bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parametric simulation of drug release from hydrogel-based matrices
Authors: Lamberti Gaetano 
Published: November 2011

Abstract

Objectives
In this work a model recently proposed to describe the drug release from hydrogel-based matrices was applied to describe the fractional drug release from matrices based on hydroxypropylmethylcellulose (HPMC) and diclofenac.

Methods
The model, firstly proposed to describe the behaviour of systems based on HPMC and theophylline and a single set of preparation variables, is based on mass balances and transport phenomena evaluation and it was solved by an FEM-based numerical code. The experimental data on the HPMC–diclofenac matrices, taken from literature, have been obtained by varying the drug loading ratio, the compression force, the powder size of both the drug and the polymer.

Key findings
A good agreement between experimental data and model predictions, as calculated in the present work, was obtained without the use of any adjustable parameters.

Conclusions
The predictive nature of the model has been confirmed, even changing the drug molecule and other preparative parameters.
Nicotine and vascular endothelial dysfunction in female ovariectomized rats: role of estrogen replacement therapy
Authors: El-Seweidy Mohamed M , Mohamed Hoda E , Asker Mervat E , Atteia Hebatallah H 
Published: November 2011

Abstract

Objectives
The protective effects of estrogen replacement therapy (ERT) against oxidative injury and endothelial dysfunction in the aortic tissues induced with nicotine in ovariectomized (OVX) rats were investigated.

Methods
Female rats were divided into a sham-operated group (n = 8) and four groups in which OVX rats received either vehicle (0.1 ml sesame oil, i.m., n = 8), or nicotine (0.1 mg/kg, s.c., n = 8), or estradiol benzoate (0.1 mg/kg, i.m., n = 8), or both nicotine and estradiol benzoate (n = 8) starting at week 5 after the surgery and continuing for the following 6 weeks.

Key findings
ERT was effective in preventing the rise in plasma lipid profile, atherogenic index and the level of induced endothelin-1 (ET-1) in nicotine-treated OVX rats. It also reduced aortic malondialdehyde, hydroxyproline levels, calcium content and caspase-3 expression induced in nicotine-treated OVX rats. ERT increased serum estradiol, high-density lipoprotein cholesterol and nitric oxide levels in nicotine-treated OVX rats. Furthermore, ERT was effective in restoring reduced glutathione and cyclic guanosine monophosphate contents and endothelial nitric oxide synthase expression in aortic tissues of nicotine-treated OVX rats.

Conclusions
Short-term ERT could be a promising therapeutic strategy to minimize nicotine-induced oxidative stress and vascular endothelial dysfunction in menopausal women subjected to environmental smoke.
In VitroPhenotypic Susceptibility of HIV-2 Clinical Isolates to CCR5 Inhibitors
Authors: Visseaux Benoit , Charpentier Charlotte , Hurtado-Nedelec Margarita , Storto Alexandre , Antoine Romain , Peytavin Gilles , Damond Florence , Matheron Sophie , Brun-Vézinet Françoise , Descamps Diane ,   the French ANRS HIV-2 Cohort (ANRS CO 05 VIH-2)
Published: November 2011

ABSTRACTHIV-2 is naturally resistant to nonnucleoside reverse transcriptase inhibitors, to a fusion inhibitor, and to some of the protease inhibitors. Maraviroc is the first drug of the new anti-CCR5 drug class and is effective only on CCR5-tropic (R5) HIV-1. No previous studies concerning HIV-2 susceptibility to maraviroc have been reported yet. We developed a phenotypic maraviroc susceptibility test using a peripheral blood mononuclear cell (PBMC) model. We analyzed the maraviroc susceptibility of 13 R5 HIV-2, 2 X4R5 (dual) HIV-2, and 2 CXCR4-tropic (X4) HIV-2 clinical isolates. We also tested, with the same protocol, 1 X4 HIV-1 and 4 R5 HIV-1 clinical isolates. For the R5 HIV-2 clinical isolates, the 50% effective concentration (EC50) for maraviroc was 0.80 nM (interquartile range [IQR], 0.48 to 1.39 nM), similar to that observed for the R5 HIV-1 isolates. The median maximum percentage of inhibition in the R5 HIV-2 isolates was 93% (IQR, 84 to 98%), similar to that observed in the R5 HIV-1 isolates. As expected, both X4 HIV-1 and HIV-2 were highly resistant to maraviroc. Our study showed for the first time that maraviroc is activein vitroagainst R5 HIV-2. The new tools we developed will allow identification of HIV-2-infected patients eligible for CCR5 inhibitor use and management of virological failure when receiving a maraviroc-based regimen.
Characteristics and capabilities of emergency departments in Abuja, Nigeria
Authors: Wen Leana S , Oshiomogho John I , Eluwa George I , Steptoe Anne P , Sullivan Ashley F , Camargo Carlos A 
Published: November 2011

ObjectivesEmergency departments (ED) are the basic unit of international emergency medicine, but often differ in fundamental features. This study sought to describe and characterise ED in the capital city of Nigeria, Abuja.MethodsAll ED open 24 h/day 7 days/week to the general public were surveyed using the national ED inventories survey instrument (http://www.emnet-nedi.org). ED staff were asked about ED characteristics with reference to calendar year 2008.ResultsTwenty-four ED participated (83% response). All were located in hospitals, which ranged in size from six to 250 beds. The majority (92% CI 73% to 100%) had a contiguous layout with medical and surgical care provided in one area. All ED saw both adults and children, with a median of 1500 annual visits (IQR 648–2328). Almost half of respondents (46%; CI 26% to 67%) thought their ED operated under capacity, none thought that their ED was over capacity. Only 4% of ED surveyed had dedicated CT scanners, 25% had cardiac monitoring and none had negative-pressure rooms. There was wide variation in the types of emergencies that were identified as being treatable 24 h/day 7 days/week; these appeared to correlate with ED consultant availability.ConclusionsAlthough ED location and layout in Abuja do not differ greatly from that in a typical US city, ED utilisation was lower and fewer resources and capabilities were available. The lack of technological and human resources raise questions about what critical technologies are needed in resource-limited settings, and whether Nigeria should consider training emergency medicine physicians to meet its workforce needs.
Epidemiological transition in a rural community of northern India: 18-year mortality surveillance using verbal autopsy
Authors: Kumar Rajesh , Kumar Dinesh , Jagnoor J , Aggarwal Arun K , Lakshmi P V M 
Published: November 2011

BackgroundInformation on causes of death is vital for planning of health services. However, vital events registration systems are weak in developing countries. Therefore, verbal autopsy (VA) tools were incorporated in a community-based surveillance system to track causes of death.Method and FindingsTrained fieldworker identified all deaths and interviewed a living relative of those who had died during 1992–2009, using VA, in eight villages of Haryana (11 864 populations). These field reports detailing events preceding death were reviewed by two trained physicians, who independently assigned an International Classification of Disease-10 code to each death. Discrepancies were resolved through reconciliation and, if necessary, adjudication. Non-communicable conditions were the leading causes of death (47.6%) followed by communicable diseases including maternal, perinatal and nutritional conditions (34.0%), and injuries (11.4%). Cause of death could not be determined in 6.9% cases. Deaths due to cardiovascular diseases showed a significant rise, whereas deaths due to diarrhoeal diseases have declined (p<0.01). Majority (90.0%) of the deceased had contacted a healthcare provider during illness but only 11.5% were admitted in hospital before death.ConclusionRising trend of cardiovascular diseases observed in a rural community of Haryana in India calls for reorientation of rural healthcare delivery system for prevention and control of chronic diseases.
Controversies and advances in non-steroidal anti-inflammatory drug (NSAID) analgesia in chronic pain management
Authors: Shah Seema , Mehta Vivek 
Published: November 2011

Abstract
Chronic pain can lead to significant disability with social and economic implications in the community. Traditional non-steroidal anti-inflammatory drugs (NSAIDs) have been part of the management of chronic pain. The risk of adverse events with traditional NSAIDs has led to the development of alternative therapeutic options. Differential blockade of the enzymes involved in pain and inflammation can offer therapeutic options without the gastrointestinal side effects. However, this may be at the expense of other major cardiovascular side effects. Pain pathways that involve peripheral transmission may be altered by local application of analgesia to the skin overlying the painful area. Recent guidelines for osteoarthritis treatment from the National Institute for Health and Clinical Excellence highlight the importance of topical NSAIDs in the armamentarium of pain management. NSAID combination drugs with gastric protection have provided alternatives to traditional NSAIDs, but the long term sequelae are unknown.
Concentrations of mercury and polychlorinated biphenyls in blood of Southern Beaufort Sea polar bears (Ursus maritimus) during spring: variations with lipids and stable isotope (δ15N, δ13C) values
Authors: Knott Katrina K. , Boyd Daryle , Ylitalo Gina M. , O’Hara Todd M. 
Published: November 2011

Polar bears ( Ursus maritimus Phipps, 1774) are exposed to heavy metal and lipophilic contaminants that are known to bioaccumulate and biomagnify. Few studies concurrently report both chemical classes in the same individuals and are thus unable to assess drivers of observed tissue concentrations, and the potential adverse biological responses to combined exposures. We examined blood concentrations of mercury (Hg) and the sum of seven polychlorinated biphenyls (Σ7PCB) from free-ranging Southern Beaufort Sea polar bears to assess which factors contributed to variations among cohorts (adult males, adult females, young) during spring. Concentrations of Hg ranged from 10.3 to 228.0 ng/g wet mass, but mean concentrations were similar between males and females independent of age. Concentrations of Σ7PCB (range 2.0–132.8 ng/g wet mass) were greater among females and young than among males. Toxicant concentrations were related to packed cell δ15N, an estimate of trophic position, after the inclusion of packed cell δ13C. Concentrations of Σ7PCB were also positively correlated with concentrations of neutral lipids (triglycerides and free fatty acids) and inversely correlated to body condition indices. Elevated concentrations of toxicants and lower body condition indices in females and young compared with males may be a sentinel to a changing arctic environment. Further assessment of the potential adverse health impacts of contaminants and nutritional stress in these cohorts is warranted.
Modulation of the Tumor Microvasculature by Phosphoinositide-3 Kinase Inhibition Increases Doxorubicin Delivery In Vivo
Authors: Qayum Naseer , Im Jaehong , Stratford Michael R. , Bernhard Eric J. , McKenna W. Gillies , Muschel Ruth J. 
Published: November 2011

Abstract
Purpose: Because effective drug delivery is often limited by inadequate vasculature within the tumor, the ability to modulate the tumor microenvironment is one strategy that may achieve better drug distribution. We have previously shown that treatment of mice bearing tumors with phosphoinositide-3 kinase (PI3K) inhibitors alters vascular structure in a manner analogous to vascular normalization and results in increased perfusion of the tumor. On the basis of that result, we asked whether inhibition of PI3K would improve chemotherapy delivery.
Experimental Design: Mice with xenografts using the cell line SQ20B bearing a hypoxia marker or MMTV-neu transgenic mice with spontaneous breast tumors were treated with the class I PI3K inhibitor GDC-0941. The tumor vasculature was evaluated by Doppler ultrasound, and histology. The delivery of doxorubicin was assessed using whole animal fluorescence, distribution on histologic sections, high-performance liquid chromatography on tumor lysates, and tumor growth delay.
Results: Treatment with GDC-0941 led to approximately three-fold increases in perfusion, substantially reduced hypoxia and vascular normalization by histology. Significantly increased amounts of doxorubicin were delivered to the tumors correlating with synergistic tumor growth delay. The GDC-0941 itself had no effect on tumor growth.
Conclusion: Inhibition of PI3K led to vascular normalization and improved delivery of a chemotherapeutic agent. This study highlights the importance of the microvascular effects of some novel oncogenic signaling inhibitors and the need to take those changes into account in the design of clinical trials many of which use combinations of chemotherapeutic agents. Clin Cancer Res; 18(1); 161–9. ©2011 AACR.
Inhibition of p38 MAPK-Dependent Excision Repair Cross-Complementing 1 Expression Decreases the DNA Repair Capacity to Sensitize Lung Cancer Cells to Etoposide
Authors: Tsai Min-Shao , Weng Shao-Hsing , Chen Huang-Jen , Chiu Yu-Fan , Huang Yu-Ching , Tseng Sheng-Chieh , Kuo Ya-Hsun , Lin Yun-Wei 
Published: November 2011

Abstract
Etoposide (VP-16), a topoisomerase II inhibitor, is an effective anticancer drug currently used for the treatment of a wide range of cancers. Excision repair cross-complementary 1 (ERCC1) is a key protein involved in the process of nucleotide excision repair. High level of ERCC1 expression in cancers is associated with resistance to DNA damage-based chemotherapy. In this study, the effects of p38 mitogen-activated protein kinase (MAPK) signal on the ERCC1 expression induced by etoposide in non–small cell lung cancer (NSCLC) cell lines was investigated. Etoposide increased phosphorylated MAPK kinase 3/6 (MKK3/6)-p38 MAPK and ERCC1 protein and mRNA levels in A549 and H1975 cells. Moreover, SB202190, a p38 inhibitor, or knockdown of p38 expression by specific short interfering RNA (siRNA) significantly decreased the etoposide-induced ERCC1 protein levels and DNA repair capacity in etoposide-exposed NSCLC cells. Enhancement of p38 activation by constitutively active MKK6 (MKK6E) increased ERCC1 protein levels. Specific inhibition of ERCC1 by siRNA significantly enhanced the etoposide-induced cytotoxicity and hypoxanthine guanine phosphoribosyltransferase (hprt) gene mutation rate. Moreover, the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) could decrease the etoposide-induced p38 MAPK-mediated ERCC1 expression and augment the cytotoxic effect and growth inhibition by etopsoside. 17-AAG and etoposide-induced synergistic cytotoxic effect and DNA repair capacity decrease could be abrogated in lung cancer cells with MKK6E or HA-p38 MAPK expression vector transfection. Our results suggest that in human NSCLC cells, ERCC1 is induced by etoposide through the p38 MAPK pathway, and this phenomenon is required for NSCLC survival and resistant DNA damage. Mol Cancer Ther; 11(3); 561–71. ©2011 AACR.
A Novel Platform for Detection of CK+ and CK− CTCs
Authors: Pecot Chad V. , Bischoff Farideh Z. , Mayer Julie Ann , Wong Karina L. , Pham Tam , Bottsford-Miller Justin , Stone Rebecca L. , Lin Yvonne G. , Jaladurgam Padmavathi , Roh Ju Won , Goodman Blake W. , Merritt William M. , Pircher Tony J. , Mikolajczyk Stephen D. , Nick Alpa M. , Celestino Joseph , Eng Cathy , Ellis Lee M. , Deavers Michael T. , Sood Anil K. 
Published: November 2011

Abstract
Metastasis is a complex, multistep process that begins with the epithelial–mesenchymal transition (EMT). Circulating tumor cells (CTC) are believed to have undergone EMT and thus lack or express low levels of epithelial markers commonly used for enrichment and/or detection of such cells. However, most current CTC detection methods target only EpCAM and/or cytokeratin (CK) to enrich epithelial CTCs, resulting in failure to recognize other, perhaps more important, CTC phenotypes that lack expression of these markers. Here, we describe a population of complex aneuploid CTCs that do not express CK or CD45 antigen in patients with breast, ovarian, or colorectal cancer. These cells were not observed in healthy subjects. We show that the primary epithelial tumors were characterized by similar complex aneuploidy, indicating conversion to an EMT phenotype in the captured cells. Collectively, our study provides a new method for highly efficient capture of previously unrecognized populations of CTCs.
Significance: Current assays for CTC capture likely miss populations of cells that have undergone EMT. Capture and study of CTCs that have undergone EMT would allow a better understanding of the mechanisms driving metastasis. Cancer Discovery; 1(7); 580–86. ©2011 AACR.
This article is highlighted in the In This Issue feature, p. 539
ApoE Suppresses Atherosclerosis by Reducing Lipid Accumulation in Circulating Monocytes and the Expression of Inflammatory Molecules on Monocytes and Vascular Endothelium
Authors: Gaudreault Nathalie , Kumar Nikit , Posada Jessica M. , Stephens Kyle B. , Reyes de Mochel Nabora Soledad , Eberlé Delphine , Olivas Victor R. , Kim Roy Y. , Harms Matthew J. , Johnson Sean , Messina Louis M. , Rapp Joseph H. , Raffai Robert L. 
Published: November 2011

Objective—
We investigated atheroprotective properties of apolipoprotein (apo) E beyond its ability to lower plasma cholesterol. We hypothesized that apoE reduces atherosclerosis by decreasing lipid accumulation in circulating monocytes and the inflammatory state of monocytes and the vascular endothelium.

Methods and Results—

We developed mice with spontaneous hyperlipidemia with and without plasma apoE. Hypomorphic apoE mice deficient in low-density lipoprotein receptor (
Apoe
h/h
Ldlr
−/−
) were compared to
Apoe
−/−
Ldlr
−/−
mice. Despite 4-fold more plasma apoE than WT mice,
Apoe
h/h
Ldlr
−/−
mice displayed similar plasma cholesterol as
Apoe
−/−
Ldlr
−/−
mice but developed 4-fold less atherosclerotic lesions by 5 months of age. The aortic arch of
Apoe
h/h
Ldlr
−/−
mice showed decreased endothelial expression of ICAM-1, PECAM-1, and JAM-A. In addition,
Apoe
h/h
Ldlr
−/−
mice had less circulating leukocytes and proinflammatory Ly6C
high
monocytes. These monocytes had decreased neutral lipid content and reduced surface expression of ICAM-1, VLA-4, and L-Selectin.
Apoe
h/h
Ldlr
−/−
mice displayed increased levels of apoA1-rich HDL that were potent in promoting cellular cholesterol efflux.

Conclusions—
Our findings suggest that apoE reduces atherosclerosis in the setting of hyperlipidemia by increasing plasma apoA1-HDL that likely contribute to reduce intracellular lipid accumulation and thereby the activation of circulating leukocytes and the vascular endothelium.
Stroke Epidemiology, Patterns of Management, and Outcomes in Fortaleza, Brazil
Authors: de Carvalho João José Freitas , Alves Monique Bueno , Viana Georgiana Álvares Andrade , Machado Cícera Borges , dos Santos Bento Fortunato Cardoso , Kanamura Alberto Hideki , Lottenberg Claudio Luiz , Neto Miguel Cendoroglo , Silva Gisele Sampaio 
Published: November 2011

Background and Purpose—
Little information exists on the epidemiology and patterns of treatment of patients admitted to Brazilian hospitals with stroke. Our objective was to describe the frequency of risk factors, patterns of management, and outcome of patients admitted with stroke in Fortaleza, the fifth largest city in Brazil.

Methods—
Data were prospectively collected from consecutive patients admitted to 19 hospitals in Fortaleza with a diagnosis of stroke or transient ischemic attack from June 2009 to October 2010.

Results—
We evaluated 2407 consecutive patients (mean age, 67.7±14.4 years; 51.8% females). Ischemic stroke was the most frequent subtype (72.9%) followed by intraparenchymal hemorrhage (15.2%), subarachnoid hemorrhage (6.0%), transient ischemic attack (3%), and undetermined stroke (2.9%). The median time from symptoms onset to hospital admission was 12.9 (3.8–32.5) hours. Hypertension was the most common risk factor. Only 1.1% of the patients with ischemic stroke received thrombolysis. The median time from hospital admission to neuroimaging was 3.4 (1.2–26.5) hours. In-hospital mortality was 20.9% and the frequency of modified Rankin Scale score ≤2 at discharge was less than 30%. Older age, prestroke disability, and having a depressed level of consciousness at admission were independent predictors of poor outcome; conversely, male gender was a predictor of good outcome.

Conclusions—
The prevalence of stroke risk factors and clinical presentation in our cohort were similar to previous series. Treatment with thrombolysis and functional independency after a stroke admission were infrequent. We also found long delays in hospital admission and in evaluation with neuroimaging and high in-hospital mortality.
The X-Chromosome Has a Different Pattern of Gene Expression in Women Compared With Men With Ischemic Stroke
Authors: Stamova Boryana , Tian Yingfang , Jickling Glen , Bushnell Cheryl , Zhan Xinhua , Liu Dazhi , Ander Bradley P. , Verro Piero , Patel Vihar , Pevec William C. , Hedayati Nasim , Dawson David L. , Jauch Edward C. , Pancioli Arthur , Broderick Joseph P. , Sharp Frank R. 
Published: November 2011

Background and Purpose—
Differences in ischemic stroke between men and women have been mainly attributed to hormonal effects. However, sex differences in immune response to ischemia may exist. We hypothesized that differential expression of X-chromosome genes in blood immune cells contribute to differences between men and women with ischemic stroke.

Methods—
RNA levels of 683 X-chromosome genes were measured on Affymetrix U133 Plus2.0 microarrays. Blood samples from patients with ischemic stroke were obtained at ≤3 hours, 5 hours, and 24 hours (n=61; 183 samples) after onset and compared with control subjects without symptomatic vascular diseases (n=109). Sex difference in X-chromosome gene expression was determined using analysis of covariance (false discovery rate ≤0.05, fold change ≥1.2).

Results—

At ≤3, 5, and 24 hours after stroke, there were 37, 140, and 61 X-chromosome genes, respectively, that changed in women; and 23, 18, and 31 X-chromosome genes that changed in men. Female-specific genes were associated with post-translational modification, small-molecule biochemistry, and cell–cell signaling. Male-specific genes were associated with cellular movement, development, cell-trafficking, and cell death. Altered sex specific X-chromosome gene expression occurred in 2 genes known to be associated with human stroke, including galactosidase A and
IDS
, mutations of which result in Fabry disease and Hunter syndrome, respectively.

Conclusions—
There are differences in X-chromosome gene expression between men and women with ischemic stroke. Future studies are needed to decipher whether these differences are associated with sexually dimorphic immune response, repair or other mechanisms after stroke, or whether some of them represent risk determinants.