bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging‐like skin changes in metabolic syndrome model mice are mediated by mineralocorticoid receptor signaling
Authors: Nagase Takashi , Akase Tomoko , Sanada Hiromi , Minematsu Takeo , Ibuki Ai , Huang Lijuan , Asada Mayumi , Yoshimura Kotaro , Nagase Miki , Shimada Tsutomu , Aburada Masaki , Nakagami Gojiro , Sugama Junko 
Published: October 2012

SummaryAging is accelerated, at least in part, by pathological condition such as metabolic syndrome (MetS), and various molecular pathways such as oxidative stress are common mediators of aging and MetS. We previously developed the aging‐like skin model by single ultraviolet (UV) irradiation on the MetS model mice. Recent studies revealed that mineralocorticoid receptor (MR) signaling plays a pivotal role for various tissue inflammation and damages in MetS. Although previous studies reported that MR is expressed in the skin and that overexpression of MR in the skin resulted in the skin atrophy, the physiological or pathological functions of MR in the skin are not fully elucidated. Here, we show the involvement of MR signaling in the aging‐like skin changes in our own model. Elevations of oxidative stress and inflammation markers were observed in the MetS mice, and the UV‐evoked aging‐like skin damages were attenuated by topical antioxidant. MR expression was higher in the MetS mouse skin, and notably, expression of its effecter gene Sgk1 was significantly upregulated in the aging‐like skin in the UV‐irradiated MetS mice. Furthermore, topical application of MR antagonist spironolactone suppressed Sgk1 expression, oxidative stress, inflammation, and the aging‐like changes in the skin. The 2‐week UV onto the non‐MetS mice, the more usual photoaging model, resulted in the skin damages mostly equivalent to the MetS mice with single UV, but they were not associated with upregulation of MR signaling. Our studies suggested an unexpected role of MR signaling in the skin aging in MetS status.
Decreasing perinatal mortality in placental abruption
Authors: TIKKANEN MINNA , LUUKKAALA TIINA , GISSLER MIKA , RITVANEN ANNUKKA , YLIKORKALA OLAVI , PAAVONEN JORMA , NUUTILA MIKA , ANDERSSON STURE , METSÄRANTA MARJO 
Published: October 2012

AbstractObjective. To study perinatal mortality associated with placental abruption. Design. Retrospective population study using the Finnish Hospital Discharge Register and Medical Birth Register data. Setting. Finland, 1987–2005. Population. Pregnancies with placental abruption and all other births without placental abruption. Methods. The national Hospital Discharge Register and Medical Birth Register were used to identify all pregnancies with placental abruption. Demographic data and delivery outcomes were collected retrospectively. Perinatal mortality associated with placental abruption was compared with that in other births. Potential risk factors were analysed. Main outcome measures. Perinatal mortality in placental abruption. Results. The study consisted of 618 735 women with 1.14 million pregnancies, 4336 of whom had placental abruption. Overall perinatal mortality with abruption was 119 per 1000 births. Placental abruption explained 7% of all perinatal deaths. The mortality among singleton births (125 per 1000) was higher than among multiple births (40 per 1000). The majority of deaths (77%) occurred in utero. Singleton perinatal mortality with abruption decreased from 173 per 1000 in 1987–1990 to 98 per 1000 in 2000–2005 (p < 0.001). In singleton births at <32 gestational weeks, overall perinatal mortality was high (345 per 1000) and was not increased by placental abruption. Prematurity, low birthweight, male fetal sex and maternal smoking were independent risk factors for placental abruption‐related perinatal mortality. Conclusions. Although mortality associated with placental abruption decreased during the study period, placental abruption still remains an important cause of perinatal mortality.
Helicobacter pylori eradication in Western Australia using novel quadruple therapy combinations
Authors: Tay C. Y. , Windsor H. M. , Thirriot F. , Lu W. , Conway C. , Perkins T. T. , Marshall B. J. 
Published: October 2012

SummaryBackgroundHelicobacter pylori eradication rates with standard triple therapy are declining worldwide. The optimal management of H. pylori is evolving and new treatment combinations for antibiotic resistant H. pylori strains are required, especially for patients with penicillin allergy.AimTo review the effectiveness of alternative antibiotic combinations and necessity of pre‐antibiotic sensitivity testing.MethodsA total of 310 consecutive patients who had failed at least one course of standard 7‐day triple therapy initially prescribed by their physicians were included in this study between year 2007 and 2011. Antibiotics were prescribed based on pre‐antibiotic sensitivity tests and, if any, patient's allergy to penicillin.ResultsIn 98.7% of the patients' samples, H. pylori was successfully cultured. The proportion resistant to clarithromycin and metronidazole was 94.1% and 67.6% respectively, with 65% resistant to both. For the in‐house primary quadruple therapy, with Proton pump inhibitor, Amoxicillin, Rifabutin and Ciprofloxacin (PARC), H. pylori was successfully eradicated in 95.2% of patients. For patients allergic to amoxicillin, an alternative quadruple therapy using Proton pump inhibitor, Bismuth subcitrate, Rifabutin and Ciprofloxacin (PBRC) gave an eradication rate of 94.2%. Patients needing alternative salvage therapy were given novel personalised combinations consisting of bismuth, rifabutin, tetracycline or furazolidone; the eradication rate was 73.8%.ConclusionsPatients who present with antibiotic resistant H. pylori can be confidently treated with PARC, PBRC or other personalised salvage therapies. These regimens can be used when treatment options are limited by penicillin allergy. Pre‐treatment H. pylori antibiotic sensitivity tests contributed to the high eradication rate in this study.
Treatment of gastric carcinoids type 1 with the gastrin receptor antagonist netazepide (YF476) results in regression of tumours and normalisation of serum chromogranin A
Authors: Fossmark R. , Sørdal Ø. , Jianu C. S. , Qvigstad G. , Nordrum I. S. , Boyce M. , Waldum H. L. 
Published: October 2012

SummaryBackgroundPatients with chronic atrophic gastritis have long‐term gastric hypoacidity, and secondary hypergastrinaemia. Some also develop gastric ECL cells carcinoids (type 1 GC). Most type 1 GC remain indolent, but some metastasise. Patients undergo surveillance, and some are treated with somatostatin analogues, endoscopic resection or surgery. Netazepide (YF476) is a highly selective, potent and orally active gastrin receptor antagonist, which has anti‐tumour activity in various rodent models of gastric neoplasia driven by hypergastrinaemia. Netazepide has been studied in healthy volunteers.AimTo assess the effect of netazepide on type 1 GC.MethodsEight patients with multiple type 1 GC received oral netazepide once daily for 12 weeks, with follow‐up at 12 weeks in an open‐label, pilot trial. Upper endoscopy was performed at 0, 6, 12 and 24 weeks, and carcinoids were counted and measured. Fasting serum gastrin and chromogranin A (CgA) and safety and tolerability were assessed at 0, 3, 6, 9, 12 and 24 weeks.ResultsNetazepide was well tolerated. All patients had a reduction in the number and size of their largest carcinoid. CgA was reduced to normal levels at 3 weeks and remained so until 12 weeks, but had returned to pre‐treatment levels at 24 weeks. Gastrin remained unchanged throughout treatment.ConclusionsThe gastrin receptor antagonist netazepide is a promising new medical treatment for type 1 gastric carcinoids, which appear to be gastrin‐dependent. Controlled studies and long‐term treatment are justified to find out whether netazepide treatment can eradicate type 1 gastric carcinoids.
Analgesia and central side‐effects: two separate dimensions of morphine response
Authors: Droney Joanne M. , Gretton Sophy K. , Sato Hiroe , Ross Joy R. , Branford Ruth , Welsh Kenneth I. , Cookson William , Riley Julia 
Published: October 2012

AimsTo present a statistical model for defining interindividual variation in response to morphine and to use this model in a preliminary hypothesis‐generating multivariate genetic association study.MethodsTwo hundred and sixty‐four cancer patients taking oral morphine were included in a prospective observational study. Pain and morphine side‐effect scores were examined using principal components analysis. The resulting principal components were used in an exploratory genetic association study of single nucleotide polymorphisms across the genes coding for the three opioid receptors, OPRM1, OPRK1 and OPRD1. Associations in multivariate models, including potential clinical confounders, were explored.ResultsTwo principal components corresponding to residual pain and central side‐effects were identified. These components accounted for 42 and 18% of the variability in morphine response, respectively, were independent of each other and only mildly correlated. The genetic and clinical factors associated with these components were markedly different. Multivariate regression modelling, including clinical and genetic factors, accounted for only 12% of variability in residual pain on morphine and 3% of variability in central side‐effects.ConclusionsAlthough replication is required, this data‐driven analysis suggests that pain and central side‐effects on morphine may be two separate dimensions of morphine response. Larger study samples are necessary to investigate potential genetic and clinical associations comprehensively.
Confirmation biases across the psychosis continuum: The contribution of hypersalient evidence‐hypothesis matches
Authors: Balzan Ryan , Delfabbro Paul , Galletly Cherrie , Woodward Todd 
Published: October 2012

ObjectivesHypersalience of evidence‐hypothesis matches has recently been proposed as the cognitive mechanism responsible for the cognitive biases, which, in turn, may contribute to the formation and maintenance of delusions. However, supporting evidence for this construct is still required. Using two tasks designed to elicit three core facets of the confirmation bias (i.e., biased search of confirming evidence; biased interpretation of confirming evidence; and biased recall of confirming evidence), this article investigated the possibility that individuals with delusions and those identified as delusion‐prone are hypersalient to evidence‐hypothesis matches.MethodsA total of 75 participants (25 diagnosed with schizophrenia with a history of delusions; 25 non‐clinical delusion‐prone; 25 non‐delusion‐prone controls) completed both tasks.ResultsThe results across both tasks showed that participants with schizophrenia and delusion‐prone participants prefer: non‐diagnostic or non‐specific positive tests over diagnostic negative tests (biased search); rate confirming evidence as more important than disconfirming evidence (biased interpretation); and remember confirming evidence with greater ease than disconfirming evidence (biased recall). Participants with higher delusional ideation also failed to integrate disconfirmatory evidence to modify prior hypotheses.ConclusionsThese results suggest that delusional ideation is linked to a hypersalience of evidence‐hypothesis matches. The theoretical implications of this cognitive mechanism on the formation and maintenance of delusions are discussed.Practitioner PointsClinical Implications

Evidence that people with delusions, and those identified as delusion‐prone, are more susceptible to confirmation biases than non‐delusion‐prone controls.
Confirmation biases may therefore play a role in the formation and maintenance of delusional beliefs.
Further evidence that one of the underlying cognitive mechanisms behind many cognitive biases in people with delusions is a hypersalience of evidence‐hypothesis matches. This has implications for psychotherapies that target delusion formation and maintenance, such as the metacognitive training (MCT) programme for people with schizophrenia.

Limitations

Heterogeneous delusional symptoms within patient group (i.e., consisted of individuals with mild to moderate active delusions and individuals with remitted delusions).
Delusion‐prone group not consistently distinct from non‐delusion‐prone group across all tasks.
Set order of tasks across participants may have led to practice effects.
A novel fluorophosphonate inhibitor of the biosynthesis of the endocannabinoid 2‐arachidonoylglycerol with potential anti‐obesity effects
Authors: Bisogno Tiziana , Mahadevan Anu , Coccurello Roberto , Chang Jae Won , Allarà Marco , Chen Yugang , Giacovazzo Giacomo , Lichtman Aron , Cravatt Benjamin , Moles Anna , Di Marzo Vincenzo 
Published: October 2012

Background and PurposeThe development of potent and selective inhibitors of the biosynthesis of the endocannabinoid 2‐arachidonoylglycerol (2‐AG) via DAG lipases (DAGL) α and β is just starting to be considered as a novel and promising source of pharmaceuticals for the treatment of disorders that might benefit from a reduction in endocannabinoid tone, such as hyperphagia in obese subjects.Experimental ApproachThree new fluorophosphonate compounds O‐7458, O‐7459 and O‐7460 were synthesized and characterized in various enzymatic assays. The effects of O‐7460 on high‐fat diet intake were tested in mice.Key ResultsOf the new compounds, O‐7460 exhibited the highest potency (IC50 = 690 nM) against the human recombinant DAGLα, and selectivity (IC50 > 10 μM) towards COS‐7 cell and human monoacylglycerol lipase (MAGL), and rat brain fatty acid amide hydrolase. Competitive activity‐based protein profiling confirmed that O‐7460 inhibits mouse brain MAGL only at concentrations ≥10 μM, and showed that this compound has only one major ‘off‐target’, that is, the serine hydrolase KIAA1363. O‐7460 did not exhibit measurable affinity for human recombinant CB1 or CB2 cannabinoid receptors (Ki > 10 μM). In mouse neuroblastoma N18TG2 cells stimulated with ionomycin, O‐7460 (10 μM) reduced 2‐AG levels. When administered to mice, O‐7460 dose‐dependently (0–12 mg·kg−1, i.p.) inhibited the intake of a high‐fat diet over a 14 h observation period, and, subsequently, slightly but significantly reduced body weight.Conclusions and ImplicationsO‐7460 might be considered a useful pharmacological tool to investigate further the role played by 2‐AG both in vitro and in vivo under physiological as well as pathological conditions.Linked ArticlesThis article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue‐4 & http://dx.doi.org/10.1111/bph.2012.167.issue‐8
Moxifloxacin modifies corneal fibroblast‐to‐myofibroblast differentiation
Authors: Chen TC , Chang SW , Wang TY 
Published: October 2012

Background and PurposeFibroblast‐to‐myofibroblast differentiation is associated with scarring, an important issue in corneal surgery. Moxifloxacin (MOX), commonly applied to prevent post‐operative infection, would benefit more if it modifies fibroblast‐to‐myofibroblast differentiation other than antimicrobial activity. Our purpose was to explore whether MOX has anti‐fibrotic effect in human corneal fibroblasts (HCFs).Experimental ApproachHCFs were incubated in MOX‐containing medium concurrently with TGF‐β1 (co‐treatment), before (pretreatment) or after (post‐treatment) adding TGF‐β1. HCF contractility was evaluated with a type I collagen gel contraction assay. Expression of α‐smooth muscle actin (α‐SMA), Smad2, phospho‐Smad2‐Ser467, Smad4 and Smad7 was determined by immunoblotting. Formation of α‐SMA‐positive filaments and distribution of active Smad2 were observed under confocal microscopy. Expression of TGF‐β receptor types I (TGFBR1) and II (TGFBR2) was assessed with flow cytometry.Key ResultsMOX did not affect gel contractility or α‐SMA filament formation in HCFs without TGF‐β1 stimulation. MOX did, however, retard HCF‐containing gel contractility and α‐SMA filament formation following TGF‐β1 stimulation in the pretreatment and co‐treatment groups but not in the post‐treatment group. MOX blocked the expression of Smad2, phospho‐Smad2‐Ser467 and TGFBR1 under TGF‐β1 incubation. Additionally, MOX enhanced Smad7 expression in TGF‐β1‐incubated HCFs, but did not interfere with TGF‐β‐triggered Smad2 nuclear translocation or Smad4 expression.Conclusions and ImplicationsMOX inhibited TGF‐β‐induced fibroblast‐to‐myofibroblast differentiation via blocking TGFBR1 and enhancing Smad7 expression. MOX should be used before or during surgery to achieve these effects. These results suggest a de novo mechanism by which MOX participates in corneal wound healing.
On the selectivity of neuronal NOS inhibitors
Authors: Pigott B , Bartus K , Garthwaite J 
Published: October 2012

Background and PurposeIsoform‐selective inhibitors of NOS enzymes are desirable as research tools and for potential therapeutic purposes. Vinyl‐l‐N‐5‐(1‐imino‐3‐butenyl)‐l‐ornithine (l‐VNIO) and Nω‐propyl‐l‐arginine (NPA) purportedly have good selectivity for neuronal over endothelial NOS under cell‐free conditions, as does N‐[(3‐aminomethyl)benzyl]acetamidine (1400W), which is primarily an inducible NOS inhibitor. Although used in numerous investigations in vitro and in vivo, there have been surprisingly few tests of the potency and selectivity of these compounds in cells. This study addresses this deficiency and evaluates the activity of new and potentially better pyrrolidine‐based compounds.Experimental ApproachThe inhibitors were evaluated by measuring their effect on NMDA‐evoked cGMP accumulation in rodent hippocampal slices, a response dependent on neuronal NOS, and ACh‐evoked cGMP synthesis in aortic rings of the same animals, an endothelial NOS‐dependent phenomenon.Key Resultsl‐VNIO, NPA and 1400W inhibited responses in both tissues but all showed less than fivefold higher potency in the hippocampus than in the aorta, implying useless selectivity for neuronal over endothelial NOS at the tissue level. In addition, the inhibitors had a 25‐fold lower potency in the hippocampus than reported previously, the IC50 values being approximately 1 μM for l‐VNIO and NPA, and 150 μM for 1400W. Pyrrolidine‐based inhibitors were similarly weak and nonselective.Conclusion and ImplicationsThe results suggest that l‐VNIO, NPA and 1400W, as well as the newer pyrrolidine‐type inhibitors, cannot be used as neuronal NOS inhibitors in cells without stringent verification. The identification of inhibitors with useable selectivity in cells and tissues remains an important goal.
5‐HT3 receptor antagonists ameliorate 5‐fluorouracil‐induced intestinal mucositis by suppression of apoptosis in murine intestinal crypt cells
Authors: Yasuda M , Kato S , Yamanaka N , Iimori M , Matsumoto K , Utsumi D , Kitahara Y , Amagase K , Horie S , Takeuchi K 
Published: October 2012

Background and PurposeChemotherapeutic agents, including 5‐fluorouracil (5‐FU), frequently cause intestinal mucositis resulting in severe diarrhoea and morphological mucosal damage. 5‐HT3 receptor antagonists are clinically effective in the treatment of nausea and emesis during cancer chemotherapy. Therefore we here have examined the effects of 5‐HT3 receptor antagonists on 5‐FU‐induced intestinal mucositis in mice.Experimental ApproachIntestinal mucositis was induced in male C57BL/6 mice by daily administration of 5‐FU (50 mg·kg−1) for 5 days. Effects of 5‐HT3 receptor antagonists, ramosetron (0.01–0.1 mg·kg−1) and ondansetron (5 mg·kg−1), on the accompanying histology, cytokine production and apoptosis were assessed.Key ResultsContinuous administration of 5‐FU to mice caused severe intestinal mucositis, which was histologically characterized by the shortening of villi and destruction of intestinal crypts, accompanied by body weight loss and diarrhoea. Daily ramosetron administration dose‐dependently reduced the severity of intestinal mucositis, body weight loss and diarrhoea. Similar beneficial effects were observed with ondansetron. The number of apoptotic, caspase‐3‐ and caspase‐8‐activated cells increased 24 h after the first 5‐FU administration, and these responses were reduced by ramosetron. The up‐regulation of TNF‐α, IL‐1β and IL‐6 following 5‐FU treatment was also attenuated by ramosetron.Conclusions and Implications5‐HT3 receptor antagonists ameliorated 5‐FU‐induced intestinal mucositis in mice, and this action could result from suppression of apoptotic responses in the intestinal crypt cells via inhibition of cytokine expression. Thus, 5‐HT3 receptor antagonists may be useful for preventing not only nausea and emesis but also intestinal mucositis during 5‐FU chemotherapy.
Overweight and obesity are not associated with dental caries among 12‐year‐old South Brazilian schoolchildren
Authors: Alves Luana Severo , Susin Cristiano , Damé‐Teixeira Nailê , Maltz Marisa 
Published: October 2012

AbstractObjectivesTo assess the association between weight status and dental caries among 12‐year‐old Brazilian schoolchildren.MethodsThis cross‐sectional study was carried out in Porto Alegre using a multistage probability sampling strategy to draw a representative sample of schoolchildren attending public and private schools. Data on demographics, socioeconomic status, oral hygiene habits, anthropometrics, and dental caries were collected. Overweight and obesity were defined according to WHO categories for BMI (body mass index)‐for‐age Z‐scores. Survey Poisson regression models were used to assess the association between weight status and dental caries. Estimates were adjusted for gender, socioeconomic status, and brushing frequency. Prevalence ratios (PR), rate ratios (RR) and 95% confidence intervals (95% CI) were reported.ResultsOne thousand five hundred and twenty‐eight of 1837 eligible schoolchildren were examined. Prevalence of overweight and obesity were 22.15% (95% CI = 20.59–23.72) and 13.61% (95% CI = 11.44–15.78), respectively. Caries experience was observed in 55.23% (95% CI = 45.26–65.19) of children. Schoolchildren presented, on average, 1.39 (95% CI = 1.07–1.71) decayed, missing or filled teeth. No significant differences in caries experience or extent were observed among BMI groups. After adjusting for important cofactors, weight status was not associated with caries prevalence (overweight, PR = 0.99; 95% CI = 0.89–1.10; obese, PR = 1.00; 95% CI = 0.87–1.16) or caries extent (overweight, RR = 0.91; 95% CI = 0.74–1.12; obese, RR = 0.86; 95% CI = 0.72–1.04).ConclusionsOur findings indicate that overweight and obese adolescents should not be regarded as at higher risk of dental caries in this population.
Is it safe to withdraw steroids within seven days of renal transplantation?
Authors: Zhang Xin , Huang Hejing , Han Shu , Fu Shangxi , Wang Liming 
Published: October 2012

AbstractBackgroundThe safety of very early steroid withdrawal (VESW) in renal transplant recipients remains unclear.MethodsLiterature searches for all randomized controlled trials comparing VESW with steroid maintenance regimens were performed using MEDLINE, EMBASE, and the Cochrane Library. Quality assessment was performed in each trial. Meta‐analyses were performed to demonstrate the pooled effects of relative risk (RR) and weighted mean difference with 95% confidence intervals (CI).ResultsA total of 3520 participants from 15 RCTs were included. VESW regimen increased the incidence of acute rejection (AR) over controls (RR = 1.46, CI = 1.20–1.79, p = 0.04). Subsequent analysis demonstrated that such difference lost significance in patients receiving tacrolimus (p = 0.16), but remained significant in patients with cyclosporin (p < 0.00001). The increased AR episodes were predominantly mild. VESW was associated with an increased incidence of delayed graft function (DGF) when steroids were withdrawn within three d post‐transplantation. Cardiovascular risk factors, including incidence of new onset diabetes and total cholesterol, were significantly reduced under VESW regimen.ConclusionsIt is safe and practical to withdraw steroids very early after renal transplantation. However, a three‐ to seven‐d course of steroids may decrease the risk for DGF relative to steroid withdrawal in <3 d. Antibody induction is effective in preventing early AR.