bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of the cyclooxygenase 2-prostaglandin-E prostanoid receptor pathway in mice exposed to house dust mite aeroallergens, and impact of exogenous prostaglandin E2
Authors: Herrerias Aida , Torres Rosa , Serra Mariona , Marco Alberto , Pujols Laura , Picado César , de Mora Fernando 
Published: October 2009

Abstract

Background
Prostaglandin E2 (PGE2), experimentally administered to asthma patients or assayed in murine models, improves allergen-driven airway inflammation. The mechanisms are unknown, but fluctuations of the endogenous cyclooxygenase (COX)-2/prostaglandin/E prostanoid (EP) receptor pathway activity likely contribute to the clinical outcome. We analyzed the activity of the pathway in mice sensitized to aeroallergens, and then studied its modulation under exogenous PGE2.

Methods
Mice were exposed to house dust mite (HDM) aeroallergens, a model that enable us to mimic the development of allergic asthma in humans, and were then treated with either subcutaneous PGE2 or the selective EP1/3 receptor agonist sulprostone. Simultaneously with airway responsiveness and inflammation, lung COX-2 and EP receptor mRNA expression were assessed. Levels of PGE2, PGI2, PGD2 were also determined in bronchoalveolar lavage fluid.

Results
HDM-induced airway hyperreactivity and inflammation were accompanied by increased COX-2 mRNA production. In parallel, airway PGE2 and PGI2, but not PGD2, were upregulated, and the EP2 receptor showed overexpression. Subcutaneous PGE2 attenuated aeroallergen-driven airway eosinophilic inflammation and reduced endogenous PGE2 and PGI2 production. Sulprostone had neither an effect on airway responsiveness or inflammation nor diminished allergen-induced COX-2 and PGE2 overexpression. Finally, lung EP2 receptor levels remained high in mice treated with PGE2, but not in those treated with sulprostone.

Conclusion
The lung COX-2/PGE2/EP2 receptor pathway is upregulated in HDM-exposed mice, possibly as an effort to attenuate allergen-induced airway inflammation. Exogenous PGE2 downregulates its endogenous counterpart but maintains EP2 overexpression, a phenomenon that might be required for administered PGE2 to exert its protective effect.
Silver nanoparticles inhibit VEGF-and IL-1β-induced vascular permeability via Src dependent pathway in porcine retinal endothelial cells
Authors: Sheikpranbabu Sardarpasha , Kalishwaralal Kalimuthu , Venkataraman Deepak , Eom Soo Hyun , Park Jongsun , Gurunathan Sangiliyandi 
Published: October 2009

Abstract
The aim of this study is to determine the effects of silver nanoparticles (Ag-NP) on vascular endothelial growth factor (VEGF)-and interleukin-1 beta (IL-1β)-induced vascular permeability, and to detect the underlying signaling mechanisms involved in endothelial cells. Porcine retinal endothelial cells (PRECs) were exposed to VEGF, IL-1β and Ag-NP at different combinations and endothelial cell permeability was analyzed by measuring the flux of RITC-dextran across the PRECs monolayer. We found that VEGF and IL-1β increase flux of dextran across a PRECs monolayer, and Ag-NP block solute flux induced by both VEGF and IL-1β. To explore the signalling pathway involved VEGF- and IL-1β-induced endothelial alteration, PRECs were treated with Src inhibitor PP2 prior to VEGF and IL-1β treatment, and the effects were recorded. Further, to clarify the possible involvement of the Src pathways in endothelial cell permeability, plasmid encoding dominant negative(DN) and constitutively active(CA) form of Src kinases were transfected into PRECs, 24 h prior to VEGF and IL-1β exposure and the effects were recorded. Overexpression of DN Src blocked both VEGF-and IL-1β-induced permeability, while overexpression of CA Src rescues the inhibitory action of Ag-NP in the presence or absence of VEGF and IL-1β. Further, an in vitro kinase assay was performed to identify the presence of the Src phosphorylation at Y419. We report that VEGF and IL-1β-stimulate endothelial permeability via Src dependent pathway by increasing the Src phosphorylation and Ag-NP block the VEGF-and IL-1β-induced Src phosphorylation at Y419. These results demonstrate that Ag-NP may inhibit the VEGF-and IL-1β-induced permeability through inactivation of Src kinase pathway and this pathway may represent a potential therapeutic target to inhibit the ocular diseases such as diabetic retinopathy.
The scent of supercolonies: the discovery, synthesis and behavioural verification of ant colony recognition cues
Authors: Brandt Miriam , van Wilgenburg Ellen , Sulc Robert , Shea Kenneth J , Tsutsui Neil D 
Published: October 2009

Abstract

Background
Ants form highly social and cooperative colonies that compete, and often fight, against other such colonies, both intra- and interspecifically. Some invasive ants take sociality to an extreme, forming geographically massive 'supercolonies' across thousands of kilometres. The success of social insects generally, as well as invasive ants in particular, stems from the sophisticated mechanisms used to accurately and precisely distinguish colonymates from non-colonymates. Surprisingly, however, the specific chemicals used for this recognition are virtually undescribed.

Results
Here, we report the discovery, chemical synthesis and behavioural testing of the colonymate recognition cues used by the widespread and invasive Argentine ant (Linepithema humile). By synthesizing pure versions of these chemicals in the laboratory and testing them in behavioural assays, we show that these compounds trigger aggression among normally amicable nestmates, but control hydrocarbons do not. Furthermore, behavioural testing across multiple different supercolonies reveals that the reaction to individual compounds varies from colony to colony -- the expected reaction to true colony recognition labels. Our results also show that both quantitative and qualitative changes to cuticular hydrocarbon profiles can trigger aggression among nestmates. These data point the way for the development of new environmentally-friendly control strategies based on the species-specific manipulation of aggressive behaviour.

Conclusion
Overall, our findings reveal the identity of specific chemicals used for colonymate recognition by the invasive Argentine ants. Although the particular chemicals used by other ants may differ, the patterns reported here are likely to be true for ants generally. As almost all invasive ants display widespread unicoloniality in their introduced ranges, our findings are particularly relevant for our understanding of the biology of these damaging invaders.
Cerebellar Purkinje cells incorporate immunoglobulins and immunotoxins in vitro: implications for human neurological disease and immunotherapeutics
Authors: Hill Kenneth E , Clawson Susan A , Rose John W , Carlson Noel G , Greenlee John E 
Published: October 2009

Abstract

Background
Immunoglobulin G (IgG) antibodies reactive with intracellular neuronal proteins have been described in paraneoplastic and other autoimmune disorders. Because neurons have been thought impermeable to immunoglobulins, however, such antibodies have been considered unable to enter neurons and bind to their specific antigens during life. Cerebellar Purkinje cells - an important target in paraneoplastic and other autoimmune diseases - have been shown in experimental animals to incorporate a number of molecules from cerebrospinal fluid. IgG has also been detected in Purkinje cells studied post mortem. Despite the possible significance of these findings for human disease, immunoglobulin uptake by Purkinje cells has not been demonstrated in living tissue or studied systematically.

Methods
To assess Purkinje cell uptake of immunoglobulins, organotypic cultures of rat cerebellum incubated with rat IgGs, human IgG, fluorescein-conjugated IgG, and rat IgM were studied by confocal microscopy in real time and following fixation. An IgG-daunorubicin immunotoxin was used to determine whether conjugation of pharmacological agents to IgG could be used to achieve Purkinje cell-specific drug delivery.

Results
IgG uptake was detected in Purkinje cell processes after 4 hours of incubation and in Purkinje cell cytoplasm and nuclei by 24-48 hours. Uptake could be followed in real time using IgG-fluorochrome conjugates. Purkinje cells also incorporated IgM. Intracellular immunoglobulin did not affect Purkinje cell viability, and Purkinje cells cleared intracellular IgG or IgM within 24-48 hours after transfer to media lacking immunoglobulins. The IgG-daunomycin immunotoxin was also rapidly incorporated into Purkinje cells and caused extensive, cell-specific death within 8 hours. Purkinje cell death was not produced by unconjugated daunorubicin or control IgG.

Conclusion
Purkinje cells in rat organotypic cultures incorporate and clear host (rat) and non-host (human or donkey) IgG or IgM, independent of the immunoglobulin's reactivity with Purkinje cell antigens. This property permits real-time study of immunoglobulin-Purkinje cell interaction using fluorochrome IgG conjugates, and can allow Purkinje cell-specific delivery of IgG-conjugated pharmacological agents. Antibodies to intracellular Purkinje cell proteins could potentially be incorporated intracellularly to produce cell injury. Antibodies used therapeutically, including immunotoxins, may also be taken up and cause Purkinje cell injury, even if they do not recognize Purkinje cell antigens.
Localization of deformed wing virus (DWV) in the brains of the honeybee, Apis mellifera Linnaeus
Authors: Shah Karan S , Evans Elizabeth C , Pizzorno Marie C 
Published: October 2009

Abstract

Background
Deformed wing virus (DWV) is a positive-strand RNA virus that infects European honeybees (Apis mellifera L.) and has been isolated from the brains of aggressive bees in Japan. DWV is known to be transmitted both vertically and horizontally between bees in a colony and can lead to both symptomatic and asymptomatic infections in bees. In environmentally stressful conditions, DWV can contribute to the demise of a honeybee colony. The purpose of the current study is to identify regions within the brains of honeybees where DWV replicates using in-situ hybridization.

Results

In-situ hybridizations were conducted with both sense and antisense probes on the brains of honeybees that were positive for DWV as measured by real-time RT-PCR. The visual neuropils demonstrated detectable levels of the DWV positive-strand genome. The mushroom bodies and antenna lobe neuropils also showed the presence of the viral genome. Weaker staining with the sense probe in the same regions demonstrates that the antigenome is also present and that the virus is actively replicating in these regions of the brain.

Conclusion
These results demonstrate that in bees infected with DWV the virus is replicating in critical regions of the brain, including the neuropils responsible for vision and olfaction. Therefore DWV infection of the brain could adversely affect critical sensory functions and alter normal bee behavior.
Combined effects of hyperglycemic conditions and HIV-1 Nef: a potential model for induced HIV neuropathogenesis
Authors: Acheampong Edward A , Roschel Cassandra , Mukhtar Muhammad , Srinivasan Alagarsamy , Rafi Mohammad , Pomerantz Roger J , Parveen Zahida 
Published: October 2009

AbstractHyperglycemic conditions associated with diabetes mellitus (DM) or with the use of antiretroviral therapy may increase the risk of central nervous system (CNS) disorders in HIV-1 infected patients. In support of this hypothesis, we investigated the combined effects of hyperglycemic conditions and HIV-1 accessory protein Nef on the CNS using bothin vitroandin vivomodels. Astrocytes, the most abundant glial cell type required for normal synaptic transmission and other functions were selected for ourin vitrostudy. The results show thatin vitrohyperglycemic conditions enhance the expression of proinflammatory cytokines including caspase-3, complement factor 3 (C3), and the production of total nitrate and 8-iso-PGF2 α as reactive oxygen species (ROS) in human astrocytes leading to cell death in a dose-dependent manner. Delivery of purified recombinant HIV-1 Nef protein, or Nef expressed via HIV-1-based vectors in astrocytes showed similar results. The expression of Nef protein delivered via HIV-1 vectors in combination with hyperglycemia further augmented the production of ROS, C3, activation of caspase-3, modulation of filamentous protein (F-protein), depolarization of the mitochondria, and loss of astrocytes. To further verify the effects of hyperglycemia and HIV-1 Nef protein on CNS individually or in combination,in vivostudies were performed in streptozotocin (STZ) induced diabetic mice, by injecting HIV-1 Nef expressing viral particles into the sub-cortical region of the brain. Ourin vivoresults were similar toin vitrofindings indicating an enhanced production of caspases-3, ROS (lipid oxidation and total nitrate), and C3 in the brain tissues of these animals. Interestingly, the delivery of HIV-1 Nef protein alone caused similar damage to CNS as augmented by hyperglycemia conditions. Taken together, the data suggests that HIV-1 infected individuals with hyperglycemia could potentially be at a higher risk of developing CNS related complications.
Transparency in Nigeria's public pharmaceutical sector: perceptions from policy makers
Authors: Garuba Habibat A , Kohler Jillian C , Huisman Anna M 
Published: October 2009

Abstract

Background
Pharmaceuticals are an integral component of health care systems worldwide, thus, regulatory weaknesses in governance of the pharmaceutical system negatively impact health outcomes especially in developing countries [1]. Nigeria is one of a number of countries whose pharmaceutical system has been impacted by corruption and has struggled to curtail the production and trafficking of substandard drugs. In 2001, the National Agency for Food and Drug Administration and Control (NAFDAC) underwent an organizational restructuring resulting in reforms to reduce counterfeit drugs and better regulate pharmaceuticals [2]. Despite these changes, there is still room for improvement. This study assessed the perceived level of transparency and potential vulnerability to corruption that exists in four essential areas of Nigeria's pharmaceutical sector: registration, procurement, inspection (divided into inspection of ports and of establishments), and distribution.

Methods
Standardized questionnaires were adapted from the World Health Organization assessment tool and used in semi-structured interviews with key stakeholders in the public and private pharmaceutical system. The responses to the questions were tallied and converted to scores on a numerical scale where lower scores suggested greater vulnerability to corruption and higher scores suggested lower vulnerability.

Results
The overall score for Nigeria's pharmaceutical system was 7.4 out of 10, indicating a system that is marginally vulnerable to corruption. The weakest links were the areas of drug registration and inspection of ports. Analysis of the qualitative results revealed that the perceived level of corruption did not always match the qualitative evidence.

Conclusion
Despite the many reported reforms instituted by NAFDAC, the study findings suggest that facets of the pharmaceutical system in Nigeria remain fairly vulnerable to corruption. The most glaring deficiency seems to be the absence of conflict of interest guidelines which, if present and consistently administered, limit the promulgation of corrupt practices. Other major contributing factors are the inconsistency in documentation of procedures, lack of public availability of such documentation, and inadequacies in monitoring and evaluation. What is most critical from this study is the identification of areas that still remain permeable to corruption and, perhaps, where more appropriate checks and balances are needed from the Nigerian government and the international community.
Occlusion of the common femoral artery by cement after total hip arthroplasty: a case report
Authors: Reilingh Mikel L , Hartemink Koen J , Hoksbergen Arjan WJ , Saouti Rachid 
Published: October 2009

Abstract

Introduction
The incidence of vascular injuries after total hip arthroplasty is extremely low. In this report we describe an unusual injury to the common femoral artery.

Case presentation
A 59-year-old Caucasian woman presented with rest pain, numbness and cramps in the operated limb after hip replacement. Cement leakage under the transverse ligament had caused occlusion of the common femoral artery necessitating vascular reconstruction. She had a good functional recovery at follow-up.

Conclusion
To the best of our knowledge, this is the first well-documented case reporting this pathomechanism of vascular lesion to the femoral artery. This case report highlights the potential risk of such a limb-threatening complication, and awareness should lead to prevention by meticulous surgical technique (correct technique of pressurization) or to early detection of the lesion.
A Rasch Analysis of the Manchester Foot Pain and Disability Index
Authors: Muller Sara , Roddy Edward 
Published: October 2009

AbstractBackgroundThere is currently no interval‐level measure of foot‐related disability and this has hampered research in this area. The Manchester Foot Pain and Disability Index (FPDI) could potentially fill this gap.ObjectiveTo assess the fit of the three subscales (function, pain, appearance) of the FPDI to the Rasch unidimensional measurement model in order to form interval‐level scores.MethodsA two‐stage postal survey at a general practice in the UK collected data from 149 adults aged 50 years and over with foot pain. The 17 FPDI items, in three subscales, were assessed for their fit to the Rasch model. Checks were carried out for differential item functioning by age and gender.ResultsThe function and pain items fit the Rasch model and interval‐level scores can be constructed. There were too few people without extreme scores on the appearance subscale to allow fit to the Rasch model to be tested.ConclusionThe items from the FPDI function and pain subscales can be used to obtain interval level scores for these factors for use in future research studies in older adults. Further work is needed to establish the interval nature of these subscale scores in more diverse populations and to establish the measurement properties of these interval‐level scores.
Utilisation of podiatry services in Australia under the Medicare Enhanced Primary Care program, 2004‐2008
Authors: Menz Hylton B 
Published: October 2009

AbstractBackgroundIn 2004, as an extension of the Enhanced Primary Care (EPC) program, the Australian Government introduced a policy of providing Medicare rebates for allied health services provided to patients with chronic or complex health conditions. The objective of this study was to evaluate the utilisation of podiatry services provided under this scheme between 2004 and 2008.MethodsData pertaining to the Medicare item 10962 for the calendar years 2004‐2008 were extracted from the Australian Medicare Benefits Schedule (MBS) database and cross‐tabulated by sex and age. Descriptive analyses were undertaken to assess sex and age differences in the number of consultations provided and to assess for temporal trends over the five‐year assessment period. The total cost to Medicare over this period was also determined.ResultsDuring the 2004‐2008 period, a total of 1,338,044 EPC consultations were provided by podiatrists in Australia. Females exhibited higher utilisation than males (63 versus 37%), and those aged over 65 years accounted for 75% of consultations. There was a marked increase in the number of consultations provided from 2004 to 2008, and the total cost of providing EPC podiatry services during this period was $62.9 M.ConclusionPodiatry services have been extensively utilised under the EPC program by primary care patients, particularly older women, and the number of services provided has increased dramatically between 2004 and 2008. Further research is required to determine whether the EPC program enhances clinical outcomes compared to standard practice.
PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro
Authors: Finn Richard S , Dering Judy , Conklin Dylan , Kalous Ondrej , Cohen David J , Desai Amrita J , Ginther Charles , Atefi Mohammad , Chen Isan , Fowst Camilla , Los Gerret , Slamon Dennis J 
Published: October 2009

Abstract
Introduction
Alterations in cell cycle regulators have been implicated in human malignancies including breast cancer. PD 0332991 is an orally active, highly selective inhibitor of the cyclin D kinases (CDK)4 and CDK6 with ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. To identify predictors of response, we determined the in vitro sensitivity to PD 0332991 across a panel of molecularly characterized human breast cancer cell lines.

Methods
Forty-seven human breast cancer and immortalized cell lines representing the known molecular subgroups of breast cancer were treated with PD 0332991 to determine IC50 values. These data were analyzed against baseline gene expression data to identify genes associated with PD 0332991 response.

Results
Cell lines representing luminal estrogen receptor-positive (ER+) subtype (including those that are HER2 amplified) were most sensitive to growth inhibition by PD 0332991 while nonluminal/basal subtypes were most resistant. Analysis of variance identified 450 differentially expressed genes between sensitive and resistant cells. pRb and cyclin D1 were elevated and CDKN2A (p16) was decreased in the most sensitive lines. Cell cycle analysis showed G0/G1 arrest in sensitive cell lines and Western blot analysis demonstrated that Rb phosphorylation is blocked in sensitive lines but not resistant lines. PD 0332991 was synergistic with tamoxifen and trastuzumab in ER+ and HER2-amplified cell lines, respectively. PD 0332991 enhanced sensitivity to tamoxifen in cell lines with conditioned resistance to ER blockade.

Conclusions
These studies suggest a role for CDK4/6 inhibition in some breast cancers and identify criteria for patient selection in clinical studies of PD 0332991.