bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with hydrogen sulfide alleviates streptozotocin‐induced diabetic retinopathy in rats
Authors: Si Yan‐Fang , Wang Jun , Guan Juan , Zhou Li , Sheng Yu , Zhao Juan 
Published: March 2013

Background and PurposeRetinopathy, as a common complication of diabetes, is a leading cause of reduced visual acuity and acquired blindness in the adult population. The aim of present study was to investigate the therapeutic effect of hydrogen sulfide on streptozotocin (STZ)‐induced diabetic retinopathy in rats.Experimental ApproachRats were injected with a single i.p. injection of STZ (60 mg·kg−1) to induce diabetic retinopathy. Two weeks later, the rats were treated with NaHS (i.p. injection of 0.1 mL·kg−1·d−1 of 0.28 mol·L−1 NaHS, a donor of H2S) for 14 weeks.Key ResultsTreatment with H2S had no significant effect on blood glucose in STZ‐induced diabetic rats. Treatment with exogenous H2S enhanced H2S levels in both plasma and retinas of STZ‐induced diabetic rats. Treatment with H2S in STZ‐treated rats improved the retinal neuronal dysfunction marked by enhanced amplitudes of b‐waves and oscillatory potentials and expression of synaptophysin and brain‐derived neurotrophic factor, alleviated retinal vascular abnormalities marked by reduced retinal vascular permeability and acellular capillary formation, decreased vitreous VEGF content, down‐regulated expressions of HIF‐1α and VEGFR2, and enhanced occludin expression, and attenuated retinal thickening and suppressed expression of extracellular matrix molecules including laminin β1 and collagen IVα3 expression in retinas of STZ‐induced diabetic rats. Treatment with H2S in retinas of STZ‐induced diabetic rats abated oxidative stress, alleviated mitochondrial dysfunction, suppressed NF‐κB activation and attenuated inflammation.Conclusions and ImplicationsTreatment with H2S alleviates STZ‐induced diabetic retinopathy in rats possibly through abating oxidative stress and suppressing inflammation.
PDE3, but not PDE4, reduces β1‐ and β2‐adrenoceptor‐mediated inotropic and lusitropic effects in failing ventricle from metoprolol‐treated patients
Authors: Molenaar Peter , Christ Torsten , Hussain Rizwan I , Engel Andreas , Berk Emanuel , Gillette Katherine T , Chen Lu , Galindo‐Tovar Alejandro , Krobert Kurt A , Ravens Ursula , Levy Finn Olav , Kaumann Alberto J 
Published: March 2013

Background and PurposePDE3 and/or PDE4 control ventricular effects of catecholamines in several species but their relative effects in failing human ventricle are unknown. We investigated whether the PDE3‐selective inhibitor cilostamide (0.3–1 μM) or PDE4 inhibitor rolipram (1–10 μM) modified the positive inotropic and lusitropic effects of catecholamines in human failing myocardium.Experimental ApproachRight and left ventricular trabeculae from freshly explanted hearts of 5 non‐β‐blocker‐treated and 15 metoprolol‐treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (‐)‐noradrenaline, mediated through β1 adrenoceptors (β2 adrenoceptors blocked with ICI118551), and (‐)‐adrenaline, mediated through β2 adrenoceptors (β1 adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of PDE inhibitors. Catecholamine potencies were estimated from –logEC50s.Key ResultsCilostamide did not significantly potentiate the inotropic effects of the catecholamines in non‐β‐blocker‐treated patients. Cilostamide caused greater potentiation (P = 0.037) of the positive inotropic effects of (‐)‐adrenaline (0.78 ± 0.12 log units) than (‐)‐noradrenaline (0.47 ± 0.12 log units) in metoprolol‐treated patients. Lusitropic effects of the catecholamines were also potentiated by cilostamide. Rolipram did not affect the inotropic and lusitropic potencies of (‐)‐noradrenaline or (‐)‐adrenaline on right and left ventricular trabeculae from metoprolol‐treated patients.Conclusions and ImplicationsMetoprolol induces a control by PDE3 of ventricular effects mediated through both β1 and β2 adrenoceptors, thereby further reducing sympathetic cardiostimulation in patients with terminal heart failure. Concurrent therapy with a PDE3 blocker and metoprolol could conceivably facilitate cardiostimulation evoked by adrenaline through β2 adrenoceptors. PDE4 does not appear to reduce inotropic and lusitropic effects of catecholamines in failing human ventricle.Linked ArticleThis article is commented on by Eschenhagen, pp 524–527 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12168
PDE4 in the human heart – major player or little helper?
Authors: Eschenhagen Thomas 
Published: March 2013

PDEs restrict the positive inotropic effects of β‐adrenoceptor stimulation by degrading cAMP. Hence, PDE inhibitors sensitize the heart to catecholamines and are therefore used as positive inotropes. On the downside, this is accompanied by exaggerated energy expenditure, cell death and arrhythmias. For many years, PDE3 was considered to be the major isoform responsible for the control of cardiac force and rhythm. However, recent work in gene‐targeted mice and rodent cells has indicated that PDE4 is also involved. Furthermore, selective PDE4 inhibitors augment catecholamine‐stimulated cAMP levels and induce arrhythmias in human atrial preparations, which suggests that PDE4 has a more prominent role in the human heart than anticipated, and that PDE4 inhibitors such as roflumilast may carry an arrhythmogenic risk. In this issue of the journal, a team of researchers from three laboratories report on the effect of PDE3 and PDE4 inhibitors on ventricular trabeculae from explanted human hearts. The key result is that the PDE4 inhibitor rolipram does not affect the positive inotropic effects of β1‐ or β2‐adrenoceptor stimulation. Given that the ventricle rather than the atria is the critical region in terms of arrhythmogenic consequences, this is an important and reassuring finding.Linked ArticleThis article is a commentary on the research paper by Molenaar et al., pp. 528–538 of this issue. To view this paper visit http://dx.doi.org/10.1111/bph.12167
Endothelium‐dependent hyperpolarization‐related relaxations diminish with age in murine saphenous arteries of both sexes
Authors: Chennupati Ramesh , Lamers Wouter H , Koehler S Eleonore , De Mey Jo G R 
Published: March 2013

Background and PurposeWe investigated the effects of aging on the contributions of NO and endothelium‐dependent hyperpolarization (EDH) to endothelium‐dependent relaxation in saphenous arteries of male and female C57BL/6J mice aged 12, 34 and 64 weeks.Experimental ApproachVasomotor responses of saphenous arteries were analysed by wire myography in the absence and presence of stimuli of the endothelium, inhibitors of NOS, and inhibitors and stimulants of small (KCa2.3) and intermediate (KCa3.1) conductance calcium‐activated potassium channels.Key ResultsArterial relaxing responses to sodium nitroprusside and to ACh in the absence of pharmacological inhibitors (indomethacin and L‐NAME), were similar in all age groups and sexes, but those mediated by endothelium‐derived NO were slightly but significantly increased in 64‐week‐old male mice. In the presence of inhibitors, 12‐week‐old animals showed pronounced ACh‐induced relaxation, which was significantly reduced in 34‐ and 64‐week‐old mice of both sexes. The EDH‐related component of ACh‐induced relaxations was abolished by TRAM‐34 (KCa3.1 blocker) or UCL 1684 (KCa2.3 blocker). Although the maximal relaxation induced by NS309 (KCa activator) was not affected by aging, the sensitivity for NS309 significantly decreased with aging. The presence of SKA‐31 (KCa modulator) potentiated relaxations induced by ACh in arteries of 12‐week‐old but not older mice.Conclusion and ImplicationsIn a small muscular artery of mice of either sex, total endothelium‐dependent relaxation is not affected by age. However, possibly due to changes in KCa channel function, the contribution of EDH to endothelium‐dependent relaxations decreased with age. The contribution of endothelium‐derived NO increases in old male mice.
RGD capsid modification enhances mucosal protective immunity of a non-human primate adenovirus vector expressing Pseudomonas aeruginosa OprF
Authors: Krause A , Whu W Z , Qiu J , Wafadari D , Hackett N R , Sharma A , Crystal R G , Worgall S 
Published: March 2013

Summary
Replication-deficient adenoviral (Ad) vectors of non-human serotypes can serve as Ad vaccine platforms to circumvent pre-existing anti-human Ad immunity. We found previously that, in addition to that feature, a non-human primate-based AdC7 vector expressing outer membrane protein F of P. aeruginosa (AdC7OprF) was more potent in inducing lung mucosal and protective immunity compared to a human Ad5-based vector. In this study we analysed if genetic modification of the AdC7 fibre to display an integrin-binding arginine–glycine–aspartic acid (RGD) sequence can further enhance lung mucosal immunogenicity of AdC7OprF. Intratracheal immunization of mice with either AdC7OprF.RGD or AdC7OprF induced robust serum levels of anti-OprF immunoglobulin (Ig)G up to 12 weeks that were higher compared to immunization with the human vectors Ad5OprF or Ad5OprF.RGD. OprF-specific cellular responses in lung T cells isolated from mice immunized with AdC7OprF.RGD and AdC7OprF were similar for T helper type 1 (Th1) [interferon (IFN)-γ in CD8+ and interleukin (IL)-12 in CD4+], Th2 (IL-4, IL-5 and IL-13 in CD4+) and Th17 (IL-17 in CD4+). Interestingly, AdC7OprF.RGD induced more robust protective immunity against pulmonary infection with P. aeruginosa compared to AdC7OprF or the control Ad5 vectors. The enhanced protective immunity induced by AdC7OprF.RGD was maintained in the absence of alveolar macrophages (AM) or CD1d natural killer T cells. Together, the data suggest that addition of RGD to the fibre of an AdC7-based vaccine is useful to enhance its mucosal protective immunogenicity.
Mechanism of cell fate choice between neural and mesodermal development during early embryogenesis
Authors: Takemoto Tatsuya 
Published: March 2013

AbstractDuring early embryogenesis, Sox2 expression distinguishes the neural plate from other embryonic domains, suggesting that the mechanism underlying the activation of the Sox2 gene is highly relevant to the development of this tissue. At the earliest stages of neural plate development, the Sox2 enhancer N1 regulates Sox2 expression in the extending posterior end of the neural plate. The N1 enhancer is initially activated in the axial stem cells, bipotential precursors of both neural and mesodermal lineages, therefore the activation does not immediately lead to Sox2 expression. A population of axial stem cells that remains in the superficial layer starts expressing Sox2, whereas another population that migrates through the primitive streak loses the N1 activity and becomes mesoderm. Multiple signaling cascades and transcription factors, including Wnt, fibroblast growth factor (FGF), bone morphogenetic protein (BMP) and Tbx6, are responsible for the regulation of Sox2 expression in axial stem cells to guide the development of the posterior neural plate and paraxial mesoderm.
Effect of chemical and mechanical debridement techniques on bacterial re‐growth on rough titanium surfaces: an in vitro study
Authors: Gustumhaugen Eva , Lönn‐Stensrud Jessica , Scheie Anne A. , Lyngstadaas S. P. , Ekfeldt Anders , Taxt‐Lamolle Sébastien 
Published: March 2013

AbstractObjectiveThe aim of this in vitro study was to compare the effect of combined chemical and mechanical debridement of titanium (Ti) surfaces inoculated with Staphylococcus epidermidis, compared with the effect of chemical debridement alone.Material and MethodsDifferent Ti surfaces were characterized with respect to roughness and subsequently inoculated with S. epidermidis. NaCl (0.9 vol.%), EDTA (12 vol.%), H2O2 (3 vol.%) or H2O2 + TiO2 nanoparticles served as chemical debridement agents, while TiBrush™ was used as the mechanical debridement tool. Safranin staining assessed biomass still attached to surfaces after debridement. Biofilm viability was assessed after re‐incubation of the debrided samples. SEM analysis was performed before and after the cleaning process.ResultsSurface average roughness (Sa) of the samples was measured at 2.22 ± 0.19 μm for group A, 0.19 ± 0.02 μm for group B, and 1.99 ± 0.10 μm for group C. When chemical debridement agents were used alone, H2O2‐containing products were most efficient in reducing the biomass load. The surface roughness did not affect the outcome of chemical debridement. However, when combining chemical and mechanical debridement, a further reduction of biofilm load and viability was observed with best effect on the smoothest surface.ConclusionsCombining H2O2‐containing chemical agents with mechanical debridement (TiBrush™) provided best reduction in biofilm mass and re‐growth, when studied in vitro.
Transperineal ultrasonography in perianal Crohn's disease and recurrent cryptogenic fistula‐in‐ano
Authors: Nevler A. , Beer‐Gabel M. , Lebedyev A. , Soffer A. , Gutman M. , Carter D. , Zbar A. P. 
Published: March 2013

AbstractAimSuccessful anal fistula care is aided by specialized imaging accurately defining the site of the internal opening and fistula type. Imaging techniques are complementary, designed to answer specific anatomical questions. There are limited data concerning the clinical value of transperineal ultrasound (TP‐US) in both cryptogenic fistula‐in‐ano and perianal Crohn's disease (PACD). The aim of the study was to assess the accuracy of TP‐US compared with operative findings in patients with perirectal sepsis.MethodPatients with recurrent cryptogenic anal fistula and PACD referred for sonography were examined using TP‐US by a single examiner blinded to the operative results. Fistulae were categorized by the Parks classification predicting the site of the internal fistula opening. Ancillary horseshoe collections, abscesses and secondary tracks were defined.ResultsFourteen patients with PACD and 27 patients with recurrent cryptogenic fistula‐in‐ano were analysed with comparative images and operative data. Correlation of fistula type for cryptogenic and PACD patients respectively was 23/27 (85.2%) and 12/14 (85.7%), with a correlative internal opening site (when found at surgery) of 16/22 (72.3%) and 12/14 (85.7%). Misclassification of fistula type in cryptogenic cases occurred in the presence of ancillary abscesses with associated acoustic shadowing. In PACD patients, TP‐US was used when anal stenosis precluded endoanal ultrasonography, assisting in the diagnosis of recto‐vaginal fistulae.ConclusionTP‐US is a useful complementary technique to assess fistula‐in‐ano and has special advantage when there is anal canal distortion, complex fistula type or suspicion of a recto‐vaginal fistula.
Clinical outcome following Doppler‐guided haemorrhoidal artery ligation: a systematic review
Authors: Pucher P. H. , Sodergren M. H. , Lord A. C. , Darzi A. , Ziprin P. 
Published: March 2013

AbstractAimDoppler‐guided haemorrhoidal artery ligation (DGHL) has experienced wider uptake and has recently received National Institute for Health and Clinical Excellence (NICE) approval in the UK. A systematic review of the literature was conducted to assess its safety and efficacy.MethodThis review was conducted in keeping with PRISMA guidelines. MEDLINE, EMBASE, Google Scholar and Cochrane Library databases were searched. Studies describing DGHL as a primary procedure and reporting clinical outcome were considered. Primary end‐points were recurrence and postoperative pain. Secondary end‐points included operation time, complications and reintervention rates. Studies were scored for quality with either Jadad score or NICE scoring guidelines.ResultsTwenty‐eight studies including 2904 patients were included in the final analysis. They were of poor overall quality. Recurrence ranged between 3% and 60% (pooled recurrence rate 17.5%), with the highest rates for grade IV haemorrhoids. Postoperative analgesia was required in 0–38% of patients. Overall postoperative complication rates were low, with an overall bleeding rate of 5% and an overall reintervention rate of 6.4%. The operation time ranged from 19 to 35 min.ConclusionDGHL is safe and efficacious with a low level of postoperative pain. It can be safely considered for primary treatment of grade II and III haemorrhoids.
Care complexity, mood, and quality of life in liver pre‐transplant patients
Authors: Lobo Elena , Stiefel Frederic , Söllner Wolfgang , Santabarbara Javier , Lobo Antonio , Huyse Frits , Marcos Guillermo , Michaud Laurent , Hohenberger Werner , Ludwig Gundula 
Published: March 2013

AbstractRationaleThis study was intended to document the frequency of care complexity in liver transplant candidates, and its association with mood disturbance and poor health‐related quality of life (HRQoL).MethodsConsecutive patients fulfilling inclusion criteria, recruited in three European hospitals, were assessed with INTERMED, a reliable and valid method for the early assessment of bio‐psychosocial health risks and needs. Blind to the results, they were also assessed with the Hospital Anxiety and Depression Scale (HADS). HRQoL was documented with the EuroQol and the SF36. Statistical analysis included multivariate and multilevel techniques.ResultsAmong patients fulfilling inclusion criteria, 60 patients (75.9%) completed the protocol and 38.3% of them were identified as “complex” by INTERMED, but significant between‐center differences were found. In support of the working hypothesis, INTERMED scores were significantly associated with all measures of both the SF36 and the EuroQol, and also with the HADS. A one point increase in the INTERMED score results in a reduction in 0.93 points in EuroQol and a 20% increase in HADS score.ConclusionsINTERMED‐measured case complexity is frequent in liver transplant candidates but varies widely between centers. The use of this method captures in one instrument multiple domains of patient status, including mood disturbances and reduced HRQoL.
Evaluation of a new endoscopic ultrasound‐guided multi‐fiducial delivery system: A prospective non‐survival study in a live porcine model
Authors: Draganov Peter V. , Chavalitdhamrong Disaya , Wagh Mihir S. 
Published: March 2013

BackgroundEndoscopic ultrasound (EUS) is an excellent tool for implanting fiducials for gastrointestinal malignancies, but a dedicated delivery system for EUS‐guided fiducial placement is not available. The aim of the present study was to evaluate the performance characteristics of a new dedicated EUS‐guided multi‐fiducial delivery system.MethodsThis was a prospective live porcine study using prototype 22‐G EUS needles preloaded with four fiducials. Primary outcomes were technical success and accuracy of fiducial placement. Secondary outcomes were ease of passage of delivery system, ease of deployment, EUS visualization of the needle, visual appearance of fiducials on EUS, fluoroscopy and computed tomography (CT) scans, time taken for fiducial placement and adverse events. Outcomes were scored on a predetermined 5‐point Likert scale (1 = best, 5 = worst).ResultsFiducial deployment was successful in 43 out of 45 needles (95.6%). All 172 fiducials (43 needles, four fiducials each)were successfully deployed on target. Fiducial placement accuracy score was 1.30 ± 0.64. All needles passed with ease (score 1.0 ± 0.0). Ease of fiducial deployment score was 1.85 ± 1.02. Mean scores for EUS visualization of the needle and fiducial were 1.02 ± 0.15 and 2.10 ± 0.91, respectively. Fluoroscopic and CT visualization of fiducials was excellent. Time for placement of four fiducials was <1 min (0.86 ± 0.50 min). No adverse events were seen.ConclusionThe new EUS‐guided multi‐fiducial delivery system provided quick, easy, and accurate fiducial deployment without adverse events.
Rett syndrome: an eye‐tracking study of attention and recognition memory
Authors: Rose Susan A , Djukic Aleksandra , Jankowski Jeffery J , Feldman Judith F , Fishman Iris , Valicenti‐Mcdermott Maria 
Published: March 2013

AimThe aim of this study was to examine attention and recognition memory for faces and patterns in Rett syndrome, a severely disabling neurodevelopmental disorder caused by mutations in the X‐linkedMECP2gene.MethodBecause Rett syndrome impairs speech and hand use, precluding most neuropsychological testing, the visual paired‐comparison paradigm (VPC) was used, together with eye tracking. In theVPC, two identical stimuli are presented for familiarization. On test, the familiar stimulus and a new one are paired, and recognition inferred from preferential looking to the novel target. Attention is measured by looking time, gaze dispersion, and number/length of fixations. Twenty‐seven female patients with Rett syndrome (mean age 10y 6mo; SD 6y 8mo, age range 2–22y) from the Rett clinic at a children's hospital were assessed in this study, along with 30 age‐ and sex‐matched typically developing participants (outpatients from the same hospital).ResultsAlthough patients with Rett syndrome showed recognition of both faces and patterns, with novelty scores greater than chance (50%), their performance was significantly poorer than that of the typically developing comparison group. Their attention to both was less mature and marked by a more narrowly focused gaze, with fewer and longer fixations. When inspecting faces, attention to the eyes was similar in both groups; however, patients with Rett syndrome tended to ignore the nose and mouth.InterpretationThis is one of the first studies to characterize attention and memory in individuals withRett syndrome. Visually based techniques, such as theVPC, open a new avenue for quantifying the cognitive phenotype associated with this syndrome.
Prevalence of early childhood disability in a rural district of Sind, Pakistan
Authors: Ibrahim Shahnaz H , Bhutta Zulfiqar A 
Published: March 2013

AimChildren born in low‐ and mid‐income countries are at a high risk of developing disabilities, yet estimates of population‐based prevalence are sparse. Our aim was to determine the prevalence of early childhood (0–5 year) disability in Sind, a rural area of Pakistan.MethodWe conducted a cross‐sectional household survey in a population of 25 196 households. The Ten Questions screen and the Signs of Disability in Newborn and Infants screen were used.ResultsThe disability prevalence in a population of 176 364 individuals was 5.5 out of 1000 in children under 2 years and 5.4 out of 1000 in children aged 2–5 years. Fifty‐six per cent were males, and 56% had the disability recognized from birth or soon after. The mortality rate of children aged 0–5 years in the area was estimated as 30 out of 1000 live births. Cerebral palsy was the most common disability identified. The Ten Questions screen had better interrater agreement than the Signs of Disability in Newborn and Infants screen.InterpretationThis is the largest reported household screening survey for early childhood disability at a population level from rural Pakistan. The comparatively low prevalence may be due to the younger age studied and high early childhood mortality. Our data highlight the importance of prospective surveillance at a population level and the need for preventive and support services.