bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of the CXC Chemokine Interferon-γ-Inducible Protein 10 Regulates the Reparative Response Following Myocardial Infarction
Authors: Bujak Marcin , Dobaczewski Marcin , Gonzalez-Quesada Carlos , Xia Ying , Leucker Thorsten , Zymek Pawel , Veeranna Vikas , Tager Andrew M. , Luster Andrew D. , Frangogiannis Nikolaos G.
Published: September 2009

Rationale:

Interferon-γ-inducible protein (IP)-10/CXCL10, an angiostatic and antifibrotic chemokine with an important role in T-cell trafficking, is markedly induced in myocardial infarcts, and may regulate the reparative response.

Objective:

To study the role of IP-10 in cardiac repair and remodeling.

Methods and Results:

We studied cardiac repair in IP-10-null and wild-type (WT) mice undergoing reperfused infarction protocols and examined the effects of IP-10 on cardiac fibroblast function. IP-10-deficient and WT animals had comparable acute infarct size. However, the absence of IP-10 resulted in a hypercellular early reparative response and delayed contraction of the scar. Infarcted IP-10
−/−
hearts exhibited accentuated early dilation, followed by rapid wall thinning during infarct maturation associated with systolic dysfunction. Although IP-10-null and WT mice had comparable cytokine expression, the absence of IP-10 was associated with marked alterations in the cellular content of the infarct. IP-10
−/−
infarcts had more intense infiltration with CD45
+
leukocytes, Mac-2
+
macrophages, and α-smooth muscle actin (α-SMA)
+
myofibroblasts than WT infarcts but exhibited reduced recruitment of the subpopulations of leukocytes, T lymphocytes and α-SMA
+
cells that expressed CXCR3, the IP-10 receptor. IP-10 did not modulate cardiac fibroblast proliferation and apoptosis but significantly inhibited basic fibroblast growth factor-induced fibroblast migration. In addition, IP-10 enhanced growth factor-mediated wound contraction in fibroblast-populated collagen lattices.

Conclusions:

Endogenous IP-10 is an essential inhibitory signal that regulates the cellular composition of the healing infarct and promotes wound contraction, attenuating adverse remodeling. IP-10-mediated actions may be due, at least in part, to direct effects on fibroblast migration and function.
Differential Healing After Sirolimus, Paclitaxel, and Bare Metal Stent Placement in Combination With Peroxisome Proliferator-Activator Receptor γ Agonists
Authors: Finn Aloke V. , John Michael , Nakazawa Gaku , Polavarapu Rohini , Karmali Vinit , Xu Xin , Cheng Qi , Davis Talina , Raghunathan Chitra , Acampado Eduardo , Ezell Tucker , Lajoie Scott , Eppihimer Michael , Kolodgie Frank D. , Virmani Renu , Gold Herman Kalman
Published: September 2009

Rationale:

Sirolimus-eluting coronary stents (SESs) and paclitaxel-eluting coronary stents (PESs) are used to reduce restenosis but have different sites of action. The molecular targets of sirolimus overlap with those of the peroxisome proliferator-activated receptor (PPAR)γ agonist rosiglitazone (RSG) but the consequence of this interaction on endothelialization is unknown.

Objective:

Using the New Zealand white rabbit iliac model of stenting, we examined the effects of RSG on SESs, PESs, and bare metal stents endothelialization.

Methods and Results:

Animals receiving SESs, PESs, or bare metal stents and either RSG (3 mg/kg per day) or placebo were euthanized at 28 days, and arteries were evaluated by scanning electron microscopy. Fourteen-day organ culture and Western blotting of iliac arteries and tissue culture experiments were conducted. Endothelialization was significantly reduced by RSG in SESs but not in PESs or bare metal stents. Organ culture revealed reduced vascular endothelial growth factor in SESs receiving RSG compared to RSG animals receiving bare metal stent or PESs. Quantitative polymerase chain reaction in human aortic endothelial cells (HAECs) revealed that sirolimus (but not paclitaxel) inhibited RSG-induced vascular endothelial growth factor transcription. Western blotting demonstrated that inhibition of molecular signaling in SES+RSG–treated arteries was similar to findings in HAECs treated with RSG and small interfering RNA to PPARγ, suggesting that sirolimus inhibits PPARγ. Transfection of HAECs with mTOR (mammalian target of rapamycin) short hairpin RNA and with Akt2 small interfering RNA significantly inhibited RSG-mediated transcriptional upregulation of heme oxygenase-1, a PPARγ target gene. Chromatin immunoprecipitation assay demonstrated sirolimus interferes with binding of PPARγ to its response elements in heme oxygenase-1 promoter.

Conclusions:

mTOR/Akt2 is required for optimal PPARγ activation. Patients who receive SESs during concomitant RSG treatment may be at risk for delayed stent healing.
The Impact of the Extended Parallel Process Model on Stroke Awareness
Authors: Davis Stephen M. , Martinelli Diana , Braxton Brian , Kutrovac Kyle , Crocco Todd
Published: September 2009

Background and Purpose—

Studies continue to reveal persistent gaps in stroke awareness despite existing stroke messages, especially when the length of time from message exposure increases. Therefore, there is a need to discover messages that promote long-term retention of stroke knowledge. We modified a standard stroke education poster using one health communications model, Extended Parallel Process, to assess its comparative effect on public stroke awareness and information retention.

Methods—

This was a single blinded, randomized, pretest, posttest study using 2 age cohorts: younger (18 to 30 years) and older (50+ years). Stroke knowledge was measured by the 28-item Stroke Action Test taken before and after viewing either an Extended Parallel Process modified poster or a standard educational poster in widespread use and again 6 weeks later.

Results—

Overall, there were 274 participants (222 younger and 52 older) with 139 randomly assigned to view the Extended Parallel Process poster and 135 assigned to view the standard poster. There was no significant difference (
P
>0.05) in the average Stroke Action Test score change between poster groups at all 3 testing intervals, although there was a nonsignificant greater drop in Stroke Action Test scores observed in the control group at the 6-week follow-up (−3.52 versus −2.60;
P
=0.46). The observed power for this difference was only 11% due to attrition of study participants (total 6-week follow-up, n=170). The younger group did significantly better on the Stroke Action Test from baseline to immediate posttest when viewing either poster (
P
<0.05).

Conclusions—

A common stroke education poster modified according to the Extended Parallel Process model did not significantly increase stroke knowledge compared with a standard control. However, the Extended Parallel Process model may promote long-term stroke knowledge retention, although further studies are needed due to insufficient power from subject attrition.
Anticonvulsant Use and Outcomes After Intracerebral Hemorrhage
Authors: Naidech Andrew M. , Garg Rajeev K. , Liebling Storm , Levasseur Kimberly , Macken Micheal P. , Schuele Stephan U. , Batjer H. Hunt
Published: September 2009

Background and Purpose—

There are few data on the effectiveness and side effects of antiepileptic drug therapy after intracerebral hemorrhage. We tested the hypothesis that antiepileptic drug use is associated with more complications and worse outcome after intracerebral hemorrhage.

Methods—

We prospectively enrolled 98 patients with intracerebral hemorrhage and recorded antiepileptic drug use as either prophylactic or therapeutic along with clinical characteristics. Antiepileptic drug administration and free phenytoin serum levels were retrieved from the electronic medical records. Patients with depressed mental status underwent continuous electroencephalographic monitoring. Outcomes were measured with the National Institutes of Health Stroke Scale and modified Rankin Scale at 14 days or discharge and the modified Rankin Scale at 28 days and 3 months. We constructed logistic regression models for poor outcome at 3 months with a forward conditional model.

Results—

Seven (7%) patients had a clinical seizure, 5 on the day of intracerebral hemorrhage. Phenytoin was associated with more fever (
P
=0.03), worse National Institutes of Health Stroke Scale at 14 days (23 [9 to 42] versus 11 [4 to 23],
P
=0.003), and worse modified Rankin Scale at 14 days, 28 days, and 3 months. In a forward conditional logistic regression model, phenytoin prophylaxis was associated with an increased risk of poor outcome (OR, 9.8; 1.4 to 68.6;
P
=0.02), entering after admission National Institutes of Health Stroke Scale and age. Excluding patients with a seizure did not change the results. Levetiracetam was not associated with demographics, seizures, complications, or outcomes.

Conclusions—

Phenytoin was associated with more fever and worse outcomes after intracerebral hemorrhage.
Induced Spreading Depression Evokes Cell Division of Astrocytes in the Subpial Zone, Generating Neural Precursor-Like Cells and New Immature Neurons in the Adult Cerebral Cortex
Authors: Xue Jing-Hui , Yanamoto Hiroji , Nakajo Yukako , Tohnai Norimitsu , Nakano Yoshikazu , Hori Takuya , Iihara Koji , Miyamoto Susumu
Published: September 2009

Background and Purpose—

New immature neurons appear out of the germinative zone, in cortical Layers V to VI, after induced spreading depression in the adult rat brain. Because neural progenitors have been isolated in the cortex, we set out to determine whether a subgroup of mature cells in the adult cortex has the potential to divide and generate neural precursors.

Methods—

We examined the expression of endogenous markers of mitotic activity, proliferating cell nuclear antigen, and vimentin as a marker for neuronal progenitor cells, if any, in the adult rat cortex after spreading depression stimulation. Immunohistochemical analysis was also performed using antibodies for proliferating cell nuclear antigen, for vimentin, and for nestin. Nestin is a marker for activity dividing neural precursors.

Results—

At the end of spreading depression (Day 0), glial fibrillary acidic protein-positive cells in the subpial zone and cortical Layer I demonstrated increased mitotic activity, expressing vimentin and nestin. On Day 1, nestin
+
cells were found spreading in deeper cortical layers. On Day 3, vimentin
−
/nestin
+
, neural precursor-like cells appeared in cortical Layers V to VI. On Day 6, new immature neurons appeared in cortical Layers V to VI. Induced spreading depression evokes cell division of astrocytes residing in the subpial zone, generating neural precursor-like cells.

Conclusions—

Although neural precursor-like cells found in cortical Layers V to VI might have been transferred from the germinative zone rather than the cortical subpial zone, astrocytic cells in the subpial zone may be potent neural progenitors that can help to reconstruct impaired central nervous system tissue. Special caution is required when observing or treating spreading depression waves accompanying pathological conditions in the brain.
Assessing Schoolwide Cultural Competence: Implications for School Leadership Preparation
Authors: Bustamante Rebecca M. , Nelson Judith A. , Onwuegbuzie Anthony J.
Published: September 2009

Purpose: The initial purpose of this mixed methods study was to assess the instrument fidelity and construct-related validity of a 33-item instrument called the Schoolwide Cultural Competence Observation Checklist (SCCOC) by eliciting school leaders’ views. The SCCOC was designed as one tool for use in conducting school culture audits, which determine how well a school responds to the needs of diverse groups. The results revealed unexpected qualitative findings from school leaders’ narrative responses to open-ended items. The implications of these findings for school leaders and school leader preparation are discussed. Research Design: On a Web-based questionnaire, practicing school leaders in two large western states responded to open- and closed-ended items on the relevance of SCCOC items to cultural competence in actual school settings. Participants’ narrative responses were analyzed using an iterative process of coding and constant comparison to identify emerging themes. Themes were validated using intercoder reliability. Findings: Research team members reached consensus on four primary themes that emerged from analysis of narrative data: policy as a paradox, programs as instrumental to culturally competent practice, school culture and climate as integral to schoolwide cultural competence, and numerous barriers to cultural competence. Under the theme of barriers, five subthemes were revealed. Conclusions: The findings inform future research and the need to focus school leader preparation on examining personal biases, privilege, and beliefs about others who are different, as well as guiding leaders to develop culturally responsive skills and knowledge and the ability to assess schoolwide cultural competence.
How to Influence Patient Oral Hygiene Behavior Effectively
Authors: Clarkson J.E. , Young L. , Ramsay C.R. , Bonner B.C. , Bonetti D.
Published: September 2009

Considerable resources are expended in dealing with dental disease easily prevented with better oral hygiene. The study hypothesis was that an evidence-based intervention, framed with psychological theory, would improve patients’ oral hygiene behavior. The impact of trial methodology on trial outcomes was also explored by the conducting of two independent trials, one randomized by patient and one by dentist. The study included 87 dental practices and 778 patients (Patient RCT = 37 dentists/300 patients; Cluster RCT = 50 dentists/478 patients). Controlled for baseline differences, pooled results showed that patients who experienced the intervention had better behavioral (timing, duration, method), cognitive (confidence, planning), and clinical (plaque, gingival bleeding) outcomes. However, clinical outcomes were significantly better only in the Cluster RCT, suggesting that the impact of trial design on results needs to be further explored.
Hutchinson-Gilford Progeria Syndrome: Its Presentation in F. Scott Fitzgerald’s Short Story ‘The Curious Case of Benjamin Button’ and Its Oral Manifestations
Authors: Maloney W.J.
Published: September 2009

Hutchinson-Gilford Progeria Syndrome (HGPS) was first documented in the medical literature in 1886. A HGPS patient has the physical characteristics and appearances of an elderly individual. In 1921, F. Scott Fitzgerald published a short story entitled ‘The Curious Case of Benjamin Button’. The main character of Fitzgerald’s fictional work is born with a very rare condition in which he looks like an elderly person. The main difference between the fictional individual and individuals with HGPS is that Fitzgerald’s character becomes younger as the years go by.

This paper serves three purposes. The first purpose is to scientifically present the possibility that Fitzgerald consciously based his character, Benjamin Button, upon individuals with HGPS. The second purpose is to describe the rare condition of HGPS, along with its many manifestations in the head and neck region. The third purpose is to postulate that HGPS individuals might not only have the appearance of an aged person, but also might actually undergo true physical aging, which would enable researchers to gain valuable information into the treatment of ailments commonly associated with the natural process of aging.
ADHD Symptomatology and Adjustment to College in China and the United States
Authors: Norvilitis Jill M. , Sun Ling , Zhang Jie
Published: September 2009

This study examined ADHD symptomatology and college adjustment in 420 participants—147 from the United States and 273 from China. It was hypothesized that higher levels of ADHD symptoms in general and the inattentive symptom group in particular would be related to decreased academic and social adjustment, career decision-making self-efficacy, and poorer study skills in both countries. Results generally supported the hypotheses, indicating that the difficulties associated with inattention are cross-cultural and not specific to the United States.
Quantitative Structure‐Property Relationships Modeling to Predict In Vitro and In Vivo Binding of Drugs to the Bile Sequestrant, Colesevelam (Welchol)
Authors: Walker Joseph R. , Brown Karen , Rohatagi Shashank , Bathala Mohinder S. , Xu Chao , Wickremasingha Prachi K. , Salazar Daniel E. , Mager Donald E.
Published: September 2009

Quantitative structure‐property relationship (QSPR) models were developed to correlate physicochemical properties of structurally unrelated drugs with extent of in vitro binding to colesevelam, and predicted values were compared with drug exposure changes in vivo following coadministration. The binding of 17 drugs to colesevelam was determined by an in vitro dissolution drug‐binding assay. Data from several clinical studies in healthy volunteers to support administration of colesevelam in diabetic patients were also collected along with existing in vivo literature data and compared with in vitro results. Steric, electronic, and hydrophobic descriptors were calculated for test compounds, and univariate and partial least squares regression approaches were used to derive QSPR models to evaluate which of the molecular descriptors correlated best with in vitro binding. A quadrant analysis evaluated the correlation between predicted/actual in vitro binding results and the in vivo data. The in vitro binding assay exhibited high sensitivity, identifying those compounds with a low probability of producing relevant in vivo drug interactions. Drug lipophilicity was identified as the primary determinant of in vitro binding to colesevelam by the final univariate and partial least squares models (R2 = 0.69 and 0.98; Q2 = 0.48 and 0.59). The in vitro assay and in silico models represent predictive tools that may allow investigators to conduct only informative clinical drug interaction studies with colesevelam.
Pharmacokinetics and Pharmacodynamics of a Bolus and Infusion of Cangrelor: A Direct, Parenteral P2Y12 Receptor Antagonist
Authors: Akers Wendell S. , Oh Jennifer J. , Oestreich Julie H. , Ferraris Suellen , Wethington Mary , Steinhubl Steven R.
Published: September 2009

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cangrelor administered as an intravenous bolus plus a continuous infusion in healthy volunteers. Twenty‐two healthy volunteers are randomized to receive 1 of 2 intravenous cangrelor dosing regimens: a 15‐μg/kg bolus followed by a 2‐μg/kg/min infusion or a 30‐μg/kg bolus followed by a 4‐μg/kg/min infusion. The infusion is continued for 60 minutes, and serial blood samples are obtained for evaluation of pharmacokinetic and pharmacodynamic parameters. Administration of an intravenous bolus followed by a continuous infusion rapidly achieves maximum concentrations of cangrelor that are associated with extensive platelet inhibition within 2 minutes. Moreover, extensive platelet inhibition is maintained throughout the infusion period with near‐full recovery of platelet function within 60 to 90 minutes of terminating the infusion. The effect of high‐dose cangrelor is more consistent and demonstrates a greater level of inhibition on adenosine diphosphate—induced P‐selectin expression; however, no significant differences are observed between the 2 dosing regimens with regard to platelet aggregation or time to recovery of platelet function. Cangrelor administered as an intravenous bolus followed by a continuous infusion in healthy volunteers offers rapid and reversible inhibition of platelet function.
Bioavailability of Mycophenolate Mofetil and Enteric‐Coated Mycophenolate Sodium Is Differentially Affected by Pantoprazole in Healthy Volunteers
Authors: Rupprecht Korbinian , Schmidt Christoph , Raspé Anne , Schweda Frank , Shipkova Maria , Fischer Wolfgang , Bucher Michael , Kees Frieder , Faerber Lothar
Published: September 2009

The influence of pantoprazole 40 mg twice daily on the bioavailability of a single dose of mycophenolate mofetil 1000 mg or enteric‐coated mycophenolate sodium is investigated in healthy volunteers. The plasma concentrations of mycophenolic acid and of the inactive metabolite mycophenolic acid glucuronide are measured by high‐performance liquid chromatography. The pharmacokinetic parameters following sole administration are similar for mycophenolate mofetil and enteric‐coated mycophenolate sodium except for the time to peak concentration, which is longer in the enteric‐coated mycophenolate sodium group. Concomitant treatment with pantoprazole significantly (P < .001) lowers the mycophenolic acid exposure following administration of mycophenolate mofetil. The peak concentrations drop by 57%, and area under the curve decreases from 0 to 12 hours by 27%. In contrast, pantoprazole does not change the pharmacokinetics of enteric‐coated mycophenolate sodium. Given that mycophenolic acid exposure correlates with the incidence of biopsy‐proven acute rejections in renal transplant recipients, these findings may have clinical implications. Administration of pantoprazole in combination with mycophenolate mofetil could possibly result in an insufficient mycophenolic acid exposure, increasing the risk of treatment failure.
Representing and sharing folksonomies with semantics
Authors: Kim Hak-Lae , Decker Stefan , Breslin John G.
Published: September 2009

Websites that provide content creation and sharing features have become quite popular recently. These sites allow users to categorize and browse content using ‘tags’ or free-text keyword topics. Since users contribute and tag social media content across a variety of social web platforms, creating new knowledge from distributed tag data has become a matter of performing various tasks, including publishing, aggregating, integrating, and republishing tag data. However, there are a number of issues in relation to data sharing and interoperability when processing tag data across heterogeneous tagging platforms. In this paper we introduce a semantic tag model that aims to explicitly offer the necessary structure, semantics and relationships between tags. This approach provides an improved opportunity for representing tag data in the form of reusable constructs at a semantic level. We also demonstrate a prototype that consumes and makes use of shared tag metadata across heterogeneous sources.
An ‘anti-Catholicism of free trade?’ Religion and the Anglo-Italian negotiations of 1863
Authors: Raponi Danilo
Published: September 2009

This article focuses on the 1863 Anglo-Italian Commercial Treaty as a case study for a wider analysis of the relations between the newly unified Italy and Britain. The importance of this treaty lies chiefly in its peculiarity, mainly due to the fact that the British proposed the inclusion of a religious clause in its text. This clause was meant to protect Protestant missionaries operating in rural parts of Italy, where religious intolerance was still frequent. The resulting confrontation showed the extent to which lack of communication between the Board of Trade and the Foreign Office hampered the pursuit of British policy aims, reflecting the then fashionable combination of free trade and Protestantism to promote a form of ‘anglicized globalization’ in Southern Europe. This resulted in the frustration of British commercial interests as defined by the Chambers of Commerce. The present article throws new light on the multi-layered nature of the British engagement with Italy, which involved different economic and religious pressure groups, and confirms Peter Marsh’s thesis about the inadequacy of the British commercial approach to continental Europe in the age of free trade.
Confronting the Stigma of Eugenics
Authors: Ramsden Edmund
Published: September 2009

Building upon the work of Thomas Gieryn and Erving Goffman, this paper will explore how the concepts of stigma and boundary work can be usefully applied to history of population science. Having been closely aligned to eugenics in the early 20th century, from the 1930s both demographers and geneticists began to establish a boundary between their own disciplines and eugenic ideology. The eugenics movement responded to this process of stigmatization. Through strategies defined by Goffman as ‘disclosure’ and ‘concealment’, stigma was managed, and a limited space for eugenics was retained in science and policy. Yet by the 1960s, a revitalized eugenics movement was bringing leading social and biological scientists together through the study of the genetic demography of characteristics such as intelligence. The success of this programme of ‘stigma transformation’ resulted from its ability to allow geneticists and demographers to conceive of eugenic improvement in ways that seemed consistent with the ideals of individuality, diversity and liberty. In doing so, it provided them with an alternative, and a challenge, to more radical and controversial programmes to realize an optimal genotype and population. The processes of stigma attribution and management are, however, ongoing, and since the rise of the nature—nurture controversy in the 1970s, the use of eugenics as a ‘stigma symbol’ has prevailed.
Nations at Ease with Radical Knowledge
Authors: Horst Maja , Irwin Alan
Published: September 2009

In response to the recent troubled history of risk-related technological development in Europe, one institutional reaction has been to advocate public deliberation as a means of achieving broad societal consensus over socio-scientific futures. We focus on ‘consensusing’ and the expectation of consensus, and consider both their roots and their performative consequences. We argue that consensus should be seen not simply as the absence of disagreement, but as a particular political and ideological formation. We consider and explore the Danish model based on the folkelig concept of the common good, before turning to the wider European movement towards consensus-building. As presented here, consensusing becomes a focus for political contestation but also for nation- and institution-building. Rather than evaluating deliberation solely in terms of its short-term instrumental effects, consensusing should also be understood as performative of national and international identity.
Abuse of Growth Hormone Increases the Risk of Persistent de Quervain Tenosynovitis
Authors: Pagonis Thomas , Ditsios Konstantinos , Givissis Panagiotis , Pagonis Athanasios , Christodoulou Anastasios
Published: September 2009

Background

de Quervain tenosynovitis usually responds well to nonsurgical treatment.

Hypothesis

Growth hormone abuse is associated with increased de Quervain tenosynovitis incidence in weight-training persons.

Study Design

Cohort study; Level of evidence, 3.

Methods

We treated 19 weight-training male patients with de Quervain tenosynovitis. Nine were abusing growth hormone (group A), and 10 were not (group B). Four group A patients elected to cease growth hormone abuse. Treatment was stratified into 3 grades: (1) splinting and nonsteroidal anti-inflammatory drugs, (2) same as first grade but with the addition of cortisone injections, and (3) surgical decompression (after failure of treatment of first and second grades). Follow-up was at 3, 9, and 24 months.

Results

First follow-up: Only 33.3% of those using growth hormone in group A responded to splinting and nonsteroidal anti-inflammatory drugs, compared with 90% in group B. Six patients (66.6%) in group A experienced persistent symptoms and received second-grade treatment, compared with 1 patient in group B (10%). Second follow-up: Four patients (44.4%) in group A moved from second- to third-grade treatment, 1 symptom-free patient (11.1%) relapsed and received second-grade treatment while 2 (22.2%) requested conservative treatment, declining surgery. Group B patients were 100% symptom-free. Final follow-up: Six patients (66.6%) in group A were operated on and 1 (11.1%) suffered from persistent de Quervain tenosynovitis, declining surgery. In group B, 1 patient relapsed and was started on second-grade treatment. No patients in group B had surgery.

Conclusion

Our results suggest that growth hormone abuse is associated with a more recalcitrant form of de Quervain tenosynovitis that does not respond well to nonsurgical treatment, thus leading to increased likelihood of surgical decompression.
Barbed Suture for Gastrointestinal Closure: A Randomized Control Trial
Authors: Demyttenaere Sebastian V , Nau Peter , Henn Matthew , Beck Catherine , Zaruby Jeffrey , Primavera Michael , Kirsch David , Miller Jeffrey , Liu James J. , Bellizzi Andrew , Melvin W. Scott
Published: September 2009

In an effort to make laparoscopic suturing more efficient, the V-Loc advanced wound closure device (Covidien, Mansfield, MA) has been produced. This device is a self-anchoring barbed suture that obviates the need for knot tying. The goal of this initial feasibility study was to investigate the use of the barbed suture in gastrointestinal enterotomy closure. A randomized study of 12 pigs comparing enterotomy closure with barbed versus a nonbarbed suture of similar tensile strength was performed. To this end, 25 mm enterotomies were made in the stomach (1 control, 1 treatment), jejunum (2 controls, 2 treatments), and descending colon (1 control, 1 treatment). Animals were killed at 3, 7, and 14 days postoperatively (4 each group) and their gastrointestinal tracts harvested; 6 of the 8 enterotomies from each pig underwent burst strength testing. The remaining 2 were fixed in formalin and sent for histological examination. All 12 pigs survived until they were killed without any major complications. Enterotomy closure with barbed suture revealed adhesion scores, burst strength pressures, and histology scores that were similar to those for the control. Jejunal closures resulted in 6 failures at 7 days (3 control, 3 barbed) and 4 failures at 14 days (2 control, 2 barbed). The barbed suture significantly reduced suturing time in the stomach, jejunum, and colon. The V-Loc wound closure device appears to offer comparable gastrointestinal closure to 3-0 Maxon while being significantly faster. Further studies with V-Loc are required to assess its use in laparoscopic surgery.
Single-Site Laparoscopic Sleeve Gastrectomy: Preclinical Use of a Novel Multi-Access Port Device
Authors: Varela J. Esteban
Published: September 2009

Introduction: Single-site laparoscopy (SSL) has emerged as an alternative technique for sleeve gastrectomy. The author describes the preclinical technique of SSL sleeve gastrectomy through a novel multichannel port device in the porcine model. Methods: Anesthetized swine underwent 3-cm longitudinal supra-umbilical incision. A multichannel port device was inserted. A gastric sleeve was created by multiple applications of a 60-mm stapler. The access device’s channel housing was removed and the sleeve specimen exteriorized. Results: The mean operative time was 60 ± 10 minutes, and the mean estimated blood loss was 30 ± 5 cc. The multichannel port device allowed induction and maintenance of pneumoperitoneum throughout the procedure (range 12-15 mm Hg) with efficient rotation and substantial abdominal wall torque and minimal instrument clashing. Conclusion: SSL sleeve gastrectomy in the porcine model was facilitated by the use of a novel multichannel port device. Clinical studies are warranted.
Evaluating the forced oscillation technique in the detection of early smoking-induced respiratory changes
Authors: Faria Alvaro CD , Lopes Agnaldo J , Jansen José M , Melo Pedro L
Published: September 2009

Background

Early detection of the effects of smoking is of the utmost importance in the prevention of chronic obstructive pulmonary disease (COPD). The forced oscillation technique (FOT) is easy to perform since it requires only tidal breathing and offers a detailed approach to investigate the mechanical properties of the respiratory system. The FOT was recently suggested as an attractive alternative for diagnosing initial obstruction in COPD, which may be helpful in detecting COPD in its initial phases. Thus, the purpose of this study was twofold: (1) to evaluate the ability of FOT to detect early smoking-induced respiratory alterations; and (2) to compare the sensitivity of FOT with spirometry in a sample of low tobacco-dose subjects.

Methods

Results from a group of 28 smokers with a tobacco consumption of 11.2 ± 7.3 pack-years were compared with a control group formed by 28 healthy subjects using receiver operating characteristic (ROC) curves and a questionnaire as a gold standard. The early adverse effects of smoking were adequately detected by the absolute value of the respiratory impedance (Z4Hz), the intercept resistance (R0), and the respiratory system dynamic compliance (Crs, dyn).Z4Hzwas the most accurate parameter (Se = 75%, Sp = 75%), followed byR0andCrs, dyn. The performances of the FOT parameters in the detection of the early effects of smoking were higher than that of spirometry (p < 0.05).

Conclusion

This study shows that FOT can be used to detect early smoking-induced respiratory changes while these pathologic changes are still potentially reversible. These findings support the use of FOT as a versatile clinical diagnostic tool in aiding COPD prevention and treatment.
Selective activation of tumor growth-promoting Ca2+ channel MS4A12 in colon cancer by caudal type homeobox transcription factor CDX2
Authors: Koslowski Michael , Türeci Özlem , Huber Christoph , Sahin Ugur
Published: September 2009

Colon cancer-associated MS4A12 is a novel colon-specific component of store-operated Ca2+ (SOC) entry sensitizing cells for epidermal growth factor (EGF)-mediated effects on proliferation and chemotaxis. In the present study, we investigated regulation of the MS4A12 promoter to understand the mechanisms responsible for strict transcriptional restriction of this gene to the colonic epithelial cell lineage. DNA-binding assays and luciferase reporter assays showed that MS4A12 promoter activity is governed by a single CDX homeobox transcription factor binding element. RNA interference (RNAi)-mediated silencing of intestine-specific transcription factors CDX1 and CDX2 and chromatin immunoprecipitation (ChIP) in LoVo and SW48 colon cancer cells revealed that MS4A12 transcript and protein expression is essentially dependent on the presence of endogenous CDX2. In summary, our findings provide a rationale for colon-specific expression of MS4A12. Moreover, this is the first report establishing CDX2 as transactivator of tumor growth-promoting gene expression in colon cancer, adding to untangle the complex and conflicting biological functions of CDX2 in colon cancer and supporting MS4A12 as important factor for normal colonic development as well as for the biology and treatment of colon cancer.
Cellular transport of anti-inflammatory pro-drugs originated from a herbal formulation of Zingiber cassumunar and Nigella sativa
Authors: Tangyuenyongwatana Prasan , Kowapradit Jariya , Opanasopit Praneet , Gritsanapan Wandee
Published: September 2009

Background

The rhizome of Zingiber cassumunar and the seed of Nigella sativa are two ingredients in Thai traditional medicine to relieve dysmenorrhea and adjust the menstrual cycle. Mixture of these two herbs produces three esters, namely (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl linoleate (1), (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl oleate (2) and (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl palmitate (3). The aim of this study is to examine in vitro absorption of these esters and evaluate their transport across the membrane.

Methods

In vitro transport of these three esters was observed in Caco-2 cell monolayers. The ester compounds 1, 2 and 3 at a concentration of 10 μM were hydrolyzed by porcine liver esterase.

Results

All esters transported across the Caco-2 cell without enzymatic hydrolysis. The apparent permeability coefficients P
app of compound 1 at 53 μM and 106 μM were 13.94 (0.60) × 10-6 and 14.33 (0.17) × 10-6cm/s respectively, while those of compound 2 were 9.45 (0.29) × 10-6 and 10.08 (0.32) × 10-6cm/s, respectively. P
app values of compound 3 were 7.48 (0.31) × 10-6cm/s at 53 μM and 8.60 (0.55) × 10-6cm/s at 106 μM. P
app values of the parent compound (compound D), i.e. (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-ol were 8.53 (0.83) × 10-6cm/s at 53 μM and 16.38 (0.61) × 10-6cm/s at 106 μM. The ester hydrolysis of compounds 1, 2 and 3 by porcine liver esterase was monitored by HPLC and the hydrolysis reactions were completed within 10 minutes.

Conclusion

Using the Caco-2 cell monolayer model, the present study finds that compounds (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl linoleate (1), (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl oleate (2) and (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-yl palmitate (3) originated from Prasaplai preparation (a Thai herbal formula) may be transported through a facilitated mechanism and serve as pro-drugs to increase the compound D level in the blood.
Determination of genomic DNA sequences for beta-tubulin isotype 1 from multiple species of cyathostomin and detection of resistance alleles in third-stage larvae from horses with naturally acquired infections
Authors: Lake Sarah L , Matthews Jacqueline B , Kaplan Ray M , Hodgkinson Jane E
Published: September 2009

Background

Genetic resistance against benzimidazole (BZ) anthelmintics is widespread in cyathostomins, the commonest group of intestinal parasitic nematodes of horses. Studies of BZ-resistant nematodes of sheep, particularly Haemonchus contortus, have indicated that an anthelmintic resistance-conferring T/A polymorphism, encoding an F (phenylalanine) to Y (tyrosine) substitution, in beta-tubulin isotype 1 is present at two loci, codons 167 and 200 (F167Y, F200Y). Recent studies using complementary (c) DNA derived from BZ-susceptible and -resistant cyathostomins identified statistical differences in the frequency of the BZ-resistant A allele at these loci. However, the lack of high-throughput genomic DNA-based detection of polymorphisms limits the study of eggs or larvae from field isolates. In the present study, we report genomic DNA sequences for beta-tubulin isotype 1 from multiple cyathostomin species, thus facilitating the development of pyrosequencing assays to genetically characterize third-stage larvae (L3s) of cyathostomins from mixed-species field isolates.

Results

Sequence analysis of the beta-tubulin isotype 1 gene in a common species, Cylicocyclus nassatus, indicates a revised genomic structure to published data, revealing that codons 167 and 200 are located on separate exons. A consensus sequence was generated from 91 and 76 individual cyathostomins for the regions spanning codons 167 and 200, respectively. A multi-species genomic DNA-based assay was established to directly pyrosequence individual L3 from field samples of unknown species and BZ sensitivity in a 96-well plate. In this format, the assay to detect F167Y gave a 50-90% success rate. The optimisation of the assay at codon 200 is currently underway. Subsequently, the genotype at F167Y was determined for 241 L3s, collected prior to and after BZ treatment. These results demonstrated a reduction in the heterozygous genotype, TTC/TAC, and an increase in the homozygous resistant genotype TAC/TAC in post-treatment samples. However, the differences in allele frequencies determined before and after BZ treatment were not statistically significant.

Conclusion

Extensive genomic DNA sequence, spanning codons 167 and 200 of the beta-tubulin isotype 1 gene, was generated from multiple cyathostomin species. The data facilitated the development of a pyrosequencing assay, capable of detecting the genotype of individual cyathostomin L3s derived from mixed-species field samples. Differences in codon 167 allele frequencies were observed in L3s isolated pre- and post-BZ treatment.
Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium
Authors: Stabler Richard A , He Miao , Dawson Lisa , Martin Melissa , Valiente Esmeralda , Corton Craig , Lawley Trevor D , Sebaihia Mohammed , Quail Michael A , Rose Graham , Gerding Dale N , Gibert Maryse , Popoff Michel R , Parkhill Julian , Dougan Gordon , Wren Brendan W
Published: September 2009

Background

The continued rise of Clostridium difficile infections worldwide has been accompanied by the rapid emergence of a highly virulent clone designated PCR-ribotype 027. To understand more about the evolution of this virulent clone, we made a three-way genomic and phenotypic comparison of an 'historic' non-epidemic 027 C. difficile (CD196), a recent epidemic and hypervirulent 027 (R20291) and a previously sequenced PCR-ribotype 012 strain (630).

Results

Although the genomes are highly conserved, the 027 genomes have 234 additional genes compared to 630, which may contribute to the distinct phenotypic differences we observe between these strains relating to motility, antibiotic resistance and toxicity. The epidemic 027 strain has five unique genetic regions, absent from both the non-epidemic 027 and strain 630, which include a novel phage island, a two component regulatory system and transcriptional regulators.

Conclusions

A comparison of a series of 027 isolates showed that some of these genes appeared to have been gained by 027 strains over the past two decades. This study provides genetic markers for the identification of 027 strains and offers a unique opportunity to explain the recent emergence of a hypervirulent bacterium.
Foxl2, a Forkhead Transcription Factor, Modulates Nonclassical Activity of the Estrogen Receptor-α
Authors: Kim So-Youn , Weiss Jeffrey , Tong Minghan , Laronda Monica M. , Lee Eun-Jig , Jameson J. Larry
Published: September 2009

Foxl2 is a forkhead transcription factor required for ovary development and ovarian follicle maturation. In this report, we identified and characterized a functional relationship between Foxl2 expression and estrogen receptor (ER)-α signaling. We show that Foxl2 has no effect on classical ERα-mediated transcription, which occurs through canonical estrogen response elements. However, Foxl2 suppresses ERα signaling through nonclassical tethered transcriptional pathways. Specifically, the selective ER modulator tamoxifen stimulates activator protein-1 (AP1)-dependent transcription via the ERα, and this enhancement is blocked by Foxl2. Two lines of evidence suggest that Foxl2 suppression is mediated by physical interactions with ERα rather than direct action at AP1 binding sites. First, ERα is coimmunoprecipitated with Foxl2. Second, activation of a upstream activating sequence (UAS) reporter by Gal4-cJun in the presence of ERα and tamoxifen was blocked by Foxl2, demonstrating suppression in the absence of an AP1 site. Cyclooxygenase-2 (COX2), which is required for ovulation, was identified through expression profiling as a candidate physiological target for nonclassical ERα signaling and thus modulation by ERα/Foxl2 interactions. This possibility was confirmed by two sets of experiments. COX2 protein levels were induced by ERα in the presence of tamoxifen, and protein expression was suppressed by Foxl2. In addition, ERα stimulation of the COX2 promoter was repressed by Foxl2. We conclude that ERα and Foxl2 interact and that Foxl2 selectively suppresses ERα-mediated transcription of AP1-regulated genes. These data provide a potential point of convergence for ERα and Foxl2 to regulate ovarian development and function.
Sex Steroid-Dependent and -Independent Action of Hydroxysteroid (17β) Dehydrogenase 2: Evidence from Transgenic Female Mice
Authors: Shen ZhongYi , Saloniemi Taija , Rönnblad Aino , Järvensivu Päivi , Pakarinen Pirjo , Poutanen Matti
Published: September 2009

We have recently generated transgenic (TG) mice overexpressing human hydroxysteroid (17β) dehydrogenase 2 enzyme (HSD17B2TG mice) under the ubiquitous chicken β-actin promoter. As shown in the present study, the HSD17B2TG female mice presented with slower gain of body weight as compared with the wild-type (WT) littermates and suffered from ovarian dysfunction and mammary gland hyperplasia associated with increased expression of multiple pregnancy-associated genes. The macroscopic phenotype observed in the mammary gland was likely to be dependent on the increased progesterone and prolactin secretion, and a normal histological appearance was observed in HSD17B2TG mammary gland transplanted into a WT host. However, a significant suppression of several known estrogen target genes in the HSD17B2TG mammary transplants in WT females was observed, suggesting that HSD17B2 modulates estrogen action in vivo. Interestingly, the growth retardation of HSD17B2TG females was not efficiently rescued in the bi-TG mice expressing both HSD17B2 and HSD17B1 enzymes, and the bi-TG mice presented with certain masculinized phenotypes, including lack of nipples and closed vagina, recently reported for HSD17B1TG females. The present data suggest that HSD17B2 expression affects both sex steroid-independent and steroid-dependent pathways.
Coming into bloom: the specification of floral meristems
Authors: Liu Chang , Thong Zhonghui , Yu Hao
Published: September 2009

In flowering plants, the founder cells from which reproductive organs form reside in structures called floral meristems. Recent molecular genetic studies have revealed that the specification of floral meristems is tightly controlled by regulatory networks that underpin several coordinated programmes, from the integration of flowering signals to floral organ formation. A notable feature of certain regulatory genes that have been newly implicated in the acquisition and maintenance of floral meristem identity is their conservation across diverse groups of flowering plants. This review provides an overview of the molecular mechanisms that underlie floral meristem specification in Arabidopsis thaliana and, where appropriate, discusses the conservation and divergence of these mechanisms across plant species.
A murine model of myeloma that allows genetic manipulation of the host microenvironment
Authors: Fowler Jessica A. , Mundy Gregory R. , Lwin Seint T. , Lynch Conor C. , Edwards Claire M.
Published: September 2009

Multiple myeloma, and the associated osteolytic bone disease, is highly dependent upon cellular interactions within the bone marrow microenvironment. A major limitation of existing myeloma models is the requirement for a specific host strain of mouse, preventing molecular examination of the bone marrow microenvironment. The aim of the current study was to develop a model of myeloma in which the host microenvironment could be modified genetically. The Radl 5T murine model of myeloma is well characterized and closely mimics human myeloma. In the current study, we demonstrate 5T myeloma establishment in recombination activating gene 2 (RAG-2)-deficient mice, which have improper B- and T-cell development. Importantly, these mice can be easily bred with genetically modified mice to generate double knockout mice, allowing manipulation of the host microenvironment at a molecular level. Inoculation of 5TGM1 myeloma cells into RAG-2−/− mice resulted in myeloma development, which was associated with tumor growth within bone and an osteolytic bone disease, as assessed by microcomputed tomography (microCT), histology and histomorphometry. Myeloma-bearing RAG-2−/− mice displayed many features that were similar to both human myeloma and the original Radl 5T model. To demonstrate the use of this model, we have examined the effect of host-derived matrix metalloproteinase 9 (MMP-9) in the development of myeloma in vivo. Inoculation of 5TGM1 myeloma cells into mice that are deficient in RAG-2 and MMP-9 resulted in a reduction in both tumor burden and osteolytic bone disease when compared with RAG-2-deficient wild-type myeloma-bearing mice. The establishment of myeloma in RAG-2−/− mice permits molecular examination of the host contribution to myeloma pathogenesis in vivo.