bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of slow infusion of a low dosage of endotoxin in healthy horses
Authors: CLARK E. SUSAN , MOORE J. N. 
Published: June 2011

SummaryThe effects of slow intravenous (iv) infusion of a very low dosage of endotoxin (a cumulative dosage of 0.03 μg/kg bodyweight [bwt] infused over 60 mins) were evaluated in six conscious healthy horses. Duodenal, right ventral colon, and caecal contractions were detected with strain gauge force transducers. Lateral caecal arterial blood flow was measured using transit time ultrasonic blood flow probes. Duodenal contractile activity was not significantly altered by infusion of endotoxin. In contrast, the contractile activity of the right ventral colon 90 and 270 mins after infusion of endotoxin was less than after infusion of saline solution (control). The contractile activity of the caecal body 30, 60, 90, 120 and 240 mins after infusion of endotoxin was significantly less than control. The contractile activity of the caecal apex 60, 90, 120, 240 and 270 mins after termination of endotoxin infusion was significantly less than control. Lateral caecal arterial blood flow was significantly less than control at the end of endotoxin infusion and at 30, 45, 60, 90, 105 and 120 mins afterwards. Average carotid arterial pressure was significantly greater than control at 210, 225, 240, 255 and 270 mins after endotoxin infusion. Infusion of endotoxin increased heart rate, respiratory rate and body temperature significantly. The decrease in caecal contractile activity occurred before the increase in body temperature. All horses became depressed and developed injected mucous membranes. Signs of abdominal pain (including stretching, pawing, kicking at abdomen) were seen in four of the six horses.
Antagonism of endotoxin‐induced disruption of equine bowel motility by flunixin and phenylbutazone
Authors: KING J. N. , GERRING E. L. 
Published: June 2011

SummaryPost operative ileus is a serious complication of abdominal surgery in horses and there is evidence that endotoxin plays a significant role in its pathogenesis. Pre‐treatment with intravenous (iv) flunixin (1.1 mg/kg bodyweight [bwt]) or phenylbutazone (4.4 mg/kg bwt) significantly antagonised the acute disruption of gastric, small intestinal and large intestinal motility induced by 0.1 μg/kg bwt iv endotoxin in ponies implanted with gastrointestinal strain gauges. Phenylbutazone was more effective than flunixin and this was significant (P<0.01) for the stomach and left dorsal colon. Both drugs reduced the acute systemic side‐effects of the endotoxin and flunixin was slightly more effective than phenylbutazone in antagonising the cardiovascular effects. These results suggest that the acute effects of endotoxin on bowel motility are mediated at least in part by a cyclooxygenase dependant pathway. Flunixin and phenylbutazone showed a relative selectivity for the cardiovascular and gastrointestinal effects of endotoxin, respectively. Phenylbutazone may be of use clinically in acute colic cases, antagonising the disruptive effects of endotoxin on bowel motility, without entirely blocking the cardiovascular effects which can indicate that the patient has a condition requiring surgery.
Bismuth-ethanedithiol incorporated in a liposome-loaded tobramycin formulation modulates the alginate levels in mucoid Pseudomonas aeruginosa
Authors: Alipour Misagh , Dorval Crystal , Suntres Zacharias E , Omri Abdelwahab 
Published: June 2011

Abstract

Objectives
This study examined the antibacterial activity, alginate modulation, and deposition of a tobramycin bismuth-ethanedithiol (Tob-Bi) conventional (free) or vesicle-entrapped (lipo) formulation against two mucoid Pseudomonas aeruginosa clinical isolates.

Methods
The inhibitory, bactericidal and biofilm eradication concentrations (in presence or absence of alginate lyase) were determined. The modulation of alginate was assessed by the carbazole assay and fluorescent-labelling of live alginate-producing biofilms by confocal microscopy. The deposition of the formulations was assessed using the immunogold-labelling technique, transmission electron microscopy, and energy dispersive X-ray spectroscopy (EDS).

Key findings
The inhibitory and bactericidal concentrations for lipo Tob-Bi compared with free Tob-Bi were reduced in all strains by 2- to 8-fold, and 2- to 32-fold, respectively. The biofilm eradication concentrations for lipo Tob-Bi compared with free Tob-Bi were reduced by 4- to 32-fold in the mucoid strains. The addition of alginate lyase transiently enhanced eradication for one mucoid strain only. The alginate levels were attenuated by more than half, and free Tob-Bi fared better than lipo Tob-Bi determined by the carbazole assay. Under confocal microscopy, alginate lyase reduced alginate levels and detached mucoid biofilms. Free and lipo Tob-Bi did not detach the bacteria from the surface, but attenuated alginate levels. Tobramycin was detected by immunogold-labelling inside the bacterium, but EDS did not detect bismuth deposits.

Conclusions
These findings substantiate a role in which tobramycin, bismuth, and alginate lyase play in eradicating mucoid P. aeruginosa growth and modulate alginate levels.
Novel intracranial brain cooling catheter to mitigate brain injuries
Authors: Moomiaie Remo M , Gould Graham , Solomon Daniel , Simmons John , Kim Jung , Botta Donald , Elefteriades John A 
Published: June 2011

BackgroundThe neuroprotective effects of cooling the spinal cord in a sheep model by a self-contained intrathecal catheter was reported recently by the authors. The present study was designed to determine if cooling catheters in the lateral ventricles of the brain can effectively cool the CSF and thereby reduce brain temperature while maintaining systemic normothermia.MethodsThe cooling catheter is a self-contained system that circulates a cold fluid and cools the CSF that circulates in the brain. The CSF in turn cools the surrounding brain by conduction. Burr holes were made in the skull and the catheter was placed into the lateral ventricles using the standard method for placement of ventriculostomy catheters. To monitor the cooling effect, four temperature probes were placed in the brain (left and right hemispheres of the brain in anterior and posterior locations to the ventricles).ResultsFive experiments were successfully completed. The mean brain temperature for all sheep decreased to 34.5°C (mean) during the 3 h cooling period (9.7% reduction from baseline brain temperature of 38.2°C). Cooling fluid was circulated through the catheter at a rate of 50 ml/min. The lowest achieved brain temperature during cooling was 26.7°C. When cooling was stopped, the brain temperature readings equilibrated with the core temperature promptly. Post mortem examination of the brains showed no morphologic changes under gross or histologic examinations.ConclusionLocalized cooling of the brain to moderate hypothermic levels while maintaining relative systemic normothermia was demonstrated in an animal model with intraventricular cooling catheters.
Prevalence of asymptomatic syringomyelia in Cavalier King Charles spaniels
Authors: Parker J. E. , Knowler S. P. , Rusbridge C. , Noorman E. , Jeffery N. D. 
Published: June 2011

The prevalence of syringomyelia was investigated in a sample population of 555 Cavalier King Charles spaniels. All dogs, which were declared by their owners to be showing no clinical signs of syringomyelia, underwent MRI to determine the presence or absence of the condition. Data were analysed by logistic regression to determine the effects of sex and age on the prevalence of syringomyelia. Only increased age was found to have a significant effect. The prevalence of syringomyelia was 25 per cent in dogs aged 12 months, increasing to a peak of 70 per cent in dogs aged 72 months or more.
Petrology and geochemistry of the Andaman ophiolite: melt–rock interaction in a suprasubduction-zone setting
Authors: Pal Tapan 
Published: June 2011

Abstract:

The Andaman ophiolite occurs as thrust slices in the outer arc of the Andaman–Java subduction zone. This ophiolite preserves the mantle sequence, layered ultramafic–mafic rocks, intrusive and extrusive rocks. The mantle sequence is represented by serpentinized lherzolite and harzburgite, hosting dunite and chromitite pods. The low Cr-number (0.2–0.4), Cr-number–TiO
2
relation of the chromites, oxygen fugacity (
f
O
2
) values (
Δ
log
f
O
2
(FMQ) = −1.90) and trace elements of mantle peridotites indicate a mid-ocean ridge basalt–suprasubduction-zone (MORB–SSZ) setting. The MORB mantle underwent a low degree of melting (
c
. 10–15%) and interacted with the subduction-zone melts. Melt–rock interaction of the peridotites in a suprasubduction zone is demonstrated by the replacement of pyroxene grains by olivine grains (Fo
90
), composition of chromites and oxygen fugacity (
Δ
log
f
O
2
(FMQ) = –1.90 to +2.16, where FMQ is the fayalite–magnetite–quartz buffer). The chromite composition of chromitite pods (Cr-number 0.72–0.75),
f
O
2
levels and trace elements for layered peridotites, and occurrence of the extrusive rocks as low-Ca boninite and island arc tholeiitic (IAT) basalt indicate interplay of both boninite and IAT melts for the Andaman ophiolite. The MORB mantle of the subducting Indian plate accreted into the mantle wedge and then melting of the accreted mantle produced boninite melt at the first stage and tholeiitic melts at the second stage.

Supplementary material:

Sample co-ordinates from the Andaman ophiolite, mineral analysis data for all the samples, modal compositions of the units of the Andaman ophiolite and details of the laboratory analyses including details of the standard are available at
http://www.geolsoc.org.uk/SUP18459
.
The lithospheric mantle and lower crust–mantle relationships under Scotland: a xenolithic perspective
Authors: Upton B.G.J. , Downes H. , Kirstein L.A. , Bonadiman C. , Hill P.G. , Ntaflos T. 
Published: June 2011

Abstract:

In the British Isles the majority of volcanic rocks containing upper mantle and lower crustal xenoliths occur in Scotland. Most of the occurrences are of Carboniferous–Permian age. This paper presents new data on the mineral chemistry of spinel lherzolite xenoliths from the five principal Scottish tectonic terranes. Compositional variations among the minerals emphasize the broad lateral heterogeneity of the subcontinental lithospheric mantle across the region. The remarkable range of Al
2
O
3
v. CaO exhibited by the clinopyroxenes compared with data from other ‘xenolith provinces' emphasizes the extremely complex tectonomagmatic history of the Scottish lithosphere. The generalized age increase from southern and central Scotland to the Northern Highland and Hebridean terranes of the north and NW, with concomitant complexity of geological history, is reflected also by trace element and isotopic studies. Reaction relationships in lherzolites from the Hebridean Terrane, owing to pervasive metasomatism, involve secondary growth of sodic feldspar. This, and light REE enrichment of clinopyroxenes, points to involvement of a natro-carbonatitic melt. Most pyroxenitic xenoliths are inferred to form a basal crustal layer with a generally sharp discontinuity above the underlying (dominantly lherzolitic) mantle. A second discontinuity is inferred to separate these ultramafic cumulates from overlying, broadly cognate metagabbroic cumulates.
A high-precision U–Pb age constraint on the Rhynie Chert Konservat-Lagerstätte: time scale and other implications
Authors: Parry S.F. , Noble S.R. , Crowley Q.G. , Wellman C.H. 
Published: June 2011

Abstract:
An isotope dilution thermal ionization mass spectrometry U–Pb zircon age of 411.5 ± 1.3 Ma obtained from an andesitic lava occurring within the Lower Devonian Rhynie Outlier (Aberdeenshire, NE Scotland) effectively dates the Rhynie Chert Konservat-Lagerstätte. Biostratigraphical constraints on the Rhynie Chert-bearing succession indicate that this age lies within the interval early (but not earliest) Pragian–(?)earliest Emsian. Accordingly, the Pragian–Emsian boundary must post-date or closely approximate to 411.5 ± 1.3 Ma, while the Lochkovian–Pragian boundary must predate 411.5 ± 1.3 Ma. Integration of this new high-precision age with an improved temporal framework for late Caledonian intrusive activity in NE Scotland suggests that the Rhynie hot-spring system (the ‘parental' hydrothermal system to the Rhynie cherts) was unrelated to any ‘Newer Granite' intrusion. Rhynie was instead powered by a basaltic andesite magma whose generation and ascent were directly linked to the transcurrent fault movements responsible for the formation of the Rhynie basin.

Supplementary material:

Details of analytical techniques (ID-TIMS U–Pb geochronology) and photomicrographs of zircon and titanite grains recovered from the Milton of Noth Andesite are available at
http://www.geolsoc.org.uk/SUP18463
.
Thermochronology, erosion surfaces and missing section in West Greenland
Authors: Green Paul F. , Japsen Peter , Chalmers James A. , Bonow Johan M. 
Published: June 2011

Abstract:

In central West Greenland, Palaeogene volcanic sequences deposited during post-rift subsidence are exposed in mountains reaching 2 km above sea level (a.s.l.), with Palaeocene marine deposits within this section at elevations up to 1.2 km a.s.l. This clearly shows that present-day elevated topography of the West Greenland margin is not a remnant of the rifting process but developed later. Integrating such geological constraints with landscape analysis and thermochronological data shows that mountain summits in central West Greenland represent an Oligocene–Miocene peneplain, which is the counterpart of a correlative unconformity offshore separating Eocene from Middle Miocene sedimentary units. Onshore the peneplain has been exhumed, uplifted to its present altitude and progressively dissected since the Late Miocene. Redfield (
Journal of the Geological Society, London
,
167
, 261–271, 2010) questioned numerous aspects of this interpretation, suggesting that ‘the AFT model-based hypothesis that [the elevated topography of West Greenland] was constructed in purely Neogene time remains an unproven speculation'. But as we illustrate here, evidence for Neogene uplift is provided by landscape analysis and geological evidence, as well as thermochronology, and integration of these independent lines of investigation provides a consistent synthesis that we regard as highly reliable. The resulting history of episodic burial and exhumation cannot be simply dismissed, and poses a major challenge to accepted tectonic and geomorphological models for the development of rifted continental margins: how do mountains form along passive continental margins millions of years after rifting and breakup?
Combining Betulinic Acid and Mithramycin A Effectively Suppresses Pancreatic Cancer by Inhibiting Proliferation, Invasion, and Angiogenesis
Authors: Gao Yong , Jia Zhiliang , Kong Xiangyu , Li Qiang , Chang David Z. , Wei Daoyan , Le Xiangdong , Suyun Huang , Huang Shengdong , Wang Liwei , Xie Keping 
Published: June 2011

Abstract
Both betulinic acid (BA) and mithramycin A (MIT) exhibit potent antitumor activity through distinct mechanisms of Sp1 inhibition. However, it is unknown whether a combination of these two compounds results in a synergistic inhibitory effect on pancreatic cancer growth and/or has a therapeutic advantage over gemcitabine. In xenograft mouse models of human pancreatic cancer, treatment with either BA or MIT alone showed dose-dependent antitumor activity but led to systemic side effects as measured by overall weight loss. Treatment with a nontoxic dose of either compound alone had only marginal antitumor effects. Importantly, combination treatment with nontoxic doses of BA and MIT produced synergistic antitumor activity, including inhibitory effects on cell proliferation, invasion, and angiogenesis. The treatment combination also produced less discernible side effects than therapeutic doses of gemcitabine. Moreover, combined treatment of BA and MIT resulted in drastic inhibition of Sp1 recruitment onto Sp1 and VEGF promoters, leading to transcriptional inhibition of both Sp1 and VEGF and downregulation of Sp1 and VEGF protein expression. Ectopic overexpression of Sp1 rendered tumor cells resistant to BA, MIT, and the combination of the two. Overall, our findings argue that Sp1 is an important target of BA and MIT and that their combination can produce an enhanced therapeutic response in human pancreatic cancer. Cancer Res; 71(15); 5182–93. ©2011 AACR.
FDG-PET as a Potential Tool for Selecting Patients with Advanced Non–Small Cell Lung Cancer Who May Be Spared Maintenance Therapy after First-Line Chemotherapy
Authors: Yoon Dok Hyun , Baek Sora , Choi Chang-Min , Lee Dae Ho , Suh Cheolwon , Ryu Jin-Sook , Moon Dae Hyuk , Lee Jung Shin , Kim Sang-We 
Published: June 2011

Abstract
Purpose: To investigate whether 18F-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) may be a potential tool to select a subgroup of patients who might be spared maintenance treatment, if the metabolic response after first-line chemotherapy could predict time-to-progression (TTP).
Experimental Design: A total of 43 patients who underwent baseline FDG-PET scan and did not show disease progression (DP) after 4 cycles of first-line chemotherapy were enrolled and underwent second FDG-PET 3 weeks after completion of the first-line chemotherapy. The primary endpoint was to compare percent decrease in maximum standard uptake value (SUVmax) between early (TTP after second PET examination &lt;8 weeks) and late (TTP ≥8 weeks) DP subgroups. Secondary endpoints were to determine whether fractional decrease in SUVmax could predict TTP and overall survival (OS), both calculated from the date of the second FDG-PET.
Results: Percent decreases in SUVmax in late DP subgroup were greater than those in early DP subgroup (mean reduction, 54.7% ± 27.2% vs. 27.8% ± 46.8%, P = 0.021). Receiver operating characteristic curves identified a 50.0% decrease in SUVmax as the optimal threshold to distinguish these subgroups. Using this value as the cutoff resulted in a positive predictive value of 82.6% and negative predictive value of 60.0% in predicting TTP ≥8 weeks. Patients with SUVmax decrease &lt;50% had significantly longer median TTP (3.0 vs. 1.5 months, P = 0.001) and OS (not reached vs. 14.2 months, P = 0.003).
Conclusions: Fractional decrease in SUVmax of the main lesion after completion of 4 cycles of chemotherapy may discriminate patients with TTP ≥8 weeks and predict TTP and OS in patients with advanced NSCLC. Clin Cancer Res; 17(15); 5093–100. ©2011 AACR.
Epigenetic Silencing of MicroRNA-34b/c Plays an Important Role in the Pathogenesis of Malignant Pleural Mesothelioma
Authors: Kubo Takafumi , Toyooka Shinichi , Tsukuda Kazunori , Sakaguchi Masakiyo , Fukazawa Takuya , Soh Junichi , Asano Hiroaki , Ueno Tsuyoshi , Muraoka Takayuki , Yamamoto Hiromasa , Nasu Yasutomo , Kishimoto Takumi , Pass Harvey I. , Matsui Hideki , Huh Nam-ho , Miyoshi Shinichiro 
Published: June 2011

Abstract
Purpose: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal prognosis. Unlike other malignancies, TP53 mutations are rare in MPM. Recent studies have showed that altered expression of microRNA (miRNA) is observed in human malignant tumors. In this study, we investigated the alterations of miR-34s, a direct transcriptional target of TP53, and the role of miR-34s on the pathogenesis of MPM.
Experimental Design: Aberrant methylation and expression of miR-34s were examined in MPM cell lines and tumors. miR-34b/c was transfected to MPM cells to estimate the protein expression, cell proliferation, invasion, and cell cycle.
Results: Aberrant methylation was present in 2 (33.3%) of 6 MPM cell lines and 13 (27.7%) of 47 tumors in miR-34a and in all 6 MPM cell lines (100%) and 40 (85.1%) of 47 tumors in miR-34b/c. Expression of miR-34a and 34b/c in all methylated cell lines was reduced and restored with 5-aza-2′-deoxycytidine treatment. Because epigenetic silencing was the major event in miR-34b/c, we investigated the functional role of miR-34b/c in MPM. miR-34b/c–transfected MPM cells with physiologic miR-34b/c expression exhibited antiproliferation with G1 cell cycle arrest and suppression of migration, invasion, and motility. The forced overexpression of miR-34b/c, but not p53, showed a significant antitumor effect with the induction of apoptosis in MPM cells.
Conclusions: We show that the epigenetic silencing of miR-34b/c by methylation is a crucial alteration and plays an important role in the tumorigenesis of MPM, suggesting potential therapeutic options for MPM. Clin Cancer Res; 17(15); 4965–74. ©2011 AACR.
Multihistology, Target-Driven Pilot Trial of Oral Topotecan as an Inhibitor of Hypoxia-Inducible Factor-1α in Advanced Solid Tumors
Authors: Kummar Shivaani , Raffeld Mark , Juwara Lamin , Horneffer Yvonne , Strassberger Agnes , Allen Deborah , Steinberg Seth M. , Rapisarda Annamaria , Spencer Shawn D. , Figg William D. , Chen Xiaohong , Turkbey Ismail Baris , Choyke Peter , Murgo Anthony J. , Doroshow James H. , Melillo Giovanni 
Published: June 2011

Abstract
Purpose: Hypoxia-inducible factor 1 (HIF-1) α is frequently overexpressed in human tumors and is associated with angiogenesis and metastasis. Topotecan, a topoisomerase I inhibitor, has been shown to inhibit HIF-1α expression in preclinical models. We designed a pilot trial to measure HIF-1α inhibition in tumor biopsies from patients with advanced solid tumors overexpressing HIF-1α, after treatment with oral topotecan.
Experimental Design: Topotecan was administered orally at 1.6 mg/m2 once daily for 5 days/week for 2 weeks, in 28-day cycles. Objectives were to determine inhibition of expression of HIF-1α and HIF-1 target genes in tumor; to assess tumor blood flow by dynamic contrast–enhanced magnetic resonance imaging (DCE-MRI); and to measure pharmacokinetics. Tumor biopsies were collected at baseline and during the second cycle of treatment.
Results: Sixteen patients were enrolled. The dose of topotecan was reduced to 1.2 mg/m2/day due to myelosuppression. Seven patients had paired tumor biopsies. In 4 patients, HIF-1α nuclear staining became undetectable after treatment (7.5%–50% staining at baseline). Decreased levels of VEGF and GLUT-1 mRNA were measured in 4 patients; the changes were concordant with reduction in HIF-1α in 3 patients. Decreased tumor blood flow and permeability were observed by DCE-MRI in 7 of 10 patients after 1 cycle. One patient had a partial response accompanied by inhibition of HIF-1α in tumor and reduction in tumor blood flow on DCE-MRI.
Conclusions: This multihistology, target assessment trial of a small molecule inhibitor of HIF-1α showed that topotecan could decrease HIF-1α expression in advanced solid tumors. Clin Cancer Res; 17(15); 5123–31. ©2011 AACR.