bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein microchips in biomedicine and biomarker discovery
Authors: Spisak Sandor , Tulassay Zsolt , Molnar Bela , Guttman Andras
Published: November 2007

Protein microarray technology is of high recent interest, especially for generating confirmatory and complementary information for transcriptomic studies. In this paper, the advantages, technical limitations, main application fields, and some early results of protein microarrays are reviewed. Today protein microchip technology is mostly available in the form of printed glass slides, bioaffinity surfaces, and tissue microarray (TMA)‐based techniques. The advantages of glass slide‐based microchips are the simplicity of their application and their relatively low cost. Affinity surface‐based protein chip techniques are applicable to minute amounts of starting material (<1 μg), but interrogation of these chips requires expensive instrumentation, such as mass spectrometers. TMAs are useful for parallel testing of antibody specificities on a broad range of histological specimens in a single slide. Protein microarrays have been successfully implemented for serum tumor marker profiling, cell physiology studies, and mRNA expression study verification. Some of the bottlenecks of the technology are protein instability, problems with nonspecific interactions, and the lack of amplification techniques to generate sufficient amounts of the lower abundance proteins. In spite of the current difficulties, protein microchips are envisioned to be available for routine biomedical and diagnostic applications provided that the ongoing technological developments are successful in improving sensitivity, specificity, and reducing costs.
Vertical dispersion of dust particles in a turbulent boundary layer
Authors: Wang H. T. , Zhou Y. H. , Dong Z. B. , Ayrault M.
Published: November 2007

The flow of glass dust particles in air was investigated experimentally over a flat bed in a wind tunnel. Particle concentrations were measured by light scattering diffusion (LSD) and digital image processing. It was verified that saltation is the main mechanism for ejection of dust particles. Vertical mean dust concentrations for ‘pure dust’ and two mixtures of dust and saltating glass particles were determined and analysed. The experiments confirmed that for the ‘pure dust’ configuration the mean concentration decreases as a power function with height. For the mixture configurations and for free stream velocities close to the threshold velocity, the mean concentration also decreases in a power function. For higher velocities, mean concentration decreases respectively as a power function or exponential function for large and small ratios of the dust:saltating particles respectively. The exponent of the power law reflects the dust:particle ratio and the free stream flow velocity. Copyright © 2007 John Wiley & Sons, Ltd.
Seasonal evolution of runoff generation on agricultural land in the Belgian loess belt and implications for muddy flood triggering
Authors: Evrard Olivier , Vandaele Karel , Bielders Charles , Wesemael Bas van
Published: November 2007

Muddy floods due to agricultural runoff are a widespread and frequent phenomenon in the European loess belt, and particularly in central Belgium. These floods are triggered when high quantities of runoff are generated on cropland and cause severe erosion. Three soil surface characteristics are relevant to determine the runoff potential of cultivated soils: soil cover by crops and residues, soil surface crusting and roughness. These characteristics have been observed on 65 cultivated fields throughout 2005. A heavy rainfall event representative for events triggering muddy floods in the region (60 mm h−1 during 30 minutes) has been simulated using a 0·5 m2 simulator on fields with the 17 most observed combinations of soil surface characteristics in central Belgium. Runoff is not observed in the case of (ploughed) bare uncrusted soils, nor in the case of soils covered by crops showing a transitional crust and a moderate roughness (1–2 cm). In the cases where runoff has been observed, mean runoff coefficients ranged from 13% (wheat in July) to 58% (sugar beet or maize in May and June). Grassed buffer strips (GBSs) and grassed waterways (GWWs) show a higher runoff coefficient (62% for GBSs and 73% for GWWs) than most cultivated soils (13–58%). Furthermore, it is demonstrated that small plot measurements can be used to estimate runoff generation at the field scale. A classification of runoff generation risk based on the surveys of soil surface characteristics has been applied to common crops of central Belgium. February as well as the period between May and September are the most critical for runoff at the field scale. However, it appears from monitoring of a 16 ha catchment that the highest runoff volumes and peak discharges are recorded between May and August after heavy rainfall, explaining why 85% of muddy floods are recorded during this period in central Belgium. Copyright © 2007 John Wiley & Sons, Ltd.
Hybrid automatic voltage control strategy and its application to Northeast China 500 kV power grid
Authors: Mei Shengwei , Xie Bangpeng , Che Wenyan , Wang Zhitao
Published: November 2007

This paper introduces an integrated control strategy based on hybrid control theory for the control of voltage and reactive power in power system substations. The strategy adopts a hierarchical, multilayer structure to achieve a multi‐objective optimization of voltage and reactive power control and improves the traditional “nine‐area diagram” control method. The new hybrid control strategy not only solves the problem of oscillatory responses caused by the changes of the on‐load tap changer (OLTC) taps and switching the shunt capacitors, but also responds to the global optimal control commands of voltage and reactive power from the master station with good steady‐state responses. The hybrid automatic voltage control (HAVC) strategy is tested via simulation of the Northeast China 500 kV grid and the results demonstrate the effectiveness of the strategy. Copyright © 2007 John Wiley & Sons, Ltd.
White matter vascular lesions are related to parietal‐to‐frontal coupling of EEG rhythms in mild cognitive impairment
Authors: Babiloni Claudio , Frisoni Giovanni B. , Pievani Michela , Vecchio Fabrizio , Infarinato Francesco , Geroldi Cristina , Salinari Serenella , Ferri Raffaele , Fracassi Claudia , Eusebi Fabrizio , Rossini Paolo M.
Published: November 2007

Do cerebrovascular and Alzheimer's disease (AD) lesions represent additive factors in the development of mild cognitive impairment (MCI) as a putative preclinical stage of AD? Here we tested the hypothesis that directionality of fronto‐parietal functional coupling of electroencephalographic (EEG) rhythms is relatively preserved in amnesic MCI subjects in whom the cognitive decline is mainly explained by white‐matter vascular load. Resting EEG was recorded in 40 healthy elderly (Nold) and 78 amnesic MCI. In the MCI subjects, white‐matter vascular load was quantified based on magnetic resonance images (0–30 visual rating scale). EEG rhythms of interest were δ (2–4 Hz), θ (4–8 Hz), α1 (8–10.5 Hz), α2 (10.5–13 Hz), β1 (13–20 Hz), and β2 (20–30 Hz). Directionality of fronto‐parietal functional coupling of EEG rhythms was estimated by directed transfer function software. As main results, (i) fronto‐parietal functional coupling of EEG rhythms was higher in magnitude in the Nold than in the MCI subjects; (ii) more interestingly, that coupling was higher at θ, α1, α2, and β1 in MCI V+ (high vascular load;N= 42; MMSE = 26) than in MCI V− group (low vascular load;N= 36; MMSE= 26.7). These results are interpreted as supporting the additive model according to which MCI state would result from the combination of cerebrovascular and neurodegenerative lesions. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.
Simultaneous EMG‐functional MRI recordings can directly relate hyperkinetic movements to brain activity
Authors: van Rootselaar Anne‐Fleur , Maurits Natasha M. , Renken Remco , Koelman Johannes H.T.M. , Hoogduin Johannes M. , Leenders Klaus L. , Tijssen Marina A.J.
Published: November 2007

Objective:

To apply and validate the use of electromyogram (EMG) recorded during functional magnetic resonance imaging (fMRI) in patients with movement disorders, to directly relate involuntary movements to brain activity.

Methods:

Eight “familial cortical myoclonic tremor with epilepsy” (FCMTE) patients, with tremor‐like cortical myoclonus and cerebellar Purkinje cell degeneration, and nine healthy controls performed hand posture and movement in an on/off fashion (block design). Superfluous movements were quantified as deviations in EMG power, positive and negative, with respect to the average EMG per session. This measure, “residual EMG” (r‐EMG), was derived by Gram–Schmidt orthogonalization. Activation maps resulting from conventional block regressors and novel r‐EMG regressors were compared.

Results:

In healthy participants, the block posture regressor identified mainly cerebellar activity and some activity in other areas belonging to motor circuitry. In FCMTE patients, no cerebellar activity was seen with the block posture regressor, compatible with cerebellar Purkinje cell changes in FCMTE. EMG power showed little variation during posture in healthy controls. Therefore, the r‐EMG regressor was almost constant and revealed no brain activity as expected. In contrast, in FCMTE patients the r‐EMG posture regressor was highly variable due to continuous myoclonic jerks. It identified sensorimotor cortical areas, compatible with cortical hyperexcitability in FCMTE patients.

Conclusion:

Conventional block regressors can be used to identify neuronal circuitry associated with a specific motor task, whereas r‐EMG regressors can help identify brain activation directly related to involuntary movements. Simultaneous EMG‐fMRI is complementary to conventional fMRI and will facilitate studies of hyperkinetic movement disorders. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.
Validation of a fully automated hippocampal segmentation method on patients with dementia
Authors: Firbank Michael J. , Barber Robert , Burton Emma J. , O'Brien John T.
Published: November 2007

We describe a fully automated method for hippocampal segmentation. The method uses SPM5 (http://www.fil.ion.ucl.ac.uk/spm/) software to segment the brain into grey/white matter, and spatially normalize the images to standard space. Grey matter pixels within a predefined hippocampal region in standard space are identified to segment the hippocampi. The method was validated on 36 subjects (9 each of Alzheimer's disease, dementia with Lewy bodies, vascular dementia, and healthy controls). The mean absolute difference in volume compared with manual segmentation was 11% (SD 9%). Linear regression between manual and automated volume gave V(auto) = V(manual) × 0.83 + 401 ml. The method provides an acceptable automated alternative to manual segmentation which may be of value in large studies. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.
Integrated local correlation: A new measure of local coherence in fMRI data
Authors: Deshpande Gopikrishna , LaConte Stephen , Peltier Scott , Hu Xiaoping
Published: November 2007

This article introduces the measure of integrated local correlation (ILC) for assessing local coherence in the brain using functional magnetic resonance imaging (fMRI) data and characterizes the measure in terms of reproducibility, the effect of physiological noise, and the dependence on image resolution. The coupling of local neuronal processes influences coherence in a voxel's neighborhood. ILC is defined, for each voxel, as the integration of its spatial correlation function. This integrated measure does not require the specification of a neighborhood and, as demonstrated by experimental data, is effectively independent of image resolution. Respiratory and cardiac fluctuations do not considerably alter the ILC value except in isolated areas in and surrounding large vessels. With resting‐state fMRI data, ILC was demonstrated to be tissue‐specific, higher in gray matter than white matter, and reproducible across consecutive runs in healthy individuals. Within the gray matter, ILC was found to be higher in the default mode network, particularly the posterior and anterior cingulate cortices. Comparing ILC maps obtained from resting state and continuous motor task data, we observed reduced local coherence in the default mode network during the task. Finally, we compared ILC and regional homogeneity by examining their ability to discriminate between gray and white matters in resting state data and found ILC to be more sensitive. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.
Time‐dependent hemispheric shift of the cortical control of volitional swallowing
Authors: Teismann Inga K. , Dziewas Rainer , Steinstraeter Olaf , Pantev Christo
Published: November 2007

An important part of the cortical processing of swallowing takes place in the sensorimotor cortex, predominantly in the left hemisphere. However, until now, only deglutition related brain activation with low time resolution exceeding a time interval of 1 s has been reported. In this study, we have examined the chronological sequence of cortical swallowing processing in humans by means of high temporal resolution magnetoencephalography (MEG). The cortical MEG activity was recorded during self‐paced volitional swallowing in 10 healthy subjects. Data were analyzed using synthetic aperture magnetometry and the group analysis was performed using a permutation test. Swallowing‐related muscle activity was recorded by electromyography. Within the time interval of 1 s of the most pronounced muscular swallowing execution, the MEG analysis revealed neural activation in the primary sensorimotor cortex. During the first 600 ms, only left hemispheric activation was found, bihemispheric activation during the next 200 ms and a right hemispheric activation during the last 200 ms. Thus, our results demonstrate a time‐dependent shift of neural activation from left to right sensorimotor cortex during deglutition with left hemispheric dominance in the early stage of volitional swallowing and right hemispheric dominance during its later part. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.
Response to paclitaxel in adenoid cystic carcinoma of the salivary glands
Authors: Till Brian G. , Martins Renato G.
Published: November 2007

Background.

Paclitaxel is not considered to be an active drug in adenoid cystic carcinoma (ACC) of the salivary glands. We report 2 consecutive cases of patients with ACC who responded to paclitaxel.

Methods.

The patients were: (1) a 58‐year‐old man with recurrent ACC who developed pulmonary metastases, had progressive disease after a good response to first‐line chemotherapy, and then achieved a partial response to weekly single‐ agent paclitaxel; and (2) a 46‐year‐old woman with extensive thoracic ACC metastases who achieved a significant response after 2 cycles of paclitaxel chemotherapy.

Results.

The first patient died of progressive disease approximately 4 months after completing paclitaxel therapy, and the second patient had disease control after 6 cycles of paclitaxel.

Conclusions.

Systemic weekly paclitaxel produced a significant response in 2 patients with ACC of the head and neck, and its use in this disease merits further study. © 2007 Wiley Periodicals, Inc. Head Neck, 2008
Submucosal purse‐string suture as a treatment of leakage around the indwelling voice prosthesis
Authors: Jacobs Kristien , Delaere Pierre R. , Poorten Vincent L. M. Vander
Published: November 2007

Background.

Leakage around the indwelling voice prosthesis is an annoying complication of tracheoesophageal speech.

Methods.

Twenty patients, who experienced peripheral leakage of the tracheoesophageal fistula, were treated with a purse‐string suture. Our aim was to get the patients free of leakage without losing their voice prosthesis. The technique was considered successful if this objective was reached and unsuccessful if eventually closure of the fistula was required.

Results.

Immediately after the procedure, no patients showed residual leakage. At 1 month, 2 patients experienced recurrent leakage. At a mean follow‐up of 19.4 months, the method was successful in 16 patients and unsuccessful in 4 patients.

Conclusions.

If peripheral leakage is not amenable to simple downsizing of the indwelling voice prosthesis, we feel the purse‐string suture is the first‐choice treatment because of its safety, efficiency, low cost, and ease of application. © 2007 Wiley Periodicals, Inc. Head Neck, 2008
Regulation of human liver δ-aminolevulinic acid synthase by bile acids
Authors: Peyer Anne-Kathrin , Jung Diana , Beer Markus , Gnerre Carmela , Keogh Adrian , Stroka Deborah , Zavolan Mihaela , Meyer Urs-A.
Published: November 2007

Aminolevulinic acid synthase 1 (ALAS1) is the rate-limiting enzyme of heme synthesis in the liver and is highly regulated to adapt to the metabolic demand of the hepatocyte. In the present study, we describe human hepatic ALAS1 as a new direct target of the bile acid–activated nuclear receptor farnesoid X receptor (FXR). Experiments in primary human hepatocytes and in human liver slices showed that ALAS1 messenger RNA (mRNA) and activity is increased upon exposure to chenodeoxycholic acid (CDCA), the most potent natural FXR ligand, or the synthetic FXR-specific agonist GW4064. Moreover, overexpression of a constitutively active form of FXR further increased ALAS1 mRNA expression. In agreement with these observations, an FXR response element was identified in the 5′ flanking region of human ALAS1 and characterized in reporter gene assays. A highly conserved FXR binding site (IR1) within a 175-bp fragment at −13 kilobases upstream of the transcriptional start site was able to trigger an FXR-specific increase in luciferase activity upon CDCA treatment. Site-directed mutagenesis of IR1 abolished this effect. Binding of FXR/retinoid acid X receptor heterodimers was demonstrated by mobility gel shift experiments.

Conclusion:

These data strongly support a role of bile acid–activated FXR in the regulation of human ALAS1 and, consequently, hepatic porphyrin and heme synthesis. These data also suggest that elevated endogenous bile acids may precipitate neuropsychiatric attacks in patients with acute hepatic porphyrias. (Hepatology 2007.)
Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis
Authors: Hassanein Tarek I. , Tofteng Flemming , Brown Robert S. , McGuire Brendan , Lynch Patrick , Mehta Ravindra , Larsen Fin S. , Gornbein Jeff , Stange Jan , Blei Andres T.
Published: November 2007

Extracorporeal albumin dialysis (ECAD) may improve severe hepatic encephalopathy (HE) in patients with advanced cirrhosis via the removal of protein or non–protein-bound toxins. A prospective, randomized, controlled, multicenter trial of the efficacy, safety, and tolerability of ECAD using molecular adsorbent recirculating system (MARS) was conducted in such patients. Patients were randomized to ECAD and standard medical therapy (SMT) or SMT alone. ECAD was provided daily for 6 hours for 5 days or until the patient had a 2-grade improvement in HE. HE grades (West Haven criteria) were evaluated every 12 hours using a scoring algorithm. The primary endpoint was the difference in improvement proportion of HE between the 2 groups. A total of 70 subjects [median age, 53; 56% male; 56% HE grade 3; 44% HE grade 4; median model for end-stage liver disease (MELD) 32 (11–50) and CPT 13 (10–15)] were enrolled in 8 tertiary centers. Patients were randomized to ECAD + SMT (n = 39) or SMT alone (n = 31). Groups were matched in demographics and clinical variables. The improvement proportion of HE was higher in ECAD (mean, 34%; median, 30%) versus the SMT group (mean, 18.9%; median, 0%) (

P

= 0.044) and was reached faster and more frequently than in the SMT group (

P

= 0.045). Subjects receiving ECAD tolerated treatment well with no unexpected adverse events.

Conclusion:

The use of ECAD may be associated with an earlier and more frequent improvement of HE (grade 3/4). Because this 5-day study was not designed to examine the impact of MARS on survival, a full assessment of the role of albumin dialysis awaits the results of additional controlled trials. (Hepatology 2007.)
Tolerogenic maturation of liver sinusoidal endothelial cells promotes B7-homolog 1-dependent CD8+ T cell tolerance
Authors: Diehl Linda , Schurich Anna , Grochtmann Regina , Hegenbarth Silke , Chen Lieping , Knolle Percy A.
Published: November 2007

Liver sinusoidal endothelial cells (LSEC) are unique organ-resident antigen-presenting cells capable of cross-presentation and subsequent tolerization of naïve CD8+ T cells. We investigated the molecular mechanisms underlying this tolerance induction in naive CD8+ T cells. MHC class I–restricted antigen presentation by LSEC led to initial stimulation of naïve CD8+ T cells, which up-regulated CD69, CD25, CD44, and programmed death (PD)-1 and proliferated similar to dendritic cell (DC)–activated CD8+ T cells. Importantly, cognate interaction with naïve CD8+ T cells triggered increased expression of co-inhibitory B7-H1 but not co-stimulatory CD80/86 molecules exclusively on LSEC but not DC. This matured phenotype of B7-H1high CD80/86low was critical for induction of CD8+ T cell tolerance by LSEC: B7-H1–deficient LSEC, that failed to interact with PD-1 on stimulated T cells, were incapable of inducing CD8+ T cell tolerance. Moreover, increased costimulation via CD28 interfered with tolerance induction, indicating that the noninducible low expression levels of CD80/86 on LSEC supported B7-H1–dependent tolerance induction. LSEC-tolerized CD8+ T cells had a distinctive phenotype from naïve and activated T cells with CD25low, CD44high, CD62Lhigh. They also expressed the homeostatic cytokine receptors CD127, CD122, and high levels of Bcl-2, indicating survival rather than deletion of tolerant CD8+ T cells. On adoptive transfer into congenic animals, tolerized CD8+ T cells failed to show specific cytotoxicity

in vivo

.

Conclusion:

Cognate interaction of LSEC with naïve CD8+ T cells elicits a unique tolerogenic maturation of LSEC and permissiveness of T cells for tolerogenic signals, demonstrating that LSEC-induced tolerance is an active and dynamic process. (Hepatology 2007.)
Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response
Authors: Dalgard Olav , Bjφro Kristian , Ring-Larsen Helmer , Bjornsson Einar , Holberg-Petersen Mona , Skovlund Eva , Reichard Olle , Myrvang Bjφrn , Sundelöf Bo , Ritland Ståle , Hellum Kjell , Frydén Aril , Florholmen Jon , Verbaan Hans
Published: November 2007

A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment-naïve HCV RNA–positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon α-2b (1.5 μg/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one-sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n = 148) or group B (n = 150). In the intention-to-treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7-17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, −0.1 to +13.9).

Conclusion:

We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks. (Hepatology 2007.)
In vivo growth inhibition of sarcoma 180 by piperlonguminine, an alkaloid amide from the Piper species
Authors: Bezerra Daniel P. , Pessoa Cláudia , Moraes Manoel Odorico de , Alencar Nylane M. N. de , Mesquita Rodney O. , Lima Michael W. , Alves Ana Paula N. N. , Pessoa Otília Deusdênia L. , Chaves João Henrique , Silveira Edilberto R. , Costa‐Lotufo Letícia V.
Published: November 2007

Many authors have already emphasized that phytochemicals from spices have biological applications. Piperlonguminine is a known alkaloid amide from peppers, including Piper divaricatum. The aim of this study was to investigate the in vitro and in vivo antitumor effects of piperlonguminine in experimental models. In order to evaluate the toxicological aspects related to piperlonguminine treatment, hematological, biochemical, histopathological and morphological analyses of treated animals were performed. Piperlonguminine did not show any significant in vitro cytotoxic effect at experimental exposure levels, but showed an in vivo antitumor effect. After 7 days of treatment, the inhibition rates were 38.71% and 40.68% at doses of 25 mg kg−1 and 50 mg kg−1, respectively. The histopathological analysis suggests that the liver and kidney were only weakly affected by piperlonguminine treatment. Neither the enzymatic activity of transaminases (AST and ALT) nor the urea levels were significantly altered. In the hematological analysis, all parameters analysed remained constant after piperlonguminine treatment. In conclusion, these data reinforce the anticancer potential of spice components. Copyright © 2007 John Wiley & Sons, Ltd.
Structure–activity relationships for thiol reactivity and rat or human hepatocyte toxicity induced by substituted p‐benzoquinone compounds
Authors: Chan Katie , Jensen Neil , O'Brien Peter J.
Published: November 2007

Covalent binding of toxic chemicals to cellular targets is a molecular interaction that initiates a wide array of adverse biological effects. The creation of a covalent bond can be cited as a key initiating step along many toxicity pathways which must be predicted in order to predict the potential of a chemical to cause specific harmful effects. Currently, quantitative structure‐activity relationship (QSAR) models are being improved by focusing on endpoints such as simple electrophile reactivity for covalent interactions rather than on commonly used complex toxicity endpoints. The cytotoxicity and electrophilic reactivity of 10 p‐substituted benzoquinone derivatives, which are well known electrophilic alkylating agents, were investigated under the premise that QSAR toxicity models can be improved when the molecular triggering event is considered. Hepatocyte toxicity was determined by incubation of individual compounds with freshly isolated rat or cryopreserved human hepatocyte suspensions. The potential for chemical reactivity between a chemical and cellular target was measured by determining non‐enzymic reactivity with glutathione, representing thiol nucleophiles. The decline in free thiol moieties was measured to characterize the electrophile reactivity. It was found that the degree of rat hepatotoxicity induced by benzoquinones correlated with the rate at which they non‐enzymically react with glutathione and to various global and atomic electronic frontier orbital parameters which described electrophilicity. Human hepatocytes showed similar results but the statistical significance was much lower. The QSAR expressions suggest that covalent binding reactivity serves as a good correlate to hepatotoxicity and could improve QSAR modeling for potential toxicity risks. Copyright © 2007 John Wiley & Sons, Ltd.
Toxicological evaluation of subchronic exposure to diphenyl diselenide in rats
Authors: Meotti Flavia Carla , Borges Vanessa Corralo , Perottoni Juliano , Nogueira Cristina Wayne
Published: November 2007

The aim of this study was to investigate the effects caused by subchronic exposure to diphenyl diselenide in rats. Adult Wistar rats were exposed to diphenyl diselenide (5–300 µmol kg−1, subcutaneously) once a day for 14 days. The subchronic administration of diphenyl diselenide at a dose of 300 µmol kg−1 significantly increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in plasma. Conversely, this exposure did not alter lactate dehydrogenase (LDH) activity, urea and creatinine levels in plasma. The activity of δ‐aminolevulinate dehydratase (δ‐ALA‐D) from liver and kidney was inhibited by high dosages of diphenyl diselenide. Diphenyl diselenide did not alter renal Na+/K+ATPase. A decline in body weight gain was associated with a decrease in food consumption in rats treated with 100 or 300 µmol kg−1 diphenyl diselenide. At these dosages (100 and 300 µmol kg−1), diphenyl diselenide did not cause histological alterations in the liver of rats. Taken together, these results demonstrated that subchronic exposure to diphenyl diselenide at high doses induced minor toxicological effects. Copyright © 2007 John Wiley & Sons, Ltd.
Microwave plasma surface modification of silicone elastomer with allylamine for improvement of biocompatibility
Authors: Ren T. B. , Weigel Th. , Groth Th. , Lendlein A.
Published: November 2007

The microwave plasma surface modification of silicone elastomer with allylamine was studied to improve the biocompatibility of the material. An effort was made to clarify the relationships among plasma conditions and surface chemical composition, physical surface properties and biocompatibility of material, as well as the stability of plasma deposited layers. ATR‐IR, XPS, Ellipsometry measurements, and contact angle measurements were used to investigate the changes of surface. The stability of plasma‐treated silicone surfaces were also studied. The results demonstrated that the temperature and pressure had a strong influence on the chemical composition and structure of surface‐deposited layer. The layer was nearly completely crosslinking when the modification was carried out at 60°C. The polymerization speed decreased linearly with temperature. The XPS analysis results showed that the nitrogen element content in the surface layer was very high, especially under low pressure. The nitrogen/carbon ratio in the layer even greatly surpassed that of the allylamine monomer. The wettability of the silicone surface was greatly improved after plasma modification, and increased with the quantities of amine groups. The plasma‐treated surfaces have good storage stability in air up to 3 months. The wettability of the surfaces decreased incipiently and then it dramatically increased with further time. The human skin fibroblasts were used to evaluate biocompatibility of plasma‐treated silicone elastomer. The surface biocompatibility was greatly improved after modification; human skin fibroblasts adhered quickly and grew well on the modified silicone surface. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
Bisphosphonate coating on titanium screws increases mechanical fixation in rat tibia after two weeks
Authors: Wermelin Karin , Aspenberg Per , Linderbäck Paula , Tengvall Pentti
Published: November 2007

Recently published data indicate that immobilized N‐bisphosphonate enhances the pullout force and energy uptake of implanted stainless steel screws at 2 weeks in rat tibia. This study compares titanium screws with and without a bisphosphonate coating in the same animal model. The screws were first coated with an ∼100‐nm thick crosslinked fibrinogen film. Pamidronate was subsequently immobilized into this film via EDC/NHS‐activated carboxyl groups within the fibrinogen matrix, and finally another N‐bisphosphonate, ibandronate, was physically adsorbed. The release kinetics of immobilized 14C‐alendronate was measured in buffer up to 724 h and showed a 60% release within 8 h. Mechanical tests demonstrated a 32% (p = 0.04) and 48% (p = 0.02) larger pullout force and energy until failure after 2 weeks of implantation, compared to uncoated titanium screws. A control study with physically adsorbed pamidronate showed no effect on mechanical fixation, probably due to a too small adsorbed amount. We conclude that the fixation of titanium implants in bone can be improved by fibrinogen matrix‐bound bisphosphonates. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
Morphology, proliferation, and osteogenic differentiation of mesenchymal stem cells cultured on titanium, tantalum, and chromium surfaces
Authors: Stiehler Maik , Lind Martin , Mygind Tina , Baatrup Anette , Dolatshahi‐Pirouz Alireza , Li Haisheng , Foss Morten , Besenbacher Flemming , Kassem Moustapha , Bünger Cody
Published: November 2007

Metallic implants are widely used in orthopedic surgery and dentistry. Durable osseous fixation of an implant requires that osteoprogenitor cells attach and adhere to the implant, proliferate, differentiate into osteoblasts, and produce mineralized matrix. In the present study, we investigated the interactions between human mesenchymal stem cells (MSCs) and smooth surfaces of titanium (Ti), tantalum (Ta), and chromium (Cr). Mean cellular area was quantified using fluorescence microscopy (4 h). Cellular proliferation was assessed by 3H‐thymidine incorporation and methylene blue cell counting assays (4 days). Osteogenic differentiation response was quantified by cell‐specific alkaline phosphatase activity (ALP) assay (4 days), expression analysis of bone‐related genes (4 days), and mineralization assay (21 days). Undifferentiated and osteogenically stimulated MSCs cultured on the different surfaces showed the same tendencies for proliferation and differentiation. MSCs exposed to Ti surfaces demonstrated enhanced proliferation compared with Ta and Cr surfaces. Cultivation of MSCs on Ta surfaces resulted in significantly increased mean cellular area and cell‐specific ALP activity compared with the other surfaces tested. Cells cultured on Cr demonstrated reduced spreading and proliferation. In conclusion, Ta metal, as an alternative for Ti, can be considered as a promising biocompatible material, whereas further studies are needed to fully understand the role of Cr and its alloys in bone implants. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Polymeric scaffolds prepared via thermally induced phase separation: Tuning of structure and morphology
Authors: Pavia F. Carfì , La Carrubba V. , Piccarolo S. , Brucato V.
Published: November 2007

Scaffolds suitable for tissue engineering applications like dermal reconstruction were prepared by Thermally Induced Phase Separation (TIPS) starting from a ternary solution PLLA/dioxane/water. The experimental protocol consisted of three consecutive steps, a first quench from the homogeneous solution to an appropriate demixing temperature (within the metastable region), a holding stage for a given residence time, and a final quench from the demixing temperature to a low temperature (within the unstable region). A large variety of morphologies, in terms of average pore size and interconnection, were obtained upon modifying the demixing time and temperature, owing to the interplay of nucleation and growth processes during the residence in the metastable state. An interesting combination of micro and macroporosity was observed for long residence times in the metastable state (above 30 min at 35°C). Preliminary degradation tests in a biological mimicking fluid (D‐MEM with bovine serum) showed a significant weight loss during the initial stages (ca. 30% in 30 days) related to the degradation of the amorphous part, followed by a negligible weight loss in the next days (few percent from 30 to 60 days). © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Corrosion of anodic TiO coatings on Ti–6Al–4V in simulated body fluid
Authors: Narayanan R. , Seshadri S. K. , Kwon Tae‐Yub , Kim Kyo‐Han
Published: November 2007

Anodic TiO coatings were produced on Ti–6Al–4V substrates using aqueous electrolytes containing dissolved calcium and phosphorus. Two baths containing Ca and P compounds, in the molar ratios 5 and 15 were used. Different coatings were produced by electrolysis for 3 and 10 h at a constant current density of 10 mA/cm2. X‐ray diffraction and X‐ray fluorescence were used to identify the phases and chemical composition respectively. Thickness of the coatings was measured using ellipsometry. Electrochemical polarization and AC impedance studies were performed on the coatings by exposing them to simulated body fluid (SBF) for a period of 1 week. The coating produced by 10‐h electrolysis from bath of Ca/P ratio 15 showed low corrosion current and high impedance to the week‐long attack of SBF. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Influence of pulse repetition rate of Er:YAG laser and dentin depth on tensile bond strength of dentin–resin interface
Authors: Gonçalves Mariane , Corona Silmara Aparecida Milori , Palma‐Dibb Regina Guenka , Pécora Jesus Djalma
Published: November 2007

The study evaluated the in vitro influence of pulse‐repetition rate of Er:YAG laser and dentin depth on tensile bond strength of dentin–resin interface. Dentin surfaces of buccal or lingual surfaces from human third molars were submitted to tensile test in different depths (superficial, 1.0 and 1.5 mm) of the same dental area, using the same sample. Surface treatments were acid conditioning solely (control) and Er:YAG laser irradiation (80 mJ) followed by acid conditioning, with different pulse‐repetition rates (1, 2, 3, or 4 Hz). Single bond/Z‐250 system was used. The samples were stored in distilled water at 37°C for 24 h, and then the first test (superficial dentine) was performed. The bond failures were analyzed. Following, the specimens were identified, grounded until 1.0‐ and 1.5‐mm depths, submitted again to the treatments and to the second and, after that, to third‐bond tests on a similar procedure and failure analysis. ANOVA and Tukey test demonstrated a significant difference (p < 0.001) for treatment and treatment × depth interaction (p < 0.05). The tested depths did not show influence (p > 0.05) on the bond strength of dentin–resin interface. It may be concluded that Er:YAG laser with 1, 2, 3, or 4 Hz combined with acid conditioning did not increase the resin tensile bond strength to dentin, regardless of dentin depth. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Rheological characterization of photopolymerized poly(vinyl alcohol) hydrogels for potential use in nucleus pulposus replacement
Authors: Bader Rebecca A. , Rochefort Willie E.
Published: November 2007

Hydrogels have been proposed as candidates for nucleus pulposus replacement because of their similarity in mechanical behavior to the native tissue when subjected to transient or static loading; however, given the viscoelastic nature of soft biological tissues, the lack of dynamic testing is a significant inadequacy in the studies performed to date. In the present work, the viscoelastic behavior of a hydrogel system obtained via photopolymerization of glycidyl methacrylate modified poly(vinyl alcohol) (PVA) was evaluated in comparison to that of the nucleus pulposus when subjected to dynamic torsional shear. The complex shear moduli and phase shift angles were modulated through the variation of PVA molecular weight and concentration of polymer prior to photopolymerization. Hydrolysis resistance was assessed by evaluation of the viscoelastic behavior of hydrogels submerged in Hank's solution for progressively longer periods of time. The phase shift angles of all hydrogels were lower than those of the nucleus pulposi; however, the complex shear moduli of the synthetic system spanned the values observed for the natural system. Over the time frame of the experiment, no changes in moduli were observed following submersion in Hank's solution. This study represents the first attempt to successfully mimic the viscoelastic nature of the nucleus pulposus exhibited under dynamic torsional loading with that of materials intended for use in tissue replacement. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Self‐assembled, fluorescent polymeric micelles of a graft copolymer containing carbazole for thermo‐controlled drug delivery in vitro
Authors: Liu Yunhai , Wu Jibing , Meng Lingzhi , Zhang Lifen , Lu Xiaoju
Published: November 2007

A novel thermosensitive amphiphilic graft copolymer PNIPAAm‐g‐PCbzEA appending carbazole group was successfully designed and synthesized by the free radical copolymerization of N‐isopropylacrylamide with hydrophobic precursor polymers of vinyl‐functionalized poly(2‐(N‐carbazolyl)ethyl acrylate) (PCbzEA) in DMF. The PNIPAAm‐g‐PCbzEA copolymer was characterized by FTIR, 1H NMR, GPC analysis, UV–vis spectroscopy and fluorescence spectroscopy. The TEM observation shows that the graft copolymer may self‐assemble into polymeric micelles exhibiting a nanospheric morphology within a narrow size range of 30–60 nm in aqueous solution. From the 1H NMR and FTIR analysis, the polymer micelles are composed of hydrophobic PCbzEA segments as the cores and the hydrophilic PNIPAAm segements as outer shells. The resulting micelles exhibited the temperature sensitivity with a lower critical solution temperature (LCST) of 31.5°C and a critical micelle concentration (CMC) of 12.9 mg/L in water. In the study of drug release, an “on–off” drug release profile was found in response to stepwise temperature changes between 20 and 40°C. The cytotoxicity assays for vero cells shows good biocompatibility of the graft copolymer in vitro. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
Immunosuppressive drug‐free operational immune tolerance in human kidney transplants recipients. Part II. Non‐statistical gene microarray analysis
Authors: Sivozhelezov Victor , Braud Christophe , Giacomelli Luca , Pechkova Eugenia , Giral Magali , Soulillou Jean‐Paul , Brouard Sophie , Nicolini Claudio
Published: November 2007

Kidney transplant is the reference treatment for patients with end‐stage renal disease, but patients may develop long‐term rejection of the graft. However, some patients do not reject the transplant, but instead are operationally tolerant state despite withdrawal of immunosuppressive treatment. In this second article we outline a microarray‐based identification of key leader genes associated respectively to rejection and to operational tolerance of the kidney transplant in humans by utilizing a non/statistical bioinformatic approach based on the identification of “key genes,” either as those mostly changing their expression, or having the strongest interconnections. A uniquely informative picture emerges on the genes controlling the human transplant from the detailed comparison of these findings with the traditional statistical SAM (Tusher et al. 2001 Proc Natl Acad Sci USA 98:5116–5121) analysis of the microarrays and with the clinical study carried out in the accompanying part I article. J. Cell. Biochem. 103: 1693–1706, 2008. © 2007 Wiley‐Liss, Inc.
Understanding the pathology and mechanisms of type I diabetic bone loss
Authors: McCabe Laura R.
Published: November 2007

Type I (T1) diabetes, also called insulin dependent diabetes mellitus (IDDM), is characterized by little or no insulin production and hyperglycemia. One of the less well known complications of T1‐diabetes is bone loss which occurs in humans and animal models. This complication is receiving increased attention because T1‐diabetics are living longer due to better therapeutics, and are faced with their existing health concerns being compounded by complications associated with aging, such as osteoporosis. Both male and female, endochondrial and intra‐membranous, and axial and appendicular bones are susceptible to T1‐diabetic bone loss. Exact mechanisms accounting for T1‐diabetic bone loss are not known. Existing data indicate that the bone defect in T1‐diabetes is anabolic rather than catabolic, suggesting that anabolic therapeutics may be more effective in preventing bone loss. Potential contributors to T1‐diabetic suppression of bone formation are discussed in this review and include: increased marrow adiposity, hyperlipidemia, reduced insulin signaling, hyperglycemia, inflammation, altered adipokine and endocrine factors, increased cell death, and altered metabolism. Differences between T1‐diabetic‐ and age‐associated bone loss underlie the importance of condition specific, individualized treatments for osteoporosis. Optimizing therapies that prevent bone loss or restore bone density will allow T1‐diabetic patients to live longer with strong healthy bones. J. Cell. Biochem. 102: 1343–1357, 2007. © 2007 Wiley‐Liss, Inc.
VEGF in biological control
Authors: Breen Ellen C.
Published: November 2007

Vascular endothelial growth factor A (VEGF‐A) belongs to a family of heparin binding growth factors that include VEGF‐B, VEGF‐C, VEGF‐D, and placental‐like growth factor (PLGF). First discovered for its ability to regulate vascular endothelial cell permeability, VEGF is a well‐known angiogenic factor that is important for vascular development and maintenance in all mammalian organs. The development of molecular tools and pharmacological agents to selectively inhibit VEGF function and block angiogenesis and/or vascular permeability has led to great promise in the treatment of various cancers, macular degeneration, and wound healing. However, VEGF is also important in animals for the regulation of angiogenesis, stem cell and monocyte/macrophage recruitment, maintenance of kidney and lung barrier functions and neuroprotection. In addition to its role in regulating endothelial cell proliferation, migration, and cell survival, VEGF receptors are also located on many non‐endothelial cells and act through autrocrine pathways to regulate cell survival and function. The following review will discuss the role of VEGF in physiological angiogenesis as well as its role in non‐angiogenic processes that take place in adult organs. J. Cell. Biochem. 102: 1358–1367, 2007. © 2007 Wiley‐Liss, Inc.
A new, unexpected action of olomoucine, a CDK inhibitor, on normal human cells: Up‐regulation of CLIMP‐63, a cytoskeleton‐linking membrane protein
Authors: Węsierska‐Gądek Józefa , Gueorguieva Marieta , Kramer Matthias P. , Ranftler Carmen , Sarg Bettina , Lindner Herbert
Published: November 2007

Inhibition of cyclin‐dependent kinases (CDKs) is a novel strategy in the therapy of human malignancies. The pharmacological CDK inhibitors representing a few distinct classes of compounds exert different target specificity. Considering the fact that dividing and quiescent cells differ in their CDK activity and in the pattern of their expression, one might expect that anti‐proliferative efficiency of the pharmacological CDK inhibitors would depend on the mitotic index of treated cells. The present article shows that olomoucine (OLO), a weak CDK2 inhibitor has new, unexpected activity. At concentrations up to 100 µM OLO did not inhibit proliferation of normal human cells, but arrested growth of human HL‐60 leukemia cells. The anti‐proliferative effect of OLO was clearly weaker than that of roscovitine (ROSC). Surprisingly, OLO at low doses strongly up‐regulated a cellular protein with approximately 65 kDa in normal, but not in immortalized and cancer cells. By mass spectrometric analysis CLIMP‐63, a cytoskeleton‐linking membrane protein was identified as the major component of the up‐regulated protein band. These results were subsequently confirmed by immunoblotting. Further experiments revealed that OLO, but not ROSC, strongly up‐regulates CLIMP‐63 in a dose‐ and time‐dependent manner solely in senescent cells. J. Cell. Biochem. 102: 1405–1419, 2007. © 2007 Wiley‐Liss, Inc.