bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigallocatechin‐3‐Gallate Attenuates Oxidative Stress and Inflammation in Obstructive Nephropathy via NF‐κB and Nrf2/HO‐1 Signalling Pathway Regulation
Authors: Wang Yanqiu , Wang Bowen , Du Feng , Su Xuesong , Sun Guangping , Zhou Guangyu , Bian Xiaohui , Liu Na 
Published: January 2015

AbstractOxidative stress and inflammation contribute importantly to the pathogenesis of chronic kidney disease (CKD). Epigallocatechin‐3‐gallate (EGCG), which is the most abundant and most active catechin polyphenol extracted from green tea, has been proved to have many bioactivities. In this study, the renoprotective effect of EGCG was evaluated in a widely used kidney disease model, the unilateral ureteral obstruction (UUO) mice model. After 14 days of EGCG administration, mean arterial blood pressure, body‐weight and obstructed kidney weight were measured. Levels of blood urea nitrogen (BUN) and creatinine (CR) and activities of glutamic–pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) in serum were estimated as indicators of renal function. Periodic acid–Schiff (PAS) staining was performed to observe the pathological changes of the obstructed kidney. Antioxidant enzymes and pro‐inflammatory cytokine production were estimated to reflect the oxidative stress and inflammatory state in the obstructed kidney. Finally, the main proteins in the NF‐κB and Nrf2 signalling pathway and DNA binding activity of NF‐κB and Nrf2 were measured to investigate the effect of EGCG on these two pathways. The results demonstrated that EGCG could restore UUO‐induced kidney weight loss and renal dysfunction. In addition, UUO‐induced oxidative stress and inflammatory responses in the obstructed kidney were also prevented by EGCG. Furthermore, EGCG could induce both NF‐κB and Nrf2 nuclear translocation in the UUO kidney and promote heme oxygenase‐1 (HO‐1) production. These results indicated that the renoprotective effect of EGCG might be through its NF‐κB and Nrf2 signalling pathway regulations.
Case study: hidden complexity of medicines use: information provided by a person with intellectual disability and diabetes to a pharmacist
Authors: Flood Bernadette , Henman Martin C. 
Published: January 2015

Accessible summaryA pharmacist spoke to people with intellectual disabilities about their medicines.One person with diabetes found it hard to manage.

He had to inject insulin.
He had to take tablets that were in a blister pack.
He did not like having diabetes and was distressed.
He did not store his insulin properly.
He often had low sugar and had to get a glucagon injection.
Pharmacists can help people who have diabetes.

They can give advice about medicines.
They can give advice about injecting and storing insulin.
People should only ask for more insulin and medicines from the pharmacy when they need them.SummaryPeople with intellectual disabilities may be ‘invisible’ to pharmacists. They are a complex group of patients many of whom have diabetes. Pharmacists may have little experience of the challenges faced by this high risk group of patients who may be prescribed high risk medications. This case report details information supplied by Pat, a 33 year old gentleman with intellectual disabilities and diabetes to a pharmacist researcher. The aim of the research project, which received ethics approval from a university research ethics committee, was to determine the views and knowledge of people with intellectual disabilities about medication use. Pat proved to be an excellent source of information concerning the complexity of ‘self care’ by a person with intellectual disabilities and diabetes. Many quality issues became evident to the pharmacist researcher during the interview. These issues included ‘self care’, diabetes distress, health literacy, medication information provision, safe practices around storage of insulin and glucagon, appropriateness of a monitored dosage system, repeat dispensing of insulin and the complexity of care co‐ordination. The international trend to deinstitutionalise the care of people with intellectual disabilities will require that this complex group of patients to get support from care givers and health and social care professionals in the community setting to ensure quality medication use. Pharmacists must rise to challenge to provide accessible patient centred pharmaceutical care to this high risk population.
Short‐term variability in QT interval and ventricular arrhythmias induced by dofetilide are dependent on high‐frequency autonomic oscillations
Authors: Champeroux P , Thireau J , Judé S , Laigot‐Barbé C , Maurin A , Sola M L , Fowler J S L , Richard S , Le Guennec J Y 
Published: January 2015

Background and PurposeThe present study was undertaken to investigate an effect of dofetilide, a potent arrhythmic blocker of the voltage‐gated K+ channel, hERG, on cardiac autonomic control. Combined with effects on ardiomyocytes, these properties could influence its arrhythmic potency.Experimental ApproachThe short‐term variability of beat‐to‐beat QT interval (STVQT), induced by dofetilide is a strong surrogate of Torsades de pointes liability. Involvement of autonomic modulation in STVQT was investigated in healthy cynomolgus monkeys and beagle dogs by power spectral analysis under conditions of autonomic blockade with hexamethonium.Key ResultsIncrease in STVQT induced by dofetilide in monkeys and dogs was closely associated with an enhancement of endogenous heart rate and QT interval high‐frequency (HF) oscillations. These effects were fully suppressed under conditions of autonomic blockade with hexamethonium. Ventricular arrhythmias, including Torsades de pointes in monkeys, were prevented in both species when HF oscillations were suppressed by autonomic blockade. Similar enhancements of heart rate HF oscillations were found in dogs with other hERG blockers described as causing Torsades de pointes in humans.Conclusions and ImplicationsThese results demonstrate for the first time that beat‐to‐beat ventricular repolarization variability and ventricular arrhythmias induced by dofetilide are dependent on endogenous HF autonomic oscillations in heart rate. When combined with evidence of hERG‐blocking properties, enhancement of endogenous HF oscillations in heart rate could constitute an earlier and more sensitive biomarker than STVQT for Torsades de pointes liability, applicable to preclinical regulatory studies conducted in healthy animals.
Involvement of neuronal TGF‐β activated kinase 1 in the development of tolerance to morphine‐induced antinociception in rat spinal cord
Authors: Xu Hao , Xu Tao , Ma Xiaqing , Jiang Wei 
Published: January 2015

Background and PurposeTolerance induced by morphine and other opiates remains a major unresolved problem in the clinical management of pain. There is now good evidence for the importance of MAPKs in morphine‐induced antinociceptive tolerance. A member of the MAPK kinase kinase family, TGF‐β activated kinase 1 (TAK1) is the common upstream kinase of MAPKs. Here, we have assessed the involvement of TAK1 in the development of tolerance to morphine‐induced analgesia.Experimental ApproachThe effects of an antagonist of TAK1 on morphine tolerance were investigated in vivo using the Randall–Selitto test, and the mechanism was investigated using Western blot and immunohistochemistry. The expression of TAK1 after chronic morphine exposure was also evaluated in vitro by immunohistochemistry.Key ResultsChronic intrathecal morphine exposure up‐regulated protein levels and phosphorylation of spinal TAK1. TAK1 immunoreactivity was co‐localized with the neuronal marker NeuN. Intrathecal administration of 5Z‐7‐oxozeaenol (OZ), a selective TAK1 inhibitor, attenuated the loss of morphine analgesic potency and morphine‐induced TAK1 up‐regulation. Furthermore, OZ decreased the up‐regulated expression of spinal p38 and JNK after repeated morphine exposure. In vitro studies demonstrated that sustained morphine treatment induced TAK1 up‐regulation, which was reversed by co‐administration of OZ. A bolus injection of OZ showed some reversal of established morphine antinociceptive tolerance.Conclusions and ImplicationsTAK1 played a pivotal role in the development of morphine‐induced antinociceptive tolerance. Modulation of TAK1 activation by the selective inhibitor OZ in the lumbar spinal cord may prove to be an attractive adjuvant therapy to attenuate such tolerance.
DHEA modulates the effect of cortisol on RACK1 expression via interference with the splicing of the glucocorticoid receptor
Authors: Pinto Antonella , Malacrida Beatrice , Oieni Jacopo , Serafini Melania Maria , Davin Annalisa , Galbiati Valentina , Corsini Emanuela , Racchi Marco 
Published: January 2015

Background and PurposeDehydroepiandrosterone (DHEA) is thought to be an anti‐glucocorticoid hormone known to be fully functional in young people but deficient in aged humans. Our previous data suggest that DHEA not only counteracts the effect of cortisol on RACK1 expression, a protein required both for the correct functioning of immune cells and for PKC‐dependent pathway activation, but also modulates the inhibitory effect of cortisol on LPS‐induced cytokine production. The purpose of this study was to investigate the effect of DHEA on the splicing mechanism of the human glucocorticoid receptor (GR).Experimental ApproachThe THP1 monocytic cell line was used as a cellular model. Cytokine production was measured by specific elisa. Western blot and real‐time RT‐PCR were used, where appropriate, to determine the effect of DHEA on GRs, serine/arginine‐rich proteins (SRp), and RACK1 protein and mRNA. Small‐interfering RNA was used to down‐regulate GRβ.Key ResultsDHEA induced a dose‐related up‐regulation of GRβ and GRβ knockdown completely prevented DHEA‐induced RACK1 expression and modulation of cytokine release. Moreover, we showed that DHEA influenced the expression of some components of the SRps found within the spliceosome, the main regulators of the alternative splicing of the GR gene.Conclusions and ImplicationsThese data contribute to our understanding of the mechanism of action of DHEA and its effect on the immune system and as an anti‐glucocorticoid agent.
Synthesis and Biological Evaluation of a Series of 2‐((1‐substituted‐1H‐1,2,3‐triazol‐4‐yl)methylthio)‐6‐(naphthalen‐1‐ylmethyl)pyrimidin‐4(3H)‐one As Potential HIV‐1 Inhibitors
Authors: Fang Zengjun , Kang Dongwei , Zhang Lingzi , Huang Boshi , Liu Huiqing , Pannecouque Christophe , De Clercq Erik , Zhan Peng , Liu Xinyong 
Published: January 2015

A series of novel S‐DABO derivatives with the substituted 1,2,3‐triazole moiety on the C‐2 side chain were synthesized using the simple and efficient CuAAC reaction, and biologically evaluated as inhibitors of HIV‐1. Among them, the most active HIV‐1 inhibitor was compound 4‐((4‐((4‐(2,6‐dichlorobenzyl)‐5‐methyl‐6‐oxo‐1,6‐dihydropyrimidin‐2‐ylthio)methyl)‐1H‐1,2,3‐triazol‐1‐yl)methyl)benzenesulfonamide (B5b7), which exhibited similar HIV‐1 inhibitory potency (EC50 = 3.22 μm) compared with 3TC (EC50 = 2.24 μm). None of these compounds demonstrated inhibition against HIV‐2 replication. The preliminary structure–activity relationship (SAR) of these new derivatives was discussed briefly.
Prenatal and neonatal risk factors associated with children's developmental status at ages 4–7: lessons from the Jiangsu China birth defects prevention cohort
Authors: Liu Y. , Li X.‐N. , Sun X.‐R. , Liu Q.‐L. , Zha S.‐W. , Chen Y.‐H. , Mao C.‐T. , Xu X.‐Y. 
Published: January 2015

AbstractBackgroundThere is limited information involving population data about the role of maternal health, fetal growth and neonatal health on children's developmental status at ages 4–7 years. Our aim was to determine the contribution of maternal, fetal and neonatal health to developmental status at ages 4–7 years.MethodsIn this 7‐year follow‐up prospective cohort study, a sample of 26 803 mothers participated in the beginning. Among their children, 19 187 voluntarily completed the development screening test or the social life ability survey, which were designed for two different age groups (<6 or ≥6 years old, respectively). Logistic regression analysis was used to link the data with the prenatal outcome card and interview questionnaire applied to pregnant women in previous study, to the analysis of various related factors such as demographic, socio‐economic, disease and menstrual history, marriage and pregnancy care.ResultUnivariate and multivariate logistic regression analysis were used separately in two age groups [4–6 (n = 8439) and 6–7 (n = 10 748) years old] to analyse relative factors. Maternal age of 25–30 years, maternal education of high school and greater, family income and not drinking during pregnancy were associated with higher scores in development.ConclusionBoth preconception and pregnancy health education and health care are the important maternal factors closely associated with children's cognitive and social competence. Public health policies for preconception care and public welfare for high‐quality childcare are essential for improving children's life.
Management of allergy to penicillins and other beta‐lactams
Authors: Mirakian R. , Leech S. C. , Krishna M. T. , Richter A. G. , Huber P. A. J. , Farooque S. , Khan N. , Pirmohamed M. , Clark A. T. , Nasser S. M. 
Published: January 2015

SummaryThe Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and an expert panel have prepared this guidance for the management of immediate and non‐immediate allergic reactions to penicillins and other beta‐lactams. The guideline is intended forUKspecialists in both adult and paediatric allergy and for other clinicians practising allergy in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking, the panel reached consensus. During the development of the guideline, allBSACImembers were consulted using a Web‐based process and all comments carefully considered. Included in the guideline are epidemiology of allergic reactions to beta‐lactams, molecular structure, formulations available in theUKand a description of known beta‐lactam antigenic determinants. Sections on the value and limitations of clinical history, skin testing and laboratory investigations for both penicillins and cephalosporins are included. Cross‐reactivity between penicillins and cephalosporins is discussed in detail. Recommendations on oral provocation and desensitization procedures have been made. Guidance for beta‐lactam allergy in children is given in a separate section. An algorithm to help the clinician in the diagnosis of patients with a history of penicillin allergy has also been included.
Respiratory syncytial virus induces indoleamine 2,3‐dioxygenase activity: a potential novel role in the development of allergic disease
Authors: Ajamian F. , Wu Y. , Ebeling C. , Ilarraza R. , Odemuyiwa S. O. , Moqbel R. , Adamko D. J. 
Published: January 2015

SummaryBackgroundInfants that develop severe bronchiolitis due to respiratory syncytial virus (RSV) are at increased risk of developing asthma later in life. We investigated a potential immunological mechanism for the association between RSV and the development of allergic inflammation. The enzyme indoleamine 2,3‐dioxygenase (IDO) has been reported to induce selective apoptosis of T helper 1 (Th1) cells and contributed to Th2‐biased immune responses.ObjectiveTo determine whether RSV infection in vitro could induce IDO expression and bioactivity in human dendritic cells, leading to a Th2‐biased immune response.MethodsHuman peripheral blood monocytes from healthy adult donors were isolated, differentiated to dendritic cells (moDC), in vitro. We studied RSV infection and mechanisms of IDO activation in moDC with subsequent effect on T‐bet expression.ResultsWe found that moDC were infected by RSV and that this induced IDO activation. RSV‐induced IDO activity was inhibited by palivizumab, UV inactivation, TL4R inhibition, and ribavirin. However, blocking endosomal TLR function with chloroquine did not inhibit IDO activity. Selective inhibitors suggested that RSV‐induced IDO activity was dependent on the retinoic acid‐inducible gene‐I (RIG‐I) related pathway via NF‐κB and p38 MAPK. Coculture of RSV‐infected moDC with activated T cells, in a transwell system, suppressed expression of T‐bet (a Th1‐associated factor) but not GATA3 (a Th2 regulator). Inhibition of IDO activity with the competitive inhibitor, 1‐methyl tryptophan, blocked the effect on T‐bet expression.Conclusion and Clinical RelevanceOur data show for the first time that RSV can induce the expression and bioactivity of IDO in human moDC, in a virus replication‐dependant fashion. We suggest that RSV activation of IDO could be a potential mechanism for the development of allergic diseases.
Vertical Bone Augmentation with an Autogenous Block or Particles in Combination with Guided Bone Regeneration: A Clinical and Histological Preliminary Study in Humans
Authors: Rocchietta Isabella , Simion Massimo , Hoffmann Maria , Trisciuoglio Davide , Benigni Marco , Dahlin Christer 
Published: January 2015

AbstractBackgroundVertical ridge augmentation with the use of solid bone blocks or particulate bone autograft, exposed or covered by a nonresorbable expanded polytetrafluoroethylene (ePTFE) membrane, are well known in the literature and have been shown to be effective in treating bone atrophy.PurposeThe aim of our study was to assess the two techniques in respect to biological properties of transplanted bone in graft revascularization and bone remodeling in conjunction with dental implants.Materials and MethodsTen patients were treated within the study, with a total of 12 sites with posterior mandibular edentulous ridges with insufficient bone to allow implant placement. Bone regeneration was performed using autogenous intraoral block graft or autogenous particulate graft with an ePTFE barrier membrane. At 6–10 months, reentry surgery was performed; bone biopsies, including microscrews, were harvested; and implants were placed.ResultsEleven sites out of 12 healed uneventfully. A mean height gain of 5.03 mm was achieved. Mean bone‐to‐implant contact and bone fill were assessed by means of histomorphometric analysis. The block specimens revealed a bone‐to‐implant contact of 42.34%, and the particulate grafts had a bone‐to‐implant contact of 26.62% (p < .012). Bone fill values reported were 68.32% and 48.28% (p < .019) for block specimens versus particulate grafts.ConclusionsThe results clearly showed that both techniques were clinically successful for subsequent implant placement and prosthetic rehabilitation. The histological outcomes, including revascularization and bone remodeling, of the two techniques differed significantly. The block grafts outperformed the particulate grafts in terms of bone‐to‐implant contact and bone fill values; however, the morbidity associated with the donor site of the block must be considered.
In Vitro Investigation of the Effect of Oral Bacteria in the Surface Oxidation of Dental Implants
Authors: Sridhar Sathyanarayanan , Wilson Thomas G. , Palmer Kelli L. , Valderrama Pilar , Mathew Mathew T. , Prasad Shalini , Jacobs Michael , Gindri Izabelle M. , Rodrigues Danieli C. 
Published: January 2015

AbstractBackgroundBacteria are major contributors to the rising number of dental implant failures. Inflammation secondary to bacterial colonization and bacterial biofilm is a major etiological factor associated with early and late implant failure (peri‐implantitis). Even though there is a strong association between bacteria and bacterial biofilm and failure of dental implants, their effect on the surface of implants is yet not clear.PurposeTo develop and establish an in vitro testing methodology to investigate the effect of early planktonic bacterial colonization on the surface of dental implants for a period of 60 days.Materials and MethodsCommercial dental implants were immersed in bacterial (Streptococcus mutans in brain‐heart infusion broth) and control (broth only) media. Immersion testing was performed for a period of 60 days. During testing, optical density and pH of immersion media were monitored. The implant surface was surveyed with different microscopy techniques post‐immersion. Metal ion release in solution was detected with an electrochemical impedance spectroscopy sensor platform called metal ion electrochemical biosensor (MIEB).ResultsBacteria grew in the implant‐containing medium and provided a sustained acidic environment. Implants immersed in bacterial culture displayed various corrosion features, including surface discoloration, deformation of rough and smooth interfaces, pitting attack, and severe surface rusting. The surface features were confirmed by microscopic techniques, and metal particle generation was detected by the MIEB.ConclusionImplant surface oxidation occurred in bacteria‐containing medium even at early stages of immersion (2 days). The incremental corrosion resulted in dissolution of metal ions and debris into the testing solution. Dissolution of metal ions and particles in the oral environment can trigger or contribute to the development of peri‐implantitis at later stages.
Peri‐implant evaluation of immediately loaded implants placed in esthetic zone in patients with diabetes mellitus type 2: a two‐year study
Authors: Aguilar‐Salvatierra Antonio , Calvo‐Guirado José Luis , González‐Jaranay Maximino , Moreu Gerardo , Delgado‐Ruiz Rafael Arcesio , Gómez‐Moreno Gerardo 
Published: January 2015

AbstractObjectivesThe aim of this study was to evaluate implant survival and primary stability parameters in patients with diabetes with different levels of glycosylated hemoglobin Alc (HbA1c) treated with immediate placement and provisionalization of implant‐supported, single‐tooth replacements over 2 years.Materials and methodsEighty‐five patients were divided into three groups according to their HbA1c levels: 33 patients in Group 1 (<6, control group); 30 patients in Group 2 (6.1–8); and 22 patients in Group 3 (8.1–10). Each patient received one‐one‐piece implant in the anterior zone of the upper maxillary. The implant survival rate was analyzed for each group, together with three variables to evaluate the general state of peri‐implant health: probe depth, bleeding on probing, marginal bone loss.ResultsMarginal bone loss increased in relation with higher HbA1c levels. For marginal bone loss in Group 1, mean resorption values ranged from 0.51 after 6 months to 0.72 after 2 years in comparison with respective values of 1.33 and 1.92 in Group 3. This pattern was repeated for bleeding on probing, both parameters showing significant differences between groups. For bleeding on probing, mean bleeding levels varied from 0.36 in Group I at 6 months after implant placement, to 0.59 in Group 3 (P = 0.041 between the three groups). Peri‐implant pocket depth showed the same tendency to increase in relation to HbA1C but differences between groups did not reach statistical significance.ConclusionsPatients with diabetes can receive implant‐based treatments with immediate loading safely, providing they present moderate HbA1c values.