bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol independent effect of LXR agonist TO‐901317 on gamma‐secretase
Authors: Czech Christian , Burns Mark P. , Vardanian Lilit , Augustin Angelique , Jacobsen Helmut , Baumann Karlheinz , Rebeck G. William 
Published: March 2007

AbstractThe balance of intracellular cholesterol has proven to be critical to the production of β‐amyloid (Aβ). Reducing cholesterol in vitro leads to decreased production of Aβ, whereas an increase in cellular cholesterol induces Aβ production. Liver X Receptor (LXR) agonists are known to increase cholesterol efflux from cells, but there are conflicting reports as to the effects of these agonists on Aβ production. We therefore examined the effects of efflux‐inducing agents on Aβ production in vitro. We used methyl‐β‐cyclodextrin and an LXR agonist (TO‐901317) to induce cholesterol efflux and studied the resulting Aβ production in a stable amyloid precursor protein (APP) ‐transfected cell line. When cholesterol efflux was induced with methyl‐β‐cyclodextrin there was a >60% decrease in Aβ40 and Aβ42 production. However, while activation of LXR using TO‐901317‐induced cholesterol efflux in the presence of a cholesterol acceptor, no changes in Aβ levels were recorded. When cells were incubated with TO‐901317 above the concentration required for maximal cholesterol efflux, there was a 150% increase in Aβ42 levels. The absence of a cholesterol acceptor from the culture media (preventing cholesterol efflux) did not blunt this increase in Aβ42, suggesting that the effects of TO‐901317 on Aβ42 are efflux independent. These results were confirmed in APP stably transfected human H4 cells, which revealed in addition to a 200% increase in Aβ42 levels, a concomitant 80% reduction in Aβ38. A cell‐free γ‐secretase assay confirmed that TO‐901317 can directly alter γ‐secretase activity. These data demonstrate that TO‐901317 can directly modulate the site of cleavage of APP by γ‐secretase in vitro.
Endogenous opioids modulate hepatocyte apoptosis in a rat model of chronic cholestasis: the role of oxidative stress
Authors: Payabvash Seyedmehdi , Kiumehr Saman , Nezami Behtash Ghazi , Zandieh Ali , Anvari Pasha , Tavangar Seyed Mohammad , Dehpour Ahmad Reza 
Published: March 2007

AbstractAims/Background: There are increasing number of evidences indicating the contribution of endogenous opioids in the pathophysiology of cholestatic liver disease. The aim of the present study was to determine the role of the endogenous‐opioid system in the modulation of hepatocytes apoptosis and liver oxidant/anti‐oxidant balance during chronic cholestasis in rats.Methods: We induced cholestasis in rats by bile duct ligation (BDL). Naltrexone, an opioid antagonist, was administered at different doses (2.5, 5, 10, 20 and 40 mg/kg/day) to cholestatic animals for 5 weeks.Results: Naltrexone prevented the cholestasis‐induced decrease of hepatic glutathione levels at higher doses (20 and 40 mg/kg/day). In the next phase of the study, we evaluated the effects of 20 mg/kg/day naltrexone treatment on hepatic damage indices and liver oxidant/anti‐oxidant balance in 5‐week BDL rats. There was a marked increase in the number of apoptotic hepatocytes as well as serum liver enzymes and hepatic lipid peroxidation levels in cholestatic rats compared with sham‐operated animals 5 weeks after the operation. Liver anti‐oxidant enzyme activities were significantly reduced in cholestatic rats compared with controls. Chronic treatment with naltrexone significantly improved all the aforementioned indices in comparison with saline‐treated cholestatic rats.Conclusion: Our findings demonstrate that the administration of opioid antagonist is protective against hepatic damage in a rat model of chronic cholestasis. We suggest that increased levels of endogenous opioids contribute to hepatocytes apoptosis in cholestasis, possibly through downregulation of liver anti‐oxidant defense.
A novel therapeutic drug (copper nicotinic acid complex) for non‐alcoholic fatty liver
Authors: Salama Ragaa H. M. , Nassar Ahmed Y. A. , Nafady Allam A. M. , Mohamed Hesham H. T. 
Published: March 2007

AbstractBackground: Fatty liver is the accumulation of fat in liver cells, which leads to disruption of the normal liver structure and function.Methods: A non‐alcoholic fatty liver rat model received copper (Cu) (I)‐nicotinate complex [CuCl(HNA)2] for 4 weeks.Results: Clinical signs and histopathological examinations showed obvious improvements in rats that received Cu complex who were continuously on an (HCFF) diet than those returned to standard diet with Cu complex. The improvement was matched in total lipids in sera and hepatic tissue, with disappearance of fat droplets from liver sections. Furthermore, the gain in body weight and the corresponding decrease in liver weight, decreased liver transaminases and alkaline phosphatase were prominent. The oxidative stress markers such as nitric oxide, lipid peroxides, glutathione and superoxide dismutase were obviously changed to healthy normal levels.Conclusion: The Cu complex may serve as a novel chemical restoring agent in fatty degenerated liver cells and for renewal of their structure and functions. However, clinical trials are required for more evaluation of the Cu complex in humans.
Hepatic steatosis correlates with the postoperative recurrence of hepatitis C virus‐associated hepatocellular carcinoma
Authors: Takuma Yoshitaka , Nouso Kazuhiro , Makino Yasuhiro , Saito Shunsuke , Takayama Hiroki , Takahara Masahiro , Takahashi Hideaki , Murakami Ichiro , Takeuchi Hitoshi 
Published: March 2007

AbstractBackground: Hepatic steatosis is a prominent feature of chronic hepatitis C. Hepatic steatosis was reported recently to be a risk factor for hepatitis C virus (HCV)‐associated hepatocellular carcinoma (HCC).Aim: To investigate whether hepatic steatosis influences the postoperative recurrence of HCV‐associated HCC.Methods: A retrospective study was conducted in 88 patients undergoing curative resection of HCV‐associated HCC. Cumulative tumour recurrence rates were compared between steatosis‐positive and steatosis‐negative patients, and the factors affecting intrahepatic recurrence were assessed.Results: The respective tumour recurrence rates at 1, 3, and 5 years were 19%, 76%, and 92% in the steatosis‐positive group, and 12%, 52%, and 60% in the steatosis‐negative group. The tumour recurrence rate of the steatosis‐positive group was significantly higher than that of the steatosis‐negative group (P=0.02). Hepatic steatosis [relative risk (RR)=3.31, 95% confidence intervals (CIs)=1.49–7.41, P=0.003], stage of fibrosis (RR=3.17, 95% CI=1.35–7.47, P=0.008), surgical procedure (RR=0.22, 95% CI=0.076–0.64, P=0.005), number of tumours (RR=5.24, 95% CI=1.63–16.80, P=0.005), size of the largest tumour (RR=3.52, 95% CI=1.28–9.69, P=0.02), and vascular invasion (RR=2.72, 95% CI=1.32–5.59, P=0.007) were independent factors for tumour recurrence rate by multivariate analysis.Conclusions: Hepatic steatosis is a useful predictor of postoperative recurrence of HCV‐related HCC.
A randomized, double‐blind, placebo‐controlled, phase III study of the human anti‐tumor necrosis factor antibody adalimumab administered as subcutaneous injections in Korean rheumatoid arthritis patients treated with methotrexate
Authors: KIM Ho‐Youn , LEE Soo‐Kon , SONG Yeong Wook , YOO Dae‐Hyun , KOH Eun‐Mi , YOO Bin , LUO Allison 
Published: March 2007

AbstractObjective:  Adalimumab is a fully human, monoclonal, antitumour necrosis factor antibody approved for the treatment of rheumatoid arthritis (RA) in more than 60 countries. We investigated the efficacy and safety of 40 mg every‐other‐week (eow) subcutaneous injections of adalimumab with methotrexate (MTX) versus placebo with MTX in Korean patients with RA with insufficient responses to MTX.Methods:  This was a 24‐week, randomized, double‐blind, placebo‐controlled, phase III study conducted at six sites in Korea. The primary efficacy endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Secondary endpoints included ACR50, ACR70, and individual ACR components. Beginning at week 18, non‐responders (< 20% reduction in swollen and tender joint counts) could switch to rescue therapy with open‐label adalimumab 40 mg eow.Results:  Of the 128 patients enrolled, 65 received adalimumab and 63 received placebo. An ACR20 response at week 24 was achieved by 61.5% of patients receiving adalimumab versus 36.5% receiving placebo (P < 0.01). ACR50 and ACR70 responses were achieved by 43.1% and 21.5% of adalimumab patients versus 14.3% and 7.9% of placebo patients (P < 0.001 and P < 0.05, respectively). Adalimumab significantly improved all seven ACR core components. Statistically significant improvements in ACR20 were observed with adalimumab as early as week 2. Adalimumab was generally well tolerated; there were no significant differences in incidences of adverse events between groups.Conclusions:  In Korean patients with RA with insufficient responses to MTX, combination therapy with adalimumab and MTX was more efficacious than placebo and MTX in reducing RA signs and symptoms.
A survey of intrapartum fetal surveillance education practices in Victorian public hospitals
Authors: BEAVES Mark , JENKINS Valerie , WALLACE Euan M. 
Published: March 2007

AbstractBackground:  The inappropriate use or interpretation of intrapartum fetal surveillance (IFS) continues to be a major contributor to adverse obstetric outcomes, suggesting that training in IFS is deficient. What professional education in intrapartum fetal sureveillance currently exists in Victorian public hospitals is unknown.Aims:  To map the current formal IFS education and competency assessment practices in Victorian public hospitals.Methods:  A structured survey comprising 25 questions was developed and mailed to both a senior obstetric and a midwifery manager in all public maternity hospitals in Victoria. Non‐respondents were followed up at 2 months.Results:  One hundred and twenty surveys were sent to 60 hospitals, of which 103 replies from 58 hospitals were received, representing a 97% hospital response rate. Only 19 (33%) of respondent hospitals had an existing education program. Hospitals with > 2000 births per annum were more likely to have a program than those with < 1000 births per annum (86% vs 23%, P = 0.004). Of the 19 existing education programs, only nine contained any fetal physiology. All respondents thought that IFS education should be compulsory for relevant staff. Only six (10%) of the hospitals had any assessment of competency but 90% of respondents thought that such an assessment should be compulsory.Conclusions:  These data reveal important deficiencies in the provision and quality of current IFS education practices in Victoria, particularly in smaller and rural hospitals. However, these deficiencies seem to reflect a lack of opportunity rather than a lack of interest.
Adequacy of prenatal care and neonatal mortality in infants born to mothers with and without antenatal high‐risk conditions
Authors: CHEN Xi‐Kuan , WEN Shi Wu , YANG Qiuying , WALKER Mark C. 
Published: March 2007

AbstractBackground:  Previous studies have found that inadequate prenatal care was associated with increased neonatal mortality in the general pregnant women.Aims:  To examine the association between adequacy of prenatal care and neonatal mortality in the presence and absence of antenatal high‐risk conditions.Methods:  We conducted a retrospective cohort study of infants based on 1995–2000 vital statistics data in the USA. The relative risk for neonatal death associated with adequacy of prenatal care was estimated by multivariate logistic regressions with adjustment of confounding factors.Results:  Inadequate prenatal care was associated with increased neonatal mortality when pregnancies were complicated by anaemia, cardiac disease, lung disease, chronic hypertension, diabetes, renal disease, pregnancy‐induced hypertension, and previous preterm/small‐for‐gestational‐age birth. The observed association also existed in the absence of these antenatal high‐risk conditions. Overutilisation of prenatal care was associated with increased risk of neonatal deaths in both the presence and the absence of antenatal high‐risk conditions. When gestational age at delivery and birthweight were further adjusted, the observed association between inadequate prenatal care and neonatal mortality was not significant in pregnancies with various high‐risk conditions.Conclusions:  Inadequate prenatal care is associated with increased neonatal death in both the presence and the absence of antenatal high‐risk conditions. The observed association between inadequate prenatal care and neonatal mortality may be mediated by increased risk of preterm delivery and low birthweight in these pregnancies. Overutilisation of prenatal care is associated with potential risks for fetal and neonatal development, leading to increased neonatal mortality.
Long‐term evaluation of animal‐assisted therapy for institutionalized elderly people: a preliminary result
Authors: KAWAMURA Namiko , NIIYAMA Masayoshi , NIIYAMA Harue 
Published: March 2007

AbstractBackground:  Many researchers theorize that animal‐assisted therapy (AAT) will have an effect on people suffering from the symptoms of dementia by evaluating short‐term‐effects. The purpose of this research was to evaluate the psychological and behavioral effects of AAT on elderly residents of a nursing home on a long‐term basis.Methods:  The subjects consisted of 10 residents of a residential nursing home. Researchers first created each participant’s goal in an agreement with the nursing home staff. Visits were made twice a month, and on each occasion three or four dogs were taken. The residents were able to freely feed, hold and play with the dogs, with each dog placed on a separate table. Data collection methods included GBS Scale Japanese Version (GBSS‐J) and Mental Function Impairment Scale (MENFIS). Data was collected four times during the period 2003–05. The scores were analyzed using SPSS11.5J.Results:  According to GBSS‐J, the scores for intellectual function, spontaneity, emotional function and other mental functions decreased during the first 6 months of the study and then increased until the twelfth month. The score for Motor function increased over the 12 months. When comparisons were made item by item, there were significant decreases in impaired orientation in space, and emotional liability during the first 6 months. According to MENFIS, the overall score tended to decrease during the first 6‐month period but increased from 6 months to 12 months. There was a tendency for scores to decrease in impaired emotional function, especially impaired suitability of emotional expression and impaired stability of emotional expression over the 12‐month period.Conclusions:  After 6 months of participation in AAT, there were improvements in mental functions, though physical functions decreased. It is suggested that after a 6 month period each subject’s needs and goals should be re‐examined.
Silver treatments for leg ulcers: a systematic review
Authors: Chambers Holly , Dumville Jo C. , Cullum Nicky 
Published: March 2007

ABSTRACTTo determine the quantity and quality of current research on the effectiveness of silver‐based dressings and topical agents for the treatment of leg ulcers, this paper presents a systematic review of randomized controlled trials (RCTs) looking at the effects of silver‐based dressings and topical agents on leg ulcer healing. Electronic databases were searched up to May 2006 for relevant randomized controlled trials. Journals and conference proceedings were also searched. The methodological quality of selected trials was assessed and statistical pooling of the results from similar studies undertaken. Rate of healing, proportion of ulcers completely healed and change in ulcer size were observed. Nine studies were considered eligible for inclusion. These studies varied in terms of the types of leg ulcers treated, interventions used, and outcomes assessed. Studies provided inconsistent evidence regarding the effects of silver‐based dressings and topical agents on leg ulcer healing. Studies generally provided poor evidence due to a lack of statistical power, poor study designs, and incomplete reporting. In conclusion, the current evidence base on the use of these silver‐based products on leg ulcers is limited, both in terms of the quantity available and the quality of the evidence. This review highlights the need for further, more rigorous research to be carried out before the use of these silver‐based interventions in routine leg ulcer management is supported.
Reduced up‐regulation of cytoprotective genes in rat cutaneous tissue during the second cycle of ischemia–reperfusion
Authors: Sisco Mark , Robert Liu W. , Kryger Zol B. , Mustoe Thomas A. 
Published: March 2007

ABSTRACTChronic wounds are major health problems that affect millions of people in the United States every year. Management of these wounds costs billions of dollars annually in the United States. Despite their clinical importance, the molecular mechanisms underlying these clinical conditions remain elusive. Repetitive ischemia–reperfusion (I–R) may play a pivotal role in chronic wound formation. The development of therapies for these wounds is hindered by the lack of animal models that allow identification of the molecular mechanisms underlying chronic wound formation. In the first study of its kind, we adapted our rat pressure sore model by imposing two cycles of ischemia (2 hours) and two cycles of reperfusion (24 hours), and we examined gene expression to better understand the molecular events that occur at the very early stages of cutaneous I–R injury with a goal of devising preventing strategies. We successfully tested our hypothesis and demonstrated that while cytoprotective genes, such as heat shock protein 70, heat shock protein 90, hypoxia‐inducible factor‐1α, vascular endothelial growth factor, and heme oxygenase‐1, were initially up‐regulated during the first cycle of I–R, their up‐regulation was subsequently reduced or completely abolished during the second cycle of I–R. These findings raise the possibility that reduced up‐regulation of these cytoprotective genes may be causally linked to cutaneous I–R injury.
Shift of homeostasis from parenchymal regeneration to fibroblast proliferation induced by lipopolysaccharide‐activated macrophages in gastric mucosal healing in vitro
Authors: Kei Wu William Ka , Yin Law Priscilla Tak , Shan Wong Helen Pui , Yee Lam Emily Kai , Ki Tai Emily Kin , Shin Vivian Yvonne , Cho Chi Hin 
Published: March 2007

ABSTRACTWound healing in the gastrointestinal tract is an orderly process involving orchestrated responses of various cell types. Lipopolysaccharides (LPS) are major components of the outer membrane of Gram‐negative bacteria, which are known to impair gastric ulcer healing in animals. The influence of LPS on intercellular communication in wound healing, however, is unknown. We examined the effects of LPS‐induced macrophage activation on the proliferative response in cultured rat gastric epithelial cells (RGM‐1) and fibroblasts JHU‐25. Rat peritoneal resident macrophages were activated with increasing doses of LPS. The supernatant from the activated macrophage preparation, designated as macrophage‐conditioned medium, was then used to treat RGM‐1 or JHU‐25 cells. Cell proliferation and migration were determined by [3H]‐thymidine incorporation and a monolayer wound‐healing assay, respectively. Macrophage‐conditioned medium significantly suppressed RGM‐1 cell proliferation but had no effect on cell migration. The same medium, however, increased JHU‐25 cell proliferation. LPS treatment alone suppressed JHU‐25 cell proliferation while it had no effect on RGM‐1 cell proliferation, indicating that the differential effects of the macrophage‐conditioned medium on cell proliferation were elicited by the factors derived from macrophages. In this regard, tumor necrosis factor (TNF)‐α stimulated while interleukin (IL)‐1β suppressed RGM‐1 cell proliferation, suggesting that IL‐1β but not TNF‐α may play a part in the mediation of the antiproliferative effect of macrophage‐conditioned medium on gastric epithelial cells. In contrast, IL‐1β suppressed while TNF‐α had no effect on JHU‐25 cell proliferation. Collectively, LPS‐activated macrophages delay gastric mucosal regeneration but promote fibroblast proliferation in vitro. Such changes may partly elucidate the detrimental effect of bacterial infection on tissue repair in the stomach.
Release of basic fibroblast growth factor from a crosslinked glycosaminoglycan hydrogel promotes wound healing
Authors: Liu Yanchun , Cai Shenshen , Shu Xiao Zheng , Shelby Jane , Prestwich Glenn D. 
Published: March 2007

ABSTRACTWe describe synthetic extracellular matrix (sECM) hydrogel films composed of co‐crosslinked thiolated derivatives of chondroitin 6‐sulfate (CS) and heparin (HP) for controlled‐release delivery of basic fibroblast growth factor (bFGF) to full‐thickness wounds in genetically diabetic (db/db) mice. In this model for chronic wound repair, full‐thickness wounds were treated with CS, CS‐bFGF, or CS‐HP‐bFGF films. At 2 and 4 weeks postinjury, wound closure and formation of the new epidermis and dermis were determined. Both CS and CS‐HP hydrogel films accelerated wound repair, even without bFGF. Addition of bFGF to CS films showed partial dose‐dependent acceleration of wound repair. Importantly, addition of bFGF to co‐crosslinked CS‐HP sECM films showed a dramatic bFGF dose‐dependent acceleration of wound healing, as well as improved dermis formation and vascularization. Compared with 27% wound closure in 2 weeks in the controls, 89% wound closure was observed for mice treated with the CS‐HP‐bFGF films. The synthetic CS‐HP sECM films mimic the chemistry and biology of heparan sulfate proteoglycans, and may have clinical potential for topical delivery of growth factors to patients with compromised wound healing.
Derivation and clinical application of special imaging by means of digital cameras and Image J freeware for quantification of erythema and pigmentation
Authors: Yamamoto Tadamasa , Takiwaki Hirotsugu , Arase Seiji , Ohshima Hiroshi 
Published: March 2007

Background: Quantification of erythema and pigmentation is useful for analysis of skin tests and management of skin diseases. However, reflectance instruments for this purpose suffer from many technical and financial disadvantages. The aim of this study was to establish a method for evaluation of the amounts of haemoglobin and melanin using ordinary digital cameras and Image J freeware.Methods: Based on the theories on the absorbance of a multilayered skin model, the erythema index (EI) and melanin index (MI) images were derived by image processing from digital colour images of the skin, which were obtained with four kinds of digital cameras. The specificity of these indices and the linearity between index values and the amounts of haemoglobin and melanin were determined by using images of various concentrations of haemoglobin and melanin solutions. The accuracy of both types of index images was also examined by comparing the index values of UV‐induced erythema and pigmentation of various intensities with those measured with a reflectance spectrophotometer.Results: The specificity of EI and MI images was good as little interference was noted with each other. The linearity between EI and haemoglobin concentration, as well as that between MI and melanin concentration was excellent. For UV‐induced erythema and pigmentation, good linear correlation was confirmed between two types of EI obtained by the two methods, as well as between two types of MI. However, the index values derived from digital images depended on the camera used as well as on the circumstantial conditions, such as the distance from objects and illumination.Conclusion: EI and MI images are reliable and useful for quantifying erythema and pigmentation, if obtained under constant and consistent conditions. Apart from financial benefits, this method has many advantages and greater clinical utility in comparison with reflectance instruments.