bluuebunny/crossref_metadata_2025_split huggingface dataset:
New biomedical devices with selective peptide recognition properties. Part 1: Characterization and cytotoxicity of molecularly imprinted polymers
Authors: Rechichi A. , Cristallini C. , Vitale U. , Ciardelli G. , Barbani N. , Vozzi G. , Giusti P. 
Published: March 2009

AbstractMolecular imprinting is a technique for the synthesis of polymers capable to bind target molecules selectively. The imprinting of large proteins, such as cell adhesion proteins or cell receptors, opens the way to important and innovative biomedical applications. However, such molecules can incur into important conformational changes during the preparation of the imprinted polymer impairing the specificity of the recognition cavities. The “epitope approach” can overcome this limit by adopting, as template, a short peptide sequence representative of an accessible fragment of a larger protein. The resulting imprinted polymer can recognize both the template and the whole molecule thanks to the specific cavities for the epitope. In this work two molecularly imprinted polymer formulations (a macroporous monolith and nanospheres) were obtained using the protected peptide Z‐Thr‐Ala‐Ala‐OMe, as template, and Z‐Thr‐Ile‐Leu‐OMe, as analogue for the selectivity evaluation, methacrylic acid, as functional monomer, and trimethylolpropane trimethacrylate and pentaerythritol triacrylate (PETRA), as cross‐linkers. Polymers were synthesized by precipitation polymerization and characterized by standard techniques. Polymerization and rebinding solutions were analyzed by high performance liquid chromatography. The highly cross‐linked polymers retained about 70% of the total template amount, against (20% for the less cross‐linked ones). The extracted template amount and the rebinding capacity decreased with the cross‐linking degree, while the selectivity showed the opposite behaviour. The PETRA cross‐linked polymers showed the best recognition (MIP 2−, α= 1.71) and selectivity (MIP 2+, α′= 5.58) capabilities. The cytotoxicity tests showed normal adhesion and proliferation of fibroblasts cultured in the medium that was put in contact with the imprinted polymers.
Electron microscope tomography: further demonstration of nanocontacts between caveolae and smooth muscle sarcoplasmic reticulum
Authors: Gherghiceanu Mihaela , Popescu L.M. 
Published: March 2009

AbstractA spatial relationship between caveolae and sarcoplasmic reticulum (SR) in smooth muscle cells (SMC) was previously reported in computer‐assisted three‐dimensional reconstruction from transmission electron microscope serial sections. The knowledge of the three‐dimensional organization of the cortical space of SMC is essential to understand caveolae function at the cellular level. Cellular tomography using transmission electron microscopy tomography (EMT) is the only available technology to reliably chart the inside of a cell and is therefore an essential technology in the study of organellar nanospatial relationships. Using EMT we further demonstrate here that caveolae and peripheral SR in visceral SMC build constantly spatial units, presumably responsible for a vectorial control of free Ca2+ cytoplasmic concentrations in definite nanospaces.
Simulation of the Vapor Intrusion Process for Nonhomogeneous Soils Using a Three‐Dimensional Numerical Model
Authors: Bozkurt Ozgur , Pennell Kelly G. , Suuberg Eric M. 
Published: March 2009

AbstractThis paper presents model simulation results of vapor intrusion into structures built atop sites contaminated with volatile or semivolatile chemicals of concern. A three‐dimensional finite element model was used to investigate the importance of factors that could influence vapor intrusion when the site is characterized by nonhomogeneous soils. Model simulations were performed to examine how soil layers of differing properties alter soil‐gas concentration profiles and vapor intrusion rates into structures. The results illustrate difference in soil‐gas concentration profiles and vapor intrusion rates between homogeneous and layered soils. The findings support the need for site conceptual models to adequately represent a site’s geology when conducting site characterizations, interpreting field data, and assessing the risk of vapor intrusion at a given site. For instance, in layered geologies, a lower permeability and diffusivity soil layer between the source and building often limits vapor intrusion rates, even if a higher permeability layer near the foundation permits increased soil‐gas flow rates into the building. In addition, the presence of water‐saturated clay layers can considerably influence soil‐gas concentration profiles. Therefore, interpreting field data without accounting for clay layers in the site conceptual model could result in inaccurate risk calculations. Important considerations for developing more accurate conceptual site models are discussed in light of the findings.
Macro‐ and Micro‐Purge Soil‐Gas Sampling Methods for the Collection of Contaminant Vapors
Authors: Schumacher Brian A. , Zimmerman John H. , Sibert Christopher R. , Varner Katrina E. , Riddick Lee A. 
Published: March 2009

AbstractPurging influence on soil‐gas concentrations for volatile organic compounds (VOCs), as affected by sampling tube inner diameter and sampling depth (i.e., system volume) for temporary probes in fine‐grained soils, was evaluated at three different field sites. A macro‐purge sampling system consisted of a standard, hollow, 3.2‐cm outer diameter (OD) drive probe with a retractable sampling point attached to an appropriate length of 0.48‐cm inner diameter (ID) Teflon® tubing. The macro‐purge sampling system had a purge system volume of 24.5 mL at a 1‐m depth. In contrast, the micro‐purge sampling systems were slightly different between the field sites and consisted of a 1.27‐cm OD drive rod with a 0.10‐cm ID stainless steel tube or a 3.2‐cm OD drive rod with a 0.0254‐cm inner diameter stainless steel tubing resulting in purge system volumes of 1.2 and 7.05 mL at 1‐m depths, respectively. At each site and location within the site, with a few exceptions, the same contaminants were identified in the same relative order of abundances indicating the sampling of the same general soil atmosphere. However, marked differences in VOC concentrations were identified between the sampling systems, with micro‐purge samples having up to 27 times greater concentrations than their corresponding macro‐purge samples. The higher concentrations are the result of a minimal disturbance of the ambient soil atmosphere during purging. The minimal soil‐gas atmospheric disturbance of the micro‐purge sampling system allowed for the collection of a sample that is more representative of the soil atmosphere surrounding the sampling point. That is, a sample that does not contain an atmosphere that has migrated from distance through the geologic material or from the surface in response to the vacuum induced during purging soil‐gas concentrations. It is thus recommended that when soil‐gas sampling is conducted using temporary probes in fine‐grained soils, the sampling system use the smallest practical ID soil‐gas tubing and minimize purge volume to obtain the soil‐gas sample with minimal risk of leakage so that proper decisions, based on more representative soil‐gas concentrations, about the site can be made.
The perceived and actual diagnostic utility of veterinary cytological samples
Authors: Skeldon N. , Dewhurst E. 
Published: March 2009

Objectives: To establish the proportion of cytology samples sent to a commercial veterinary laboratory that yields diagnostically useful information in the context of current use and perceptions of cytology. Methods: Nine hundred and forty‐five cytology submissions were retrospectively collected and categorised according to diagnostic utility. A survey into the use and perceptions of cytology was distributed at the British Small Animal Veterinary Association Congress 2008. Results: A specific diagnosis was reached in 23·1 per cent of samples and a cytological diagnosis in 35·3 per cent. 22·4 per cent of samples yielded some useful information, but 19·2 per cent were unacceptable. Seventy‐four participants in the survey took an average of 3·9 cytological samples per week, of which they examined 27·0 per cent in‐house only, 21·6 per cent in‐house before sending to an external laboratory and 51·4 per cent were sent externally without prior examination. “To obtain a definitive diagnosis” was the principal reason cited for performing cytology. Clinical Significance: Results suggest that cytology is underused and may be applied in an inappropriate context in the UK. It is hoped that illustrating the diagnostic outcome of samples received by a commercial laboratory will encourage increased, appropriate use of cytology.
Sex‐Specific Impact of Aldosterone Receptor Antagonism on Ventricular Remodeling and Gene Expression after Myocardial Infarction
Authors: Kanashiro‐Takeuchi Rosemeire M. , Heidecker Bettina , Lamirault Guillaume , Dharamsi Jennifer W. , Hare Joshua M. 
Published: March 2009

AbstractAldosterone receptor antagonism reduces mortality and improves post‐myocardial infarction (Ml) remodeling. Because aldosterone and estrogen signaling pathways interact, we hypothesized that aldosterone blockade is sex‐specific. Therefore, we investigated the mpact of eplerenone on left ventricular (LV) remodeling and gene expression of male infarcted rats versus female infarcted rats. Ml and Sham animals were randomized to receive eplerenone (100 mg/kg/day) or placebo 3 days post‐surgery for 4 weeks and assessed by echocardiography. In the Ml placebo group, left ventricular end‐diastolic dimension (LVEDD) increased from 7.3 ± 0.4 mm to 10.2 ± 1.0 mm (p < 0.05) and ejection fraction (EF) decreased from 82.3 + 4% to 45.5 + 11% (p < 0.05) in both sexes (p= NS between groups). Eplerenone attenuated LVEDD enlargement more effectively in females (8.8 ± 0.2 mm, p < 0.05 vs. placebo) than in males (9.7 ± 0.2 mm, p= NS vs. placebo) and improved EF in females (56.7 ± 3%, p < 0.05 vs. placebo) but not in males (50.6 + 3%, p= NS vs. placebo). Transcriptomic analysis using Rat_230–2.0 microarrays (Affymetrix) revealed that in females 19% of downregu‐lated genes and 44% of upregulated genes post‐MI were restored to normal by eplerenone. In contrast, eplerenone only restored 4% of overexpressed genes in males. Together, these data suggest that aldosterone blockade reduces Ml‐induced cardiac remodeling and phenotypic alterations of gene expression preferentially in females than in males. The use of transcriptomic signatures to detect greater benefit of eplerenone in females has potential implications for personalized medicine.
Unexpected Hepatotoxicity of Rifampin and Saquinavir/Ritonavir in Healthy Male Volunteers
Authors: Schmitt Christophe , Riek Myriam , Winters Katie , Schutz Malte , Grange Susan 
Published: March 2009

ABSTRACTObjectives.  Rifampin is a potent inducer of the cytochrome P450 3A4 isoenzyme (CYP3A4) that metabolizes most protease inhibitor (PI) antiretrovirals. This study was designed to evaluate the steady‐state pharmacokinetics and tolerability of the coadministration of the PIs saquinavir and ritonavir (a CYP3A4 inhibitor used as a pharmacoenhancer of other PIs) and rifampin when coadministered in healthy HIV‐negative volunteers.Methods.  In an open‐label, randomized, one sequence, two‐period crossover study involving 28 healthy HIV‐negative volunteers, arm 1 was randomized to receive saquinavir/ritonavir 1000/100 mg twice daily while arm 2 received rifampin 600 mg once daily for 14 days. Both arms were then to receive concomitant saquinavir/ritonavir and rifampin for 2 additional weeks. Vital signs, electrocardiography, laboratory analyses, and blood levels of total saquinavir, ritonavir, rifampin, and desacetyl‐rifampin, the primary metabolite of rifampin, were measured.Results.  In arm 1, 10/14 (71%) and, in arm 2, 11/14 (79%) participants completed the first study phase; eight participants in arm 1 and nine in arm 2 went on to receive both saquinavir/ritonavir and rifampin. Following substantial elevations (≥ grade 2) in hepatic transaminases in participants receiving the coadministered agents, the study was discontinued prematurely. Two participants in arm 1 displayed moderate elevations after five and four doses of rifampin, respectively. In arm 2, all participants experienced severe elevations within 4 days of initiating saquinavir/ritonavir. Clinical symptoms (e.g., nausea, vomiting, abdominal pain, and headache) were more common and severe in arm 2. Clinical symptoms abated and transaminases normalized following drug discontinuation. Limited pharmacokinetic data suggest a possible relationship between transaminase elevation and elevated rifampin and desacetyl‐rifampin concentrations.Conclusions.  Although not confirmed in HIV‐infected patients, the data indicate that rifampin should not be coadministered with saquinavir/ritonavir.
Protective effect of bicyclol on liver injury induced by hepatic warm ischemia/reperfusion in rats
Authors: Yao Xiao‐min , Chen Hui , Li Yan 
Published: March 2009

Aim:  Bicyclol is a synthetic anti‐hepatitis drug with anti‐oxidative property. The purpose of this study was to investigate the effect of bicyclol on hepatic ischemia/reperfusion (I/R) injury and related mechanisms.Methods:  Rats were subjected to 90 min of hepatic ischemia followed by reperfusion for 1, 3, 6 and 24 h. Three doses of bicyclol were orally administered before ischemia. Liver injury was evaluated by biochemical and histopathological examinations. Liver malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) contents, and plasma endotoxin levels were spectrophotometrically measured. The expressions of inflammatory and anti‐inflammatory cytokines were detected by reverse transcription polymerase chain reaction and enzyme‐linked immunosorbent assay. Liver intercellular adhesion molecule‐1 (ICAM‐1) was examined by immunohistochemistry, and the expressions of nuclear factor (NF)‐κB, inhibitor of NF‐κB (IκB) and toll‐like receptor 4 (TLR4) were determined by western blot.Results:  Bicyclol significantly inhibited the elevations of serum alanine aminotransferase, total bilirubin and plasma endotoxin levels, alleviated the formation of liver MDA and nitrite/nitrate, restored impaired antioxidant SOD, attenuated hepatic necrosis and neutrophil infiltration, and also improved the 7‐day survival in I/R rats. Additionally, bicyclol markedly downregulated the overexpression of ICAM‐1, modulated the expression of inflammatory/anti‐inflammatory cytokines and inhibited the expression of NF‐κB and TLR4 in I/R rats.Conclusion:  Bicyclol had a remarkable protective effect on hepatic I/R injury, which was partially due to inhibiting the expression of TLR4 and NF‐κB via its ability to attenuate oxidative stress and endotoxin.
Prophylaxis in people with haemophilia
Authors: Franchini Massimo , Tagliaferri Annarita , Coppola Antonio 
Published: March 2009

SummaryA four-decade clinical experience and recent evidence from randomised controlled studies definitively recognised primary prophylaxis, i.e. the regular infusion of factor concentrates started after the first haemarthrosis and/or before the age of two years, as the first-choice treatment in children with severe haemophilia. The available data clearly show that preventing bleeding since an early age enables to avoid or reduce the clinical impact of muscle-skeletal impairment from haemophilic arthropathy and the related consequences in psycho-social development and quality of life of these patients. In this respect, the aim of secondary prophylaxis, defined as regular long-term treatment started after the age of two years or after two or more joint bleeds, is to avoid (or delay) the progression of arthropathy. The clinical benefits of secondary prophylaxis have been less extensively studied, especially in adolescents and adults; also in the latter better outcomes and quality of life for earlier treatment have been reported. This review summarises evidence from literature and current clinical strategies for prophylactic treatment in patients with severe haemophilia, also focusing on challenges and open issues (optimal regimen and implementation, duration of treatment, long-term adherence and outcomes, cost-benefit ratios) in this setting.
Relation of circulating matrix Gla-protein and anticoagulation status in patients with aortic valve calcification
Authors: Krueger Thilo , Westenfeld Ralf , Kühl Harald Peter , Brandenburg Vincent , Mahnken Andreas Horst , Stanzel Sven , Vermeer Cees , Cranenburg Ellen , Floege Jürgen , Kelm Malte , Schurgers Leon , Koos Ralf 
Published: March 2009

SummaryMatrix-Gla Protein (MGP) is a vitamin K-dependent protein acting as a local inhibitor of vascular calcification. Vitamin K-antagonists (oral anticoagulant; OAC) inhibit the activation of MGP by blocking vitamin K-metabolism. The aim of this study was to investigate the effect of long-term OAC treatment on circulating MGP levels in humans and on MGP expression in mice. Additionally, we tested the association between circulating inactive MGP (ucMGP) levels and the presence and severity of AVC in patients with aortic valve disease (AVD). We analysed circulating ucMGP levels in 191 consecutive patients with echocardiographically proven calcific AVD and 35 control subjects. The extent of AVC in the patients was assessed by multislice spiral computed tomography. Circulating ucMGP levels were significantly lower in patients with AVD (348.6 ± 123.1 nM) compared to the control group (571.6 ± 153.9 nM, p < 0.001). Testing the effect of coumarin in mice revealed that also the mRNA expression of MGP in the aorta was downregulated. Multifactorial analysis revealed a significant effect of glomerular filtration rate and long-term OAC therapy on circulating ucMGP levels in the patient group. Subsequently, patients on long-term OAC had significantly increased AVC scores. In conclusion, patients with calcific AVD had significantly lower levels of circulating ucMGP as compared to a reference population, free of coronary and valvular calcifications. In addition, our data suggest that OAC treatment may decrease local expression of MGP, resulting in decreased circulating MGP levels and subsequently increased aortic valve calcifications as an adverse side effect.
Leukocyte- and platelet-derived microparticles correlate with thrombus weight and tissue factor activity in an experimental mouse model of venous thrombosis
Authors: Hawley Angela , Farris Diana , Ballard Nicole , Wrobleski Shirley , Myers Jr Daniel , Henke Peter , Wakefield Thomas , Ramacciotti Eduardo 
Published: March 2009

SummaryMicroparticles (MP) are lipid vesicles from platelets, leukocytes and endothelial cells that are involved in early thrombogenesis. We evaluated a detailed time-course analysis of MPs on thrombogenesis and the associated tissue factor (TF) activity in wild-type, in gene-deleted for E- and P-selectins and with high levels of P-selectin expression after the initiation of venous thrombosis in mice.Inferior vena cava (IVC) ligation was performed on C57BL/6 mice (n =191, 59 = wild-type [WT], 55 = gene-deleted for E- and P – selectins [knock-outs, EPKO] and 77 = elevated levels of soluble P-selectin, named Delta Cytoplasmic Tail (ΔCT). Animals were euthanised at various time points to assess MP production, origin and thrombus weight. MPs were re-injected into separate mice at concentrations of 80,000 and 160,000 units, as well as from different ages. In addition, MPs from thrombosed animals were pooled and TF activity quantitated using a chromogenic assay. Thrombus weight correlated negatively with MPs derived from leukocytes, and positively with MPs derived from platelets for WT animals (p<0.05), while MPs from platelets presented a positive correlation to thrombus weight in the WT and EPKO groups (p<0.01). Total MPs correlated negatively with thrombus weight in the ΔCT group (p<0.05). MP re-injections led to greater thrombus weight, while older MP reinjections tended to form larger thrombus than younger. Finally, TF bearing MPs showed a significant correlation to MP concentrations (R=0.99). In conclusion, MPs appear to be an important element in venous thrombogenesis.
Endothelial adapter proteins in leukocyte transmigration
Authors: van Buul Jaap , Hordijk Peter 
Published: March 2009

SummaryLeukocyte transendothelial migration (TEM) requires endothelial signalling. This signalling is initiated by clustering of cell-surface adhesion molecules and transmitted into the endothelium by a group of associated or co-clustered adapter proteins. These adapter proteins, such as cortactin and filamin, connect the adhesion molecules to the actin cytoskeleton as well as to signalling enzymes and downstream pathways. This short review aims to define common themes in adapter protein binding in endothelial cells and to propose critical functions that are exerted by these adapters in leukocyte transendothelial migration.
Effects of microgravity and hypergravity on platelet functions
Authors: Wang Yuedan , Yan Rong , Shi Quanwei , Wang Zhicheng , Yuan Yanhong , Cheng Hong , Li Suping , Fan Yubo , Zhuang Fengyuan , Dai Kesheng 
Published: March 2009

SummaryMany serious thrombotic and haemorrhagic diseases or fatalities have been documented in human being exposed to micro-gravity or hypergravity environments, such as crewmen in space, roller coaster riders, and aircrew subjected to high-G training. Some possible related organs have been examined to explore the mechanisms underlying these gravity change-related diseases. However, the role of platelets which are the primary players in both thrombosis and haemostasis is unknown. Here we show that platelet aggregation induced by ristocetin or collagen and platelet adhesion to von Willebrand factor (VWF) were significantly decreased after platelets were exposed to simulated microgravity. Conversely, these platelet functions were increased after platelets were exposed to hypergravity. The tail bleeding time in vivo was significantly shortened in mice exposed to high-G force, whereas, was prolonged in hindlimb unloaded mice. Furthermore, three of 23 mice died after 15 minutes of –8 Gx stress. Platelet thrombi disseminated in the heart ventricle and blood vessels in the brain, lung, and heart from the dead mice. Finally, glycoprotein (GP) Ibα surface expression and its association with the cytoskeleton were significantly decreased in platelets exposed to simulated microgravity, and obviously increased in hypergravity-exposed platelets. These data indicate that the platelet functions are inhibited in microgravity environments, and activated under high-G conditions, suggesting a novel mechanism for gravity change-related haemorrhagic and thrombotic diseases. This mechanism has important implications for preventing and treating gravity change-related diseases, and also suggests that special attentions should be paid to human actions under different gravity conditions.