bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF‐α) pathways
Authors: Dal Bó Wladmir , Luiz Ana Paula , Martins Daniel F. , Mazzardo‐Martins Leidiane , Santos Adair R.S. 
Published: June 2012

AbstractEugenol is utilized together with zinc oxide in odontological clinical for the cementation of temporary prostheses and the temporary restoration of teeth and cavities. This work explored the antinociceptive effects of the eugenol in different models of acute pain in mice and investigated its possible modulation of the inhibitory (opioid) and excitatory (glutamatergic and pro‐inflammatory cytokines) pathways of nociceptive signaling. The administration of eugenol (3–300 mg/kg, p.o., 60 min or i.p., 30 min) inhibited 82 ± 10% and 90 ± 6% of the acetic acid‐induced nociception, with ID50 values of 51.3 and 50.2 mg/kg, respectively. In the glutamate test, eugenol (0.3–100 mg/kg, i.p.) reduced the response behavior by 62 ± 5% with an ID50 of 5.6 mg/kg. In addition, the antinociceptive effect of eugenol (10 mg/kg, i.p.) in the glutamate test was prevented by the i.p. treatment for mice with naloxone. The pretreatment of mice with eugenol (10 mg/kg, i.p.) was able to inhibit the nociception induced by the intrathecal (i.t.) injection of glutamate (37 ± 9%), kainic (acid kainite) (41 ± 12%), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) (55 ± 5%), and substance P (SP) (39 ± 8%). Furthermore, eugenol (10 mg/kg, i.p.) also inhibited biting induced by tumor necrosis factor alpha (TNF‐α, 65 ± 8%). These results extend our current knowledge of eugenol and confirm that it promotes significant antinociception against different mouse models of acute pain. The mechanism of action appears to involve the modulation of the opioid system and glutamatergic receptors (i.e., kainate and AMPA), and the inhibition of TNF‐α. Thus, eugenol could represent an important compound in the treatment for acute pain.
Prognostic value of serum PIIINP, MMP1 and TIMP1 levels in hypertensive patients: a community‐based prospective cohort study
Authors: Agrinier Nelly , Thilly Nathalie , Boivin Jean‐Marc , Dousset Brigitte , Alla François , Zannad Faiez 
Published: June 2012

AbstractThe purpose of this study was to examine the prognostic value of serum ECM biomarkers in hypertensive patients with no history of cardiovascular events. In a community‐based cohort study of 125 hypertensive patients free of cardiovascular events, we collected clinical data and blood samples to assess serum levels of amino‐terminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase type 1(MMP1) and tissue inhibitor of MMPs type 1(TIMP1). Left ventricular hypertrophy (LVH) was assessed using the ECG Cornell product. Patients were followed up for death or cardiovascular hospitalisation. We used Cox regression models to assess the prognostic value of ECM biomarkers. The sample included 60.8% women; the mean (±SD) age was 62.9 (±11.4) years. Patients were followed up for a median of 5.5 years, during which 23 events (five deaths) occurred. PIIINP (3.2 ± 1.0 vs. 2.6 ± 0.8 μg/L, P = 0.001) and TIMP1 (886 ± 168 vs. 751 ± 202 μg/L, P < 0.001) levels were higher in the presence of LVH than with no LVH. Basal MMP1 serum levels were significantly associated with CV events (MMP1: HR, 1.06; 95%CI [1.02–1.09]). Adjusting for confounders did not modify this result. Cardiac fibrosis, as assessed with serum ECM biomarkers, might develop early in hypertensive patients and is predictive of cardiovascular events or death.
A template model for studying anticancer drug efflux transporter inhibitors in vitro
Authors: Sostelly Alexandre , Payen Léa , Guitton Jérôme , Pietro Attilio Di , Falson Pierre , Honorat Mylène , Valdameri Glaucio , Geze Annabelle , Boumendjel Ahcène , Freyer Gilles , Tod Michel 
Published: June 2012

AbstractEfflux transporters play an important role in drug absorption and also in multidrug resistance. ABCG2 (BCRP) is an efflux transporter conferring cross‐resistance to mitoxantrone (Mit), irinotecan (CPT11), and its active metabolite SN38. MBLI87, a new ABCG2 inhibitor has proven its efficacy against ABCG2‐mediated efflux in vitro and in vivo. This work aimed at modeling and quantifying the cellular interaction between MBLI87 and different substrates using a mechanistic template model. An in vitro competition experiment study was carried out with HEK293 cells overexpressing ABCG2 exposed to fixed concentrations of substrates (Mit, CPT11, SN38) and to MBLI87 at several concentration levels. A nonlinear mixed‐effects transport inhibition model was developed to fit intracellular drug concentrations. In this model, drugs cross the cell membrane through passive diffusion, active drug efflux is ABCG2 mediated, interaction between substrates and inhibitor occurs within the transporter. The interaction was found to be noncompetitive. The MBLI87 Ki was estimated to 141 nm for Mit, 289 nm for CPT11, and 1160 nm for SN38. The ratio of intrinsic transport clearance divided by diffusion clearance was estimated to 2.5 for Mit, 1.01 for CPT11, and 5.4 for SN38. The maximal increase in the intracellular substrate concentration that is possible to achieve by inhibition of the transporter was estimated to 1.5 for Mit, 0.1 for CPT11, and 4.4 for SN38. This mechanistic template model describes both drug accumulation and cellular transport, and the mixed‐effects approach allows an estimation of intra‐ and interassay variability. This model is of great interest to study cytotoxic cellular pharmacokinetics.
Volatile anaesthetics and cardioprotection – lessons from animal studies
Authors: Muntean Danina M. , Ordodi Valentin , Ferrera René , Angoulvant Denis 
Published: June 2012

AbstractVolatile anaesthetics emerged as important cardioprotective agents in both animal models of ischaemia/reperfusion injury and humans with coronary artery disease. Their administration before a prolonged ischaemic episode is known as anaesthetic preconditioning, whereas when given at the very onset of reperfusion, the strategy is termed anaesthetic postconditioning. Both types of anaesthetic conditioning reduce, albeit not to the same degree, the extent of myocardial injury. They share similar, albeit not identical, intracellular signal transduction pathways with their widely investigated counterparts, ischaemic pre‐ and postconditioning. Despite a wealth of preclinical evidence for cardioprotection for anaesthetic conditioning strategies, their translation into clinical therapy has been rather disappointing. This review highlights the major findings on the cardioprotective effects of volatile anaesthetics in experimental settings. It explores hypotheses that may explain the lack of efficacy observed in several past clinical studies paving the way for future preclinical and translational studies.
Thymoquinone as an anticancer agent: evidence from inhibition of cancer cells viability and invasion in vitro and tumor growth in vivo
Authors: Attoub Samir , Sperandio Olivier , Raza Haider , Arafat Kholoud , Al‐Salam Suhail , Al Sultan Mahmood Ahmed , Al Safi Maha , Takahashi Takashi , Adem Abdu 
Published: June 2012

AbstractPhytochemical compounds are emerging as a new generation of anticancer agents with limited toxicity in cancer patients. The purpose of this study was to investigate the potential impact of thymoquinone (TQ), the major constituent of black seed, on survival, invasion of cancer cells in vitro, and tumor growth in vivo. Exposure of cells derived from lung (LNM35), liver (HepG2), colon (HT29), melanoma (MDA‐MB‐435), and breast (MDA‐MB‐231 and MCF‐7) tumors to increasing TQ concentrations resulted in a significant inhibition of viability through the inhibition of Akt phosphorylation leading to DNA damage and activation of the mitochondrial‐signaling proapoptotic pathway. We provide evidence that TQ at non‐toxic concentrations inhibited the invasive potential of LNM35, MDA‐MB‐231, and MDA‐MB231‐1833 cancer cells. Moreover, we demonstrate that TQ synergizes with DNA‐damaging agent cisplatin to inhibit cellular viability. The anticancer activity of thymoquinone was also investigated in athymic mice inoculated with the LNM35 lung cells. Administration of TQ (10 mg/kg/i.p.) for 18 days inhibited the LNM35 tumor growth by 39% (P < 0.05). Tumor growth inhibition was associated with significant increase in the activated caspase‐3. The in silico target identification suggests several potential targets of TQ mainly HDAC2 proteins and the 15‐hydroxyprostaglandin dehydrogenase. In this context, we demonstrated that TQ treatment resulted in a significant inhibition of HDAC2 proteins. In view of the available experimental findings, we contend that thymoquinone and/or its analogues may have clinical potential as an anticancer agent alone or in combination with chemotherapeutic drugs such as cisplatin.
Up‐regulated aldo‐keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha‐fetoprotein and hepatocellular carcinoma
Authors: Sato Shunsuke , Genda Takuya , Hirano Katsuharu , Tsuzura Hironori , Narita Yutaka , Kanemitsu Yoshio , Kikuchi Tetsu , Iijima Katsuyori , Wada Ryo , Ichida Takafumi 
Published: June 2012

AbstractBackgroundElevated serum alpha‐fetoprotein (AFP) is not only a diagnostic marker for hepatocellular carcinoma (HCC), but is also a risk factor for HCC in chronic hepatitis C patients who do not have HCC.AimThe aim was to analyse the hepatic gene expression signature in chronic hepatitis C patients with elevated AFP, who were at high risk for HCC.MethodsLiver tissue samples from 48 chronic hepatitis C patients were stratified by their serum AFP levels and analysed for gene expression profiles. The association between aldo‐keto reductase family 1 member B10 (AKR1B10) expression and serum AFP was confirmed by quantitative real‐time reverse transcription polymerase chain reaction (qRT‐PCR) and immunohistochemical analyses. A matched case‐control study was performed to evaluate the risk of AKR1B10 expression for HCC development.ResultsDistinct hepatic gene expression patterns were demonstrated in patients with elevated AFP (≥10 ng/mL) and normal AFP (<10 ng/mL). Of the 627 differently expressed genes, the most abundantly expressed gene in patients with elevated AFP was AKR1B10 (fold change, 26.2; P < 0.001), which was originally isolated as an overexpressed gene in human HCC. The qRT‐PCR and immunohistochemical studies confirmed a proportional correlation between AKR1B10 expression and serum AFP. A matched case‐control study identified that AKR1B10 up‐regulation (>6%) was an independent risk factor for HCC development (hazard ratio, 21.4; P = 0.001).Conclusion
AKR1B10 was up‐regulated in association with serum AFP, and was an independent risk factor for HCC in chronic hepatitis C patients, suggesting its possible involvement at a very early stage of hepatocarcinogenesis.
Ocular Problems in the Patient with End‐Stage Renal Disease
Authors: Mullaem Gaia , Rosner Mitchell H. 
Published: June 2012

AbstractThe patient with end‐stage renal disease (ESRD) is at risk for development of eye disease. This risk is related to the comorbid conditions that are often seen in ESRD patients as well as to the unique effects of hemodialysis and the uremic state in leading to changes in the conjunctivae, cornea, retina, and macula. The most common ocular complaints in ESRD patients include red, irritated eyes, and may be associated with elevations in the calcium‐phosphate product. In those patients with chronically elevated calcium‐phosphate products, band keratopathy may result. Other eye conditions include macular edema, ischemic optic neuropathy, elevated intraocular pressure, retinal detachment, and retinal hemorrhage. Prompt recognition of these conditions that may threaten a patient’s vision is required. This may prove challenging to the nephrologist in the dialysis unit where a detailed ophthalmological examination is difficult. However, a basic knowledge of the common ocular diseases encountered in the dialysis patient forms a framework for deciding which patients require urgent consultation with an ophthalmologist.
IDENTIFICATION OF CRYPTIC SPECIES IN THE LESSONIA NIGRESCENS COMPLEX (PHAEOPHYCEAE, LAMINARIALES)1
Authors: González Alejandra , Beltrán Jessica , Hiriart‐Bertrand Luciano , Flores Verónica , de Reviers Bruno , Correa Juan A. , Santelices Bernabé 
Published: June 2012

The kelp Lessonia nigrescens Bory is the most ecologically and economically important seaweed in rocky intertidal and shallow subtidal habitats along the temperate Pacific South American coasts. Recent molecular studies suggest the existence of two lineages, one (northern lineage) from 17° S to 30° S and a second (central lineage) from 29° S to 41° S. To identify and name these lineages we performed morphological, nomenclatural and field studies. Four external and three internal anatomical traits permitted a morphological separation of the two lineages. The internal structure of both lineages was different from the isolectotype of Lessonia nigrescens. It is therefore concluded that the name Lessonia nigrescens should not be used for the Chilean material. Chordaria spicata Suhr appears as the oldest available name for the central lineage, while Lessonia berteroana Montagne is the oldest name for the northern lineage. In both cases, the type material consisted of small‐sized, apical branches of larger plants. The new combination Lessonia spicata (Suhr) Santelices is proposed for the central lineage and we reinstate Lessonia berteroana for the northern lineage. Laminaria scissa Suhr is reduced to synonym of L. spicata. Representative specimens of Lessonia nigrescens were not found during new visits to its type locality in Cape Horn and along Chile. Future studies should verify the status of this species.
Thyroid hormone induces sprouting angiogenesis in adult heart of hypothyroid mice through the PDGF‐Akt pathway
Authors: Chen Jinghai , Ortmeier Steven B. , Savinova Olga V. , Nareddy Vijaya B. , Beyer April J. , Wang Dajun , Gerdes A. Martin 
Published: June 2012

AbstractStudy of physiological angiogenesis and associated signalling mechanisms in adult heart has been limited by the lack of a robust animal model. We investigated thyroid hormone‐induced sprouting angiogenesis and the underlying mechanism. Hypothyroidism was induced in C57BL/6J mice by feeding with propylthiouracil (PTU). One year of PTU treatment induced heart failure. Both 12 weeks‐ (young) and 1 year‐PTU (middle age) treatment caused a remarkable capillary rarefaction observed in capillary density. Three‐day Triiodothyronine (T3) treatment significantly induced cardiac capillary growth in hypothyroid mice. In cultured left ventricle (LV) tissues from PTU‐treated mice, T3 also induced robust sprouting angiogenesis where pericyte‐wrapped endothelial cells formed tubes. The in vitro T3 angiogenic response was similar in mice pre‐treated with PTU for periods ranging from 1.5 to 12 months. Besides bFGF and VEGF164, PDGF‐BB was the most robust angiogenic growth factor, which stimulated notable sprouting angiogenesis in cultured hypothyroid LV tissues with increasing potency, but had little effect on tissues from euthyroid mice. T3 treatment significantly increased PDGF receptor beta (PDGFR‐β) protein levels in hypothyroid heart. PDGFR inhibitors blocked the action of T3 both on sprouting angiogenesis in cultured LV tissue and on capillary growth in vivo. In addition, activation of Akt signalling mediated in T3‐induced angiogenesis was blocked by PDGFR inhibitor and neutralizing antibody. Our results suggest that hypothyroidism leads to cardiac microvascular impairment and rarefaction with increased sensitivity to angiogenic growth factors. T3‐induced cardiac sprouting angiogenesis in adult hypothyroid mice was associated with PDGF‐BB, PDGFR‐β and downstream activation of Akt.
CBCT device dependency on the transfer accuracy from computer‐aided implantology procedures
Authors: Dreiseidler Timo , Tandon Daniel , Kreppel Matthias , Neugebauer Jörg , Mischkowski Robert A. , Zinser Max J. , Zöller Joachim E. 
Published: June 2012

AbstractObjectivesTo evaluate the potential influence of different cone‐beam computed tomography (CBCT) devices on the transfer accuracy of an open‐source system for computer‐aided implantology (CAI).Material and methodsA total of 108 implants in 18 partially edentulous patient‐equivalent models were planned and fully guided implants were inserted using an open‐source CAI system with three different CBCT devices. After follow‐up CBCT and fiducial marker‐matching procedure, linear horizontal, vertical, and maximal three‐dimensional deviations, as well as angle deviations between the virtual planning data and the surgical results were calculated. Variance analysis was carried out to prove whether or not the observed differences between the CBCT devices were statistically significant.ResultsThe observed mean three‐dimensional deviation rates between virtually planned and achieved implant positions varied by around 400 μm (45%) at the implant's base and around 540 μm (50%) at the implant's tip in dependence to the applied CBCT device. Mean vertical deviations varied around 370 μm (76%) at the implant's base and 350 μm (69%) at the implant's tip, whereas axes deviations varied around 0.81° (40%) between the three investigated CBCT devices. Except for the axes deviations and the horizontal linear deviations at the implants base, observed differences reached significance level between the CBCT devices.ConclusionsUntil now, the potential influence from different CBCT devices on the transfer accuracy of CAI systems has not yet been investigated. Data from the present study confirm for the first time the in vitro CBCT device dependency on the transfer accuracy of CAI systems reaching up to axes deviations of 0.6 angle degree and linear deviations around half a millimeter.
Fermi's SIBYL: mining the gamma-ray sky for dark matter subhaloes
Authors: Mirabal N. , Frías-Martinez V. , Hassan T. , Frías-Martinez E. 
Published: June 2012

Abstract
Dark matter annihilation signals coming from Galactic subhaloes may account for a small fraction of unassociated point sources detected in the second Fermi-LAT Catalogue (2FGL). To investigate this possibility, we present sibyl, a Random Forest classifier that offers predictions on class memberships for unassociated Fermi-LAT sources at high Galactic latitudes using gamma-ray features extracted from the 2FGL. sibyl generates a large ensemble of classification trees that are trained to vote on whether a particular object is an active galactic nucleus (AGN) or a pulsar. After training on a list of 908 identified/associated 2FGL sources, sibyl reaches individual accuracy rates of up to 97.7 per cent for AGNs and 96.5 per cent for pulsars. Predictions for the 269 unassociated 2FGL sources at |b|≥ 10° suggest that 216 are potential AGNs and 16 are potential pulsars (with majority votes greater than 70 per cent). The remaining 37 objects are inconclusive, but none is an extreme outlier. These results could guide future quests for dark matter Galactic subhaloes.
Sex determination meltdown upon biological control introduction of the parasitoid Cotesia rubecula?
Authors: de Boer Jetske G. , Kuijper Bram , Heimpel George E. , Beukeboom Leo W. 
Published: June 2012

AbstractNatural enemies may go through genetic bottlenecks during the process of biological control introductions. Such bottlenecks are expected to be particularly detrimental in parasitoid Hymenoptera that exhibit complementary sex determination (CSD). CSD is associated with a severe form of inbreeding depression because homozygosity at one or multiple sex loci leads to the production of diploid males that are typically unviable or sterile. We observed that diploid males occur at a relatively high rate (8–13% of diploid adults) in a field population of
Cotesia rubecula in Minnesota, USA, where this parasitoid was introduced for biological control of the cabbage white
Pieris rapae. However, our laboratory crosses suggest two‐locus CSD in a native Dutch population of
C. rubecula and moderately high diploid males survival (approximately 70%), a scenario expected to produce low proportions of diploid males. We also show that courtship behavior of diploid males is similar to that of haploid males, but females mated to diploid males produce only very few daughters that are triploid. We use our laboratory data to estimate sex allele diversity in the field population of
C. rubecula and discuss the possibility of a sex determination meltdown from two‐locus CSD to effective single‐locus CSD during or after introduction.
Reproductive success of captively bred and naturally spawned Chinook salmon colonizing newly accessible habitat
Authors: Anderson Joseph H. , Faulds Paul L. , Atlas William I. , Quinn Thomas P. 
Published: June 2012

AbstractCaptively reared animals can provide an immediate demographic boost in reintroduction programs, but may also reduce the fitness of colonizing populations. Construction of a fish passage facility at Landsburg Diversion Dam on the Cedar River, WA, USA, provided a unique opportunity to explore this trade‐off. We thoroughly sampled adult Chinook salmon (Oncorhynchus tshawytscha) at the onset of colonization (2003–2009), constructed a pedigree from genotypes at 10 microsatellite loci, and calculated reproductive success (RS) as the total number of returning adult offspring. Hatchery males were consistently but not significantly less productive than naturally spawned males (range in relative RS: 0.70–0.90), but the pattern for females varied between years. The sex ratio was heavily biased toward males; therefore, inclusion of the hatchery males increased the risk of a genetic fitness cost with little demographic benefit. Measurements of natural selection indicated that larger salmon had higher RS than smaller fish. Fish that arrived early to the spawning grounds tended to be more productive than later fish, although in some years, RS was maximized at intermediate dates. Our results underscore the importance of natural and sexual selection in promoting adaptation during reintroductions.
Magnesium Reduces Carotid Intima‐Media Thickness in a Mouse Model of Pseudoxanthoma Elasticum: A Novel Treatment Biomarker
Authors: Kupetsky‐Rincon Erine A. , Li Qiaoli , Uitto Jouni 
Published: June 2012

AbstractPseudoxanthoma elasticum (PXE), which demonstrates progressive build‐up of calcium phosphate and proteoglycan deposits in skin, eye, and arteries, has been associated with myocardial infarctions, stroke, and blindness. In a mouse model of PXE, a magnesium‐enriched diet prevents mineralization of the vibrissae capsule, an early biomarker for PXE. However, biomarkers for therapeutic responses in PXE have not been identified in humans. Because PXE patients have an increased carotid intima‐media thickness (CIMT), a risk factor for cardiovascular disease and stroke, we analyzed the feasibility of CIMT as a treatment endpoint before and after magnesium supplementation in a mouse model of PXE (Abcc6−/−). CIMT was measured in 1‐year‐old Abcc6−/− and Abcc6+/+ mice fed either standard rodent diet with or without magnesium oxide supplementation for 2 months. Baseline CIMT in Abcc6−/− versus Abcc6+/+ mice was increased (p value = 0.009), whereas CIMT in magnesium‐treated versus untreated Abcc6−/− mice was reduced (p value = 0.024). CIMT is a novel treatment endpoint in this mouse model and may serve as a predictive biomarker of therapeutic response in PXE patients. In that context, magnesium oxide significantly reduced CIMT in PXE mice, and may be useful for disease prevention in PXE patients. Clin Trans Sci 2012; Volume #: 1–6