bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioequipotency of idraparinux and idrabiotaparinux after once weekly dosing in healthy volunteers and patients treated for acute deep vein thrombosis
Authors: Trellu Marc , Fau Jean‐Baptiste , Cortez Pierre , Cheng Sue , Paty Isabelle , Boëlle Emmanuelle , Donat François , Sanderink Ger‐Jan 
Published: October 2012

AimTo assess the bioequipotency of equimolar doses of idraparinux (2.5 mg) and idrabiotaparinux (3.0 mg).MethodIn a phase I study, 48 healthy male volunteers were randomized to a single subcutaneous injection of idrabiotaparinux or idraparinux, followed by plasma sampling over 27 days. In a prospective substudy of the phase III EQUINOX trial, 228 patients treated for acute symptomatic deep vein thrombosis received idrabiotaparinux or idraparinux once weekly for 6 months. Plasma sampling was performed within 5 days following the last injection. The primary pharmacodynamic endpoint was the inhibition of activated factor X (FXa) activity. Maximal anti‐FXa activity (Amax) and area under anti‐FXa activity vs. time curve (AAUC) were calculated. Safety and tolerability were also assessed.ResultsIn both studies, pharmacodynamic anti‐FXa vs. time profiles of idrabiotaparinux and idraparinux were superimposable. Ratio estimates (90% confidence intervals [CIs]) for idrabiotaparinux : idraparinux were 0.96 (0.89, 1.04) for Amax and 0.95 (0.87, 1.04) for AAUC in the phase I study, and 1.11 (1.00, 1.22) for Amax and 1.06 (0.96, 1.16) for AAUC at month 6 in the EQUINOX substudy. Idrabiotaparinux and idraparinux were considered bioequipotent because 90% CIs were within the pre‐specified interval (0.80, 1.25). Study treatments were well tolerated.ConclusionPharmacodynamic parameters reported after single dose in healthy volunteers and after repeated once weekly dosing in patients demonstrated the bioequipotency of idrabiotaparinux and idraparinux based on FXa inhibition. These outcomes support the use of an idrabiotaparinux dose bioequipotent to an idraparinux dose in large clinical trials, and the possibility to substitute idrabiotaparinux to idraparinux for the treatment of venous thromboembolism.
(E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal has an antiproliferative effect on NSCLC cells induced by p38 MAPK‐mediated suppression of NF‐κB and up‐regulation of TNFRSF10B (DR5)
Authors: Kollipara Pushpa Saranya , Jeong Heon Sang , Han Sang Bae , Hong Jin Tae 
Published: October 2012

Background And PurposeThe Maillard Reaction Products (MRPs) are known to be effective in chemoprevention. Here we focused on the anticancer effects of (E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal (a MRP) on human non‐small‐cell lung cancer (NSCLC) cells and its mechanism of action.Experimental ApproachWe analysed the activity of (E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal on NSCLC cells (NCI‐H460 and A549) by use of Western blot analysis for major apoptotic proteins, MAPK, NF‐κB and death receptor expression. We also used RT‐PCR to determine its effects on death receptor mRNA expression, EMSA for effects on NF‐κB DNA binding activity and colony formation assay for effects of inhibitors on (E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal's actions.Key Results(E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal induced a concentration (10–40 μg·mL−1)‐ and time (30 min–72 h)‐dependent inhibitory effect on the growth of NSCLC cells due to induction of apoptosis. Concomitantly, it significantly increased the expression of apoptotic proteins such as cleaved caspase‐3, cleaved caspase‐9, Bax and p53, but down‐regulated the expression of anti‐apoptotic proteins Bcl‐2, cIAP1 and cIAP2. This effect was induced by up‐regulation of MAPK and death receptor proteins TNFRSF12, TNFRSF10B and TNFRSF21, but suppression of NF‐κB. Of the death receptors activated, only TNFRSF10B knock down with siRNA reversed the effect of (E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal. Even though all the MAPKs were activated, only pretreatment with a p38 MAPK inhibitor reversed (E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal‐induced cell growth inhibition, increase in cleaved caspase‐3, ‐9 and TNFRSF10B expression, and NF‐κB inactivation.Conclusions And Implications(E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal induces apoptosis in NSCLC cells by p38 MAPK‐mediated suppression of NF‐κB and activation of TNFRSF10B, which then activates the caspase‐3 and caspase‐9 pathways.
Antithrombotic effect of Z4A5 on coronary thrombosis in a canine model of acute unstable angina
Authors: Jing Bo‐Bin , Li Ying‐Xue , Zhang Hui , Ren Shu‐Ting , Wang Mei , Li Yi‐Ping , Shen Xin‐Liang , Wang Yi‐Li , Zang Wei‐Jin , Wang Bing 
Published: October 2012

Background and PurposeThe glycoprotein IIb/IIIa receptor is the final common pathway of platelet aggregation, regardless of the agonist, and thus represents an ideal therapeutic target for blocking coronary thrombosis. In this study, the anti‐platelet and antithrombotic actions of Z4A5, a new glycoprotein IIb/IIIa receptor inhibitor, were evaluated in a canine model of acute unstable angina.Experimental ApproachZ4A5 was given i.v. as a bolus followed by 60 min of continuous infusion at doses of 30 μg·kg−1 + 1 μg·kg−1·min−1, 30 μg·kg−1 + 5 μg·kg−1·min−1 or 300 μg·kg−1 + 5 μg·kg−1·min−1. Its antithrombotic effect was evaluated in a model of coronary thrombosis, the injured, stenosed left circumflex coronary artery, in which platelet‐dependent cyclic flow reductions (CFRs) were induced by vascular compression and constriction to simulate clinical acute unstable angina. Platelet aggregation and coagulation parameters were determined in platelet‐rich plasma and platelet poor plasma respectively.Key ResultsThe Z4A5 infusion induced a dose‐dependent reduction in CFR frequency, which returned to baseline levels after the termination of the infusion at low doses. At medium dose that inhibited most part of platelet aggregation, it increased tongue bleeding time marginally with no dramatic changes in haemodynamic and coagulation parameters. Furthermore, the inhibition of ADP‐induced platelet aggregation and prolonged bleeding time observed during Z4A5 infusion reverted to baseline levels after the termination of the infusion.Conclusions and ImplicationsZ4A5 is an effective antithrombotic agent for coronary artery thrombosis with a rapid‐on and rapid‐off pharmacological profile, and could be used as an alternative treatment of coronary artery ischaemic syndromes.
Pharmacological characterization of LPS and opioid interactions at the toll‐like receptor 4
Authors: Stevens CW , Aravind S , Das S , Davis RL 
Published: October 2012

Background and PurposePrevious work in our laboratory showed opioid agents inhibit cytokine expression in astrocytes. Recently, Watkins and colleagues hypothesized that opioid agonists activate toll‐like receptor 4 (TLR4) signalling, which leads to neuroinflammation. To test this hypothesis, we characterized LPS and opioid effects on TLR4 signalling in reporter cells.Experimental ApproachNF‐κB reporter cells expressing high levels of TLR4 were used to compare LPS and opioid effects on NF‐κB activation, a pathway activated by TLR4 stimulation.Key ResultsLPS increased TLR4 signalling in a concentration‐dependent manner and was antagonized by LPS antagonist (LPS‐RS, from Rhodobacter sphaeroides). A concentration ratio analysis showed that LPS‐RS was a competitive antagonist. The opioid agonists, morphine and fentanyl, produced minor activation of TLR4 signalling when given alone. When tested following LPS stimulation, opioid agonists inhibited NF‐κB activation but this inhibition was not blocked by the general opioid antagonist, naloxone, nor by the selective μ opioid receptor antagonist, β‐FNA. Indeed, both naloxone and β‐FNA also inhibited NF‐κB activation in reporter cells. Further examination of fentanyl and β‐FNA effects revealed that both opioid agents inhibited LPS signalling in a non‐competitive fashion.Conclusions and ImplicationsThese results show that LPS‐RS is a competitive antagonist at the TLR4 complex, and that both opioid agonists and antagonists inhibit LPS signalling in a non‐competitive fashion through a non‐GPCR, opioid site(s) in the TLR4 signalling pathway. If confirmed, existing opioid agents or other drug molecules more selective at this novel site may provide a new therapeutic approach to the treatment of neuroinflammation.
The clinical utility of serum tartrate‐resistant acid phosphatase 5b in the assessment of bone resorption in patients on peritoneal dialysis
Authors: Yamada Shunsuke , Tsuruya Kazuhiko , Yoshida Hisako , Taniguchi Masatomo , Haruyama Naoki , Tanaka Shigeru , Eriguchi Masahiro , Nakano Toshiaki , Kitazono Takanari 
Published: October 2012

SummaryObjectivesSerum tartrate‐resistant acid phosphatase 5b (TRACP5b) is a bone resorption marker used in the assessment of bone metabolic status. The present study was designed to determine the clinical characteristics and utility of measuring serum TRACP5b levels in peritoneal dialysis (PD) patients.DesignCross‐sectional study.PatientsForty‐one patients receiving PD treatment in a single centre.MeasurementSerum levels of the bone turnover markers TRACP5b, N‐terminal cross‐linking telopeptide of type 1 collagen (NTX), bone‐specific alkaline phosphatase (BAP), and parathyroid hormone (PTH) were simultaneously measured. The correlation of serum TRACP5b with other established bone markers was analysed after logarithmic transformation. Multivariate linear regression analysis was performed to examine the effects of both renal and peritoneal Kt/V (an index for solute clearance) for urea on bone markers using age, sex, body mass index, and PTH as covariates. Bone markers were also measured in three patients before and after treatment with cinacalcet hydrochloride, alphacalcidol, and raloxifene hydrochloride.ResultsLog TRACP5b was significantly correlated with log NTX, log BAP and log PTH. In the multivariate analysis, peritoneal Kt/V was not correlated with log NTX, log BAP or log TRACP5b. In contrast, renal Kt/V was significantly correlated with log NTX only. Responses to drug treatment were more accurately determined from serum TRACP5b and BAP than from serum NTX.ConclusionsSerum TRACP5b and BAP are potentially useful biomarkers for the evaluation of bone turnover in PD patients because they correlate well with other established bone markers and they are not influenced by renal and peritoneal clearances.
Preclinical safety and stability study of a next generation telescope prosthesis for end‐stage macular degeneration
Authors: Rosen Eli , Sachs Dan , Eliahu Shmulik Ben , Assia Ehud I , Kleinmann Guy 
Published: October 2012

AbstractBackgroundTo assess the surgical procedure, safety and stability of a next generation injectable telescope prosthesis in a rabbit model.MethodsAfter removal of the crystalline lenses of eight New Zealand White rabbits, the next generation device was randomly implanted in one eye, and the available telescope prosthesis (Normal device) was implanted in the fellow eye. Operative parameters (incision, capsulorrhexis size and operative time), intraoperative and postoperative complications rates, endothelial cell density changes and the distance between the corneal endothelium and the telescope (central clearance distance) were measured and compared between the groups.ResultsIncision size and capsulorrhexis size were smaller, and operative time was shorter in the next generation group in comparison with the Normal group. No difference was found in the intraoperative and postoperative complication rates between the groups. Endothelial cell density loss observed in the next generation group was less than the loss in the Normal group, but the difference was not significant statistically. The central clearance distance was significantly larger in the next generation group in comparison with the Normal group (P = 0.001).ConclusionsThe next generation telescope was implanted through a smaller incision, with a shorter surgical time and a larger central clearance distance in the rabbit eyes, in comparison with the Normal group. The next generation device may allow reduced trauma to the corneal endothelium, better control during surgery and induce less astigmatism while preserving the optical advantages of the Food and Drug Administration‐approved telescope prosthesis.
Femtosecond laser‐assisted cataract surgery compared with conventional cataract surgery
Authors: Abell Robin G , Kerr Nathan M , Vote Brendan J 
Published: October 2012

AbstractBackgroundTo investigate the safety and efficacy of the Catalys (Optimedica, Santa Clara, CA, USA) femtosecond laser‐assisted cataract surgery system compared with conventional phacoemulsification cataract extraction.DesignProspective, consecutive, parallel cohort study.ParticipantsThe first 200 eyes undergoing conventional cataract surgery to the first 200 eyes undergoing femtosecond laser‐assisted cataract surgery between April and July 2012.MethodsFemtosecond laser‐assisted cataract surgery involved anterior capsulotomy and lens fragmentation based on optical coherence tomography‐guided treatment mapping. Conventional cataract surgery involved manual continuous curvilinear capsulorhexis. Both procedures were completed by standard phacoemulsification and insertion of an intraocular lens.Main Outcome MeasuresEffective phacoemulsification time and intraoperative complication rates.ResultsPatient demographics were similar between both groups. There was no statistically significant difference in intraoperative complications between femtosecond laser‐assisted cataract surgery and conventional surgery. There was one posterior capsule rupture in both groups (0.5%; not significant). One hundred per cent of cases treated with the femtosecond laser had a complete capsulotomy. Vacuum time decreased with experience. Effective phacoemulsification time was reduced by 70% in the femtosecond group (P < 0.0001). Twenty‐six cases in the femtosecond group versus one case in the conventional group had 0 effective phacoemulsification time (P < 0.0001).ConclusionFemtosecond laser‐assisted cataract surgery appears to be as safe as conventional cataract surgery in the short term and results in significantly lower effective phacoemulsification time. Although it may allow for greater efficiency and decreased postoperative complications, further research is needed into long‐term safety aspects such as corneal endothelial cell loss.
Intravitreal injections: a review of the evidence for best practice
Authors: Fagan Xavier J , Al‐Qureshi Salmaan 
Published: October 2012

AbstractIntravitreal injection is a common procedure performed by ophthalmologists. It is a quick and targeted treatment for a number of ophthalmic conditions. Despite this, the potential to cause serious complications and patient discomfort cannot be ignored. This article presents the level of evidence in the scientific literature supporting common practices such as location of the procedure, anaesthetic choice, sterile procedure techniques, comparison of some common pharmaceutical agents and the use of antibiotics.
Effect of insurance status on patients admitted for acute diverticulitis
Authors: Mills A. M. , Holena D. N. , Kallan M. J. , Carr B. G. , Reinke C. E. , Kelz R. R. 
Published: October 2012

AbstractAimThe study aimed to evaluate the relationship between insurance status and the management and outcome of acute diverticulitis in a nationally representative sample.MethodA retrospective cohort analysis of a nationally representative sample of 1 031 665 hospital discharges of patients admitted for acute diverticulitis in the 2006–2009 Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project data set. The main outcome measures included state at presentation (complicated/uncomplicated), management (medical/surgical), time to surgical intervention, type of operation and inpatient death.ResultsIn total, 207 838 discharges were identified (including 37.0% with private insurance, 49.3% in Medicare, 5.6% in Medicaid and 5.8% uninsured) representing 1 031 665 total discharges nationally. Medicare patients were more likely to present with complicated diverticulitis compared with private insurance patients (23.8% vs 15.1%). Time to surgical intervention differed by insurance status. After adjusting for patient, hospital and treatment factors, Medicare patients were less likely than those with private insurance to undergo a procedure (Medicare OR = 0.86, 95% CI: 0.82–0.91), while the uninsured were more likely to undergo drainage (OR = 1.30, 95% CI: 1.16–1.46) or a colostomy only (OR = 1.70, 95% CI: 1.24–2.33). All patients without private insurance were more likely to die in hospital (Medicare OR = 1.29, 95% CI: 1.09–1.52; Medicaid OR = 1.55, 95% CI: 1.22–1.97; uninsured OR = 1.41, 95% CI: 1.07–1.87).ConclusionIn a nationally representative sample of patients with acute diverticulitis, patient management and outcome varied significantly by insurance status, despite adjustment for potential confounders. Providers might need to heighten surveillance for complications when treating patients without private insurance to improve outcome.
miR‐16 inhibits the proliferation and angiogenesis‐regulating potential of mesenchymal stem cells in severe pre‐eclampsia
Authors: Wang Yaping , Fan Hongye , Zhao Guangfeng , Liu Dan , Du Leilei , Wang Zhiqun , Hu Yali , Hou Yayi 
Published: October 2012

Pre‐eclampsia is thought to be a systemic disease of maternal endothelial cell dysfunctions. miRNAs regulate various basic biological functions in cells, including stem cells. Mesenchymal stem cells exist in almost all tissues and are the key cellular source for tissue repair and regeneration. Our aims are to investigate whether miRNAs regulate MSCs in fetal–maternal interfaces to influence the pathogenesis of pre‐eclampsia. The differential expression of miRNAs in decidua‐derived mesenchymal stem cells of all patients with severe pre‐eclampsia (n = 20) and normal groups (n = 20) was first screened by microarray analysis and validated by quantitative real‐time PCR analysis. The integrated bioinformatics analysis showed that miR‐16 showed the highest number of connections in the miRNA GO network and the miRNA gene network. Moreover, over‐expressed miR‐16 inhibited the proliferation and migration of decidua‐derived mesenchymal stem cells and induced cell‐cycle arrest by targeting cyclin E1. Interestingly, over‐expression of miR‐16 by decidua‐derived mesenchymal stem cells reduced the ability of human umbilical vein endothelial cells to form blood vessels and reduced the migration of trophoblast cells. Furthermore, decidua‐derived mesenchymal stem cell‐expressed endothelial growth factor VEGF‐A was involved in migration of trophoblast cells and human umbilical vein endothelial cells as well as tube and network formation. Importantly, the levels of cyclin E1 and VEGF‐A were negatively correlated with the level of miR‐16 expression in decidua‐derived mesenchymal stem cells from the patients with severe pre‐eclampsia. Together, these data suggest that the alteration of miR‐16 expression in decidua‐derived mesenchymal stem cells may be involved in the development of pre‐eclampsia.
Cytokines as diagnostic markers of pulpal inflammation
Authors: ElSalhy M. , Azizieh F. , Raghupathy R. 
Published: October 2012

AbstractAimTo measure and compare the levels of the cytokines IL‐2, IL‐6, IL‐8, IL‐10, TNF‐α and IFN‐γ in pulpal blood from irreversible pulpitis, asymptomatic caries exposure and normal pulps.MethodologyBlood was obtained from pulp exposure sites using cotton pellets. Twenty‐five samples were obtained from normal teeth, 40 from asymptomatic caries‐exposed pulps and 43 from irreversible pulpitis teeth. Cytokine levels were determined by high‐sensitivity ELISA. Data were statistically analysed using Kruskal–Wallis and Mann–Whitney U‐tests.ResultsSignificantly higher levels (P < 0.05) of IL‐6, IL‐8, IL‐10, TNF‐α and IFN‐γ were detected in caries‐exposed pulps and irreversible pulpitis as compared to normal teeth. IL‐2 and IL‐10 levels were significantly higher (P < 0.05) in caries‐exposed pulps as compared to irreversible pulpitis, whilst IL‐8 was significantly higher (P < 0.001) in irreversible pulpitis as compared to caries‐exposed teeth. Most interestingly, IL‐6/IL‐10 and IL‐8/IL‐10 ratios were significantly higher (P < 0.001) in irreversible pulpitis compared with both caries‐exposed and normal teeth.ConclusionLevels of IL‐8 and the ratios of IL‐6/IL‐10 and IL‐8/IL‐10 have the potential to be indicators of pulpal inflammation in caries exposure cases. Cytokine estimation in pulpal blood may help in the diagnosis of pulpal inflammation.
Geographical structure and cryptic lineages within common green iguanas, Iguana iguana
Authors: Stephen Catherine L. , Reynoso Víctor H. , Collett William S. , Hasbun Carlos R. , Breinholt Jesse W. 
Published: October 2012

AbstractAimOur aim was to investigate genetic structure in Neotropical populations of common green iguanas (Iguana iguana) and to compare that structure with past geological events and present barriers. Additionally, we compared levels of divergence between lineages within Iguana with those within closely related genera in the subfamily Iguaninae.LocationNeotropics.MethodsDNA sequence data were collected at four loci for up to 81 individuals from 35 localities in 21 countries. The four loci, one mitochondrial (ND4) and three nuclear (PAC, NT3, c‐mos), were chosen for their differences in coalescent and mutation rates. Each locus was analysed separately to generate gene trees, and in combination in a species‐level analysis.ResultsThe pairwise divergence between Iguana delicatissima and I. iguana was much greater than that between sister species of Conolophus and Cyclura and non‐sister species of Sauromalus, at both mitochondrial (mean 10.5% vs. 1.5–4%, respectively) and nuclear loci (mean 1% vs. 0–0.18%, respectively). Furthermore, divergences within I. iguana were equal to or greater than those for interspecific comparisons within the outgroup genera. Phylogenetic analyses yielded four strongly supported, geographically defined mitochondrial clades (3.8–5% divergence) within I. iguana. Three of the four clades were found using PAC (0.18–1.65% divergence) and two using NT3 (0.6% divergence) alone. The primary divergence, recovered in three polymorphic loci, was between individuals north and south of the Isthmus of Panama. The southern group was differentiated into clades comprising individuals on either side of the northern Andes, using both PAC and ND4.Main conclusionsDeep genetic divergences were found within I. iguana that are congruent with past and current geological barriers. These divisions are greater than sister species comparisons in other Iguaninae genera, indicating the possible presence of cryptic species. Geological changes from the mid‐Miocene through the Plio‐Pleistocene have shaped the pattern of divergence in I. iguana. The uplift of the northern Andes presented a barrier between South American I. iguana populations by 4 Ma. Populations north of the Isthmus of Panama form a clade that is distinct from those to the south, and may have expanded northwards following the closing of the Isthmus of Panama 2.5 Ma.