bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoid‐stimulated, transcription‐independent release of annexin A1 by cochlear Hensen cells
Authors: Kalinec F , Webster P , Maricle A , Guerrero D , Chakravarti DN , Chakravarti B , Gellibolian R , Kalinec G 
Published: November 2009

Background and purpose:  The current clinical strategy to protect the auditory organ against inflammatory damage by migrating leukocytes is the local delivery of glucocorticoids. However, the mechanism by which glucocorticoids confer this protection remains unknown. Therefore, we investigated the cellular and molecular targets of glucocorticoids in the cochlea that could be involved in preventing leukocyte migration.Experimental approach:  We used microscopy as well as immunocytochemical and microfluidic techniques to elucidate the effect of dexamethasone, hydrocortisone and prednisolone on the cellular and intracellular distribution of annexin A1 (ANXA1) – a glucocorticoid target known to inhibit leukocyte migration by receptor‐mediated signalling – in the cochlea and isolated cochlear cells of guinea pigs.Key results:  All the cells lining the scala media – the cochlear compartment containing the auditory organ – express ANXA1 and the ANXA1 receptor FPR2/ALX is present in the scala media, as well as in other cochlear ducts. The majority of ANXA1 in the scala media is stored inside lipid droplets within cochlear Hensen cells. Glucocorticoids activate a myosin IIC‐mediated mechanism that drives ANXA1 from the lipid droplets to the apical region of the Hensen cells, where ANXA1 is released to the external milieu by a process involving ABC transporters.Conclusions and implications:  These findings suggest that ANXA1 could be a major mediator of the anti‐inflammatory effects of glucocorticoids in the cochlea and identify new molecular targets for prevention of sudden sensorineural hearing loss.
The impact of GPCR structures on pharmacology and structure‐based drug design
Authors: Congreve Miles , Marshall Fiona 
Published: November 2009

After many years of effort, recent technical breakthroughs have enabled the X‐ray crystal structures of three G‐protein‐coupled receptors (GPCRs) (β1 and β2 adrenergic and adenosine A2a) to be solved in addition to rhodopsin. GPCRs, like other membrane proteins, have lagged behind soluble drug targets such as kinases and proteases in the number of structures available and the level of understanding of these targets and their interaction with drugs. The availability of increasing numbers of structures of GPCRs is set to greatly increase our understanding of some of the key issues in GPCR biology. In particular, what constitutes the different receptor conformations that are involved in signalling and the molecular changes which occur upon receptor activation. How future GPCR structures might alter our views on areas such as agonist‐directed signalling and allosteric regulation as well as dimerization is discussed. Knowledge of crystal structures in complex with small molecules will enable techniques in drug discovery and design, which have previously only been applied to soluble targets, to now be used for GPCR targets. These methods include structure‐based drug design, virtual screening and fragment screening. This review considers how these methods have been used to address problems in drug discovery for kinase and protease targets and therefore how such methods are likely to impact GPCR drug discovery in the future.This article is part of a themed section on Molecular Pharmacology of GPCR. To view the editorial for this themed section visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00695.x
TRANSFUSION COMPLICATIONS: Declining hepatitis C virus (HCV) prevalence in pregnant women: impact of anti‐HCV screening of donated blood
Authors: Ohto Hitoshi , Ishii Tsutomu , Kitazawa Junichi , Sugiyama Seiji , Ujiie Niro , Fujimori Keiya , Ariga Hiromichi , Satoh Tomoko , Nollet Kenneth E. , Okamoto Hiroaki , Hoshi Tanji 
Published: November 2009

BACKGROUND:Screening blood donors for hepatitis C virus (HCV) antibody has effectively mitigated transfusion transmission of HCV. We conducted a post hoc analysis to clarify the impact of donor screening on a general population of reproductive‐age females and their offspring.STUDY DESIGN AND METHODS:Anti‐HCV screening in Japan started in late‐1989. In a cohort studied between May 1990 and November 2004, a total of 22,664 consecutive serum samples from pregnant women were screened for anti‐HCV. Reactive samples were further tested for HCV RNA. Linear structural regression was applied to identify causal relationships.RESULTS:Anti‐HCV–reactive rates declined significantly by two measures. First, among women known to have been transfused, rates fell from 14.8% to 3.1% with the implementation of anti‐HCV screening (p < 0.01). Nevertheless, this is 10 times higher than the 0.3% reactive rate seen in a similar cohort of nontransfused women. Second, rates fell from 1.8% among women born in 1955 or before to 0.3% for women born in 1966 or later (p < 0.01). Among 103 anti‐HCV–reactive women, 31 (30%) had been transfused and another 17 (17%) had other identifiable risk factors. The remaining 55 (53%) had no clear risk factor. Blood transfusion accounted for 19% of anti‐HCV acquisition, by path analysis. Only one infant in this cohort was vertically infected with HCV.CONCLUSION:Anti‐HCV screening of donated blood and hygienic improvements have markedly decreased HCV infection of pregnant women with a transfusion history; however, 70% of anti‐HCV–reactive women were deemed to be infected via routes other than transfusion.
BLOOD DONORS AND BLOOD COLLECTION: The aging population poses a global challenge for blood services
Authors: Ali Akif , Auvinen Marja‐Kaisa , Rautonen Jukka 
Published: November 2009

BACKGROUND: The Finnish transfusion registry data suggest some alarming signals and future challenges that are likely to be faced by transfusion services as populations continue to age.STUDY DESIGN AND METHODS: Computerized data collection was performed on all potentially transfused patients in Finland, thus covering ∼70% of all blood usage. We simulated the red blood cell (RBC) usage according to the Finnish practice on different age groups but the population demographics from other countries.RESULTS: The Finnish data demonstrate a marked increase in RBC consumption with increasing age among recipients, beginning at around 50 years of age. The 70‐ to 80‐year‐olds have an eightfold higher RBC consumption than 20‐ to 40‐year‐olds.CONCLUSIONS: A large part of the variation in RBC use per capita can be explained by the age distribution of the different populations and not by the different national and regional treatment policies and protocols used. If current efforts are not enough to serve the changing population demographic and if increasing demands for blood products cannot be met, there is need to consider unprecedented measures such as reversing certain donor deferrals or even exporting blood from country to country.
Evaluation of a Bifurcation Drug‐Eluting Stent System versus Provisional T‐Stenting in a Perfused Synthetic Coronary Artery Model
Authors: RIZIK DAVID G. , KLAG JOSEPH M. , TENAGLIA ALAN , HATTEN THOMAS R. , BARNHART MARIANNE , WARNACK BORIS 
Published: November 2009

Background: Provisional T‐stenting is a widely used strategy for the treatment of coronary artery bifurcation lesions. However, the use of conventional stents in this setting is limited by multiple factors; this includes technical considerations such as wire wrap when accessing the involved vessel, and stent overlap at or near the carina of the lesion. In addition, current slotted tube stent technology tends to be associated with gaps in the coverage of the side branch ostium, which may result in restenosis in that segment of the lesion. The Pathfinder device, now more commonly referred to as the Xience Side Branch Access System (Xience SBA) is a drug‐eluting stent (DES) designed specifically to assist in the treatment of bifurcation lesions by allowing wire access into the side branch, irrespective of the treatment strategy to be employed.
Methods: The Xience SBA drug‐eluting stent was compared with the standard Vision coronary stent system using a provisional T‐stenting strategy in a perfused synthetic model of the coronary vasculature with side branch angulations of 30°, 50°, 70°, and 90°. Stent delivery was performed under fluoroscopic guidance. Following the procedure, high‐resolution 2D Faxitron imaging was used to evaluate deployment accuracy of the side branch stent relative to the main branch stent.
Results: Deployment of the Xience SBA was accomplished in the same total time as the standard stents in a provisional T‐stenting approach (14.9 vs. 14.6 minutes). However, the time required to achieve stent deployment in the main branch was less with the Xience SBA (4.0 vs. 6.6 minutes), and as a result, total contrast usage (49.4 vs. 69.4 cm3) and fluoroscopy time (5.1 vs. 6.2 minutes) was lower. Additionally, the Xience SBA had a lower incidence of wire wrap (22% vs. 89%) and less distal protrusion of the side branch stent into the main branch (0.54 vs. 1.21 mm). Significant gaps in ostial side branch coverage were not seen in either group.
Conclusions: The Xience Side Branch Access DES is a viable device for consistently accessing coronary bifurcation lesions; it allows for easy wire access into the side branch. This may assist the operator in overcoming those well‐recognized limitations associated with use of standard one‐ or two‐stent strategies. In this perfused synthetic coronary model, Xience SBA deployment required less contrast usage and shorter fluoroscopy times. Further testing of this device is warranted.
PPARγ ligands inhibit telomerase activity and hTERT expression through modulation of the Myc/Mad/Max network in colon cancer cells
Authors: Toaldo Cristina , Pizzimenti Stefania , Cerbone Angelo , Pettazzoni Piergiorgio , Menegatti Elisa , Daniela Berardi , Minelli Rosalba , Giglioni Barbara , Dianzani Mario Umberto , Ferretti Carlo , Barrera Giuseppina 
Published: November 2009

AbstractIn human cells the length of telomeres depends on telomerase activity. This activity and the expression of the catalytic subunit of human telomerase reverse transcriptase (hTERT) is strongly up‐regulated in most human cancers. hTERT expression is regulated by different transcription factors, such as c‐Myc, Mad1 and Sp1. In this study, we demonstrated that 15d‐PG J2 and rosiglitazone (an endogenous and synthetic peroxisome proliferators activated receptor γ (PPARγ) ligand, respectively) inhibited hTERT expression and telomerase activity in CaCo‐2 colon cancer cells. Moreover, both ligands inhibited c‐Myc protein expression and its E‐box DNA binding activity. Additionally, Mad1 protein expression and its E‐box DNA binding activity were strongly increased by 15d‐PG J2 and, to a lesser extent, by rosiglitazone. Sp1 transcription factor expression and its GC‐box DNA binding activity were not affected by both PPARγ ligands. Results obtained by transient transfection of CaCo‐2 cells with pmaxFP‐Green‐PRL plasmid constructs containing the functional hTERT core promoter (including one E‐box and five GC‐boxes) and its E‐box deleted sequences, cloned upstream of the green fluorescent protein reporter gene, demonstrated that 15d‐PG J2, and with minor effectiveness, rosiglitazone, strongly reduced hTERT core promoter activity. E‐boxes for Myc/Mad/Max binding showed a higher activity than GC‐boxes for Sp1. By using GW9662, an antagonist of PPARγ, we demonstrated that the effects of 15d‐PG J2 are completely PPARγ independent, whereas the effects of rosiglitazone on hTERT expression seem to be partially PPARγ independent. The regulation of hTERT expression by 15d‐PG J2 and rosiglitazone, through the modulation of the Myc/Max/Mad1 network, may represent a new mechanism of action of these substances in inhibiting cell proliferation.
Functionalized self‐assembling peptide hydrogel enhance maintenance of hepatocyte activity in vitro
Authors: Genové Elsa , Schmitmeier Stephanie , Sala Ana , Borrós Salvador , Bader Augustinus , Griffith Linda G. , Semino Carlos E. 
Published: November 2009

AbstractThere is a major challenge in maintaining functional hepatocytes in vivo as these cells rapidly lose their metabolic properties in culture. In this work we have developed a bioengineered platform that replaces the use of the collagen I – in the traditional culture sandwich technique – by a defined extracellular matrix analogue, the self‐assembling peptide hydrogel RAD16‐I functionalized with biologically active motifs. Thus, after examining side by side the two culture systems we have found that in both cases hepatocytes acquired similar parenchymal morphology, presence of functional bile canaliculi structures, CYP3A2 induction by dexamethasone, urea production, secretion of proteins such as apolipoprotein (class A1, E, J), α1‐microglobulin, α1‐macroglobulin, retinol binding protein, fibronectin, α1‐inhibitor III and biotin‐dependent carboxylases. Interestingly, by assessing in more detail some other hepatic markers, one of the functionalized matrix analogues – carrying the 67 kD laminin receptor ligand – enhanced the gene expression of albumin, HNF4‐α, MDR2 and tyrosine aminotransferase. We conclude that the use of a synthetic culture system with designed matrix functionalization has the advantage in controlling specific cellular responses.
Efficacy of a bioactive glass–ceramic (Biosilicate®) in the maintenance of alveolar ridges and in osseointegration of titanium implants
Authors: Roriz Virgílio M. , Rosa Adalberto L. , Peitl Oscar , Zanotto Edgar D. , Panzeri Heitor , De Oliveira Paulo T. 
Published: November 2009

AbstractObjectives: The aims of this research were to evaluate the efficacy of a bioactive glass–ceramic (Biosilicate®) and a bioactive glass (Biogran®) placed in dental sockets in the maintenance of alveolar ridge and in the osseointegration of Ti implants.Material and methods: Six dogs had their low premolars extracted and the sockets were implanted with Biosilicate®, Biogran® particles, or left untreated. After the extractions, measurements of width and height on the alveolar ridge were taken. After 12 weeks a new surgery was performed to take the final ridge measurements and to insert bilaterally three Ti implants in biomaterial‐implanted and control sites. Eight weeks post‐Ti implant placement block biopsies were processed for histological and histomorphometric analysis. The percentages of bone–implant contact (BIC), of mineralized bone area between threads (BABT), and of mineralized bone area within the mirror area (BAMA) were determined.Results: The presence of Biosilicate® or Biogran® particles preserved alveolar ridge height without affecting its width. No significant differences in terms of BIC, BAMA, and BABT values were detected among Biosilicate®, Biogran®, and the non‐implanted group.Conclusions: The results of the present study indicate that filling of sockets with either Biosilicate® or Biogran® particles preserves alveolar bone ridge height and allows osseointegration of Ti implants. To cite this article:
Roriz VM, Rosa AL, Peitl O, Zanotto ED, Panzeri H, de Oliveira PT. Efficacy of a bioactive glass–ceramic (Biosilicate®) in the maintenance of alveolar ridges and in osseointegration of titanium implants. Clin. Oral Impl. Res. 21, 2010; 148–155. doi: 10.1111/j.1600‐0501.2009.01812.x
Porous titanium granules promote bone healing and growth in rabbit tibia peri‐implant osseous defects
Authors: Wohlfahrt Johan Caspar , Monjo Marta , Rønold Hans Jacob , Aass Anne Merete , Ellingsen Jan Eirik , Lyngstadaas Staale Petter 
Published: November 2009

AbstractObjectives: The aim of this study was to investigate the osteoconductive properties and biological performance of porous titanium granules used in osseous defects adjacent to titanium implants.Material and methods: In this animal experimental study, calibrated defects were prepared in the tibias of 24 New Zealand rabbits. The defects were randomized into two tests and one control group. The test defects were grafted with either metallic or oxidized porous titanium granules (PTG or WPTG, respectively), whereas control defects were left empty (sham). The defects were closed with a submerged coin shaped titanium implant. Defects were left for healing for 4 weeks. After healing, the implants were removed and the new bone tissue formed onto the implant surface was analyzed for run × 2, osteocalcin, collagen‐I, tartrate‐resistant acid phosphatase, H+‐ATPase, tumor necrosis factor‐α, interleukin (IL)‐6 and IL‐10 gene expression using reverse transcriptase polymerase chain reactuion. Wound fluid from the healed defects was analyzed for lactate dehydrogenase and alkaline phosphatase activity. Finally osteoconductivity was analyzed by micro‐computed tomography and histology.Results: Significantly more new bone formed in PTG and WPTG grafted defects compared with sham. The new bone grew both through the porosities of the granules and onto the implant surfaces. The WPTG group showed significantly less expression of key inflammation markers, but with no significant difference in a marker for necrosis. The WPTG also showed a significant increase in collagen‐I mRNA expression compared with PTG.Conclusion: The results suggest that PTG and WPTG are both osteoconductive materials that can be used to promote bone formation in osseous defects adjacent to titanium implants without hampering implant osseointegration. To cite this article:
Wohlfahrt JC, Monjo M, Rønold HJ, Aass AM, Ellingsen JE, Lyngstadaas SP. Porous titanium granules promote bone healing and growth in rabbit tibia peri‐implant osseous defects. Clin. Oral Impl. Res. 21, 2010; 165–173. doi: 10.1111/j.1600‐0501.2009.01813.x
In vivo and in vitro biofilm formation on two different titanium implant surfaces
Authors: Bürgers Ralf , Gerlach Till , Hahnel Sebastian , Schwarz Frank , Handel Gerhard , Gosau Martin 
Published: November 2009

AbstractObjectives: The aim of the present in vitro and human in vivo study was twofold: first, to evaluate the initial biofilm formation on different titanium implant surfaces by means of two highly sensitive fluorescent techniques and, second, to correlate these findings to different surface properties.Materials and methods: In vivo biofilm formation was induced on purely machined (Pt) and on sand‐blasted and acid‐etched titanium (Prom) specimens, which were mounted buccally on individual splints and worn by six study participants for 12 h. In vitro bacterial adhesion was also investigated after incubation with Streptococcus sanguinis suspension (37°C, 2 h). Adherent bacteria were quantified by the following fluorescence techniques: Resazurin staining in combination with an automated fluorescence reader or live/dead cell labeling and fluorescence microscopy. Surface roughness (Ra) was determined with a perthometer, and surface free energy (SFE) was measured with a goniometer.Results: Prom showed a significantly higher median Ra (0.95 μm) and a significantly lower median SFE (18.3 mJ/m2) than Pt (Ra=0.15 μm; SFE=39.6 mJ/m2). The in vitro and in vivo tests showed a significantly higher bacterial adhesion to Prom than to Pt, and the initial biofilm formation on Pt corresponded to the circular surface modifications on the machined substratum. Both observations may be attributed to the predominant influence of surface roughness on bacterial adhesion. No significant differences in the percentage of dead cells among all adhering bacteria were found between Prom (23.7%) and Pt (29.1%). Ectopic solitary epithelial cells from the oral mucosa – strongly adhering to the substratum – were found on each Prom specimen, but not on any of the Pt surfaces.Conclusions: Initial bacterial adhesion to differently textured titanium surfaces is primarily influenced by Ra, whereas the influence of SFE seems to be of only minor importance. Therefore, the micro‐structured parts of an implant that are exposed to the oral cavity should be highly polished to prevent plaque accumulation. Both tested fluorometric techniques proved to be highly sensitive and reproducible in the quantification of biofilm formation on titanium implant surfaces. To cite this article:
Bürgers R, Gerlach T, Hahnel S, Schwarz F, Handel G, Gosau M. In vivo and in vitro biofilm formation on two different titanium implant surfaces. Clin. Oral Impl. Res. 21, 2010; 156–164 doi: 10.1111/j.1600‐0501.2009.01815.x
ORIGINAL ARTICLE: Imbalance of T‐cell Transcription Factors Contributes to the Th1 Type Immunity Predominant in Pre‐eclampsia
Authors: Jianjun Zhou , Yali Hu , Zhiqun Wang , Mingming Zheng , Xia Zhao 
Published: November 2009

Problem  Extensive studies have demonstrated that Th1 type immunity is predominant in pre‐eclampsia, but there is little concern with regard to the intracellular mechanisms behind this initial T‐cell polarization. In this study, we investigated whether the imbalance of the T‐cell transcription factors contributes to it.Method of study  A total of 15 pre‐eclamptic patients and 15 healthy pregnant women were enrolled in this study. The expression levels of transcription factors for Th1 (T‐bet), Th2 (GATA3), Th17 (RORc) and Treg (FOXP3) cells, together with the Th1/Th2 status, were simultaneously investigated in both peripheral blood mononuclear cells (PBMCs) and decidua.Results  The expression levels of FOXP3 mRNA were decreased in both PBMCs and decidua from pre‐eclamptic patients compared with healthy pregnant women (P < 0.05), and T‐bet mRNA and RORc mRNA were significantly increased (P < 0.05), while Th1/Th2 balance shifted toward the Th1 immunity. Furthermore, there was a negative correlation between FOXP3 mRNA and Th1 cells (P < 0.05), and the expression level of T‐bet mRNA correlated strongly with Th1 cells (P < 0.05).Conclusion  Decreased expression of FOXP3 mRNA and increased expression of T‐bet mRNA may contribute to Th1 type immunity predominant in pre‐eclampsia.
ORIGINAL ARTICLE: Comparative Analysis of Peripheral Natural Killer Cells in the Two Phases of the Ovarian Cycle
Authors: Pantazi Ageliki , Tzonis Panagiotis , Perros Gerasimos , Graphou Olga , Keramitsoglou Theodora , Koussoulakos Stavros , Margaritis Loukas , Varla‐Leftherioti Marighoula 
Published: November 2009

ProblemChanges in endometrial Natural Killer (NK) cells during the luteal phase of the ovarian cycle are important in initiating/maintaining a subsequent pregnancy. In the present study it was investigated whether during the menstrual cycle changes occur also in peripheral blood (PB) NKs.Method of studyBlood samples during the follicular and the luteal phase were collected from 30 women without fertility problems. Samples were analyzed by flow‐cytometry for: (1) NK cells (CD3−CD16+CD56+) and (2) intracellular production of interferon‐γ (IFN‐γ) by NK cells. For the comparison and correlation of the two populations between the two phases, Wilcoxon signed‐rank test and Spearman’s Coefficient were used.ResultsThe differences in percentages of CD3−CD16+CD56+ cells and that of CD3−CD16+CD56+/IFN‐γ+ cells between the follicular and the luteal phase were not statistically significant (10.61 ± 5.11 versus 9.76 ± 4.57 and 6.48 ± 7.90 versus 7.30 ± 6.77, respectively, P > 0.05). The correlation between the two variables (NK% and NK/IFN‐γ%) was weakly positive (P = 0.07) only in the follicular phase.ConclusionThe study did not reveal menstrual cycle‐depended changes in PB NK cells. Thus, a suggestion to measure these cells in a specific phase of the cycle in order to predict the outcome of a subsequent pregnancy in women with fertility problems is objected.