bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative therapies: what role do they have in the management of lupus?
Authors: Chou C-T.
Published: October 2010

Systemic lupus erythematosus (SLE) is an autoimmune disease with higher morbidity and mortality among ethnic Chinese patients than Whites. Corticosteroid and other immunosuppressive drugs, including cyclophosphamide, azathioprine, and hydroxychloroquine are traditional therapies for this disease. Since the year 2000, mycophenolate mofetil and rituximab have been widely used in refractory SLE or severe lupus nephritis. Because the high disease activity remains, even after active therapy, and serious side effects from Western medicines may develop, more than 40% of SLE patients in Western countries are pursuing complementary and alternative therapies (CATs). CAT remedies are multiplex, and include herbal medicines, diets and vitamins, acupuncture, chiropractice, folk medicine, massage, spiritual healing, etc. Many herbal formulas have been used but in general their efficacy in treating lupus is doubted because of the lack of strong evidence. Tripterygium (T2) has demonstrated good efficacy in rheumatoid arthritis (RA) and SLE, but widespread use is limited due to the side effects. Through randomized clinical trials, we hope in the future that some Chinese medicines may be found helpful as CATs for SLE.
The Paradoxical Impunity of Private Military Companies: Authority and the Limits to Legal Accountability
Authors: Leander Anna
Published: October 2010

The impunity of private military companies (PMCs) appears increasingly puzzling. Not only is there widespread awareness and public debate about violations of the spirit — if not the letter — of the law; there is also a ‘mad scramble’ to improve regulation. In spite of this, legal accountability remains problematic. This situation is usually explained either as an expression of the techno-legal difficulties created by the move from government to governance or as reflecting the social, political and economic capital of PMCs. By contrast, this article suggests that the paradox of PMC impunity is best understood by reference to the particular form of authority such organizations enjoy — that is, by reference to their ‘symbolic’ capital. The article shows that PMC authority is grounded in three interrelated discourses/practices relative to risk/security, market governance and exercise of the state’s monopoly on violence. These leave an imprint on the legal accountability sought. The centrality of the risk/security discourse paves the way for exceptionalism; that of the role of market governance for ad-hocism; and that of the discourse of respect for the state’s monopoly on violence for inconsequentialism. The result is the coexistence of PMCs’ relative impunity with intense contestation and legal innovation
Securitization of HIV/AIDS in Context: Gendered Vulnerability in Burundi
Authors: Seckinelgin Hakan , Bigirumwami Joseph , Morris Jill
Published: October 2010

In this article, it is argued that concerns about the impact of HIV/AIDS on national and international security do not adequately address the ways in which people, particularly women, are made vulnerable to HIV/AIDS in conflicts. In fact, policies inspired by the security framing of HIV/AIDS can engender new vulnerabilities in post-conflict contexts. The article analyses the ways in which gender relations create vulnerabilities for various groups when such relations are put under pressure during periods of conflict. Drawing on research conducted in Burundi, the article argues that postulated links between security and HIV/AIDS fail to take into account the vulnerability structures that exist in societies, the ways in which these are instrumentalized during conflict and in post-conflict contexts, and how they are also maintained and changed as a result of people’s experiences during conflict.
ESDP and Institutional Change: The Case of Belgium
Authors: Vanhoonacker Sophie , Jacobs An D.
Published: October 2010

Since 2003, the European Union has launched more than 20 civilian and military missions across the world. This new role as a crisis manager has not only triggered the creation of more Brussels-based institutions, but has also brought new challenges for the domestic level. The national ministries in the EU member-states are responsible for delivering the civilian or military resources necessary for the implementation of the missions. This article raises the question whether and to what extent the European Security and Defence Policy (ESDP) has affected national administrative structures in terms of both competence allocation and coordination, and examines which factors account for processes of change. The proposed analytical framework builds upon the Europeanization literature and complements the historical institutionalist argument with an actor-based approach emphasizing the preferences and beliefs of the principal political actors. The analytical framework is tested in a case study of Belgium (1999—2007).
‘Like pulling down Durham Cathedral and building a brothel’: Women as ‘new consumer’ fans?
Authors: Pope Stacey
Published: October 2010

The experiences of female sports fans have been largely marginalized in academic research. This article aims to bring women’s experiences as sports fans to the fore. It also explores assumptions of homogeneity which seem to underlie much research on male and female fans. This has perhaps led to a gendered binary whereby female sports fans are often depicted as ‘new consumer’ fans and are perceived as ‘inauthentic’ in their support. Drawing on Glaser and Strauss’s (2008) ‘grounded theory’ approach, 51 semi-structured interviews were conducted with female football fans in the East Midlands city of Leicester in England. This article focuses on two themes which emerged from this research: women, football and a sense of place; and women and stadium modernization. These findings begin to explore some of the complexities of female fan attachment and emphasize the need to examine the diversity of women’s experiences as sports fans. I propose that future research on sports fandom would benefit from a greater sensitivity to heterogeneity in both men’s and women’s experiences.
“Coyote Was Walking. . .”: Management Education in Indian Time
Authors: Verbos Amy Klemm , Kennedy Deanna M. , Gladstone Joe S.
Published: October 2010

The authors present a Coyote story to illustrate Native American perspectives on time, teaching, and learning. Coyote stories invoke Indian Time, a traditional Native American perception of time that progresses through events rather than minutes on a clock. Coyote, a trickster, wanders and investigates, interacting with animate creatures and inanimate objects. He inspires us to pursue creative, multidirectional approaches of understanding and reflective, self-discovered approach to learning. Whereas management and management education typically edify a single-time perspective, that of clock time, you may find wisdom in nonlinear Indian Time and reflective learning through timeless stories.
The Case of Juvenile Polygraphy as a Clinical Ethics Dilemma
Authors: Chaffin Mark
Published: October 2010

Polygraph interrogations are used by half of all surveyed juvenile sex offender (JSO) treatment programs in the United States. This is a distinctive and controversial practice that is rarely if ever used with other juvenile delinquent populations, and that is rarely used or is banned from JSO treatment programs in other countries. Clinical polygraphy is an ethically sensitive issue because it involves mental health therapists in involuntary coercive interrogations of minors. This article reviews core mental health professional ethics principles for juveniles. JSO polygraphy is used as an illustrative issue for applying human rights principles to a practice in light of its benefits, risks, and available alternatives.
Potato Shrinkage During Hot Air Drying
Authors: Frías A. , Clemente G. , Mulet A.
Published: October 2010

Shrinkage is one of the most important physical changes that occur during the dehydration of foods. In this work, the effect of the temperature (35, 40, 50, 60 and 70 °C) and air velocity (7, 8, 9 and 10 m/s) on bulk volumetric shrinkage was investigated. Volume changes were evaluated by image analysis. It was found that neither temperature nor air velocity had any significant effects on bulk shrinkage in this system. The bulk shrinkage of the potato cubes was well correlated with the moisture content of the sample during drying (R2 = 97.28). Volume varied linearly with the moisture content changes under the studied conditions. The volume of lost water and the decrease in volume of the samples during dehydration were similar.
Preferential increase of B-cell activating factor in the cerebrospinal fluid of neuromyelitis optica in a white population
Authors: Vaknin-Dembinsky Adi , Brill Livnat , Orpaz Naama , Abramsky Oded , Karussis Dimitrios
Published: October 2010

Background: Anti-aquaporin-4 antibodies are believed to have a central pathogenetic role in neuromyelitis optica (NMO). B-cell activating factor (BAFF) is one of the crucial factors that determines the fate and survival of B cells and may play a role in induction of antibody-mediated autoimmunity.

Objectives: To evaluate the blood and cerebrospinal fluid (CSF) levels of BAFF in NMO and multiple sclerosis (MS) patients.

Methods: Peripheral blood samples were collected from 21 definite NMO patients, 22 healthy controls and 45 MS patients and CSF from 8 NMO and 11 MS patients. BAFF levels were measured using an ELISA technique.

Results: We found significantly higher levels of BAFF in the CSF of NMO patients compared with that in MS (215.6 ± 41 pg/ml in NMO and 77.4 ± 11 pg/ml in MS, p < 0.001). There were no differences in serum BAFF levels between NMO, MS and healthy donors. MS patients treated with interferon-beta (IFNβ) or glatiramer acetate (GA) had significantly higher serum BAFF levels, as compared with untreated patients (1227 ± 203 pg/ml in untreated MS, 2253 ± 83.4 pg/ml in GA-treated, p < 0.01, and 2106 ± 277.9 pg/ml in interferon-treated, p < 0.05)

Conclusion: The presence of increased BAFF, a soluble factor associated with B-cell activation in the proximity of the disease target organ (CSF) in NMO, and its increase in association with immunomodulating treatments, may help our understanding of the immunopathogenetic mechanisms involved in this disease and contribute to more successful and targeted therapeutic intervention.
Trauma and terror - suicide bombs and their medical management
Authors: Page Piers
Published: October 2010

The increasing use of suicide bombs has brought a new set of problems for the modern clinician. To competently manage these, the clinician must have an appreciation of the underlying ballistic principles of these attacks and their common manifestations as patterns of injury. There are forensic implications in managing the casualties of such an attack, as well as those of scene and resource management. The risks of intentional and unintentional incorporation of biohazardous materials are also discussed.
Global support for the death penalty
Authors: Unnever James
Published: October 2010

The recently released Gallup International 2000 Millennium Survey Poll collected data from individuals residing in 59 countries. The focus of this research was to analyze these data to examine whether the abolition movement has ushered in a new ‘collective sensibility’ about the death penalty or whether global attitudes toward capital punishment are characterized by deep divisions. The research assumes that the long-term stability of abolition will be assured when the vast majority of the citizens of the world oppose the use of the death penalty. The findings reveal that there are deep cleavages in worldwide support for capital punishment. The article highlights five divides in support for capital punishment and then separately discusses the results from the human rights and minority group threat analyses.
Architecture/dance: choreographing and inhabiting spaces with Anna and Lawrence Halprin
Authors: Merriman Peter
Published: October 2010

In this paper I build upon geographical writings on non-representational theory and dance by exploring how the pioneering avant-garde dancer Anna Halprin and landscape architect Lawrence Halprin attempted to choreograph a range of bodies and environments in 1950s and 1960s California. In contrast to geographic writings which have focussed on the regulatory and oppressive politics which are frequently embroiled in the choreographing of specific traditions of dance, I highlight the complex and contested nature of choreography, before focusing on the Left-leaning, libertarian, democratic, counter-cultural choreographic experiments of Anna and Lawrence Halprin. I examine the evolution of Anna and Lawrence’s philosophical approaches to creativity and the arts, highlighting the importance of Bauhaus principles of interdisciplinary working and charting their early attempts to rethink landscape architecture and dance through an understanding of the spaces of choreography and performance, and the performativities and choreographies of spaces. I then focus on Anna and Lawrence’s interdisciplinary ‘Experiments in Environment’ workshops of 1966 and 1968, which marked a turning point in their respective approaches to choreography, participation, and collective exploration and creativity. I examine their pioneering attempts to include diverse communities and audiences in their performance and design projects, and I build upon recent work on the politics of non-representational theory and affect by showing how Anna and Lawrence sought to engineer affects and emotions with explicitly positive, inclusive, egalitarian, democratic, and communitarian aims.
‘Half-breeds,’ racial opacity, and geographies of crime: law’s search for the ‘original’ Indian
Authors: Mawani Renisa
Published: October 2010

Discussions of hybridity have proliferated in cultural geography and in social and cultural theory. What has often been missing from these accounts are the ways in which mixed-race identities have been forged, contested, and embodied spatially. Inspired by recent calls in cultural geography to rematerialize race and drawing from the growing literature on law and geography, this article examines the material dimensions of hybridity, how it was legally produced, gained traction, and slipped in the quotidian spaces of everyday encounters. Focused on late-19th and early-20th-century British Columbia (Canada), I trace the emergence of the ‘half-breed’ as a new racial personage and juridical taxonomy that unsettled racial hierarchies and spatial distinctions between aboriginal and white settler populations. Unlike other colonial contexts, mixed-race peoples on Canada’s west coast did not threaten European superiority alone but were believed to endanger the protection and assimilation of aboriginal peoples. Proximities between ‘half-breeds’ and ‘Indians’ were politically charged for two reasons. First, racial differentiations between these populations were often imperceptible, and second, their putative distinctions were closely bound up with concerns over territory and with aboriginal well-being. The racial opacity of mixed-race peoples created some sites of mobility for those in-between. However, their unknowability shored up the uncertainties of colonial knowledge production and the limits of existing racial repertoires, creating persistent demands for new markers of racial otherness in the process. Crime and immorality became potent signifiers of racial inferiority aimed at differentiating half-breeds from Indians and providing authorities with additional optics through which to problematize and govern their affective and geographical encounters.
More-than-human histories and the failure of grand state schemes: sylviculture in the New Forest, England
Authors: Griffin Carl J.
Published: October 2010

As James Scott’s Seeing Like a State attests, forests played a central role in the rise of the modern state, specifically as test spaces for evolving methods of managing state resources at a distance, and as the location for grand state schemes. Together, such ambitions necessitated both the elimination of local understandings of forest management — to be replaced by centrally controlled scientific precision — and a narrowing of state vision. Forests thus began to be conflated with trees (and their timber) alone. All other aspects of the forest, both human and non-human, were ignored. Through the lens of the 18th and early 19th century New Forest in southern England, this paper examines the impact of government attempts to shift the focus of state forests from being remnant medieval hunting spaces to spaces of income generation through the creation of vast sylvicultural plantations. This state scheme not only reworked the relationship between the metropole and the provinces — something effected through systematic surveys and novel bureaucratic procedures — but also dramatically impacted upon the biophysical and cultural geographies of the forest. By equating forest space with trees alone, the British state failed to legislate for the actions of both local commoners and non-human others in resisting their schemes. Indeed, subsequent oppositions proved not only the tenacity of commoners in protecting their livelihoods but also the destructive power of non-human actants, specifically rabbits and mice. The paper concludes that grand state schemes necessarily fail due to their own internal illogic: the narrowing of state vision creates blind spots in which human and non-human lives assert their own visions.
Remarks on Sacrifice and Punishment
Authors: Ptacek Melissa
Published: October 2010

In this commentary, I explore affirmative responses to the question of whether the notion of sacrifice illuminates the nature of punitive acts such as executions and lynchings. In the end, however, I maintain that the notion of sacrifice is incompatible with such efforts and may serve more to obscure than to illuminate. Not only are key aspects of sacrifice overlooked in such analyses, but attention is diverted from the specific punitive violence of law. Finally, I propose that, when separated from its sacrificial framework, René Girard’s figure of the scapegoat may be helpful to understanding this punitive violence.
Are computer keyboards a cross-infection risk in a dental clinic?
Authors: Patel Sarika , Porter Kathryn , Sammons Rachel L
Published: October 2010

Computers in dental surgeries located within the patient treatment room could potentially pose a risk of cross-infection of patients and operators. The aims of this investigation were to determine the degree of contamination of computer keyboards located in clinics and study rooms in a teaching dental hospital, to determine the survival time of micro-organisms on keyboards and to compare the efficiency of two common disinfectants in disinfecting keyboards. All keyboards were found to be contaminated with a variety of micro-organisms including Staphylococcus aureus, coagulasenegative staphylococci, Gram-negative rods and cocci. A range of Gram-positive and -negative bacteria and Candida albicans were able to survive up to 10 days in dried suspensions on computer keys. Seventy per cent isopropanol wipes proved effective in reducing the numbers of viable test organisms on keys by at least 96% and reducing contamination of keyboards in routine use. The data suggest that computers in dental study areas and clinics act as reservoirs of potentially pathogenic organisms including S. aureus and should be regularly disinfected to reduce the risk of cross-infection.
Explaining Not-in-My-Backyard Responses to Different Social Groups
Authors: van Alphen Laura M. , Dijker Anton J. M. , Bos Arjan E. R. , van den Borne Bart H. W. , Curfs Leopold M. G.
Published: October 2010

To examine why people are reluctant to engage in intergroup contact, the present study asked members of a nationwide online panel ( N = 555) to imagine that they would get individuals of a particular social group as next-door neighbors. Respondents were randomly assigned to one of five different social groups hypothesized to differ in emotion-arousing potential: elderly people, people with mild or severe intellectual disability, economic refugees, and young offenders. It was found that differences in acceptance between these groups could be well explained by emotions aroused while anticipating contact yet less well by differences in previous contact with these groups. Furthermore, emotions appeared to be uniquely related to preferred interpersonal relationships. It is concluded that research on how to reduce prejudice through intergroup contact should be complemented with a better understanding of why people are reluctant to engage in such contact in the first place.
Transfusion-related acute lung injury: from bedside to bench and back
Authors: Shaz Beth H. , Stowell Sean R. , Hillyer Christopher D.
Published: October 2010

Over the past 60 years, the transfusion medicine community has attained significant knowledge regarding transfusion-related acute lung injury (TRALI) through the bedside to bench and back to the bedside model. First, at the bedside, TRALI causes hypoxia and noncardiogenic pulmonary edema, typically within 6 hours of transfusion. Second, bedside studies showed a higher incidence in plasma and platelet products than in red blood cell products (the fatal TRALI incidence for plasma is 1:2-300 000 products; platelet, 1:3-400 000; red blood cells, 1:25 002 000), as well as an association with donor leukocyte antibodies (∼ 80% of cases). Third, at the bench, antibody-dependent and antibody-independent mechanisms have been described, requiring neutrophil and pulmonary endothelial cell activation. Antibodies, as well as alternate substances in blood products, result in neutrophil activation, which, in a susceptible patient, result in TRALI (2-hit hypothesis). Fourth, back to the bedside, policy changes based on results of these studies, such as minimizing use of plasma and platelet products from donors with leukocyte antibodies, have decreased the incidence of TRALI. Thus, steps to mitigate TRALI are in place, but a complete mechanistic understanding of the pathogenesis of TRALI and of which patients are at highest risk remains to be elucidated.
Delta-like ligand 4–Notch signaling regulates bone marrow–derived pericyte/vascular smooth muscle cell formation
Authors: Stewart Keri Schadler , Zhou Zhichao , Zweidler-McKay Patrick , Kleinerman Eugenie S.
Published: October 2010

Delta-like ligand 4 (DLL4) is essential for the formation of mature vasculature. However, the role of DLL4-Notch signaling in pericyte/vascular smooth muscle cell (vSMC) development is poorly understood. We sought to determine whether DLL4-Notch signaling is involved in pericyte/vSMC formation in vitro and during vasculogenesis in vivo using 2 Ewing sarcoma mouse models. Inhibition of DLL4 with the antibody YW152F inhibited pericyte/vSMC marker expression by bone marrow (BM) cells in vitro. Conversely, transfection of 10T1/2 cells with the active domains of Notch receptors led to increased expression of pericyte/vSMC markers. Furthermore, the blood vessels of Ewing sarcoma tumors from mice treated with YW152F had reduced numbers of BM-derived pericytes/vSMCs, fewer open lumens, and were less functional than the vessels in tumors of control-treated mice. Tumor growth was also inhibited. These data demonstrate a specific role for DLL4 in the formation of BM-derived pericytes/vSMCs and indicate that DLL4 may be a novel therapeutic target for the inhibition of vasculogenesis.
Langerhans cells are not required for graft-versus-host disease
Authors: Li Hongmei , Kaplan Daniel H. , Matte-Martone Catherine , Tan Hung Sheng , Venkatesan Srividhya , Johnson Kody , Demetris Anthony J. , McNiff Jennifer , Shlomchik Mark J. , Shlomchik Warren D.
Published: October 2010

Graft-versus-host disease (GVHD) is initiated and maintained by antigen-presenting cells (APCs) that prime alloreactive donor T cells. APCs are therefore attractive targets for GVHD prevention and treatment. APCs are diverse in phenotype and function, making understanding how APC subsets contribute to GVHD necessary for the development of APC-targeted therapies. Langerhans cells (LCs) have been shown to be sufficient to initiate skin GVHD in a major histocompatibility complex–mismatched model; however, their role when other host APC subsets are intact is unknown. To address this question, we used mice genetically engineered to be deficient in LCs by virtue of expression of diphtheria toxin A under the control of a BAC (bacterial artificial chromosome) transgenic hu-man Langerin locus. Neither CD8- nor CD4-mediated GVHD was diminished in recipients lacking LCs. Similarly, CD8- and CD4-mediated GVHD, including that in the skin, was unaffected if bone marrow came from donors that could not generate LCs, even though donor LCs engrafted in control mice. Engraftment of donor LCs after irradiation in wild-type hosts required donor T cells, with immunofluorescence revealing patches of donor and residual host LCs. Surprisingly, donor LC engraftment in Langerin-diphtheria toxin A (DTA) transgenic hosts was independent of donor T cells, suggesting that a Langerin+ cell regulates repopulation of the LC compartment.
Construction of an almond linkage map in an Australian population Nonpareil × Lauranne
Authors: Tavassolian Iraj , Rabiei Gholmereza , Gregory Davina , Mnejja Mourad , Wirthensohn Michelle G , Hunt Peter W , Gibson John P , Ford Christopher M , Sedgley Margaret , Wu Shu-Biao
Published: October 2010

Background

Despite a high genetic similarity to peach, almonds (Prunus dulcis) have a fleshless fruit and edible kernel, produced as a crop for human consumption. While the release of peach genome v1.0 provides an excellent opportunity for almond genetic and genomic studies, well-assessed segregating populations and the respective saturated genetic linkage maps lay the foundation for such studies to be completed in almond.

Results

Using an almond intraspecific cross between 'Nonpareil' and 'Lauranne' (N × L), we constructed a moderately saturated map with SSRs, SNPs, ISSRs and RAPDs. The N × L map covered 591.4 cM of the genome with 157 loci. The average marker distance of the map was 4.0 cM. The map displayed high synteny and colinearity with the Prunus T × E reference map in all eight linkage groups (G1-G8). The positions of 14 mapped gene-anchored SNPs corresponded approximately with the positions of homologous sequences in the peach genome v1.0. Analysis of Mendelian segregation ratios showed that 17.9% of markers had significantly skewed genotype ratios at the level of P < 0.05. Due to the large number of skewed markers in the linkage group 7, the potential existence of deleterious gene(s) was assessed in the group. Integrated maps produced by two different mapping methods using JoinMap® 3 were compared, and their high degree of similarity was evident despite the positional inconsistency of a few markers.

Conclusions

We presented a moderately saturated Australian almond map, which is highly syntenic and collinear with the Prunus reference map and peach genome V1.0. Therefore, the well-assessed almond population reported here can be used to investigate the traits of interest under Australian growing conditions, and provides more information on the almond genome for the international community.
A high-throughput cloning system for reverse genetics in Trypanosoma cruzi
Authors: Batista Michel , Marchini Fabricio K , Celedon Paola AF , Fragoso Stenio P , Probst Christian M , Preti Henrique , Ozaki Luiz S , Buck Gregory A , Goldenberg Samuel , Krieger Marco A
Published: October 2010

Background

The three trypanosomatids pathogenic to men, Trypanosoma cruzi, Trypanosoma brucei and Leishmania major, are etiological agents of Chagas disease, African sleeping sickness and cutaneous leishmaniasis, respectively. The complete sequencing of these trypanosomatid genomes represented a breakthrough in the understanding of these organisms. Genome sequencing is a step towards solving the parasite biology puzzle, as there are a high percentage of genes encoding proteins without functional annotation. Also, technical limitations in protein expression in heterologous systems reinforce the evident need for the development of a high-throughput reverse genetics platform. Ideally, such platform would lead to efficient cloning and compatibility with various approaches. Thus, we aimed to construct a highly efficient cloning platform compatible with plasmid vectors that are suitable for various approaches.

Results

We constructed a platform with a flexible structure allowing the exchange of various elements, such as promoters, fusion tags, intergenic regions or resistance markers. This platform is based on Gateway® technology, to ensure a fast and efficient cloning system. We obtained plasmid vectors carrying genes for fluorescent proteins (green, cyan or yellow), and sequences for the c-myc epitope, and tandem affinity purification or polyhistidine tags. The vectors were verified by successful subcellular localization of two previously characterized proteins (Tc Rab7 and PAR 2) and a putative centrin. For the tandem affinity purification tag, the purification of two protein complexes (ribosome and proteasome) was performed.

Conclusions

We constructed plasmids with an efficient cloning system and suitable for use across various applications, such as protein localization and co-localization, protein partner identification and protein expression. This platform also allows vector customization, as the vectors were constructed to enable easy exchange of its elements. The development of this high-throughput platform is a step closer towards large-scale trypanosome applications and initiatives.
CCL2 modulates cytokine production in cultured mouse astrocytes
Authors: Semple Bridgette D , Frugier Tony , Morganti-Kossmann M Cristina
Published: October 2010

Background

The chemokine CCL2 (also known as monocyte chemoattractant protein-1, or MCP-1) is upregulated in patients and rodent models of traumatic brain injury (TBI), contributing to post-traumatic neuroinflammation and degeneration by directing the infiltration of blood-derived macrophages into the injured brain. Our laboratory has previously reported thatCcl2-/- mice show reduced macrophage accumulation and tissue damage, corresponding to improved motor recovery, following experimental TBI. Surprisingly,Ccl2-deficient mice also exhibited delayed but exacerbated secretion of key proinflammatory cytokines in the injured cortex. Thus we sought to further characterise CCL2's potential ability to modulate immunoactivation of astrocytesin vitro.

Methods

Primary astrocytes were isolated from neonatal wild-type andCcl2-deficient mice. Established astrocyte cultures were stimulated with various concentrations of lipopolysaccharide (LPS) and interleukin (IL)-1β for up to 24 hours. Separate experiments involved pre-incubation with mouse recombinant (r)CCL2 prior to IL-1β stimulation in wild-type cells. Following stimulation, cytokine secretion was measured in culture supernatant by immunoassays, whilst cytokine gene expression was quantified by real-time reverse transcriptase polymerase chain reaction.

Results

LPS (0.1-100 μg/ml; 8 h) induced the significantly greater secretion of five key cytokines and chemokines inCcl2-/- astrocytes compared to wild-type cells. Consistently, IL-6 mRNA levels were 2-fold higher inCcl2-deficient cells. IL-1β (10 and 50 ng/ml; 2-24 h) also resulted in exacerbated IL-6 production fromCcl2-/- cultures. Despite this, treatment of wild-type cultures with rCCL2 alone (50-500 ng/ml) did not induce cytokine/chemokine production by astrocytes. However, pre-incubation of wild-type astrocytes with rCCL2 (250 ng/ml, 12 h) prior to stimulation with IL-1β (10 ng/ml, 8 h) significantly reduced IL-6 protein and gene expression.

Conclusions

Our data indicate that astrocytes are likely responsible for the exacerbated cytokine response seenin vivopost-injury in the absence of CCL2. Furthermore, evidence that CCL2 inhibits cytokine production by astrocytes following IL-1β stimulation, suggests a novel, immunomodulatory role for this chemokine in acute neuroinflammation. Further investigation is required to determine the physiological relevance of this phenomenon, which may have implications for therapeutics targeting CCL2-mediated leukocyte infiltration following TBI.
Interaction of human dipeptidyl peptidase IV and human immunodeficiency virus type-1 transcription transactivator in Sf9 cells
Authors: Tansi Felista L , Blanchard Véronique , Berger Markus , Tauber Rudolf , Reutter Werner , Fan Hua
Published: October 2010

Background

Dipeptidyl peptidase IV (DPPIV) also known as the T cell activation marker CD26 is a multifunctional protein which is involved in various biological processes. The association of human-DPPIV with components of the human immunodeficiency virus type-1 (HIV1) is well documented and raised some discussions. Several reports implicated the interaction of human-DPPIV with the HIV1 transcription transactivator protein (HIV1-Tat) and the inhibition of the dipeptidyl peptidase activity of DPPIV by the HIV1-Tat protein. Furthermore, enzyme kinetic data implied another binding site for the HIV1-Tat other than the active centre of DPPIV. However, the biological significance of this interaction of the HIV1-Tat protein and human-DPPIV has not been studied, yet. Therefore, we focused on the interaction of HIV1-Tat protein with DPPIV and investigated the subsequent biological consequences of this interaction inSpodoptera frugiperdacells, using the BAC-TO-BAC baculovirus system.

Results

The HIV1-Tat protein (Tat-BRU) co-localized and co-immunoprecipitated with human-DPPIV protein, following co-expression in the baculovirus-drivenSf9cell expression system. Furthermore, tyrosine phosphorylation of DPPIV protein was up-regulated in Tat/DPPIV-co-expressing cells after 72 h culturing and also in DPPIV-expressingSf9cells after application of purified recombinant Tat protein. As opposed to the expression of Tat alone, serine phosphorylation of the Tat protein was decreased when co-expressed with human-DPPIV protein.

Conclusions

We show for the first time that human-DPPIV and HIV1-Tat co-immunoprecipitate. Furthermore, our findings indicate that the interaction of HIV1-Tat and human-DPPIV may be involved in signalling platforms that regulate the biological function of both human-DPPIV and HIV1-Tat.
Biomechanical investigation of a novel ratcheting arthrodesis nail
Authors: McCormick Jeremy J , Li Xinning , Weiss Douglas R , Billiar Kristen L , Wixted John J
Published: October 2010

Background

Knee or tibiotalocalcaneal arthrodesis is a salvage procedure, often with unacceptable rates of nonunion. Basic science of fracture healing suggests that compression across a fusion site may decrease nonunion. A novel ratcheting arthrodesis nail designed to improve dynamic compression is mechanically tested in comparison to existing nails.

Methods

A novel ratcheting nail was designed and mechanically tested in comparison to a solid nail and a threaded nail using sawbones models (Pacific Research Laboratories, Inc.). Intramedullary nails (IM) were implanted with a load cell (Futek LTH 500) between fusion surfaces. Constructs were then placed into a servo-hydraulic test frame (Model 858 Mini-bionix, MTS Systems) for application of 3 mm and 6 mm dynamic axial displacement (n = 3/group). Load to failure was also measured.

Results

Mean percent of initial load after 3-mm and 6-mm displacement was 190.4% and 186.0% for the solid nail, 80.7% and 63.0% for the threaded nail, and 286.4% and 829.0% for the ratcheting nail, respectively. Stress-shielding (as percentage of maximum load per test) after 3-mm and 6-mm displacement averaged 34.8% and 28.7% (solid nail), 40.3% and 40.9% (threaded nail), and 18.5% and 11.5% (ratcheting nail), respectively. In the 6-mm trials, statistically significant increase in initial load and decrease in stress-shielding for the ratcheting vs. solid nail (p= 0.029,p= 0.001) and vs. threaded nail (p= 0.012,p= 0.002) was observed. Load to failure for the ratcheting nail; 599.0 lbs, threaded nail; 508.8 lbs, and solid nail; 688.1 lbs.

Conclusion

With significantly increase of compressive load while decreasing stress-shielding at 6-mm of dynamic displacement, the ratcheting mechanism in IM nails may clinically improve rates of fusion.
Recurrent post-partum coronary artery dissection
Authors: Rajab Taufiek K , Khalpey Zain , Kraemer Bernhard , Resnic Frederic S , Gallegos Robert P
Published: October 2010

Coronary artery dissection is a rare but well-described cause for myocardial infarction during the post-partum period. Dissection of multiple coronary arteries is even less frequent. Here we present a case of recurrent post-partum coronary artery dissections. This unusual presentation poses unique problems for management. A 35 year-old female, gravida 3 para 2, presented with myocardial infarction 9 weeks and 3 days post-partum. Cardiac catheterization demonstrated left anterior descending (LAD) dissection but an otherwise normal coronary anatomy. The lesion was treated with four everolimus eluting stents. Initially the patient made an unremarkable recovery until ventricular fibrillation arrest occurred on the following day. Unsynchronized cardioversion restored a normal sinus rhythm and repeat catheterization revealed new right coronary artery (RCA) dissection. A wire was passed distally, but it was unclear whether this was through the true or false lumen and no stents could be placed. However, improvement of distal RCA perfusion was noted on angiogram. Despite failure of interventional therapy the patient was therefore treated conservatively. Early operation after myocardial infarction has a significantly elevated risk of mortality and the initial dissection had occurred within 24 hours. This strategy proved successful as follow-up transthoracic echocardiography after four months demonstrated a preserved left ventricular ejection fraction of 55-60% without regional wall motion abnormalities. The patient remained asymptomatic from a cardiac point of view.
Outdoor Temperature, Age, Sex, Body Mass Index, and Diabetic Status Determine the Prevalence, Mass, and Glucose-Uptake Activity of 18F-FDG-Detected BAT in Humans
Authors: Ouellet Veronique , Routhier-Labadie Annick , Bellemare William , Lakhal-Chaieb Lajmi , Turcotte Eric , Carpentier André C. , Richard Denis
Published: October 2010

Context: In humans, the prevalence, mass, and glucose-uptake activity of 18F-fluorodeoxyglucose (18F-FDG)-detected brown adipose tissue (BAT), which are expectedly enhanced by a cold stimulus, also appear modulated by other factors that still have to be disentangled.

Objective: The objective of the study was to investigate the factors determining the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans.

Research Design and Methods: We retrospectively analyzed all 18F-FDG positron emission tomography/computed tomography examinations performed between January 2007 and December 2008 at our institution for 18F-FDG uptake within the cervical/supraclavicular, mediastinal, paravertebral, and perirenal fat areas. The influence of outdoor temperature, sex, age, body mass index (BMI), plasma glucose level, diabetes diagnosis, day length, and cancer status on the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT depots was investigated.

Results: Three hundred twenty-eight of the 4842 patients (6.8%) had 18F-FDG-detected BAT. The prevalence of 18F-FDG BAT was negatively associated with outdoor temperature (P < 0.0001), age (P < 0.0001), BMI (P < 0.0001), and diabetes status (P = 0.0003). Moreover, there was a significant age × sex interaction for the prevalence of 18F-FDG BAT (the younger the subjects, the greater the sex difference). The mass and glucose-uptake activity of 18F-FDG-detected BAT also decreased with increasing outdoor temperature (P < 0.0001), age (P < 0.0001), and BMI (P < 0.0001). They were lower in men than in women (P < 0.001) and lower in diabetic than in nondiabetic patients (P = 0.0002).

Conclusions: The present study identifies outdoor temperature, age, sex, BMI, and diabetes status as determinants of the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT.
Longitudinal Association between Growth Hormone Therapy and Obstructive Sleep Apnea in a Child with Prader-Willi Syndrome
Authors: Nixon Gillian M. , Rodda Christine P. , Davey Margot J.
Published: October 2010

Context: Descriptions of the development of symptoms of upper airway obstruction and sudden death of children with Prader-Willi Syndrome (PWS) while on GH therapy have led to concern about GH contributing to obstructive sleep apnea (OSA), especially early in treatment. However, two studies using monitoring with polysomnography (PSG) have not shown deterioration in OSA after 6 wk on GH, except as related to upper respiratory tract infections.

Objective: The aim was to describe the evolution of OSA in a girl with PWS on GH treatment in order to highlight important aspects of long-term clinical monitoring for patients with PWS on GH treatment.

Patient and Research Design: GH was commenced when the patient was 2.9 yr of age. PSG was performed at baseline and 7 wk after commencing GH, plus at intervals throughout treatment based on symptoms of OSA.

Intervention: GH was given at doses ranging from 4.2 to 4.7 mg/m2 · wk over a period of 3 yr.

Main Outcome Measure: OSA was quantified by PSG.

Results: OSA was not present at baseline or after 7 wk on GH but developed after 6 months, following a small increase in GH dose. Cessation of GH was accompanied by resolution of OSA. GH was restarted 2 yr later, again associated with the development of OSA that resolved after cessation of GH.

Conclusion: This case highlights that OSA may develop late in GH treatment. Children should be monitored for the symptoms of OSA throughout GH treatment, and PSG should be repeated if symptoms develop.
Metabolomics Identifies Novel Hnf1α-Dependent Physiological Pathways in Vivo
Authors: Bonzo Jessica A. , Patterson Andrew D. , Krausz Kristopher W. , Gonzalez Frank J.
Published: October 2010

Mutations in the HNF1A gene cause maturity-onset diabetes of the young type 3, one of the most common genetic causes of non-insulin-dependent (type 2) diabetes mellitus. Although the whole-body Hnf1a-null mouse recapitulates the low insulin levels and high blood glucose observed in human maturity-onset diabetes of the young type 3 patients, these mice also suffer from Laron dwarfism and aminoaciduria, suggesting a role for hepatocyte nuclear factor 1α (Hnf1α) in pathophysiologies distinct from non-insulin-dependent (type 2) diabetes mellitus. In an effort to identify pathways associated with inactivation of Hnf1α, an ultraperformance liquid chromatography coupled to mass spectrometry-based metabolomics study was conducted on urine samples from wild-type and Hnf1a-null mice. An increase in phenylalanine metabolites is in agreement with the known regulation of the phenylalanine hydroxylase gene by Hnf1α. This metabolomic approach also identified urinary biomarkers for three tissue-specific dysfunctions previously unassociated with Hnf1α function. 1) Elevated indolelactate coupled to decreased xanthurenic acid also indicated defects in the indole and kynurenine pathways of tryptophan metabolism, respectively. 2) An increase in the neutral amino acid proline in the urine of Hnf1a-null mice correlated with loss of renal apical membrane transporters of the Slc6a family. 3) Further investigation into the mechanism of aldosterone increase revealed an overactive adrenal gland in Hnf1a-null mice possibly due to inhibition of negative feedback regulation. Although the phenotype of the Hnf1a-null mouse is complex, metabolomics has opened the door to investigation of several physiological systems in which Hnf1α may be a critical regulatory component.
Development and in-vitro evaluation of a colon-specific controlled release drug delivery system
Authors: Talukder Rahmat M , Fassihi Reza
Published: October 2010

The major challenges in targeting drug to various parts of the gastrointestinal tract include control of drug release with respect to its environment and transit time. These two variables should be taken into consideration in designing a rational colonic drug delivery system. To this end, a swelling matrix core containing pectin, hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose and 5-aminosalicylic acid was developed. This was subjected to a dual coating operation: an inner pH-sensitive enteric and an outer semi-permeable membrane coat with a pore former. In-vitro dissolution studies were carried out in USP apparatus-I using sequential pH media. The first 2 h of dissolution studies were done in HCl buffer at pH 1.5, the next 2 h in pH 5.5 and, finally, in phosphate buffer at pH 6.8 with and without pectinolytic enzyme present. Less than 2% drug was released in the first 6 h and about 90% released in the following 12 h in a controlled manner. The stability studies of the coated systems were performed for 90 days under various conditions and it was found that drug release was not adversely affected. Results indicate that this delivery system has potential for site-specific delivery of drugs to the colon irrespective of transit time and rapid changes in the proximal pH of the gastrointestinal tract.
Lack of difference in pulmonary absorption of digoxin, a P-glycoprotein substrate, inmdr1a-deficient andmdr1a-competent mice
Authors: Manford Fergus , Riffo-Vasquez Yanira , Spina Domenico , Page Clive P , Hutt Andrew J , Moore Vanessa , Johansson Fredrik , Forbes Ben
Published: October 2010

Although in-vitro experiments have suggested that P-glycoprotein (P-gp) may have an important influence on the disposition of inhaled drugs, the effect of P-gp on absorption from the lung in-vivo has not been reported previously. The aim of this study was to compare the pulmonary absorption of digoxin, a well-characterised substrate for P-gp, in mdr1a (–/–) (P-gp-deficient) and mdr1a (+/+) (P-gp-competent) mice. Digoxin was administered by intratracheal instillation over 3–4 s, a method demonstrated to result in dispersion of the dose to all regions of the lung. Drug distribution was determined in the lungs, plasma, brain, heart, liver and kidney of individual mice after 5, 10, 30, 60 and 90 min. Digoxin was cleared rapidly from the lung after intratracheal administration. No differences were observed in the maximum serum concentrations between mdr1a (+/+) and mdr1a (–/–) mice (37.8 ± 6.9 and 38.8 ± 15.8 ng mL−1, respectively). The serum concentration versus time profiles were similar in both strains; the area under the drug serum concentration versus time curve (AUC) was 2010 and 1812 ng mL−1 min in mdr1a (–/–) and mdr1a (+/+) mice, respectively. For organs harvested at the end of the experiment (90 min), the only significant difference between the strains was the markedly elevated concentration of digoxin in the brains of mdr1a (–/–) mice. In conclusion, digoxin is rapidly absorbed from the mouse lung following tracheal instillation, with no difference in the rate or extent of absorption between mdr1a-deficient and -competent mice. This suggests that, in contrast to the scenario suggested by in-vitro data, P-gp in the respiratory epithelium may have little influence on the disposition of drugs that are well absorbed from the lung.