bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antihyperalgesic/Antinociceptive Effects of Ceftriaxone and Its Synergistic Interactions with Different Analgesics in Inflammatory Pain in Rodents
Authors: Stepanovic´-Petrovic´ Radica M. , Micov Ana M. , Tomic´ Maja A. , Kovacˇevic´ Jovana M. , Boškovic´ Bogdan D. 
Published: September 2013

Abstract

Background:
The β-lactam antibiotic ceftriaxone stimulates glutamate transporter GLT-1 expression and is effective in neuropathic and visceral pain models. This study examined the effects of ceftriaxone and its interactions with different analgesics (ibuprofen, celecoxib, paracetamol, and levetiracetam) in somatic and visceral pain models in rodents.

Methods:
The effects of ceftriaxone (intraperitoneally/intraplantarly), analgesics (orally), and their combinations were examined in the carrageenan-induced paw inflammatory hyperalgesia model in rats (n = 6–12) and in the acetic acid-induced writhing test in mice (n = 6–10). The type of interaction between ceftriaxone and analgesics was determined by isobolographic analysis.

Results:
Pretreatment with intraperitoneally administered ceftriaxone (10–200 mg/kg per day) for 7 days produced a significant dose-dependent antihyperalgesia in the somatic inflammatory model. Acute administration of ceftriaxone, via either intraperitoneal (10–200 mg/kg) or intraplantar (0.05–0.2 mg per paw) routes, produced a significant and dose-dependent but less efficacious antihyperalgesia. In the visceral pain model, significant dose-dependent antinociception of ceftriaxone (25–200 mg/kg per day) was observed only after the 7-day pretreatment. Isobolographic analysis in the inflammatory hyperalgesia model revealed approximately 10-fold reduction of doses of both drugs in all examined combinations. In the visceral nociception model, more than 7- and 17-fold reduction of doses of both drugs was observed in combinations of ceftriaxone with ibuprofen/paracetamol and celecoxib/levetiracetam, respectively.

Conclusions:
Ceftriaxone exerts antihyperalgesia/antinociception in both somatic and visceral inflammatory pain. Its efficacy is higher after a 7-day pretreatment than after acute administration. The two-drug combinations of ceftriaxone and the nonsteroidal analgesics/levetiracetam have synergistic interactions in both pain models. These results suggest that ceftriaxone, particularly in combinations with ibuprofen, celecoxib, paracetamol, or levetiracetam, may provide useful approach to the clinical treatment of inflammation-related pain.
Complete Genome Sequence of a Cytomegalovirus Towne-BAC (Bacterial Artificial Chromosome) Isolate Maintained in Escherichia coli for 10 Years and Then Serially Passaged in Human Fibroblasts
Authors: Brechtel Teal , Tyner Molly , Tandon Ritesh 
Published: September 2013

ABSTRACT
Here, we present the complete genome sequence of a cytomegalovirus, the Towne-BAC (bacterial artificial chromosome) isolate, which was maintained in bacterial cells for 10 years and then serially passaged in human fibroblasts for 10 passages. A total of 132 nucleotide differences were discovered in the Towne sequence compared to the reference sequence (GenBank accession no. AC146851).
Draft Genome Sequence of the Earliest Cronobacter sakazakii Sequence Type 4 Strain, NCIMB 8272
Authors: Masood Naqash , Moore Karen , Farbos Audrey , Hariri Sumyya , Paszkiewicz Konrad , Dickins Ben , McNally Alan , Forsythe Stephen 
Published: September 2013

ABSTRACT

The
Cronobacter sakazakii
clonal lineage defined as sequence type 4 (ST4) is associated with severe cases of neonatal meningitis and persistence in powdered infant formula. For genome sequencing of the earliest deposited culture collection strain of
Cronobacter sakazakii
ST4, we used the strain NCIMB 8272, originally isolated from milk powder in 1950.
RAC1: An Emerging Therapeutic Option for Targeting Cancer Angiogenesis and Metastasis
Authors: Bid Hemant K. , Roberts Ryan D. , Manchanda Parmeet K. , Houghton Peter J. 
Published: September 2013

Abstract
Angiogenesis and metastasis are well recognized as processes fundamental to the development of malignancy. Both processes involve the coordination of multiple cellular and chemical activities through myriad signaling networks, providing a mass of potential targets for therapeutic intervention. This review will focus on one master regulator of cell motility, RAC1, and the existing data with regard to its role in cell motility, including particular roles for tumor angiogenesis and invasion/metastasis. We also emphasize the preclinical investigations carried out with RAC1 inhibitors to evaluate the therapeutic potential of this target. Herein, we explore potential future directions as well as the challenges of targeting RAC1 in the treatment of cancer. Recent insights at the molecular and cellular levels are paving the way for a more directed and detailed approach to target mechanisms of RAC1 regulating angiogenesis and metastasis. Understanding these mechanisms may provide insight into RAC1 signaling components as alternative therapeutic targets for tumor angiogenesis and metastasis. Mol Cancer Ther; 12(10); 1925–34. ©2013 AACR.
Big Punches Come in Nanosizes for Chemoprevention
Authors: Sharma Dipali , Sukumar Saraswati 
Published: September 2013

AbstractLiterature to support the chemopreventive potential of several bioactive molecules has been prolific and convincing, but the clinical development of these agents has been slow. Major hurdles for development of bioactive chemoprevention approaches include low potency, lack of reliable formulations with high bioavailability that are suitable for oral administration, and relevant preclinical primary prevention models that use meaningful doses that can be translated to humans. The paper presented in this issue (Grandhi and colleagues) is an important step forward in this direction. It shows the efficacy of an oral, low dose, solid-lipid nanoparticles encapsulated curcumin and aspirin combined with free sulforaphane for long-term chemoprevention of pancreatic cancer in a carcinogen-induced hamster model. Reproducing this benefit in multiple cancer models, accompanied by development of intermediate markers of response will allow rapid translation of these findings. It will constitute the first successful multipronged attack at key pathways known to initiate and promote carcinogenesis. Cancer Prev Res; 6(10); 1007–10. ©2013 AACR.
Soluble Jagged1 Inhibits Pulmonary Hypertension by Attenuating Notch Signaling
Authors: Xiao Yongguang , Gong Dan , Wang Wei 
Published: September 2013

Objective—
Notch signaling has been implicated in the development of pulmonary arterial hypertension (PH) as reflected by increased expression of Notch member proteins that induce the proliferation of pulmonary arterial smooth muscle cells (PASMCs). Soluble Jagged1 (sJag1) has been shown to inhibit Notch signaling in vitro and in vivo; however, its capacity to suppress PH remains unknown.

Approach and Results—

Notch1, Notch3, Jagged1, and Herp2 protein were highly expressed in both the mouse model of hypoxia-induced PH and the rat model of monocrotaline-induced PH. By attenuation and reversal of multiple pathological processes that were associated with PH, adenoviral sJag1 transfection significantly reduced the proliferation and enhanced the apoptosis of PASMCs in PH, whereas vehicle had no effect. The sJag1 inhibitory effect on Notch activation is likely related to its interference with ligand-induced signaling. Importantly, the administration with adenoviral sJag1 improved the survival rate of PH rats. Furthermore, sJag1 can restore the PH-PASMCs phenotype from the dedifferentiated to the differentiated state, by giving a positive effect on the physical binding of myocardin to the CC(A/T)
n
GG (CArG)-containing regions of vascular smooth muscle cells–specific promoters.

Conclusions—
Our results demonstrated that the potential therapeutic use of the sJag1 may not only inhibit the proliferation of PASMCs but also restore the PH-PASMCs phenotype from the dedifferentiated to the differentiated state through interference with Notch–Herp2 signaling.
Loss of Cellular Inhibitor of Apoptosis Protein 2 Reduces Atherosclerosis in Atherogenic apoE
−/−
C57BL/6 Mice on High‐Fat Diet
Authors: Sleiman Lyne , Beanlands Rob , Hasu Mirela , Thabet Mohamed , Norgaard Alex , Chen YX , Holcik Martin , Whitman Stewart 
Published: September 2013

Background

Cellular inhibitor of apoptosis protein 2 (c
IAP
2) is predicted to participate in atherosclerosis; however, its direct role in atherosclerosis development has not been investigated. We aimed to examine and assess the loss of c
IAP
2 on atherosclerosis lesion development.

Methods and Results

We used
apoE
−/−
C57BL/6 male mice, either c
IAP
2
−/−
or c
IAP
2
+/+
. At 8 weeks, mice were fed a high‐fat diet (
HFD
) for 4 and 12 weeks. Aortic root was serially sectioned and stained with
Sudan
IV,
CD
68, α‐actin, and terminal deoxynucleotidyl transferase dUTP nick end labeling (
TUNEL
).

c
IAP
2

−/−
mice displayed a significant decrease in atherosclerotic lesion's macrophage number after 4 weeks of
HFD
. Similarly, decrease in lesion area at 4 and 12 weeks
HFD
was detected by use of en face analysis (

c
IAP
2

−/−
0.58±0.37% versus

c
IAP
2

+/+
1.51±0.79% [
P
=0.0056]); (

c
IAP
2

−/−
9.34±4.88% versus

c
IAP
2

+/+
17.65±6.24% [
P
=0.0019]). Aortic root lesion area after 4 and 12 weeks of
HFD
also decreased (

c
IAP
2

−/−
0.0328±0.014 mm
2
versus

c
IAP
2

+/+
0.0515±0.021 mm
2
[
P
=0.022]); (

c
IAP
2

−/−
0.3614±0.1157 mm
2
versus

c
IAP
2

+/+
0.4901±0.125 mm
2
[
P
=0.065]).
TUNEL
analysis after 4 and 12 weeks of
HFD
showed a 2.5‐fold increase in
TUNEL
+ cells (

c
IAP
2

−/−
4.47±2.26% versus

c
IAP
2

+/+
1.74±0.98% [
P
=0.036]); (

c
IAP
2

−/−
2.39±0.75% versus

c
IAP
2

+/+
1.29±0.47% [
P
=0.032]).
Smooth muscle cell
content in

c
IAP
2

−/−
mice was 3.075±3.3% compared with

c
IAP
2

+/+
with 0.085±0.1% (
P
=0.0071).

Conclusions

Results uncover a key role for c
IAP
2 in atherosclerotic lesion development, and targeting it may represent a novel therapeutic strategy.
Noninvasive MRI Monitoring of the Effect of Interventions on Endothelial Permeability in Murine Atherosclerosis Using an Albumin‐Binding Contrast Agent
Authors: Phinikaridou Alkystis , Andia Marcelo E. , Passacquale Gabriella , Ferro Albert , Botnar René M. 
Published: September 2013

Background

Endothelial dysfunction promotes atherosclerosis. We investigated whether in vivo magnetic resonance imaging (
MRI
) using an albumin‐binding contrast agent, gadofosveset, could monitor the efficacy of minocycline and ebselen in reducing endothelial permeability and atherosclerotic burden in the brachiocephalic artery of high‐fat diet (
HFD
)–fed ApoE
−/−
mice.

Methods and Results

ApoE
−/−
mice were scanned 12 weeks after commencement of either a normal diet (controls) or an
HFD
.
HFD
‐fed ApoE
−/−
mice were either untreated or treated with minocycline or ebselen for 12 weeks. Delayed‐enhancement
MRI
and T
1
mapping of the brachiocephalic artery, 30 minutes after injection of gadofosveset, showed increased vessel wall enhancement and relaxation rate (R
1
, s
−1
) in untreated
HFD
‐fed ApoE
−/−
mice (R
1
=3.8±0.52 s
−1
) compared with controls (R
1
=2.15±0.34 s
−1
,
P
<0.001). Conversely, minocycline‐treated (R
1
=2.7±0.17 s
−1
,
P
<0.001) and ebselen‐treated (R
1
=2.7±0.23 s
−1
,
P
<0.001) ApoE
−/−
mice showed less vessel wall enhancement compared with untreated
HFD
‐fed ApoE
−/−
mice. Mass spectroscopy showed a lower gadolinium concentration in the brachiocephalic artery of treated (minocycline=28.5±3 μmol/L, ebselen=32.4±4 μmol/L) compared with untreated
HFD
‐fed ApoE
−/−
mice (191±4.8 μmol/L) (
P
<0.02). Both interventions resulted in a lower plaque burden as measured by delayed‐enhancement
MRI
(minocycline=0.14±0.02 mm
2
, ebselen=0.20±0.09 mm
2
, untreated=0.44±0.01 mm
2
;
P
<0.001) and histology (minocycline=0.13±0.05 mm
2
, ebselen=0.18±0.02 mm
2
, untreated=0.32±0.04 mm
2
;
P
<0.002). Endothelium cells displayed fewer structural changes and smaller gap junction width in treated compared with untreated animals as seen by electron microscopy (minocycline=42.3±8.4 nm, ebselen=56.5±17 nm, untreated=2400±39 nm;
P
<0.001). Tissue flow cytometry of the brachiocephalic artery showed lower monocyte/macrophage content in both ebselen‐ and minocycline‐treated mice (8.06±3.2% and 7.62±1.73%, respectively) compared with untreated animals (20.1±2.2%) (
P
=0.03), with significant attenuation of the proinflammatory Ly6C
high
subtype (untreated mice, 42.64±6.1% of total monocytes; ebselen, 14.07±9.5% of total monocytes; minocycline, 26.42±0.6% of total monocytes).

Conclusions

We demonstrate that contrast‐enhanced
MRI
with an albumin‐binding contrast agent can be used to noninvasively monitor the effect of interventions on endothelial permeability and plaque burden. Blood albumin leakage could be a surrogate marker for the in vivo evaluation of interventions that aim at restoring endothelial integrity.
A constructed HLA-A2-restricted pMAGE-A1278–286 tetramer detects specific cytotoxic T lymphocytes in tumour tissues in situ
Authors: Mongkhoune Sodaly , Xie Yu-An , Wang Yu-Qing , Chen Yue , Zhou Nuo , Peng Yi , He Jian , Yu Xia , Zhou Su-Fang , Luo Guo-Rong , Zhao Yong-Xiang , Lu Xiao-Ling 
Published: September 2013

Objective To construct a human leucocyte antigen (HLA)-A2-restricted peptide 278–286 of melanoma-associated antigen family A, 1 (pMAGE-A1278–286) tetramer to analyse the distribution of cytotoxic T lymphocytes (CTLs) in tumour tissue and tumour-adjacent normal tissue. Methods A HLA-A2-pMAGE-A1278–286 tetramer was constructed. The distribution of pMAGE-A1278–286-specific CTLs was investigated in tumour tissues and tumour-adjacent normal tissues from patients with hepatocellular carcinoma using in situ HLA-A2-pMAGE-A1278–286 tetramer staining. Results Sodium dodecyl sulphate–polyacrylamide gel electrophoresis analysis indicated that HLA-A2 heavy and light chain proteins were successfully obtained. The successful construction of the HLA-A2-pMAGE-A1278–286 monomer was confirmed with Western blot analysis using W6/32 antibody. Flow cytometry confirmed the specific binding of HLA-A2-pMAGE-A1278–286 tetramer to pMAGE-A1278–286-specific CTLs. In situ HLA-A2-pMAGE-A1278–286 tetramer staining demonstrated that the number of pMAGE-A1278–286-specific CTLs in tumour tissues was significantly higher than in tumour-adjacent normal tissues. Conclusions The HLA-A2-pMAGE-A1278–286 tetramer was useful for the detection of pMAGE-A1278–286-specific CTLs in both tumour tissues and tumour-adjacent normal tissues. In situ tetramer staining is a powerful tool for investigating the distribution of pMAGE-A1278–286-specific CTLs in the tumour microenvironment.
Season of infectious mononucleosis and risk of multiple sclerosis at different latitudes; the EnvIMS Study
Authors: Lossius Andreas , Riise Trond , Pugliatti Maura , Bjørnevik Kjetil , Casetta Ilaria , Drulovic Jelena , Granieri Enrico , Kampman Margitta T , Landtblom Anne-Marie , Lauer Klaus , Magalhaes Sandra , Myhr Kjell-Morten , Pekmezovic Tatjana , Wesnes Kristin , Wolfson Christina , Holmøy Trygve 
Published: September 2013

Background: Seasonal fluctuations in solar radiation and vitamin D levels could modulate the immune response against Epstein-Barr virus (EBV) infection and influence the subsequent risk of multiple sclerosis (MS). Methods: Altogether 1660 MS patients and 3050 controls from Norway and Italy participating in the multinational case-control study of Environmental Factors In Multiple Sclerosis (EnvIMS) reported season of past infectious mononucleosis (IM). Results: IM was generally reported more frequently in Norway ( p=0.002), but was associated with MS to a similar degree in Norway (odds ratio (OR) 2.12, 95% confidence interval (CI) 1.64–2.73) and Italy (OR 1.72, 95% CI 1.17–2.52). For all participants, there was a higher reported frequency of IM during spring compared to fall ( p<0.0005). Stratified by season of IM, the ORs for MS were 1.58 in spring (95% CI 1.08–2.31), 2.26 in summer (95% CI 1.46–3.51), 2.86 in fall (95% CI 1.69–4.85) and 2.30 in winter (95% CI 1.45–3.66). Conclusions: IM is associated with MS independently of season, and the association is not stronger for IM during spring, when vitamin D levels reach nadir. The distribution of IM may point towards a correlation with solar radiation or other factors with a similar latitudinal and seasonal variation.
Longitudinal assessment in COPD patients: multidimensional variability and outcomes
Authors: Casanova Ciro , Aguirre-Jaíme Armando , de Torres Juan P. , Pinto-Plata Victor , Baz Rebeca , Marin Jose M. , Divo Miguel , Cordoba Elizabeth , Basaldua Santiago , Cote Claudia , Celli Bartolomé R. 
Published: September 2013

The value and timing of multidimensional assessments in chronic obstructive pulmonary disease (COPD) remains unclear because there is little information about their variability and relationship to outcome. The aim of this study was to determine the progression of COPD using clinical and spirometric variability over time with mortality as the outcome.We determined the annual intra-individual variability of forced expiratory volume in 1 s (FEV1) and BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index in 403 patients with at least five measurements. The pattern was defined as “stable” if the annual change remained constant in ≥66% of the observations and “unstable” if it did not meet that threshold. We explored the minimum number of yearly observations that related to mortality in the 704 patients of the cohort.The “unstable” pattern of FEV1was seen in 53% and 40% of patients using a threshold of 40 mL·year−1and 100 mL·year−1, respectively. There was a slightly more “stable” pattern in the BODE index (62% for 1 point). A profile associated with mortality was defined by a baseline measurement followed by annual measurements for 2 years of the BODE index, but not its individual components, including FEV1(p<0.001).Progression of COPD measured using FEV1is inconsistent and relates poorly to outcome. Monitoring the more stable BODE index better assesses disease progression.
Impact of heart failure on the behavior of human neonatal stem cells in vitro
Authors: Klose Kristin , Roy Rajika , Brodarac Andreja , Kurtz Andreas , Ode Andrea , Kang Kyung-Sun , Bieback Karen , Choi Yeong-Hoon , Stamm Christof 
Published: September 2013

Abstract

Background
Clinical cardiac cell therapy using autologous somatic stem cells is restricted by age and disease-associated impairment of stem cell function. Juvenile cells possibly represent a more potent alternative, but the impact of patient-related variables on such cell products is unknown. We therefore evaluated the behavior of neonatal cord blood mesenchymal stem cells (CB-MSC) in the presence of serum from patients with advanced heart failure (HF).

Methods
Human serum was obtained from patients with severe HF (n = 21) and from healthy volunteers (n = 12). To confirm the systemic quality of HF in the sera, TNF-α and IL-6 were quantified. CB-MSC from healthy neonates were cultivated for up to 14 days in medium supplemented with 10% protein-normalized human HF or control serum or fetal calf serum (FCS).

Results
All HF sera contained increased cytokine concentrations (IL-6, TNF-α). When exposed to HF serum, CB-MSC maintained basic MSC properties as confirmed by immunophenotyping and differentiation assays, but clonogenic cells were reduced in number and gave rise to substantially smaller colonies in the CFU-F assay. Cell cycle analysis pointed towards G1 arrest. CB-MSC metabolic activity and proliferation were significantly impaired for up to 3 days as measured by MTS turnover, BrdU incorporation and DAPI + nuclei counting. On day 5, however, CB-MSC growth kinetics approached control serum levels, though protein expression of cell cycle inhibitors (p21, p27), and apoptosis marker Caspase 3 remained elevated. Signal transduction included the stress and cytokine-induced JNK and ERK1/2 MAP kinase pathways.

Conclusions
Heart failure temporarily inhibits clonality and proliferation of “healthy” juvenile MSC in vitro. Further studies should address the in vivo and clinical relevance of this finding.
Four issues in undernutrition-related health impact modeling
Authors: Scovronick Noah , Chalabi Zaid , Wilkinson Paul 
Published: September 2013

AbstractUndernutrition modeling makes it possible to evaluate the potential impact of such events as a food-price shock or harvest failure on the prevalence and severity of undernutrition. There are, however, uncertainties in such modeling. In this paper we discuss four methodological issues pertinent to impact estimation: (1) the conventional emphasis on energy intake rather than dietary quality; (2) the importance of the distribution of nutrient intakes; (3) the timing of both the ‘food shock’ and when the response is assessed; and (4) catch-up growth and risk accumulation.
Endoglucanases: insights into thermostability for biofuel applications
Authors: Yennamalli Ragothaman M , Rader Andrew J , Kenny Adam J , Wolt Jeffrey D , Sen Taner Z 
Published: September 2013

Abstract
Obtaining bioethanol from cellulosic biomass involves numerous steps, among which the enzymatic conversion of the polymer to individual sugar units has been a main focus of the biotechnology industry. Among the cellulases that break down the polymeric cellulose are endoglucanases that act synergistically for subsequent hydrolytic reactions. The endoglucanases that have garnered relatively more attention are those that can withstand high temperatures, i.e., are thermostable. Although our understanding of thermostability in endoglucanases is incomplete, some molecular features that are responsible for increased thermostability have been recently identified. This review focuses on the investigations of endoglucanases and their implications for biofuel applications.
Decision aid on disclosure of mental health status to an employer: feasibility and outcomes of a randomised controlled trial
Authors: Henderson Claire , Brohan Elaine , Clement Sarah , Williams Paul , Lassman Francesca , Schauman Oliver , Dockery Lisa , Farrelly Simone , Murray Joanna , Murphy Caroline , Slade Mike , Thornicroft Graham 
Published: September 2013

BackgroundMany mental health service users delay or avoid disclosing their condition to employers because of experience, or anticipation, of discrimination. However, non-disclosure precludes the ability to request ‘reasonable adjustments’. There have been no intervention studies to support decisionmaking about disclosure to an employer.AimsTo determine whether the decision aid has an effect that is sustained beyond its immediate impact; to determine whether a large-scale trial is feasible; and to optimise the designs of a larger trial and of the decision aid.MethodIn this exploratory randomised controlled trial (RCT) in London, participants were randomly assigned to use of a decision aid plus usual care or usual care alone. Follow-up was at 3 months. Primary outcomes were: (a) stage of decision-making; (b) decisional conflict; and (c) employment-related outcomes (trial registration number: NCT01379014).ResultsWe recruited 80 participants and interventions were completed for 36 out of 40 in the intervention group; in total 71 participants were followed up. Intention-to-treat analysis showed that reduction in decisional conflict was significantly greater in the intervention group than among controls (mean improvement −22.7 (s.d. = 15.2) v. −11.2 (s.d. = 18.1), P = 0.005). More of the intervention group than controls were in full-time employment at follow-up (P = 0.03).ConclusionsThe observed reduction in decisional conflict regarding disclosure has a number of potential benefits which next need to be tested in a definitive trial.