bluuebunny/crossref_metadata_2025 huggingface dataset:
Stem cell biology and its therapeutic applications in the setting of spinal cord injury
Authors: Bambakidis Nicholas C. , Butler John , Horn Eric M. , Wang Xukui , Preul Mark C. , Theodore Nicholas , Spetzler Robert F. , Sonntag Volker K. H.
Published: March 2008

✓ The development of an acute traumatic spinal cord injury (SCI) inevitably leads to a complex cascade of ischemia and inflammation that results in significant scar tissue formation. The development of such scar tissue provides a severe impediment to neural regeneration and healing with restoration of function. A multimodal approach to treatment is required because SCIs occur with differing levels of severity and over different lengths of time. To achieve significant breakthroughs in outcomes, such approaches must combine both neuroprotective and neuroregenerative treatments. Novel techniques modulating endogenous stem cells demonstrate great promise in promoting neuroregeneration and restoring function.
Stem cell–mediated regeneration of the intervertebral disc: cellular and molecular challenges
Authors: Jandial Rahul , Aryan Henry E. , Park John , Taylor William T. , Snyder Evan Y.
Published: March 2008

✓ Regenerative medicine and stem cells hold great promise for intervertebral disc (IVD) disease. The therapeutic implications of utilizing stem cells to repair degenerated discs and treat back pain are highly anticipated by both the clinical and scientific communities. Although the avascular environment of the IVD poses a challenge for stem cell–mediated regeneration, neuroprogenitor cells have been discovered within degenerated discs, allowing scientists to revisit the hostile environment of the IVD as a target for stem cell therapy. Issues now under investigation include the timing of cell delivery and manipulation of stem cells to make them more efficient and adaptive in the IVD niche. This review covers the mechanisms underlying disc degeneration as well as the molecular and cellular challenges involved in directing stem cells to the desired cell type for intradiscal transplantation.
Stem cells: new frontiers of ethics, law, and policy
Authors: Scott Christopher Thomas
Published: March 2008

✓ After the successful isolation of human embryonic stem cells in 1998, ethics and policy debates centered on the moral status of the embryo—whether the 2- to 4-day-old blastocyst is a person, and whether we should protect it at all costs. As the research has moved quickly forward, however, new questions have emerged for the study of stem cell ethics, law, and policy. Powerful new lines made without eggs or embryos have recently been reported, the intellectual property and regulatory environment is uncertain, and clinical trials using adult stem cells and cells derived from embryonic stem cells are about to commence. The new landscape of ethics, law, and policy is discussed in the context of these developments, with an emphasis on the evaluation of risks and benefits for first-in-human clinical studies.
Brain tumor stem cells and the tumor microenvironment
Authors: Jandial Rahul , U Hoisang , Levy Michael L. , Snyder Evan Y.
Published: March 2008

✓ Recent advances in stem cell research and developmental neurobiology have uncovered new perspectives from which to investigate various forms of cancer. Specifically, the hypothesis that tumors consist of a subpopulation of malignant cells similar to stem cells is of great interest to scientists and clinicians and has been dubbed the “cancer stem cell hypothesis.” The region in which this assertion is most relevant is within the brain. Cancer stem cells have been isolated from brain tumors that exhibit characteristics of differentiation and proliferation normally seen only in neural stem cells. These cancer stem cells may be responsible for tumor origin, survival, and proliferation. Furthermore, these cells must be considered within their immediate microenvironment when investigating mechanisms of tumorigenesis. Evidence of brain tumor stem cells is reviewed along with the role of tumor environment as the context within which these cells should be understood.
Inhibition of oligodendrocyte precursor cell differentiation by myelin-associated proteins
Authors: Syed Yasir A. , Baer Alexandra S. , Lubec Gert , Hoeger Harald , Widhalm Georg , Kotter Mark R.
Published: March 2008

Object

Promoting repair of central nervous system (CNS) white matter represents an important approach to easing the course of a number of tragic neurological diseases. For this purpose, strategies are currently being evaluated for transplanting cells capable of generating new oligodendrocytes into areas of demyelination and/or enhancing the potential of endogenous stem/precursor cells to give rise to new oligodendrocytes. Emerging evidence, however, indicates that increasing the presence of cells capable of forming new myelin sheaths is not sufficient to promote repair because of unknown inhibitors that accumulate in lesions as a consequence of myelin degeneration and impair the generation of new oligodendrocytes. The aim of the present study was to characterize the nature of the inhibitory molecules present in myelin.

Methods

Differentiation of primary rat oligodendrocyte precursor cells (OPCs) in the presence of CNS and peripheral nervous system myelin was assessed by immunocytochemical methods. The authors further characterized the nature of the inhibitors by submitting myelin membrane preparations to biochemical precipitation and digestion. Finally, OPCs were grown on purified Nogo-A, oligodendrocyte myelin glycoprotein, and myelin-associated glycoprotein, the most prominent inhibitors of axon regeneration.

Results

Myelin membrane preparations induced a differentiation block in OPCs that was associated with down-regulation of expression of the transcription factor Nkx2.2. The inhibitory activity in myelin was restricted to the CNS and was predominantly associated with white matter. Furthermore, the results demonstrate that myelin proteins that are distinct from the most prominent inhibitors of axon outgrowth are specific inhibitors of OPC differentiation.

Conclusions

The inhibitory effect of unknown myelin-associated proteins should be considered in future treatment strategies aimed at enhancing CNS repair.
Recent advances in cell-based therapy for Parkinson disease
Authors: Astradsson Arnar , Cooper Oliver , Vinuela Angel , Isacson Ole
Published: March 2008

✓ In this review, the authors discuss recent advances in the field of cell therapy for Parkinson disease (PD). They compare and contrast recent clinical trials using fetal dopaminergic neurons. They attribute differences in cell preparation techniques, cell type specification, and immunosuppression as reasons for variable outcome and for some of the side effects observed in these clinical trials. To address ethical, practical, and technical issues related to the use of fetal cell sources, alternative sources of therapeutic dopaminergic neurons are being developed. The authors describe the progress in enrichment and purification strategies of stem cell–derived dopaminergic midbrain neurons. They conclude that recent advances in cell therapy for PD will create a viable long-term treatment option for synaptic repair for this debilitating disease.
A population‐based study of craniosynostosis in metropolitan Atlanta, 1989–2003
Authors: Boulet Sheree L. , Rasmussen Sonja A. , Honein Margaret A.
Published: March 2008

Craniosynostosis is a birth defect characterized by premature fusion of one or more cranial sutures. We describe the birth prevalence of craniosynostosis and related risk factors among infants born to residents of metropolitan Atlanta during 1989–2003. Data from the Metropolitan Atlanta Congenital Defects Program (MACDP) were used to identify infants with craniosynostosis. Case records with a code for craniosynostosis were reviewed to substantiate the diagnosis of craniosynostosis and to classify infants as having isolated craniosynostosis (no other unrelated major defects), multiple defects (one or more additional major, unrelated defects), or a syndrome (recognized or strongly suspected single‐gene condition or chromosome abnormality). Vital records data on births of Georgia residents were used to analyze craniosynostosis prevalence by year of birth, maternal race and age, parity, plurality, and infants' sex, birth weight, and gestational age. We identified 281 infants born with craniosynostosis in metropolitan Atlanta during 1989–2003: 84% with isolated craniosynostosis, 7% with multiple defects, and 9% with syndromes. The birth prevalence was 4.3 per 10,000 births, results consistent with findings from other population‐based studies using similar case definitions. Apert syndrome was diagnosed in 40% of the syndromic cases, and sagittal synostosis was diagnosed in 39% of the cases of nonsyndromic craniosynostosis. Maternal age 35 years or older, multiple birth, male sex, and birth weight >4,000 g were risk factors for craniosynostosis. Published 2008 Wiley‐Liss, Inc.
Revisitinghmeasured on UK LIS and IR academics
Authors: Sanderson Mark
Published: March 2008

A brief communication appearing in this journal ranked UK‐based LIS and (some) IR academics by theirh‐indexusing data derived from the Thomson ISI Web of Science™ (WoS). In this brief communication, the same academics were re‐ranked, using other popular citation databases. It was found that for academics who publish more in computer science forums, theirhwas significantly different due to highly cited papers missed by WoS; consequently, their rank changed substantially. The study was widened to a broader set of UK‐based LIS and IR academics in which results showed similar statistically significant differences. A variant ofh,hmx, was introduced that allowed a ranking of the academics using all citation databases together.
Domain‐independent automatic keyphrase indexing with small training sets
Authors: Medelyan Olena , Witten Ian H.
Published: March 2008

Keyphrases are widely used in both physical and digital libraries as a brief, but precise, summary of documents. They help organize material based on content, provide thematic access, represent search results, and assist with navigation. Manual assignment is expensive because trained human indexers must reach an understanding of the document and select appropriate descriptors according to defined cataloging rules. We propose a new method that enhances automatic keyphrase extraction by using semantic information about terms and phrases gleaned from a domain‐specific thesaurus. The key advantage of the new approach is that it performs well with very little training data. We evaluate it on a large set of manually indexed documents in the domain of agriculture, compare its consistency with a group of six professional indexers, and explore its performance on smaller collections of documents in other domains and of French and Spanish documents.
Incomplete cellular depopulation may explain the high failure rate of bovine ureteric grafts
Authors: Spark J I , Yeluri S , Derham C , Wong Y T , Leitch D
Published: March 2008

Background

The aim was to assess the results of a decellularized bovine ureter graft (SynerGraft®) for complex venous access.

Methods

Bovine ureter conduits were implanted in patients with a failed fistula or access graft in whom native vessels were unsuitable as conduits. Graft histories were obtained from all patients who had undergone this procedure at one institution. Failed grafts were explanted and subjected to histological examination. A sample of fresh bovine ureter was immunostained for galactose (α1 → 3) galactose (α-Gal).

Results

Nine patients with a median age of 46 (range 25–70) years underwent complex venous access surgery between August 2004 and November 2006 using a SynerGraft®. Graft types included loop superficial femoral artery to stump of long saphenous vein (four patients), loop brachial artery to vein (two), brachial artery to axillary vein (two) and left axillary artery to innominate vein (one). Three grafts developed aneurysmal dilatation and two thrombosed. Histological assessment of the explanted bovine ureters revealed acute and chronic transmural inflammation. Immunostaining of fresh bovine ureter suggested residual cells and the xenoantigen α-Gal.

Conclusion

Graft failure with aneurysmal dilatation and thrombosis in complex arteriovenous conduits using bovine ureter may be due to residual xenoantigens.
Mesh for hernia repair
Authors: Klinge U
Published: March 2008

Randomized control trials may be inappropriate
Relation between parenting stress and psychopathic traits among children
Authors: Fite Paula J. , Greening Leilani , Stoppelbein Laura
Published: March 2008

Parenting stress was examined as a correlate of psychopathic traits, specifically narcissism, callous/unemotional traits, and impulsivity, among school‐aged children while controlling for the variance explained by aggressive behavior. Participants included 212 children ranging from 6 to 12 years of age (M = 8.3 years) who were admitted to an acute child psychiatric inpatient unit for treatment. Parents completed standardized measures of aggression (Child Behavior Checklist; CBCL), psychopathic traits (Antisocial Process Screening Device; APSD), and parenting stress (Parenting Stress Index; PSI) at the time of the child's admission. Multiple regression analyses revealed that high levels of the PSI dimension attachment difficulties were associated with high levels of narcissism and callous/unemotional traits among the children while statistically controlling for aggression. The PSI dimension role restriction was also found to be negatively related to narcissism. These findings suggest that specific aspects of parenting stress may be related to child psychopathic traits and might aid with conceptualizing and developing treatment approaches for childhood behavior problems. Copyright © 2008 John Wiley & Sons, Ltd.
Judicial gatekeeping and the social construction of the admissibility of expert testimony
Authors: Merlino Mara L. , Murray Colleen I. , Richardson James T.
Published: March 2008

Content analysis of 192 U.S. District Court cases was conducted to investigate judges' evaluations of expert characteristics and evidence characteristics for toxicology, psychological/psychiatric, and damages testimony. Judges evaluated more expert characteristics, but not more evidence characteristics, as the number of months post‐Daubert increased (Hypotheses 1 and 2). More evidence characteristics were evaluated when evidence was quantitatively rather than qualitatively based (Hypothesis 3). The greatest number of evidence characteristics examined was for toxicology evidence (Hypothesis 4). Fewer expert characteristics were evaluated for admissible evidence, but more evidence characteristics were evaluated for inadmissible evidence (Hypothesis 5). All analyses were significant at .05. Implications for judges, attorneys, and experts are discussed. Copyright © 2008 John Wiley & Sons, Ltd.
Predictors of verdict and punitive damages in high‐stakes civil litigation
Authors: Vinson Katherine V. , Costanzo Mark A. , Berger, Ph.D. Dale E.
Published: March 2008

This research investigated demographic and attitudinal– psychological predictors of verdict and amount of punitive damages awarded in high‐stakes civil litigation. Four hundred and forty‐six surrogate jurors, selected to be representative of actual jurors, were exposed to realistic case presentations in insurance, tobacco, and pharmaceutical cases that were about to go to trial. Hierarchical regression revealed that perceptions of the existence of a litigation crisis predicted verdict in the tobacco and pharmaceutical cases after controlling for all other variables. Demographic variables predicted verdict and punitive damage awards only modestly and in different ways in the three cases. Need for cognition, strength of will and rationality, and a perception that there is a litigation crisis predicted the amount of punitive damages awarded in the tobacco case. Litigation crisis also predicted the amount of punitive damages awarded in the pharmaceutical case. Implications for jury selection are discussed. Copyright © 2008 John Wiley & Sons, Ltd.
Constrained Dansyl Derivatives Reveal Bacterial Specificity of Highly Conserved Thymidylate Synthases
Authors: Calò Sanuele , Tondi Donatella , Ferrari Stefania , Venturelli Alberto , Ghelli Stefano , Costi Maria Paola
Published: March 2008

The elucidation of the structural/functional specificities of highly conserved enzymes remains a challenging area of investigation, and enzymes involved in cellular replication are important targets for functional studies and drug discovery. Thymidylate synthase (TS, ThyA) governs the synthesis of thymidylate for use in DNA synthesis. The present study focused on Lactobacillus casei TS (LcTS) and Escherichia coli TS (EcTS), which exhibit 50 % sequence identity and strong folding similarity. We have successfully designed and validated a chemical model in which linear, but not constrained, dansyl derivatives specifically complement the LcTS active site. Conversely, chemically constrained dansyl derivatives showed up to 1000‐fold improved affinity for EcTS relative to the inhibitory activity of linear derivatives. This study demonstrates that the accurate design of small ligands can uncover functional features of highly conserved enzymes.
Partial splenic embolization for cancer patients with thrombocytopenia requiring systemic chemotherapy
Authors: Kauffman Christopher R. , Mahvash Armeen , Kopetz Scott , Wolff Robert A. , Ensor Joe , Wallace Michael J.
Published: March 2008

BACKGROUND.

Partial splenic embolization (PSE) has been used to improve hematologic parameters related to hypersplenism. The purpose of this study was to review our institutional experience with PSE for cancer patients with thrombocytopenia because of splenic sequestration precluding the administration of systemic therapy (ST).

METHODS.

A retrospective review of cancer patients undergoing PSE was undertaken. Twenty‐eight patients underwent PSE to correct thrombocytopenia to facilitate the initiation or resumption of ST. Primary and secondary endpoints of the current study included a platelet count increase > 150 K/UL and the initiation of ST, respectively. Periprocedural laboratory values and adverse events were recorded.

RESULTS.

Thirty PSEs were performed in 28 patients. Two patients underwent repeat PSE because of recurrent thrombocytopenia after the successful initiation of ST. For procedures with adequate follow‐up, primary and secondary endpoints were achieved in 96.3% (26 of 27 patients) and 95.7% (22 of 23 patients) of patients, respectively. The mean platelet count was 81 K/UL immediately before PSE and peaked at 293 K/UL after PSE. For 23 patients with frequent laboratory follow‐up, the mean time to a platelet count > 150 K/UL was 10 days. The mean hospital stay was 4.5 days. Postprocedure abdominal pain occurred in all patients. Fever was documented in 16 patients and pulmonary consolidation/atelectasis or effusion was documented in 10 patients; 9 patients received empiric antibiotic coverage. The median overall survival was 9.40 months (95% confidence interval, 8.2–10.7 months) among the 28 patients after PSE.

CONCLUSIONS.

PSE is a safe and effective means of managing thrombocytopenia secondary to hypersplenism to facilitate the administration of ST in patients with cancer. Cancer 2008. © 2008 American Cancer Society.
Endometrioid epithelial ovarian cancer
Authors: Storey Dawn J. , Rush Robert , Stewart Moira , Rye Tzyvia , Al‐Nafussi Awatif , Williams Alistair R. , Smyth John F. , Gabra Hani
Published: March 2008

BACKGROUND.

Clinicopathological features and outcome of women with endometrioid and serous ovarian adenocarcinoma were compared.

METHODS.

Between 1984 and 2004, baseline and follow‐up data were prospectively recorded on 1545 patients with ovarian cancer. Of these, 270 had pure endometrioid tumors; 659 had pure serous adenocarcinoma of the ovary. Response to platinum‐based chemotherapy (PBC) overall survival, stage‐for‐stage median progression‐free survival (PFS), and cause‐specific median survival were compared. Independent predictors of survival were examined by using multivariate analyses.

RESULTS.

Median age of diagnosis for patients with endometrioid tumors was younger than those with serous adenocarcinoma of the ovary (60 years vs 62 years; P = .013). They presented more often with early disease (stage I and II; 50% vs 17%; P < .001), had less ascites, and had better performance status both overall and for stage II and III disease. More endometrioid tumors were optimally debulked overall (71% vs 45%; P < .001), but there was no difference according to stage. Objective and CA125 PBC response rates were not significantly different, but median PFS was better for patients with endometrioid tumors (24 months vs 13 months; P < .0001) as was overall median survival (48 months vs 22 months; P < .0001). This relation remained for stage II and III disease and for moderately and poorly differentiated tumors. Patients with concurrent endometrioid ovarian and endometrial malignancies had a survival advantage compared with those with ovarian malignancies alone. Independent predictors of survival after PBC were histological type, debulking status, and disease stage.

CONCLUSIONS.

Despite similar PBC response rates, endometrioid histology is associated with better survival compared with serous adenocarcinoma of the ovary, even with stage III or poorly differentiated tumors. Cancer 2008. © 2008 American Cancer Society.
Distributing RePast agent‐based simulations with HLA
Authors: Minson R. , Theodoropoulos G. K.
Published: March 2008

Large, experimental multi‐agent system (MAS) simulations are highly demanding tasks, both computationally and developmentally. Agent toolkits provide reliable templates for the design of even the largest MAS simulations, without offering a solution to computational limitations. Conversely, distributed simulation architectures offer performance benefits, but the introduction of parallel logic can complicate the design process significantly. The motivations of distribution are not limited to this question of processing power. True interoperation of sequential agent‐simulation platforms would allow agents designed using different toolkits to transparently interact in common abstract domains. This paper discusses the design and implementation of a system capable of harnessing the computational power of a distributed simulation infrastructure with the design efficiency of an agent toolkit. The system permits integration, through a higher‐level architecture (HLA) federation, of multiple instances of the Java‐based lightweight agent‐simulation toolkit RePast. This paper defines abstractly the engineering process necessary in creating such middleware, and reports on the experience in the specific case of the RePast toolkit. The paper also presents performance results that illustrate that significant speedup can be achieved through the integration of RePast with HLA. Copyright © 2008 John Wiley & Sons, Ltd.
The development of a geospatial data Grid by integrating OGC Web services with Globus‐based Grid technology
Authors: Di Liping , Chen Aijun , Yang Wenli , Liu Yang , Wei Yaxing , Mehrotra Piyush , Hu Chaumin , Williams Dean
Published: March 2008

Geospatial science is the science and art of acquiring, archiving, manipulating, analyzing, communicating, modeling with, and utilizing spatially explicit data for understanding physical, chemical, biological, and social systems on the Earth's surface or near the surface. In order to share distributed geospatial resources and facilitate the interoperability, the Open Geospatial Consortium (OGC), an industry–government–academia consortium, has developed a set of widely accepted Web‐based interoperability standards and protocols. Grid is the technology enabling resource sharing and coordinated problem solving in dynamic, multi‐institutional virtual organizations. Geospatial Grid is an extension and application of Grid technology in the geospatial discipline. This paper discusses problems associated with directly using Globus‐based Grid technology in the geospatial disciplines, the needs for geospatial Grids, and the features of geospatial Grids. Then, the paper presents a research project that develops and deploys a geospatial Grid through integrating Web‐based geospatial interoperability standards and technology developed by OGC with Globus‐based Grid technology. The geospatial Grid technology developed by this project makes the interoperable, personalized, on‐demand data access and services a reality at large geospatial data archives. Such a technology can significantly reduce problems associated with archiving, manipulating, analyzing, and utilizing large volumes of geospatial data at distributed locations. Copyright © 2008 John Wiley & Sons, Ltd.
Service‐oriented approach to collaborative visualization
Authors: Wang H. , Brodlie K. W. , Handley J. W. , Wood J. D.
Published: March 2008

This paper presents a new service‐oriented approach to the design and implementation of visualization systems in a Grid computing environment. The approach evolves the traditional dataflow visualization system, based on processes communicating via shared memory or sockets, into an environment in which visualization Web services can be linked in a pipeline using the subscription and notification services available in Globus Toolkit 4. A specific aim of our design is to support collaborative visualization, allowing a geographically distributed research team to work collaboratively on visual analysis of data. A key feature of the system is the use of a formal description of the visualization pipeline, using the skML language first developed in the gViz e‐Science project. This description is shared by all collaborators in a session. In co‐operation with the e‐Viz project, we generate user interfaces for the visualization services automatically from the skML description. The new system is called notification‐service‐based collaborative visualization. A simple prototype has been built and is used to illustrate the concepts. Copyright © 2008 John Wiley & Sons, Ltd.
The XtreemFS architecture—a case for object‐based file systems in Grids
Authors: Hupfeld Felix , Cortes Toni , Kolbeck Björn , Stender Jan , Focht Erich , Hess Matthias , Malo Jesus , Marti Jonathan , Cesario Eugenio
Published: March 2008

In today's Grids, files are usually managed by Grid data management systems that are superimposed on existing file and storage systems. In this paper, we analyze this predominant approach and argue that object‐based file systems can be an alternative when adapted to the characteristics of a Grid environment. We describe how we are solving the challenge of extending the object‐based storage architecture for the Grid in XtreemFS, an object‐based file system for federated infrastructures. Copyright © 2008 John Wiley & Sons, Ltd.
Functionalized Multiwalled Carbon Nanotubes Through In Situ Electropolymerization of Brilliant Cresyl Blue for Determination of Epinephrine
Authors: Yi Hongchao , Zheng Dongyun , Hu Chengguo , Hu Shengshui
Published: March 2008

In this work, a polymeric brilliant cresyl blue (BCB) and dihexadecyl phosphate (DHP) dispersed Multi‐walled carbon nanotubes (MWNTs) composite film modified glass carbon electrode (PBCB‐MWNTs‐DHP/GCE) denoted as epinephrine (EP) sensor was prepared by an in‐situ electropolymerization method. The electrochemical response of EP at the sensor is much better. Voltammetric investigations indicated that the improved response of EP at the sensor mainly arose from the enhanced adsorption of EP at PBCB‐MWNTs‐DHP film, perhaps through the hydrogen bonding and π–π interactions between EP and PBCB. The sensor was applied to the determination of EP in injection by a standard addition method and the results were satisfied.
Electrocatalytic Reduction of Nitrite by Phosphotungstic Heteropolyanion. Application for Its Simple and Selective Determination
Authors: Ojani Reza , Rahmanifar Mohamad‐Safi , Naderi Padideh
Published: March 2008

Three couples of reversible redox peaks of the PW12O403− (PW12) anion, which are composed of two one‐electron and one two‐electron processes occur in the potential range from +0.25 to −0.7 V in aqueous solutions. The electrocatalytic reduction of nitrite has been studied by the first redox couple of the PW12 anion at the surface of a carbon paste electrode. Cyclic voltammetric and chronoamperometric techniques were used to investigate the suitability of PW12 anion as a mediator for nitrite electrocatalytic reduction in aqueous solution with strongly acidic concentration of H2SO4. Results showed that H2SO4 1.00 M is the best medium for this purpose. In the optimum concentration of H2SO4, the electrocatalytic ability about 500 mV can be seen and the homogeneous second‐order rate constant (ks) for nitrite coupled catalytically to PW12 anion was calculated as 2.52×103 M−1 s−1 using the Nicholson–Shain method. According to our voltammetric experiments, the catalytic reduction peak current was linearly dependent on the nitrite concentration and the linearity range obtained was 3×10−5 to 1.00×10−3 M. The detection limit has been found to be 2.82×10−5 M (2σ). This method has been applied as a selective, simple, and precise method for determination of nitrite in real samples.
Masked smoking‐related images modulate brain activity in smokers
Authors: Zhang Xiaochu , Chen Xiangchuan , Yu Yongqiang , Sun Delin , Ma Ning , He Sheng , Hu Xiaoping , Zhang Daren
Published: March 2008

The questions of whether and how indiscriminate drug‐related stimuli could influence drug‐users are important to our understanding of addictive behavior, but the answers are still inconclusive. In the present preliminary functional magnetic resonance imaging study using a backward masking paradigm, the effect of indiscriminate smoking‐related stimuli on 10 smokers and 10 nonsmokers was examined. The BOLD response showed a significant reduction (P = 0.001) in the right amygdala of smokers when they viewed but did not perceive masked smoking‐related stimuli, while no significant differences were found in the nonsmoker group. More voxels in anterior cingulate cortex were negatively correlated with the amygdala during the masked smoking‐related picture condition in smokers but not in nonsmokers, whereas more positively correlated voxels were observed during the masked neutral condition. The BOLD response in drug‐users indicates the amygdala responds to drug‐related stimuli that are below the perceptual threshold. The functional connectivity data suggest a functional interaction between the amygdala and the anterior cingulate cortex when drug users view 33ms back‐masked drug‐related stimuli. This observation suggests that the amygdala plays an important role in the indiscriminate drug‐related cue process. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Large‐scale neural model validation of partial correlation analysis for effective connectivity investigation in functional MRI
Authors: Marrelec G. , Kim J. , Doyon J. , Horwitz B.
Published: March 2008

Recent studies of functional connectivity based upon blood oxygen level dependent functional magnetic resonance imaging have shown that this technique allows one to investigate large‐scale functional brain networks. In a previous study, we advocated that data‐driven measures of effective connectivity should be developed to bridge the gap between functional and effective connectivity. To attain this goal, we proposed a novel approach based on the partial correlation matrix. In this study, we further validate the use of partial correlation analysis by employing a large‐scale, neurobiologically realistic neural network model to generate simulated data that we analyze with both structural equation modeling (SEM) and the partial correlation approach. Unlike real experimental data, where the interregional anatomical links are not necessarily known, the links between the nodes of the network model are fully specified, and thus provide a standard against which to judge the results of SEM and partial correlation analyses. Our results show that partial correlation analysis from the data alone exhibits patterns of effective connectivity that are similar to those found using SEM, and both are in agreement with respect to the underlying neuroarchitecture. Our findings thus provide a strong validation for the partial correlation method. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Microwave assisted extraction for the determination of ethyl glucuronide in urine by gas chromatography‐mass spectrometry
Authors: Freire Iván Álvarez , Barrera Ana María Bermejo , Silva Purificación Cid , Duque María Jesús Tabernero , Gómez Purificación Fernández , Eijo Patricia López
Published: March 2008

Alcohol is the most frequently abused ‘addictive substance’ that causes serious social problems throughout the world; thus alcoholism is of particular interest in clinical and forensic medicine. Ethyl glucuronide (EtG) is a marker of recent alcohol consumption that detects alcohol use reliably over a definite time period. The present paper describes a new method for the determination of EtG in urine. It was based both on microwave assisted extraction (MAE) to extract the analyte from urine samples, and gas chromatography‐mass spectrometry (GC‐MS) to identify and quantify the EtG in selected ion monitoring (SIM) mode. The method was applied to 33 urine samples from alcohol users, obtaining positive results in all cases. It was fully validated including a linear range (0.1–100 µg ml−1) and the main precision parameters. In summary, the use of microwave assisted extraction turned out to be a substantially simpler, faster and more sensitive procedure than any other conventional sample preparations. Copyright © 2008 John Wiley & Sons, Ltd.
Inhibition by vitamin C of apoptosis induced by N‐nitrosamines in HepG2 and HL‐60 cells
Authors: Arranz Nuria , Haza Ana I. , García Almudena , Delgado Ma Eugenia , Rafter Joseph , Morales Paloma
Published: March 2008

The aim of this study was to evaluate the effect of vitamin C towards N‐nitrosopyrrolidine (NPYR)‐ and N‐nitrosodimethylamine (NDMA)‐induced apoptosis in human hepatoma (HepG2) and leukemia (HL‐60) cell lines using flow cytometry analysis and the terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling assay (TUNEL). None of the vitamin C concentrations tested (1–100 µm) caused cytotoxicity in HepG2 cells. However, there were significant losses of HL‐60 cells viability, measured by MTT assay, 72 h after treatment with 50 and 100 µm vitamin C (29 and 46%, respectively). Moreover, an increase of lactate dehydrogenase release was significant with 50 µm at 72 h (28%) and with 100 µm of vitamin C at 48 and 72 h (27 and 36%, respectively). Also, the percentage of apoptotic HL‐60 cells found in TUNEL assay increased to 21% when they were treated with 100 µm vitamin C for 72 h. Thus, in subsequent simultaneous treatments with NPYR (30 and 50 mm) or NDMA (27 and 68 mm) and vitamin C, concentrations of 5–50 µm vitamin C were used. Our results revealed that vitamin C, at all concentrations and times tested, reduced the apoptosis induced by NPYR and NDMA in both cell lines, showing a similar effect in HepG2 and HL‐60 cells towards NPYR (50 mm) — 65 and 63% of reduction, respectively — whereas towards NDMA (27 mm) the inhibition was higher in HL‐60 than in HepG2 cells — 75 and 57%, respectively. Therefore, our findings suggest that inhibition of apoptosis may be one of the mechanisms by which vitamin C exerts its protective effect. Copyright © 2008 John Wiley & Sons, Ltd.
Role of hematopoietic microenvironment in prolonged impairment of B cell regeneration in age‐related stromal‐cell‐impaired SAMP1 mouse: effects of a single dose of 5‐fluorouracil
Authors: Tsuboi Isao , Hirabayashi Yoko , Harada Tomonori , Koshinaga Morimichi , Kawamata Tatsuro , Kanno Jun , Inoue Tohru , Aizawa Shin
Published: March 2008

In this study, we examined the age‐associated defect of stromal cells, which support B cell development, treated with 5‐fluorouracil (5‐FU) to induce severe perturbation of hematopoiesis, including B lymphocyte development, using SAMP1 mice exhibiting senescence‐mimicking stromal‐cell impairment after 30 weeks of age. Significant findings of this study are as follows: first, a marked and prolonged decrease in number of CFU‐preB cells in non‐SCI mice (58% of the steady‐state level) associated with more markedly depressed number of CFU‐preB cells in SCI mice (20% of the steady‐state level), despite the absence of difference in the number of CFU‐GMs during the period; second, in the non‐SCI mice, a significant and prolonged up‐regulation of GM‐CSF and IL‐6, positive regulators of myelopoiesis and suppressive factors of B lymphopoiesis, was observed. In SCI mice, greater and prolonged suppression of B lymphopoiesis was clearly demonstrated by the significant up‐regulation of the negative regulator TNF‐α associated with the concomitant marked down‐regulation of the positive regulator SDF‐1, although the increases of GM‐CSF and IL‐6 were limited. That is, ‘negative complementation’ makes preB recovery after 5‐FU treatment impaired and prolonged. Principal component analysis clearly showed differences in the cytokine expression patterns in both early and later phases and the time course of the expression pattern of each cytokine between SCI and non‐SCI mice without supervising information. An impaired regulation of the expressions of not only positive but also negative regulators after 5‐FU treatment was, in part, the cause of the impaired regeneration of CFU‐preB cells in SCI mice. Copyright © 2008 John Wiley & Sons, Ltd.
Effect of inflammation on kidney function and pharmacokinetics of COX‐2 selective nonsteroidal anti‐inflammatory drugs rofecoxib and meloxicam
Authors: Harirforoosh Sam , Jamali Fakhreddin
Published: March 2008

Chronic arthritis adversely affects glomerular function and nonsteroidal anti‐inflammatory drugs (NSAIDs) reduce electrolyte urinary excretion. In addition, both acute and chronic inflammations may alter clearance of drugs. We studied (a) the effects of inflammation on the renal function and pharmacokinetics of rofecoxib and meloxicam; (b) whether inflammation could exacerbate reduced electrolytes excretion changes observed with NSAIDs; and (c) the influence of inflammation on distribution of these drugs into the kidney. Single oral doses of rofecoxib (10 mg kg−1), meloxicam (3 mg kg−1) or placebo were administered to normal or pre‐adjuvant arthritic rats. Blood and urine samples were collected for the measurement of plasma nitrite, BUN and creatinine. The urinary excretion of sodium and potassium was also determined. Nitrite, BUN and plasma creatinine were increased starting on day 9 in the groups with inflammation. Sodium and potassium excretion rates were not affected by inflammation. Meloxicam did not alter the electrolyte excretion in any of the groups. Rofecoxib significantly decreased sodium and potassium excretion in normal rats and potassium excretion in inflamed rats. Inflammation significantly increased plasma concentrations of rofecoxib, but not meloxicam. The ratios of the kidney:plasma concentrations were not significantly altered by inflammation following either drug. Inflammation altered kidney function, demonstrated by increases in BUN and plasma creatinine. However, it did not influence the urinary electrolytes excretion. Since we have observed similar patterns of the effect of NSAIDs on kidney under healthy and inflammatory conditions, one may conclude that inflammation does not exacerbate the adverse effect. Copyright © 2008 John Wiley & Sons, Ltd.
Combined treatment with naringin and vitamin C ameliorates streptozotocin‐induced diabetes in male Wistar rats
Authors: Punithavathi V. R. , Anuthama R. , Prince P. Stanely Mainzen
Published: March 2008

Diet and nutrition have substantial impact on reducing the incidence of diabetes mellitus, where oxidative stress is an important etiopathological factor. The combined protective role of low dose of naringin (15 mg kg−1) and vitamin C (25 mg kg−1) and high dose of naringin (30 mg kg−1) and vitamin C (50 mg kg−1) on streptozotocin (STZ)‐induced toxicity was studied in male Wistar rats. To induce type II diabetes mellitus, rats were injected with STZ intraperitoneally at a dose of 45 mg kg−1 body weight. STZ‐induced diabetic rats showed significant increase in blood glucose, water intake, food intake and glycated hemoglobin and significant decrease in plasma insulin, total hemoglobin, body weight and liver glycogen. Diabetic rats also showed significant decrease in the activity of hexokinase and significant increase in the activities of glucose‐6‐phosphatase and fructose‐1,6‐bisphosphatase in liver and kidney. The levels of plasma thiobarbituric acid reactive substances, lipid hydroperoxides and vitamin E were elevated while the level of reduced glutathione was decreased in diabetic rats. Glycoprotein components such as hexose, hexosamine, fucose and sialic acid were increased in plasma, liver and kidney of diabetic rats. Oral administration of high doses of naringin (30 mg kg−1) and vitamin C (50 mg kg−1) to diabetic rats for a period of 21 days normalized all the above‐mentioned biochemical parameters. The effect exerted by naringin (30 mg kg−1) and vitamin C (50 mg kg−1) was similar to the effect exerted by insulin (6 units kg−1). Thus, our study shows the antihyperglycemic and antioxidant effects of naringin and vitamin C in STZ‐induced type II diabetes mellitus in rats. Copyright © 2008 John Wiley & Sons, Ltd.
In vitro oxime protection of human red blood cell acetylcholinesterase inhibited by diisopropyl‐fluorophosphate
Authors: Lorke D. E. , Hasan M. Y. , Arafat K. , Kuča K. , Musilek K. , Schmitt A. , Petroianu G. A.
Published: March 2008

Oximes are enzyme reactivators used in treating poisoning with organophosphorus cholinesterase (AChE) inhibitors. The oxime dose which can be safely administered is limited by the intrinsic toxicity of the substances such as their own AChE‐inhibiting tendency. Clinical experience with the available oximes is disappointing. To meet this need, new AChE reactivators of potential clinical utility have been developed. The purpose of the study was to estimate in vitro both the intrinsic toxicity and the extent of possible protection conferred by established (pralidoxime, obidoxime, HI‐6, methoxime, trimedoxime) and experimental (K‐type) oximes, using diisopropyl‐fluoro‐phosphate (DFP) as an AChE inhibitor. The IC50 of DFP against human red blood cell AChE was determined (∼120 nm). Measurements were then repeated in the presence of increasing oxime concentrations, leading to an apparent increase in DFP IC50. Calculated IC50 values were plotted against oxime concentrations to obtain an IC50 shift curve. The slope of this shift curve (tanα) was used to quantify the magnitude of the protective effect (nm IC50 increase per µm oxime). We show that, in the case of a linear relationship between oxime concentration and IC50, the binding constant K, determined using the Schild equation, equals IC50/DFP/tanα. Based on the values of tanα and of the binding constant K, some of the new K‐oxime reactivators are far superior to pralidoxime (tanα = 0.8), obidoxime (1.5), HI‐6 (0.8), trimedoxime (2.9) and methoxime (5.9), with K‐107 (17), K‐108 (20), and K‐113 (16) being the outstanding compounds. Copyright © 2008 John Wiley & Sons, Ltd.
Vinylic telluride derivatives as promising pharmacological compounds with low toxicity
Authors: Borges V. C. , Savegnago L. , Pinton S. , Jesse C. R. , Alves D. , Nogueira C. W.
Published: March 2008

The aim of the present study was to evaluate pharmacological and toxicological properties of (Z)‐2‐(methylthio)‐1‐(butyltelluro)‐1‐phenylethene 1a, (Z)‐1‐(4‐methylphenylsulfonyl)‐2‐(phenyltelluro)‐2‐phenylethene 1b, (Z)‐2‐(butyltelluro)‐1‐(benzylthio)‐1‐heptene 1c and (Z)‐2‐(phenylthio)‐1‐(butyltelluro)‐1‐phenylethene 1d. In vitro, vinylic telluride derivatives 1a, 1d and 1c were more effective in reducing lipid peroxidation than compound 1b. The maximal inhibitory effect of vinylic telluride derivatives on lipid peroxidation was in the following order: 1a = 1d > 1c > 1b. Compound 1b was more potent in inhibiting δ‐ALA‐D activity (δ‐aminolevulinate dehydratase) than compounds 1c and 1d. Based on the in vitro properties presented by compounds 1a (an antioxidant) and 1b (a pro‐oxidant), toxicological parameters were assessed in vivo and ex vivo in rats. Calculated LD50 of compounds 1a and 1b, administered by oral route, were 20.5 and 1.44 µmol kg−1, respectively. Compound 1b induced behavioral alterations in the open field test. Renal and spleenic δ‐ALA‐D activities were inhibited in rats treated orally with compound 1a. Compound 1b stimulated δ‐ALA‐D activity in liver and spleen of rats. Rats treated with compound 1b had increased hepatic, renal and spleenic lipid peroxidation. Renal and hepatic markers were not altered when compounds 1a and 1b were administered to rats at doses of around LD50, while compound 1a at high doses changed aspartate aminotransferase activity and urea levels. Based on in vitro results, this study demonstrated that compounds 1a and 1d are promising antioxidant compounds. Ex vivo data reinforce compound 1a as a promising drug for more detailed pharmacological studies. Copyright © 2008 John Wiley & Sons, Ltd.
Surface modification of non‐woven poly (ethylene terephthalate) fibrous scaffold for improving cell attachment in animal cell culture
Authors: Zhang Weiyuan , Yi Xiaoping , Sun Xiangming , Zhang Yuanxing
Published: March 2008

BACKGROUND: The development of carriers with biocompatible surfaces are required to meet the needs in animal cell culture. In this work, poly (ethylene terephthalate) (PET) fibrous scaffold surfaces were chemically modified to introduce diethylaminoethyl (DEAE) groups. A packed‐bed bioreactor with DEAE‐conjugated PET fibrous scaffolds was investigated for continuous production of HBsAg by r‐CHO cells.

RESULTS: The changes of surface properties were characterized by surface hydrophilicity, Attenuated total reflectance (ATR) analysis, element measurement, and scanning electron microscopy. The results showed that this treatment could improve surface hydrophilicity and roughness. Using an r‐CHO cell line as model cells, the feasibility of the DEAE‐conjugated PET fibrous scaffold in animal cell culture was evaluated by means of cell attachment efficiency measurement, MTT (3‐(4,5)‐dimethylthiathiazo(‐z‐yl)‐3,5‐di‐phenytetrazoliumromide) assay, and scanning electron microscopy observation. Enhancement of cell attachment and proliferation was exhibited in the cell culture on DEAE‐conjugated PET fibrous scaffolds. r‐CHO cells were cultured for continuous HBsAg production in a packed‐bed bioreactor with DEAE‐conjugated PET fibrous scaffolds. A cell density of 1.2 × 107 cells mL−1 working volume, cell viability of 92.8% and maximum HBsAg concentration of 3.1 mg L−1 were achieved.

CONCLUSION: The packed‐bed bioreactor system with DEAE‐conjugated PET fibrous scaffolds has the potential for industrial animal cell culture application. Copyright © 2008 Society of Chemical Industry