bluuebunny/crossref_metadata_2025_split huggingface dataset:
The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy
Authors: Dragani Alfredo , Pascale Silvia , Recchiuti Antonio , Mattoscio Domenico , Lattanzio Stefano , Petrucci Giovanna , Mucci Luciana , Ferrante Elisabetta , Habib Aida , Ranelletti Franco O. , Ciabattoni Giovanni , Davì Giovanni , Patrono Carlo , Rocca Bianca 
Published: November 2009

AbstractWe tested whether cyclooxygenase 2 (COX-2) expression and unacetylated COX-1 in newly formed platelets might contribute to persistent thromboxane (TX) biosynthesis in aspirin-treated essential thrombocythemia (ET). Forty-one patients on chronic aspirin (100 mg/day) and 24 healthy subjects were studied. Platelet COX-2 expression was significantly increased in patients and correlated with thiazole orange–positive platelets (r = 0.71, P < .001). The rate of TXA2 biosynthesis in vivo, as reflected by urinary 11-dehydro-TXB2 (TXM) excretion, and the maximal biosynthetic capacity of platelets, as reflected by serum TXB2, were higher in patients compared with aspirin-treated healthy volunteers. Serum TXB2 was significantly reduced by the selective COX-2 inhibitor NS-398 added in vitro. Patients were randomized to adding the selective COX-2 inhibitor, etoricoxib, or continuing aspirin for 7 days. Etoricoxib significantly reduced by approximately 25% TXM excretion and serum TXB2. Fourteen of the 41 patients were studied again 21 (± 7) months after the first visit. Serum TXB2 was consistently reduced by approximately 30% by adding NS398 in vitro, while it was completely suppressed with 50μM aspirin. Accelerated platelet regeneration in most aspirin-treated ET patients may explain aspirin-persistent TXA2 biosynthesis through enhanced COX-2 activity and faster renewal of unacetylated COX-1. These findings may help in reassessing the optimal antiplatelet strategy in ET.
Osteoclasts are important for bone angiogenesis
Authors: Cackowski Frank C. , Anderson Judith L. , Patrene Kenneth D. , Choksi Rushir J. , Shapiro Steven D. , Windle Jolene J. , Blair Harry C. , Roodman G. David 
Published: November 2009

Abstract
Increased osteoclastogenesis and angiogenesis occur in physiologic and pathologic conditions. However, it is unclear if or how these processes are linked. To test the hypothesis that osteoclasts stimulate angiogenesis, we modulated osteoclast formation in fetal mouse metatarsal explants or in adult mice and determined the effect on angiogenesis. Suppression of osteoclast formation with osteoprotegerin dose-dependently inhibited angiogenesis and osteoclastogenesis in metatarsal explants. Conversely, treatment with parathyroid hormone related protein (PTHrP) increased explant angiogenesis, which was completely blocked by osteoprotegerin. Further, treatment of mice with receptor activator of nuclear factor-κB ligand (RANKL) or PTHrP in vivo increased calvarial vessel density and osteoclast number. We next determined whether matrix metalloproteinase-9 (MMP-9), an angiogenic factor predominantly produced by osteoclasts in bone, was important for osteoclast-stimulated angiogenesis. The pro-angiogenic effects of PTHrP or RANKL were absent in metatarsal explants or calvaria in vivo, respectively, from Mmp9−/− mice, demonstrating the importance of MMP-9 for osteoclast-stimulated angiogenesis. Lack of MMP-9 decreased osteoclast numbers and abrogated angiogenesis in response to PTHrP or RANKL in explants and in vivo but did not decrease osteoclast differentiation in vitro. Thus, MMP-9 modulates osteoclast-stimulated angiogenesis primarily by affecting osteoclasts, most probably by previously reported migratory effects on osteoclasts. These results clearly demonstrate that osteoclasts stimulate angiogenesis in vivo through MMP-9.
Circulating levels of matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and their complex MMP-9/NGAL in breast cancer disease
Authors: Provatopoulou Xeni , Gounaris Antonia , Kalogera Eleni , Zagouri Flora , Flessas Ioannis , Goussetis Evgenios , Nonni Afroditi , Papassotiriou Ioannis , Zografos George 
Published: November 2009

Abstract

Background
Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity.

Methods
The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays.

Results
Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01). Significant correlations were observed between MMP-9 and NGAL serum levels and breast disease severity score (r = 0.229, p < 0.006 and r = 0.206, p < 0.01, respectively), whereas a non-significant correlation was found for their complex. MMP-9, NGAL and their complex MMP-9/NGAL levels were not correlated with either Body Mass Index (BMI) or age of patients.

Conclusion
These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.
Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitro
Authors: Aljofan Mohamad , Sganga Michael L , Lo Michael K , Rootes Christina L , Porotto Matteo , Meyer Adam G , Saubern Simon , Moscona Anne , Mungall Bruce A 
Published: November 2009

AbstractBackgroundUsing a recently described monolayer assay amenable to high throughput screening format for the identification of potential Nipah virus and Hendra virus antivirals, we have partially screened a low molecular weight compound library (>8,000 compounds) directly against live virus infection and identified twenty eight promising lead molecules. Initial single blind screens were conducted with 10 μM compound in triplicate with a minimum efficacy of 90% required for lead selection. Lead compounds were then further characterised to determine the median efficacy (IC50), cytotoxicity (CC50) and thein vitrotherapeutic index in live virus and pseudotype assay formats.ResultsWhile a number of leads were identified, the current work describes three commercially available compounds: brilliant green, gentian violet and gliotoxin, identified as having potent antiviral activity against Nipah and Hendra virus. Similar efficacy was observed against pseudotyped Nipah and Hendra virus, vesicular stomatitis virus and human parainfluenza virus type 3 while only gliotoxin inhibited an influenza A virus suggesting a non-specific, broad spectrum activity for this compound.ConclusionAll three of these compounds have been used previously for various aspects of anti-bacterial and anti-fungal therapy and the current results suggest that while unsuitable for internal administration, they may be amenable to topical antiviral applications, or as disinfectants and provide excellent positive controls for future studies.
Human cases of simultaneous echinococcosis and tuberculosis - significance and extent in China
Authors: Yang Yu Rong , Gray Darren J , Ellis Magda K , Yang Shu Kun , Craig Philip S , McManus Donald P 
Published: November 2009

Abstract
During analysis of retrospective community survey data, we identified two patients from Xiji County, south Ningxia Hui Autonomous Region with simultaneous echinococcosis and tuberculosis (TB), representing the first such reports for China. As the echinococcosis chronicity increased, the immune profile in both subjects changed from a Th1 to Th2 response, as shown by a TB skin test, originally positive, becoming negative. Such an elevated Th2 immune profile, with subsequent suppression of the Th1 immune response, is a common feature of chronic helminth infections. Given the difficulties in definitive diagnosis, and the potential increased susceptibility for TB infection in patients with advanced echinococcosis, we suggest that combined TB/echinococcosis surveys be undertaken in this area in the future. This would allow early diagnosis of both TB and echinococcosis cases with better prognosis for effective and sustainable treatment outcomes, ultimately reducing associated morbidity and mortality, and also the overall financial costs to the individual and the public health care system in this under developed part of China.
The molecular basis for stability of heterochromatin-mediated silencing in mammals
Authors: Hiragami-Hamada Kyoko , Xie Sheila Q , Saveliev Alexander , Uribe-Lewis Santiago , Pombo Ana , Festenstein Richard 
Published: November 2009

Abstract
The archetypal epigenetic phenomenon of position effect variegation (PEV) in Drosophila occurs when a gene is brought abnormally close to heterochromatin, resulting in stochastic silencing of the affected gene in a proportion of cells that would normally express it. PEV has been instrumental in unraveling epigenetic mechanisms. Using an in vivo mammalian model for PEV we have extensively investigated the molecular basis for heterochromatin-mediated gene silencing. Here we distinguish 'epigenetic effects' from other cellular differences by studying ex vivo cells that are identical, apart from the expression of the variegating gene which is silenced in a proportion of the cells. By separating cells according to transgene expression we show here that silencing appears to be associated with histone H3 lysine 9 trimethylation (H3K9me3), DNA methylation and the localization of the silenced gene to a specific nuclear compartment enriched in these modifications. In contrast, histone H3 acetylation (H3Ac) and lysine 4 di or tri methylation (H3K4me2/3) are the predominant modifications associated with expression where we see the gene in a euchromatic compartment. Interestingly, DNA methylation and inaccessibility, rather than H3K9me3, correlated most strongly with resistance to de-repression by cellular activation. These results have important implications for understanding the contribution of specific factors involved in the establishment and maintenance of gene silencing and activation in vivo.
Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion
Authors: Cohen Mitchell J , Brohi Karim , Calfee Carolyn S , Rahn Pamela , Chesebro Brian B , Christiaans Sarah C , Carles Michel , Howard Marybeth , Pittet Jean-François 
Published: November 2009

Abstract
Introduction
High mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not known and therefore constitutes the aim of the present study.

Methods
One hundred sixty eight patients were studied as part of a prospective cohort study of severe trauma patients admitted to a single Level 1 Trauma center. Blood was drawn within 10 minutes of arrival to the emergency room before the administration of any fluid resuscitation. HMGB1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, von Willebrand Factor (vWF), angiopoietin-2 (Ang-2), Prothrombin time (PT), prothrombin fragments 1+2 (PF1+2), soluble thrombomodulin (sTM), protein C (PC), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and D-Dimers were measured using standard techniques. Base deficit was used as a measure of tissue hypoperfusion. Measurements were compared to outcome measures obtained from the electronic medical record and trauma registry.

Results
Plasma levels of HMGB1 were increased within 30 minutes after severe trauma in humans and correlated with the severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and hyperfibrinolysis as well with a systemic inflammatory response and activation of complement. Non-survivors had significantly higher plasma levels of HMGB1 than survivors. Finally, patients who later developed organ injury, (acute lung injury and acute renal failure) had also significantly higher plasma levels of HMGB1 early after trauma.

Conclusions
The results of this study demonstrate for the first time that HMGB1 is released into the bloodstream early after severe trauma in humans. The release of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response.
Correlation between parameters at initiation of renal replacement therapy and outcome in patients with acute kidney injury
Authors: Ostermann Marlies , Chang René WS 
Published: November 2009

Abstract
Introduction
Renal replacement therapy (RRT) is a fully established treatment for critically ill patients with acute kidney injury (AKI) but there are no scientifically established criteria when to initiate it. Our objectives were to describe the epidemiology of critically ill patients with AKI receiving RRT and to evaluate the relationship between biochemical, physiological and comorbid factors at time of RRT and ICU mortality.

Methods
Retrospective analysis of demographic and physiologic data of 1,847 patients who received RRT for AKI in 22 ICUs in UK and Germany between 1989 - 1999.

Results
54.1% of RRT patients died in ICU. ICU survivors were younger, had a lower APACHE II score and fewer failed organ systems on admission to ICU compared to non-survivors. Multivariate analysis showed that at time of initiation of RRT, independent risk factors for ICU mortality were mechanical ventilation [odds ratio (OR) 6.03], neurological failure (OR 2.48), liver failure (OR 2.44), gastrointestinal failure (OR 2.04), pre-existing chronic illnesses (OR 1.74), haematological failure (OR 1.74), respiratory failure (OR 1.62), oligoanuria (OR 1.6), age (OR 1.03), serum urea (OR 1.004) and cardiovascular failure (OR 1.3). A higher pH at initiation of RRT was independently associated with a better outcome. Failure to correct acidosis and development of more organ failure within 48 hours after initiation of RRT were also associated with an increased risk of dying in ICU.

Conclusions
Oligoanuria, acidosis and concomitant dysfunction of other organs at time of RRT were associated with poor survival. In contrast, serum creatinine and urea levels only had a weak correlation with outcome after RRT.
Rerouting of a Follicle-Stimulating Hormone Analog to the Regulated Secretory Pathway
Authors: Pearl Christopher A. , Jablonka-Shariff Albina , Boime Irving 
Published: November 2009

AbstractLH and FSH are produced by the same gonadotrope cells of the anterior pituitary but differ in their mode of secretion. This coordinated secretion of LH and FSH is essential for normal follicular development and ovulation in females and for spermatogenesis in males. The structural signals encoded in the LH and FSH subunits that govern the intracellular sorting of LH through the regulated secretory pathway and FSH through the constitutive pathway are largely unknown. Our laboratory recently identified the seven amino acid carboxy tail of LHβ as a sorting signal for LH in GH3 cells. Here we compared the morphological features of GH3 cells expressing an FSH analog containing the heptapeptide (FL7AA) with wild-type FSH using confocal microscopy. These experiments were performed to develop a rerouting model for examining structure-function links between secretion pathways of FSH/LH and their biological action. Both FSH- and LH-expressing cells exhibit a fluorescence pattern of randomly dispersed cytoplasmic puncta. FL7AA expressing cells have more intracellular accumulation compared with wild-type FSH and display a unique halo pattern of fluorescence near the plasma membrane. Such a pattern was not observed in cells expressing FSH or LH. Our results demonstrate that this FSH analog containing the carboxy heptapeptide of LHβ is rerouted to the regulated secretory pathway in GH3 cells. This rerouted gonadotropin provides a unique model to study the trafficking, regulation, and function of LH and FSH.
Insulin Sensitization of Human Preadipocytes through Glucocorticoid Hormone Induction of Forkhead Transcription Factors
Authors: Tomlinson Julianna J. , Boudreau Adèle , Wu Dongmei , Salem Houssein Abdou , Carrigan Amanda , Gagnon Annemarie , Mears Alan J. , Sorisky Alexander , Atlas Ella , Haché Robert J. G. 
Published: November 2009

AbstractGlucocorticoids are synthesized locally in adipose tissue and contribute to metabolic disease through the facilitation of adipose tissue expansion. Here we report that exposure of human primary preadipocytes to glucocorticoids increases their sensitivity to insulin and enhances their subsequent response to stimuli that promote differentiation. This effect was observed in primary human preadipocytes but not in immortalized 3T3-L1 murine preadipocytes or in fully differentiated primary human adipocytes. Stimulation of insulin signaling was mediated through induction of insulin receptor (IR), IR substrate protein 1 (IRS1), IRS2, and the p85 regulatory subunit of phosphoinositide-3-3-kinase, which led to enhanced insulin-mediated activation of Akt. Although induction of IRS2 was direct, induction of IR and IRS1 by glucocorticoids occurred subsequent to primary induction of the forkhead family transcription factors FoxO1A and FoxO3A. These results reveal a new role for glucocorticoids in preparing preadipocytes for differentiation.
Prevalence and Risk Factors for Acute Kidney Injury Associated with Parenteral Polymyxin B Use
Authors: Mendes Carlos AC , Cordeiro José A , Burdmann Emmanuel A 
Published: November 2009

Background: The main adverse effect of polymyxin B is nephrotoxicity. There are few data on polymyxin-associated renal injury. Objective: To assess the prevalence of and risk factors for acute kidney injury (AKI) in patients treated with polymyxin B. Methods: The studied population included 114 patients who received at least 3 consecutive days of intravenous polymyxin B and had baseline serum creatinine (SCr) and at least one further SCr measurement during treatment. AKI was defined as an SCr increase to 1.8 mg/dL or greater in patients with baseline SCr less than 1.5 mg/dL, or an increase greater than or equal to 50% in baseline SCr when it was already greater than or equal to 1.5 mg/dL, or need for dialysis. Results: AKI developed in 22% of the patients. They were older, had a higher baseline SCr, had a higher frequency of baseline SCr greater than or equal to 1.5 mg/dL, used other nephrotoxic drugs and furosemide more often, and required vasoactive drugs and mechanical ventilation more frequently. Progression to renal failure was significantly more probable when the bacteria were isolated in the abdomen, catheter, or blood. AKI patients had a higher mortality rate (92% vs 53%; p < 0.001). Logistic regression identified abnormal baseline SCr (odds ratio [OR] 3.51); need for vasoactive drugs (OR 3.03); and abdomen, blood, or catheter as the infection site (OR 3.82) as independent risk factors for AKI. Conclusions: Patients who developed AKI had a strikingly elevated mortality rate. Polymyxin B should be used with extreme caution in patients who have an abnormal baseline SCr; use vasoactive drugs; or have abdomen, blood, or catheter as the infection site.
Sexual dimorphism in cortical bone size and strength but not density is determined by independent and time-specific actions of sex steroids and IGF-1: Evidence from pubertal mouse models
Authors: Callewaert Filip , Venken Katrien , Kopchick John J , Torcasio Antonia , van Lenthe G Harry , Boonen Steven , Vanderschueren Dirk 
Published: November 2009

Abstract
Although it is well established that males acquire more bone mass than females, the underlying mechanism and timing of this sex difference remain controversial. The aim of this study was to assess the relative contribution of sex steroid versus growth hormone–insulin-like growth factor 1 (GH–IGF-1) action to pubertal bone mass acquisition longitudinally in pubertal mice. Radial bone expansion peaked during early puberty (3 to 5 weeks of age) in male and female mice, with significantly more expansion in males than in females (+40%). Concomitantly, in 5 week old male versus female mice, periosteal and endocortical bone formation was higher (+70%) and lower (−47%), respectively, along with higher serum IGF-1 levels during early puberty in male mice. In female mice, ovariectomy increased radial bone expansion during early puberty as well as the endocortical perimeter. In male mice, orchidectomy reduced radial bone expansion only during late puberty (5 to 8 weeks of age), whereas combined androgen and estrogen deficiency modestly decreased radial bone expansion during early puberty, accompanied by lower IGF-1 levels. GHRKO mice with very low IGF-1 levels, on the other hand, showed limited radial bone expansion and no skeletal dimorphism. From these data we conclude that skeletal sexual dimorphism is established during early puberty and depends primarily on GH–IGF-1 action. In males, androgens and estrogens have stimulatory effects on bone size during late and early puberty, respectively. In females, estrogens limit bone size during early puberty. These longitudinal findings in mice provide strong evidence that skeletal dimorphism is determined by independent and time-specific effects of sex steroids and IGF-1. © 2010 American Society for Bone and Mineral Research
Globalization and African cinema: distribution and reception in the anglophone region
Authors: Mhando Martin 
Published: November 2009

When Tommy Lott advanced his 'no-theory theory' on the definition of black cinema, he argued that a theory remains a theory only up to the time when the meanings it advances 'are no longer applicable'. He was aware of the complexity of theorizing on an ongoing activity based on an essentialized
notion.
What I see as a possible arena of contention and re-theorizing is the versatility of cultures in appropriating processes of knowledge distribution. What I am advocating here is seeing the film and video distribution practices that continue to grow in Africa as loci of sociological
and ontological questionings. Is the experience of media within cultures dependent on exposure to western media concepts? Isn't exposure itself merely a limited rather than a limiting experience? How far are 'appropriations' related to media sociality? How do community media express themselves
outside the boundaries of expectations and definitions of authoritative media?