bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke
Authors: Rodríguez-González Raquel , Sobrino Tomás , Rodríguez-Yáñez Manuel , Millán Mónica , Brea David , Miranda Elena , Moldes Octavio , Pérez Juan , Lomas David A , Leira Rogelio , Dávalos Antoni , Castillo José 
Published: May 2011

Abstract

Background
Neuroserpin has shown neuroprotective effects in animal models of cerebral ischemia and has been associated with functional outcome after ischemic stroke. Our aim was to study whether neuroserpin serum levels could be associated to biomarkers of excitotoxicity, inflammation and blood brain barrier disruption.

Methods
We prospectively included 129 patients with ischemic stroke (58.1% male; mean age, 72.4 ± 9.6 years) not treated with tPA within 12 hours (h) of symptoms onset (mean time, 4.7 ± 2.1 h). Poor functional outcome at 3 months was considered as a modified Rankin scale score >2. Serum levels of neuroserpin, Interleukin 6 (IL-6), Intercellular adhesion molecule-1 (ICAM-1), active Matrix metalloproteinase 9 (MMP-9), and cellular fibronectin (cFn) (determined by ELISA) and glutamate (determined by HPLC) were measured on admission, 24 and 72 h. The main variable was considered the decrease of neuroserpin levels within the first 24 h. ROC analysis was used to select the best predictive value for neuroserpin to predict poor functional outcome due to a lack of linearity.

Results
The decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels at 24 hours of glutamate (r = -0.642), IL-6 (r = -0.678), ICAM-1 (r = -0.345), MMP-9 (r = -0.554) and cFn (r = -0.703) (all P < 0.0001). In the multivariate analysis, serum levels of glutamate (OR, 1.04; CI95%, 1.01-1.06, p = 0.001); IL-6 (OR, 1.4; CI95%, 1.1-1.7, p = 0.001); and cFn (OR, 1.3; CI95%, 1.1-1.6, p = 0.002) were independently associated with a decrease of neuroserpin levels <70 ng/mL at 24 h after adjusting for confounding factors.

Conclusions
These findings suggest that neuroprotective properties of neuroserpin may be related to the inhibition of excitotoxicity, inflammation, as well as blood brain barrier disruption that occur after acute ischemic stroke.
Human papillomavirus vaccine introduction in low-income and middle-income countries: guidance on the use of cost-effectiveness models
Authors: Jit Mark , Demarteau Nadia , Elbasha Elamin , Ginsberg Gary , Kim Jane , Praditsitthikorn Naiyana , Sinanovic Edina , Hutubessy Raymond 
Published: May 2011

Abstract

Background
The World Health Organization (WHO) recommends that the cost effectiveness of introducing human papillomavirus (HPV) vaccination is considered before such a strategy is implemented. However, developing countries often lack the technical capacity to perform and interpret results of economic appraisals of vaccines. To provide information about the feasibility of using such models in a developing country setting, we evaluated models of HPV vaccination in terms of their capacity, requirements, limitations and comparability.

Methods
A literature review identified six HPV vaccination models suitable for low-income and middle-income country use and representative of the literature in terms of provenance and model structure. Each model was adapted by its developers using standardised data sets representative of two hypothetical developing countries (a low-income country with no screening and a middle-income country with limited screening). Model predictions before and after vaccination of adolescent girls were compared in terms of HPV prevalence and cervical cancer incidence, as was the incremental cost-effectiveness ratio of vaccination under different scenarios.

Results
None of the models perfectly reproduced the standardised data set provided to the model developers. However, they agreed that large decreases in type 16/18 HPV prevalence and cervical cancer incidence are likely to occur following vaccination. Apart from the Thai model (in which vaccine and non-vaccine HPV types were combined), vaccine-type HPV prevalence dropped by 75% to 100%, and vaccine-type cervical cancer incidence dropped by 80% to 100% across the models (averaging over age groups). The most influential factors affecting cost effectiveness were the discount rate, duration of vaccine protection, vaccine price and HPV prevalence. Demographic change, access to treatment and data resolution were found to be key issues to consider for models in developing countries.

Conclusions
The results indicated the usefulness of considering results from several models and sets of modelling assumptions in decision making. Modelling groups were prepared to share their models and expertise to work with stakeholders in developing countries.
Please see related article: http://www.biomedcentral.com/1741-7007/9/55
Minocycline fails to modulate cerebrospinal fluid HIV infection or immune activation in chronic untreated HIV-1 infection: results of a pilot study
Authors: Ho Emily L , Spudich Serena S , Lee Evelyn , Fuchs Dietmar , Sinclair Elizabeth , Price Richard W 
Published: May 2011

Abstract

Background
Minocycline is a tetracycline antibiotic that has been shown to attenuate central nervous system (CNS) lentivirus infection, immune activation, and brain injury in model systems. To initiate assessment of minocycline as an adjuvant therapy in human CNS HIV infection, we conducted an open-labelled pilot study of its effects on cerebrospinal fluid (CSF) and blood biomarkers of infection and immune responses in 7 viremic subjects not taking antiretroviral therapy.

Results
There were no discernable effects of minocycline on CSF or blood HIV-1 RNA, or biomarkers of immune activation and inflammation including: CSF and blood neopterin, CSF CCL2, CSF white blood cell count, and expression of cell-surface activation markers on CSF and blood T lymphocytes and monocytes.

Conclusions
This pilot study of biological responses to minocycline suggests little potential for its use as adjunctive antiviral or immunomodulating therapy in chronic untreated HIV infection.
Human Immunodeficiency Virus Type 1 Vif causes dysfunction of Cdk1 and CyclinB1: implications for cell cycle arrest
Authors: Sakai Keiko , Barnitz R Anthony , Chaigne-Delalande Benjamin , Bidère Nicolas , Lenardo Michael J 
Published: May 2011

Abstract
The two major cytopathic factors in human immunodeficiency virus type 1 (HIV-1), the accessory proteins viral infectivity factor (Vif) and viral protein R (Vpr), inhibit cell-cycle progression at the G2 phase of the cell cycle. Although Vpr-induced blockade and the associated T-cell death have been well studied, the molecular mechanism of G2 arrest by Vif remains undefined. To elucidate how Vif induces arrest, we infected synchronized Jurkat T-cells and examined the effect of Vif on the activation of Cdk1 and CyclinB1, the chief cell-cycle factors for the G2 to M phase transition. We found that the characteristic dephosphorylation of an inhibitory phosphate on Cdk1 did not occur in infected cells expressing Vif. In addition, the nuclear translocation of Cdk1 and CyclinB1 was disregulated. Finally, Vif-induced cell cycle arrest was correlated with proviral expression of Vif. Taken together, our results suggest that Vif impairs mitotic entry by interfering with Cdk1-CyclinB1 activation.
Antiviral activity of Acacia nilotica against Hepatitis C Virus in liver infected cells
Authors: Rehman Sidra , Ashfaq Usman A , Riaz Sana , Javed Tariq , Riazuddin Sheikh 
Published: May 2011

Abstract
Hepatitis C virus (HCV) belonging to the family Flaviviridae has infected 3% of the population worldwide and 6% of the population in Pakistan. The only recommended standard treatment is pegylated INF-α plus ribavirin. Due to less compatibility of the standard treatment, thirteen medicinal plants were collected from different areas of Pakistan on the basis of undocumented antiviral reports against different viral infections. Medicinal plants were air dried, extracted and screened out against HCV by infecting HCV inoculums of 3a genotype in liver cells. RT-PCR results demonstrate that acetonic and methanolic extract of Acacia nilotica (AN) showed more than 50% reduction at non toxic concentration. From the above results, it can be concluded that by selecting different molecular targets, specific structure-activity relationship can be achieved by doing mechanistic analysis. So, additional studies are required for the isolation and recognition of antiviral compound in AN to establish its importance as antiviral drug against HCV. For further research, we will scrutinize the synergistic effect of active antiviral compound in combination with standard PEG INF-α and ribavirin which may be helpful in exploring further gateways for antiviral therapy against HCV.
Successful surgical resection of infected left atrial myxoma in a case complicated with disseminated intravascular coagulation and multiple cerebral infarctions: case report
Authors: Yoshioka Daisuke , Takahashi Toshiki , Ishizaka Toru , Higuchi Takuya 
Published: May 2011

Abstract
Cardiac myxoma is the most common primary cardiac tumour, but infected cardiac myxoma is relatively rare. Infected cardiac myxoma is very fragile, and has a potential to lead to catastrophic disorder with systemic bacteremia, systemic mycotic embolism, and disseminated intravascular coagulation (DIC).
We present here the successful surgical treatment of a case of infected left atrial myxoma with septic shock, DIC and cerebral infarction without hemorrahage. Collective review of 58 reported cases with infected cardiac myxoma revealed that surgical treatment for it were still challenging and its result was poor. Until date, only one successful surgical treatment for a case complicated by DIC and cerebral infarctions has been reported, and our report describes second such case of successful resection. Even though this report is limited to a case, only aggressive and prompt surgical intervention could relieve the intractable conditions in such a patient with extremely high risk.
Rapamycin-loaded nanoparticles for inhibition of neointimal hyperplasia in experimental vein grafts
Authors: Zou Junjie , Zhang Xiwei , Yang Hongyu , Zhu Yi , Ma Hao , Wang Shui 
Published: May 2011

Abstract

Background
Nanoparticles possess several advantages as a carrier system for intracellular delivery of therapeutic agents. Rapamycin is an immunosuppressive agent which also exhibits marked antiproliferative properties. We investigated whether rapamycin-loaded nanoparticles(NPs) can reduce neointima formation in a rat model of vein graft disease.

Methods
Poly(lactic-co-glycolic acid) (PLGA) NPs containing rapamycin was prepared using an oil/water solvent evaporation technique. Nanoparticle size and morphology were determined by dynamic light scattering methodology and electron microscopy. In vitro cytotoxicity of blank, rapamycin-loaded PLGA (RPLGA) NPs was studied using MTT Assay. Excised rat jugular vein was treated ex vivo with blank-NPs, or rapamycin-loaded NPs, then interposed back into the carotid artery position using a cuff technique. Grafts were harvested at 21 days and underwent morphometric analysis as well as immunohistochemical analysis.

Results
Rapamycin was efficiently loaded in PLGA nanoparticles with an encapsulation efficiency was 87.6%. The average diameter of NPs was 180.3 nm. The NPs-containing rapamycin at 1 ng/ml significantly inhibited vascular smooth muscular cells proliferation. Measurement of rapamycin levels in vein grafts shown that the concentration of rapamycin in vein grafts at 3 weeks after grafting were 0.9 ± 0.1 μg/g. In grafted veins without treatment intima-media thickness was 300.4 ±181.5 μm after grafting 21 days. Whereas, Veins treated with rapamycin-loaded NPs showed a reduction of intimal-media thickness of 150.2 ± 62.5 μm (p = 0.001). CD-31 staining was used to measure luminal endothelial coverage in grafts and indicated a high level of endothelialization in 21 days vein grafts with no significant effect of blank or rapamycin-loaded NPs group.

Conclusions
We conclude that sustained-release rapamycin from rapymycin loaded NPs inhibits vein graft thickening without affecting the reendothelialization in rat carotid vein-to-artery interposition grafts and this may be a promising therapy for the treatment of vein graft disease.
Viral load testing in a resource‐limited setting: quality control is critical
Authors: Greig Jane , du Cros Philipp , Klarkowski Derryck , Mills Clair , Jørgensen Steffen , Harrigan P Richard , O'Brien Daniel P 
Published: May 2011

BackgroundWorld Health Organization guidelines now recommend routine use of viral load testing, where available, for patients receiving antiretroviral treatment (ART). However, its use has not been routinely implemented in many resource‐limited settings due to cost, availability and accessibility. Viral load testing is complex, making its application in resource‐limited settings challenging. We describe the issues encountered by Médecins Sans Frontières (MSF) when using routine viral load testing in a large HIV programme in sub‐Saharan Africa.MethodsBetween October 2005 and August 2006, more than 1200 patients on ART had viral load tests at baseline and at three‐month intervals performed by a local reference laboratory that was quality assured by an experienced international institution. Concerns with reliability of results halted testing. The quality control measures instituted with a second laboratory and outcomes of these were documented.ResultsIn 2005 and 2006, only 178 of 334 (53%) previously ART‐naïve patients tested after six to 12 months of treatment had viral loads of less than 1000 copies/mL. Similar MSF programmes elsewhere demonstrated virological suppression rates of more than 85%, and duplicate testing showed unacceptable discordance. Laboratory problems encountered included: disregarded quality control; time delays; requirement for retesting; and duplicate sample variations. Potentially harmful clinical outcomes of inaccurate viral load results include: unnecessary ART regimen changes; unnecessary enhanced adherence counselling after “false failures”; and undetected virological failure.ConclusionsViral load testing performed without rigorous quality control carries the risk of erroneous and potentially damaging results. Viral load testing should be utilized only if robust quality assurance has been implemented. Our experience in this and other settings led to the development of a guide for assessing the suitability of a laboratory for viral load testing that can be used to help achieve reliable results.
A child with hyperferritinemia: Case report
Authors: Serra Melania , Longo Filomena , Roetto Antonella , Sandri Alessandro , Piga Antonio 
Published: May 2011

Abstract
Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare condition caused by mutations in the gene coding for the light chain of ferritin; it does not lead to iron overload, but it is associated with the risk of developing a bilateral nuclear cataract also in childhood. On the contrary, a raise of serum ferritin levels is a common finding in pediatrics. We describe here a case of HHCS that offers some interesting clues for the daily practice. Our patient is a 6 year old Italian boy who came to our attention after some time of diagnostic uncertainties because of persistently high levels of ferritin with no apparent cause. We were guided to the suspect of this syndrome by the family history (5 members with various degrees of cataract developed in first infancy). High levels of serum ferritin and specific genetic testing (mutation A37C) confirmed the diagnosis. This case underlines the need of considering rare genetic syndromes, including hereditary hyperferritinemia cataract syndrome, in the differential diagnosis of raised serum ferritin in children and the importance of paying attention to family history in considering a patient with isolated raised levels of serum ferritin.
Ovariectomy and overeating palatable, energy-dense food increase subcutaneous adipose tissue more than intra-abdominal adipose tissue in rats
Authors: Gloy Viktoria , Langhans Wolfgang , Hillebrand Jacquelien JG , Geary Nori , Asarian Lori 
Published: May 2011

Abstract

Background
Menopause is associated with increased adiposity, especially increased deposition of intra-abdominal (IA) adipose tissue (AT). This differs from common or 'dietary' obesity, i.e., obesity apparently due to environmentally stimulated overeating, in which IAAT and subcutaneous (S) AT increase in similar proportions. The effect of menopause on adiposity is thought to be due to the decreased secretion of ovarian estrogens. Ovariectomy in rats and other animals is a commonly used model of menopause. It is well known that ovariectomy increases adiposity and that this can be reversed by estradiol treatment, but whether ovariectomy selectively increases IAAT has not been measured directly. Therefore, we used micro-computed tomography (microCT) to investigate this question in both chow-fed and dietary-obese rats.

Methods
Ovariectomized, ovariectomized and estradiol treated, and sham-operated (intact) rats were fed chow or chow plus Ensure (Abbott Nutrition; n = 7/group). Total (T) AT, IAAT and SAT were measured periodically by microCT. Regional distribution of AT was expressed as IAAT as a percentage of TAT (%IAAT). Excesses in these measures were calculated with respect to chow-fed intact rats to control for normal maturational changes. Chemical analysis of fat was done in chow-fed intact and ovariectomized rats at study end. Data were analyzed by t-tests and planned comparisons.

Results
Body mass, TAT, total fat mass, fat-free body mass, and %IAAT all increased in chow-fed intact rats during the 41 d study. In chow-fed rats, ovariectomy increased excess body mass, TAT, fat mass, fat-free body mass, and SAT, but had little effect on IAAT, in chow-fed rats, leading to a decrease in %IAAT. Ensure feeding markedly increased SAT, IAAT and TAT and did not significantly affect %IAAT. Ovariectomy had similar effects in Ensure-fed rats as in chow-fed rats, although less statistically reliable. Estradiol treatment prevented all the effects of ovariectomy.

Conclusions
Both ovariectomy in rats and menopause are associated with increased TAT. After ovariectomy, fat is preferentially deposited as SAT and lean body mass increases, whereas after menopause fat is preferentially deposited as IAAT and lean body mass decreases. These opposite effects of ovariectomy and menopause on regional AT distribution and lean body mass indicate that ovariectomy in rats is not a homologous model of menopause-associated changes in body composition that should be used with great caution in investigations of adiposity-related diseases.
TNF-related apoptosis-inducing ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation
Authors: McGrath Emmet E , Marriott Helen M , Lawrie Allan , Francis Sheila E , Sabroe Ian , Renshaw Stephen A , Dockrell David H , Whyte Moira K B 
Published: May 2011

ABSTRACTNovel therapeutics targeting neutrophilic inflammation are a major unmet clinical need in acute and chronic inflammation. The timely induction of neutrophil apoptosis is critical for inflammation resolution, and it is thought that acceleration of apoptosis may facilitate resolution at inflammatory sites. We previously demonstrated that a death receptor ligand, TRAIL, accelerates neutrophil apoptosis in vitro. We examined the role of TRAIL in neutrophil-dominant inflammation in WT and TRAIL-deficient mice. TRAIL deficiency did not alter constitutive neutrophil apoptosis, whereas exogenous TRAIL accelerated apoptosis of murine peripheral blood neutrophils. We compared TRAIL-deficient and WT mice in two independent models of neutrophilic inflammation: bacterial LPS-induced acute lung injury and zymosan-induced peritonitis. In both models, TRAIL-deficient mice had an enhanced inflammatory response with increased neutrophil numbers and reduced neutrophil apoptosis. Correction of TRAIL deficiency and supraphysiological TRAIL signaling using exogenous protein enhanced neutrophil apoptosis and reduced neutrophil numbers in both inflammatory models with no evidence of effects on other cell types. These data indicate the potential therapeutic benefit of TRAIL in neutrophilic inflammation.
MicroRNA-146a regulates both transcription silencing and translation disruption of TNF-α during TLR4-induced gene reprogramming
Authors: El Gazzar Mohamed , Church Ashley , Liu Tiefu , McCall Charles E 
Published: May 2011

ABSTRACTFollowing the TLR-dependent initiation phase of acute systemic proinflammatory responses such as sepsis, an adaptive phase represses or activates a specific pattern of gene expression until the inflammation resolves. Here, we used the THP-1 sepsis cell model of bacterial LPS/endotoxin tolerance to show that TLR4-induced miR-146a supports the feed-forward adaptive processes that silence transcription and disrupt translation of acute proinflammatory genes. First, we found that miR-146a regulates a pathway that promotes the binding of transcription repressor RelB to the TNF-α promoter, a step known to precede histone and DNA modifications, which generate facultative heterochromatin to silence acute proinflammatory genes. However, once RelB binding occurred, miR-146a inhibition could not reverse compacted chromatin, and endotoxin tolerance persisted. Second, we observed that miR-146a regulates a pathway that supports assembly of the translation repressor complex of TNF-α by preventing the interaction of the RNA-binding protein effector Ago2 and RBM4. We also determined that once endotoxin tolerance is established, and specific genes have been reprogrammed, transcription and translation disruption can be reversed only by simultaneously depleting RelB and inhibiting miR-146a. Thus, miR-146a induction supports the TLR4-dependent shift from initiation to gene-specific repression at two levels. Our results also imply that therapies designed to reverse endotoxin tolerance as potential therapies for sepsis should be directed at the transcription and translation pathways of reprogramming.
Cortical Consolidation due to Increased Mineralization and Endosteal Contraction in Young Adult Men: A Five-Year Longitudinal Study
Authors: Ohlsson Claes , Darelid Anna , Nilsson Martin , Melin Johanna , Mellström Dan , Lorentzon Mattias 
Published: May 2011

Abstract

Context:
Peak bone mass is an important factor in the lifetime risk of developing osteoporosis. Large, longitudinal studies investigating the age of attainment of site-specific peak bone mass are lacking.

Objective and Main Outcome Measures:
The main outcome measures were to determine the site-specific development of peak bone mass in appendicular and axial skeletal sites and in the trabecular and cortical bone compartments, using both dual x-ray absorptiometry and peripheral computed tomography.

Design, Setting, and Population:
In total, 833 men [aged 24.1 ± 0.6 yr (mean ± sd)] from the original population-based Gothenburg Osteoporosis and Obesity Determinants Study (n = 1068) were included in this follow-up examination at 61.2 ± 2.3 months. Areal bone mineral density (aBMD) was measured with dual x-ray absorptiometry, whereas cortical and trabecular volumetric bone mineral density and bone size were measured by peripheral computed tomography at baseline and at the 5-yr follow-up.

Results:
During the 5-yr study period, aBMD of the total body, lumbar spine, and radius increased by 3.4, 4.2, and 7.8%, respectively, whereas a decrease in aBMD of the total hip of 1.9% was observed (P &lt; 0.0001). Increments of 2.1 and 0.7% were seen for cortical volumetric bone mineral density of the radius and tibia, respectively (P &lt; 0.0001), whereas cortical thickness increased by 3.8% at the radius and 6.5% at the tibia due to diminished endosteal circumference (radius 2.3% and tibia 4.6%, P &lt; 0.0001).

Conclusion:
aBMD decreased at the hip but increased at the spine and radius, in which the increment was explained by continued mineralization and augmented cortical thickness due to endosteal contraction in men between ages 19 and 24 yr.