorly controlled type 2 diabetes and assessed the effects of clinical factors on neuropsychological functions.

Materials and Methods:  Forty‐two patients with type 2 diabetes and 32 non diabetic control subjects were matched for age, sex ratio, and level of education. Attention & working memory, processing speed, verbal memory, visuospatial memory, visuoconstruction, and executive function were tested. Information about physical function, alcohol use, hypertension, dyslipidemia, and myocardial infarction was retrieved from personal interviews and medical records.

Results:  Diabetic patients demonstrated mild cognitive deterioration in attention & working memory, processing speed, verbal memory, and executive function. In particular, neuropsychological decline became prominent when tasks related with speed and verbal stimuli became unstructured and complex. Age was significantly associated with the majority of neuropsychological tests, whereas tasks dealing with working memory and executive function were associated with age only in the diabetic group. Duration of diabetes was associated with Backward Digit Span.

Conclusions:  Accelerated aging had a major influence on cognitive decline in the diabetic group, whereas diminished performance in working memory and executive function might have been more related to diabetes‐related cognitive impairment. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00170.x, 2011)
Combined decongestive therapy including equine manual lymph drainage to assist management of chronic progressive lymphoedema in draught horses
Authors: Powell H. , Affolter V. K.
Published: October 2011

Equine chronic progressive lymphoedema (CPL) is a disabling disorder of draught horse breeds. Combined decongestive therapy (CDT) is the treatment of choice for lymphoedema in man and has been adapted for use in horses. Equine CDT, which includes manual lymph drainage (MLD) and subsequent bandaging with short stretch bandages, was expected to improve the signs of CPL in draught horses because CPL resembles primary lymphoedema in man. Five affected horses ‐ Gypsy cob (n = 1), Clydesdale (n = 1), Shires (n = 3) ‐ were included. Lesions were documented pre‐ and post treatment. Percentage volume loss of the distal legs was calculated using the disc model. Initial plans for daily CDT had to be adapted; intermittent treatment of Chorioptes infections required alternating between CDT and MLD in 4/5 horses. Concurrent pyoderma (1/5 horses) was treated throughout the study. Development of unrelated lameness (hoof abscess) allowed limited CDT treatment only in one horse. Marked softening of previously firm tissue indicated the change from ‘brawny’ to pitting oedema in 2/5 horses. Fibrotic nodules and folds in the pasterns became markedly softened and smaller in 2/5 horses. Skin surface notably improved in all horses: hyperkeratosis decreased, erosions and ulcerations healed completely and crusts disappeared. After 2 weeks, a mean volume reduction of 11.25% was seen, ranging from 4.75–21.74% and quality of movement improved. This pilot study documents evidence that CDT assists management of CPL. Current CPL management is limited to palliative treatments of secondary infections. Whilst not a permanent treatment, CDT offers a promising tool to manage horses with CPL, improving their quality of life and potential usefulness. More extensive and prolonged studies with a larger number of horses are warranted to evaluate the full potential of CDT.
Deconstructing national leadership: Politicians’ accounts of electoral success and failure in the Irish Lisbon Treaty referenda
Authors: Burns Michele , Stevenson Clifford
Published: October 2011

The Self Categorization approach to national leadership proposes that leaders rhetorically construct national identity as essentialized and inevitable in order to consensualize and mobilize the population. In contrast, discursive studies have demonstrated how national politicians flexibly construct the nation to manage their own accountability in local interactions, though this in turn has neglected broader leadership processes. The present paper brings both approaches together to examine how and when national politicians construct versions of national identity in order to account for their failure as well as success in mobilizing the electorate. Eight semi‐structured conversational style interviews were conducted with a strategic sample of eight leading Irish politicians on the subject of the 2008/2009 Irish Lisbon Treaty referenda. Using a Critical Discourse Psychology approach, the hegemonic repertoire of the ‘settled will’ of the informed and consensualized Irish nation was identified across all interviews. Politicians either endorsed the ‘settled will’ repertoire as evidence of their successful leadership, or rejected the repertoire by denying the rationality or unity of the populace to account for their failure. Our results suggest national identity is only constructed as essentialized and inevitable to the extent that it serves a strategic political purpose.
Motivating effort: A theoretical synthesis of the self‐sufficiency and two‐market theories
Authors: Yam Kai Chi , Bumpus Matthew F. , Hill Laura G.
Published: October 2011

We conducted two experimental studies to examine the effect of introducing social and monetary incentives on participants’ (1) effort and (2) willingness to participate in a study. We found that extra credit invoked both communal sharing (CS, social reward) and market pricing (MP, monetary reward) schemas, thus leading to higher willingness to participate and greater effort in an experiment compared to an equivalent cash reward. Consistent with the potential combinational nature of different labour markets proposed by the relational theory, our results suggest that the labour market framework of monetary versus social incentive is not mutually exhaustive of all types of incentive, and the combinational effect created by introducing both labour markets may be the best motivator.
The Elastic-Plastic Response of Thin Spherical Shells to Internal Blast Loading
Authors: Baker W. E.
Published: October 2011

In this paper, the theory is developed for the elastic-plastic response of a thin spherical shell to spherically symmetric internal transient pressure loading. Analytic solutions are obtained to the linear, small-deflection equations of motion for shell materials which exhibit various degrees of strain-hardening. Numerical solutions obtained by digital computer are also presented for the equations for large deflections obtained by accounting for shell thinning and increase in radius during deformation. The theory is compared with experiment, and is shown to be in good agreement.
Stresses in a Circular Cylinder Having an Infinite Row of Spherical Cavities Under Tension
Authors: Atsumi Akira
Published: October 2011

A problem of finding the stresses in an infinite circular cylinder having an infinite row of spherical cavities of the same size under axial tension is studied theoretically. Maximum stresses in the cylinder are calculated by a perturbation method, in each case the radius of the cavity and the distance between the centers of the neighboring cavities being varied. From consideration of the results obtained, some conclusions are made regarding the effects of the surface and the cavities on the stresses.
On the Theoretical Analysis of a Dynamic Thermocouple: 2—The Continuous Area Interface
Authors: Hughes W. F. , Gaylord E. W.
Published: October 2011

The dynamic thermocouple formed by the moving junctions of two dissimilar metals is analyzed for the case of two semi-infinite bodies of dissimilar metals having continuous contact and nonuniform temperature distribution over a circular area. A procedure is given for determining the potential measured by the thermocouple leads placed in the two respective bodies at an infinite distance away from the contact area in terms of the Seebeck emf corresponding to the contact-area temperature distribution. This thermocouple potential at infinity is solved completely for a circular contact area, and numerical examples are given for the case of radial symmetry. It is found that the potential at infinity is not in general equal to the area average Seebeck emf. Instead, it is shown that the potential at infinity is equal to the average Seebeck emf weighted by the area divided by its distance from the perimeter of the circle. This result together with comparison with the results of a previous paper leads to the conclusion that the temperature near the perimeter of a contact area has a greater influence on the thermocouple emf than the temperature in the interior of the contact area.
The Approximate Analysis of Certain Boundary-Value Problems
Authors: Conway H. D.
Published: October 2011

A simple method is given which is suitable for the approximate analysis of certain boundary-value problems, including, for example, the small deflections of clamped plates and the torsion of prismatic bars. The analysis is particularly simple and lends itself well to the use of the digital computer. The method is applied here to four problems, the uniformly loaded, clamped square, and equilateral-triangle plates, and the torsion of bars of square and hexagonal cross section. The results agree well with the exact solutions, where these are known.
Prediction of Creep Failure Time for Pressure Vessels
Authors: Rimrott F. P. J. , Mills Earl J. , Marin Joseph
Published: October 2011

When a pressure vessel is subjected to internal pressure and is made from a material which exhibits creep, the vessel will expand. If the internal pressure is held constant during expansion, the load on the wall will increase. At the same time, the thickness of the wall decreases. The result of these two simultaneous effects is that the expansion of the vessel is continuously accelerated until the wall thickness has decreased and the load increased to such an extent that the strength of the material is no longer sufficient and fracture of the vessel occurs. The time-to-fracture in the case of simple tensile creep was predicted theoretically by Orowan [8] and shown by Hoff [1] to be in good agreement with experimental results, The basis of their approach is to use true stress and true strain. The creep-failure time is then defined as the time at which the true strain reaches infinity. The present paper extends the foregoing concept to the problem of combined stresses. The creep-failure time is determined for thin, thick, and very thick-walled cylindrical vessels of circular cross section with closed ends subjected to constant internal pressure. The theory is based upon the usual assumptions for predicting creep deformation under combined stress [4–7]. A power relation is used to express the creep rate versus stress relation in simple tension.
Yield Conditions for Rotationally Symmetric Shells Under Axisymmetric Loading
Authors: Hodge P. G.
Published: October 2011

The yield condition for a rotationally symmetric shell may be represented as a surface in a four-dimensional stress space. The exact yield surface according to the Tresca yield condition is compared with various approximations. A new approximation is suggested which combines the advantages of mathematical simplicity and reasonable accuracy. The theory is illustrated with reference to a spherical cap under uniform pressure.
An Approximate Analysis of the Influence of Aerodynamic Heating and Initial Twist on the Torsional Stiffness of Thin Wings
Authors: Han Lit S.
Published: October 2011

In the present paper, approximate formulas are derived, based on the “fiber-stress” concept, for the combined influence of aerodynamic heating and initial twist on the torsional stiffness of a thin wing. Criteria are established for calculating the critical temperature difference between that of the edges and that of the mid-chord position, for preventing possible aeroelastic reversals or buckling. Formulas are valid for wings with large aspect ratios.
Postbuckling Behavior of Rectangular Plates With Small Initial Curvature Loaded in Edge Compression—(continued)
Authors: Yamaki Noboru
Published: October 2011

In the previous paper [1], the title problem is theoretically treated under eight different boundary conditions and numerical solutions are obtained for the deflection, edge shortening, and effective width of the square plate in edgewise compression. As a continuation of this work, the stress state in the buckled plate is investigated and numerical results for the square plate are given graphically. Further the formulas for the ultimate load of the square plate in each case are derived by using the maximum-shear theory for the beginning of yielding and comparison is made with the previous results and experiments.
Thermal Transfer in Turbulent Gas Streams. Effect of Turbulence on Local Transport From Spheres
Authors: Short W. W. , Brown R. A. S. , Sage B. H.
Published: October 2011

The present investigation was undertaken because of the paucity of data concerning the effect of level of turbulence upon local thermal transport from spheres in a free stream. A series of measurements was made of the local thermal transport in the forward hemisphere and a part of the after hemisphere of a silver sphere 0.5 in. diam. The measurements were made in an undisturbed air stream and at several positions in the wake of a grid inserted in the air stream. The apparent level of longitudinal turbulence was varied between 0.013 and 0.15 for Reynolds numbers up to 3600. At an apparent level of turbulence of 0.013 and a Reynolds number of 3600, the local thermal transfer varied by a factor of eight around the sphere. Increasing the apparent level of turbulence to 0.15 increased the over-all thermal transfer 20 per cent. The local thermal transfer varied by a factor of five at the latter level of turbulence.