bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaginal repair with mesh versus colporrhaphy for prolapse: a randomised controlled trial
Authors: Carey M , Higgs P , Goh J , Lim J , Leong A , Krause H , Cornish A 
Published: July 2009

Objective  To compare vaginal repair augmented by mesh with traditional colporrhaphy for the treatment of pelvic organ prolapse.Design  Prospective randomised controlled trial.Setting  Tertiary teaching hospital.Population  One hundred and thirty‐nine women with stage ≥2 prolapse according to the pelvic organ prolapse quantification (POP‐Q) system requiring both anterior and posterior compartment repair.Methods  Subjects were randomised to anterior and posterior vaginal repair with mesh augmentation (mesh group, n = 69) or traditional anterior and posterior colporrhaphy (no mesh group, n = 70).Main outcome measures  The primary outcome was the absence of POP‐Q stage ≥2 prolapse at 12 months. Secondary outcomes were symptoms, quality‐of‐life outcomes and satisfaction with surgery. Complications were also reported.Results  For subjects attending the 12‐month review, success in the mesh group was 81.0% (51 of 63 subjects) compared with 65.6% (40/61) in the no mesh group and was not significantly different (P‐value = 0.07). A high level of satisfaction with surgery and improvements in symptoms and quality‐of‐life data were observed at 12 months compared to baseline in both groups, but there was no significant difference in these outcomes between the two groups. Vaginal mesh exposure occurred in four women in the mesh group (5.6%). De novo dyspareunia was reported by five of 30 (16.7%) sexually active women in the mesh group and five of 33 (15.2%) in the no mesh group at 12 months.Conclusion  In this study, vaginal surgery augmented by mesh did not result in significantly less recurrent prolapse than traditional colporrhaphy 12 months following surgery.
Curcumin suppresses expression of low‐density lipoprotein (LDL) receptor, leading to the inhibition of LDL‐induced activation of hepatic stellate cells
Authors: Kang Qiaohua , Chen Anping 
Published: July 2009

Background and purpose:  Obesity is often accompanied by hypercholesterolemia characterized by elevated levels of plasma low‐density lipoprotein (LDL) and associated with non‐alcoholic steatohepatitis, which could progress to hepatic fibrosis. Hepatic stellate cells (HSCs) are the major effectors of hepatic fibrogenesis. This study aims to clarify effects of LDL on activation of HSC, to evaluate roles of curcumin in suppressing these effects and to further elucidate the underlying molecular mechanisms.Experimental approaches:  HSCs were prepared from rats and cell proliferation was measured by cell proliferation assays (MTS assays). Transient transfection assays were performed to evaluate gene promoter activities. Real‐time polymerase chain reaction and Western blotting were used to analyse the expression of genes.Key results:  LDL stimulated HSC activation in vitro, which was attenuated by curcumin. Curcumin reduced the abundance of LDL receptor (LDLR) in activated HSCs, decreasing cellular cholesterol. Curcumin‐dependent activation of peroxisome proliferator‐activated receptor‐γ (PPARγ) differentially regulated the expression of the transcription factors, sterol regulatory element‐binding proteins (SREBPs), in activated HSCs, resulting in the suppression of LDLR gene expression.Conclusions and implications:  Curcumin suppressed LDLR gene expression in activated HSCs in vitro by activating PPARγ and differentially regulating gene expression of SREBPs, reducing cellular cholesterol and attenuating the stimulatory effects of LDL on HSC activation. These results provide novel insights into the roles and mechanisms of curcumin in the inhibition of LDL‐induced HSC activation. This curcumin, a constituent of turmeric, may be useful in preventing hypercholesterolemia‐associated hepatic fibrogenesis.
Central antinociception induced by µ‐opioid receptor agonist morphine, but not δ‐ or κ‐, is mediated by cannabinoid CB1receptor
Authors: da Fonseca Pacheco Daniela , Klein André , Perez Andréa Castro , da Fonseca Pacheco Cinthia Mara , de Francischi Janetti Nogueira , Lopes Reis Gláucia Maria , Duarte Igor Dimitri Gama 
Published: July 2009

Background and purpose: It has been demonstrated that cannabinoids evoke the release of endogenous opioids to produce antinociception; however, no information exists regarding the participation of cannabinoids in the antinociceptive mechanisms of opioids. The aim of the present study was to determine whether endocannabinoids are involved in central antinociception induced by activation of µ‐, δ‐ and κ‐opioid receptors.Experimental approach: Nociceptive threshold to thermal stimulation was measured according to the tail‐flick test in Swiss mice. Morphine (5 µg), SNC80 (4 µg), bremazocine (4 µg), AM251 (2 and 4 µg), AM630 (2 and 4 µg) and MAFP (0.1 and 0.4 µg) were administered by the intracerebroventricular route.Key results: The CB1‐selective cannabinoid receptor antagonist AM251 completely reversed the central antinociception induced by morphine in a dose‐dependent manner. In contrast, the CB2‐selective cannabinoid receptor antagonist AM630 did not antagonize this effect. Additionally, the administration of the anandamide amidase inhibitor, MAFP, significantly enhanced the antinociception induced by morphine. In contrast, the antinociceptive effects of δ‐ and κ‐opioid receptor agonists were not affected by the cannabinoid antagonists. The antagonists alone caused no hyperalgesic or antinociceptive effects.Conclusions and implications: The results provide evidence for the involvement of cannabinoid CB1receptors in the central antinociception induced by activation of µ‐opioid receptors by the agonist morphine. The release of endocannabinoids appears not to be involved in central antinociception induced by activation of κ‐ and δ‐opioid receptors.
Salicylate, an aspirin metabolite, specifically inhibits the current mediated by glycine receptors containing α1‐subunits
Authors: Lu Y‐G , Tang Z‐Q , Ye Z‐Y , Wang H‐T , Huang Y‐N , Zhou K‐Q , Zhang M , Xu T‐L , Chen L 
Published: July 2009

Background and purpose:  Aspirin or its metabolite sodium salicylate is widely prescribed and has many side effects. Previous studies suggest that targeting neuronal receptors/ion channels is one of the pathways by which salicylate causes side effects in the nervous system. The present study aimed to investigate the functional action of salicylate on glycine receptors at a molecular level.Experimental approach:  Whole‐cell patch‐clamp and site‐directed mutagenesis were deployed to examine the effects of salicylate on the currents mediated by native glycine receptors in cultured neurones of rat inferior colliculus and by glycine receptors expressed in HEK293T cells.Key results:  Salicylate effectively inhibited the maximal current mediated by native glycine receptors without altering the EC50 and the Hill coefficient, demonstrating a non‐competitive action of salicylate. Only when applied simultaneously with glycine and extracellularly, could salicylate produce this antagonism. In HEK293T cells transfected with either α1‐, α2‐, α3‐, α1β‐, α2β‐ or α3β‐glycine receptors, salicylate only inhibited the current mediated by those receptors that contained the α1‐subunit. A single site mutation of I240V in the α1‐subunit abolished inhibition by salicylate.Conclusions and implications:  Salicylate is a non‐competitive antagonist specifically on glycine receptors containing α1‐subunits. This action critically involves the isoleucine‐240 in the first transmembrane segment of the α1‐subunit. Our findings may increase our understanding of the receptors involved in the side effects of salicylate on the central nervous system, such as seizures and tinnitus.
NCX 2057, a novel NO‐releasing derivative of ferulic acid, suppresses inflammatory and nociceptive responses in in vitro and in vivo models
Authors: Ronchetti Daniela , Borghi Valentina , Gaitan Gema , Herrero Juan F. , Impagnatiello Francesco 
Published: July 2009

Background and purpose:  We previously reported that NCX 2057, a compound comprising a nitric oxide (NO)‐releasing moiety and the natural antioxidant, ferulic acid (FA), inhibits pro‐inflammatory mediators through NO‐mediated gene regulation. Here, we have assessed the activities of NCX 2057 in models of inflammatory and neuropathic pain, and characterized its effects on cyclooxygenase (COX)‐1 and COX‐2.Experimental approach:  Anti‐nociceptive and anti‐inflammatory activities of NCX 2057 were measured in vitro and in vivo in models of inflammatory (carrageenan) and neuropathic (chronic constriction injury; CCI) pain. Effects of NCX 2057 were measured on COX‐1 and COX‐2 activities in RAW 264.7 macrophages.Key results:  NCX 2057 dose‐dependently inhibited single motor unit responses to noxious mechanical stimulation (ID50= 100 µmol·kg−1) and wind‐up responses in rats with paw inflammation induced by carrageenan. Moreover, NCX 2057 inhibited allodynic responses following CCI of the sciatic nerve [ipsilateral Paw Withdrawal Threshold (g): vehicle: 41.4 ± 3.3; NCX 2057: 76.3 ± 4.8 FA: 37.9 ± 15.5 at 175 µmol·kg−1]. NCX 2057 reversed carrageenan‐induced hyperalgesic responses in mice and inhibited prostaglandin E2 formation in paw exudates. Finally, NCX 2057 competitively inhibited COX‐1 and COX‐2 activities in whole RAW macophages (IC50= 14.7 ± 7.4 and 21.6 ± 7.5 µM, respectively). None of these properties were exhibited by equivalent treatments with FA or standard NO donor compounds.Conclusions and implications:  These studies indicate that NCX 2057 is effective in chronic inflammatory and neuropathic pain models, probably because of its particular combination of anti‐COX, antioxidant and NO‐releasing properties.
Rape Law in 19th‐Century America: Some Thoughts and Reflections on the State of the Field
Authors: Block Mary R. 
Published: July 2009

AbstractRape is a serious crime with a long history that has not received much study until very recently. Historians should study the crime of rape in 19th‐century America for many reasons, but mostly because it can tell us much about how the law operated in practice and about 19th‐century notions of manhood, womanhood, sex, and violence. Historians have produced several studies on rape in the American South, while other regions of the nation have received scant attention for the 19th century. Scholars should consider studies of 19th‐century rape at the micro and macro levels and should utilize interdisciplinary approaches in their analyses.
Teucrium poliumin prevention of steatohepatitis in rats
Authors: Amini Rahim , Nosrati Narges , Yazdanparast Razieh , Molaei Mahsa 
Published: July 2009

AbstractBackground:In this study, we tried to evaluate whether the ethyl acetate (EtOAc) extract ofTeucrium polium, with a high antioxidant activity, is able to prevent the incidence of nonalcoholic steatohepatitis.Methods:Nonalcoholic steatohepatitis was induced in male N‐Mary rats using a methionine/choline‐deficient (MCD) diet. Rats were given normal diet (A), normal diet+EtOAc extract (B), MCD diet (C) and MCD diet+EtOAc (D).Results:The MCD diet led to grade 1 liver steatosis, inflammation and ballooning degeneration. In group D, these factors abated to grade 0 in 80% of the rats. In groups receiving the EtOAc extract, lipoprotein profiles had significantly improved relative to those not receiving the extract. Also, a dramatic reduction was observed in the sera alkaline phosphatase, aspartate aminotransferase and alanine aminoteransferase activities. The activities of the liver superoxide dismutase, glutathione peroxidase and glutathione reductase enzymes were also enhanced.Conclusion:The EtOAc extract could reverse the adverse effects of the MCD diet.
Identification of bacterial DNA in neutrocytic and non‐neutrocytic cirrhotic ascites by means of a multiplex polymerase chain reaction
Authors: Bruns Tony , Sachse Svea , Straube Eberhard , Assefa Sentayehu , Herrmann Andreas , Hagel Stefan , Lehmann Marc , Stallmach Andreas 
Published: July 2009

AbstractBackground: Even though bacterial cultures of ascitic fluid are negative in up to 65% of the cases of spontaneous bacterial peritonitis (SBP); bacterial DNA (bactDNA) has been frequently detected in episodes of SBP as well as in culture‐negative non‐neutrocytic ascites.Aims: To evaluate multiplex polymerase chain reaction (PCR) for pathogen identification in SBP and to determine the prevalence of ascitic bactDNA and its prognostic relevance in hospitalized patients with liver cirrhosis.Methods: Ascitic fluid from 68 consecutive patients who underwent diagnostic paracentesis was analysed for polymorphonuclear leucocyte (PMN) count, bacterial culture and bactDNA. BactDNA was identified by gel analysis after multiplex PCR of selectively enriched prokaryotic nucleic acids. Correlations of bactDNA status with PMN count, bacterial culture result and 3‐month mortality were determined for neutrocytic and for non‐neutrocytic ascites.Results: 11/68 patients presented with an elevated ascitic PMN count. BactDNA was detected in 5/5 culture‐positive neutrocytic samples, in 1/6 culture‐negative neutrocytic samples and in 8/56 culture‐negative non‐neutrocytic samples. Three‐month mortality did not differ with respect to ascitic bactDNA status (7/14 vs. 14/47, P=0.162). 3‐month mortality was increased in the presence of ascitic bactDNA for patients older than 65 years (4/5 vs. 4/14, P=0.046) and for patients with a model for end‐stage liver disease score >15 (7/10 vs. 9/30, P=0.025).Conclusions: Identification of ascitic bactDNA is an appropriate alternative to bacterial ascite culture for pathogen identification in patients at risk for SBP. Its prognostic relevance as a proposed marker of bacterial translocation for certain risk groups has to be further evaluated.
Microvascular optical assessment confirms the presence of peripheral autonomic dysfunction in primary biliary cirrhosis
Authors: Stevens Sam , Allen John , Murray Alan , Jones David , Newton Julia 
Published: July 2009

AbstractBackground: Autonomic dysfunction (AD) is a significant problem in primary biliary cirrhosis (PBC) and is equally present in early disease stages. Currently, AD in PBC is considered to be central in origin. The aim of this study was to examine peripheral mechanisms in the pathogenesis of AD in PBC using novel microvascular optical assessments for this patient group.Methods: Twenty‐four early stage PBC patients and 24 age‐matched controls attended for two microvascular optical‐based measurement techniques. Firstly, the regulation of microvascular blood volume to the periphery was assessed using multisite photoplethysmography (PPG) by examining the degree of correlation between the right and left sides of the body, with reduced correlation consistent with peripheral AD. Secondly, the peripheral vasomotor reflex response to standing was dynamically tested using laser Doppler flowmetry to quantify the degree of autonomic tone in peripheral vasoconstriction.Results: PBC patients had a significantly reduced right to left side blood volume multisite PPG correlation compared with controls when corrected for age, body mass index, heart rate and systolic blood pressure [impaired synchronization between pulse wave amplitude between right and left fingers and right and left ears (both P<0.05)]. The veno‐arteriolar reflex on standing in PBC patients was significantly lower than for the controls, consistent with poorer autonomic tone for vasoconstriction in PBC (P<0.01).Conclusions: This study provides evidence for the presence of peripheral autonomic nervous system involvement in PBC. Prospective studies are now warranted to determine the full clinical potential of microvascular optical assessment in PBC.
Oxidative stress induced lung cancer and COPD: opportunities for epigenetic therapy
Authors: Lawless Matthew W. , O’Byrne Kenneth J. , Gray Steven G. 
Published: July 2009

Abstract

Oxidative stress, epigenetics, NSCLC and COPD
Linking epigenetics and oxidative stress to the development of COPD and NSCLC
Epigenetics, COPD, NSCLC and oxidative stress pathways/genes
Theophylline – a novel agonist of HDACs
Dietary HDAC inhibitors as therapeutic agents to target ‐ COPD or NSCLC?
Sulforaphane
Curcumin
Epigallocatechin 3‐gallate (EGCG)
Can dietary epigenetic inhibitors work in the clinical setting?
Caveats
Conclusions

Reactive oxygen species (ROS) form as a natural by‐product of the normal metabolism of oxygen and play important roles within the cell. Under normal circumstances the cell is able to maintain an adequate homeostasis between the formation of ROS and its removal through particular enzymatic pathways or via antioxidants. If however, this balance is disturbed a situation called oxidative stress occurs. Critically, oxidative stress plays important roles in the pathogenesis of many diseases, including cancer. Epigenetics is a process where gene expression is regulated by heritable mechanisms that do not cause any direct changes to the DNA sequence itself, and disruption of epigenetic mechanisms has important implications in disease. Evidence is emerging that histone deacetylases (HDACs) play decisive roles in regulating important cellular oxidative stress pathways including those involved with sensing oxidative stress and those involved with regulating the cellular response to oxidative stress. In particular aberrant regulation of these pathways by HDACs may play critical roles in cancer progression. In this review we discuss the current evidence linking epigenetics and oxidative stress and cancer, using chronic obstructive pulmonary disease and non‐small cell lung cancer to illustrate the importance of epigenetics on these pathways within these disease settings.
Explant‐derived human dental pulp stem cells enhance differentiation and proliferation potentials
Authors: Spath L. , Rotilio V. , Alessandrini M. , Gambara G. , De Angelis L. , Mancini M. , Mitsiadis T. A. , Vivarelli E. , Naro F. , Filippini A. , Papaccio G. 
Published: July 2009

AbstractNumerous stem cell niches are present in the different tissues and organs of the adult human body. Among these tissues, dental pulp, entrapped within the ‘sealed niche’ of the pulp chamber, is an extremely rich site for collecting stem cells. In this study, we demonstrate that the isolation of human dental pulp stem cells by the explants culture method (hD‐DPSCs) allows the recovery of a population of dental mesenchymal stem cells that exhibit an elevated proliferation potential. Moreover, we highlight that hD‐DPSCs are not only capable of differentiating into osteoblasts and chondrocytes but are also able to switch their genetic programme when co‐cultured with murine myoblasts. High levels of MyoD expression were detected, indicating that muscle‐specific genes in dental pulp cells can be turned on through myogenic fusion, confirming thus their multipotency. A perivascular niche may be the potential source of hD‐DPSCs, as suggested by the consistent Ca2+ release from these cells in response to endothelin‐1 (ET‐1) treatment, which is also able to significantly increase cell proliferation. Moreover, response to ET‐1 has been found to be superior in hD‐DPSCs than in DPSCs, probably due to the isolation method that promotes release of stem/progenitor cells from perivascular structures. The ability to isolate, expand and direct the differentiation of hD‐DPSCs into several lineages, mainly towards myogenesis, offers an opportunity for the study of events associated with cell commitment and differentiation. Therefore, hD‐DPSCs display enhanced differentiation abilities when compared to DPSCs, and this might be of relevance for their use in therapy.
PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease
Authors: Morel Milena , Couturier Julien , Lafay‐Chebassier Claire , Paccalin Marc , Page Guylène 
Published: July 2009

Abstract
Introduction
Control of translation
Dysfunctions of protein synthesis mediated by PKR‐ and mTOR‐dependent signalling pathways
Crosslink between the up‐regulation of PKR/eIF2α and the down‐regulation of mTOR/RS6K in AD
PKR: a potential biomarker of AD diagnosis
Conclusion and perspectives
Amyloid β‐peptide (Aβ) deposits and neurofibrillary tangles are key hallmarks in Alzheimer's disease (AD). Aβ stimulates many signal transducers involved in the neuronal death. However, many mechanisms remain to be elucidated because no definitive therapy of AD exists. Some studies have focused on the control of translation which involves eIF2 and eIF4E, main eukaryotic factors of initiation. The availability of these factors depends on the activation of the double‐stranded RNA‐dependent protein kinase (PKR) and the mammalian target of rapamycin (mTOR), respectively. mTOR positively regulates the translation while PKR results in a protein synthesis shutdown. Many studies demonstrated that the PKR signalling pathway is up‐regulated in cellular and animal models of AD and in the brain of AD patients. Interestingly, our results showed that phosphorylated PKR and eIF2α levels were significantly increased in lymphocytes of AD patients. These modifications were significantly correlated with cognitive and memory test scores performed in AD patients. On the contrary, the mTOR signalling pathway is down‐regulated in cellular and animal models of AD. Recently, we showed that p53, regulated protein in development and DNA damage response 1 and tuberous sclerosis complex 2 could represent molecular links between PKR and mTOR signalling pathways. PKR could be an early biomarker of the neuronal death and a critical target for a therapeutic programme in AD.
Symplastic glomus tumor – a rare but distinct benign histological variant with analogy to other ‘ancient’ benign skin neoplasms
Authors: Kamarashev Jivko , French Lars E , Dummer Reinhard , Kerl Katrin 
Published: July 2009

A 78‐year‐old woman presented with a nail deformity of the index finger of the left hand associated with paroxysmal pain upon cold exposure. Histologically, a well‐circumscribed tumor of 3 mm diameter was found in the dermis. The neoplastic cells in some areas were of pronouncedly variable size and cytomorphology, mostly epithelioid in shape, with eosinophilic cytoplasm and indistinctly defined cell borders. Pronounced nuclear pleomorphism and atypia were striking features, but no mitotic figures were noted. Multinuclear cells were present as were numerous small‐to‐medium vessels throughout the tumor. The tumor stroma showed myxoid areas.Immunohistochemistry showed cytoplasmic and membranous expression of smooth muscle actin and vimentin. The histological features and immunoprofile were consistent with the diagnosis of symplastic glomus tumor, a rare histological variant, which has been defined as a glomus tumor exhibiting marked nuclear atypia, in the absence of any other criteria for malignancy. The biological behavior of the tumor is benign. It is essential to differentiate this entity from malignant glomus tumor, which has metastatic potential. Even prominent cellular atypia and nuclear pleomorphism in a glomus tumor as in our case is not a marker of malignancy in the absence of additional criteria.