bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statin‐induced calcification in human mesenchymal stem cells is cell death related
Authors: Kupcsik Laszlo , Meurya Thomas , Flury Matthias , Stoddart Martin , Alini Mauro 
Published: October 2008

AbstractStatins are widely used in clinics to lower cholesterol levels. Recently, they have been shown to positively affect bone formation and bone mass in a rat model. The aim of this study was to investigate the effect of pravastatin, simvastatin and lovastatin on the osteoblastic differentiation of human mesenchymal stem cells (MSCs)in vitro. Cell number, alkaline phosphatase (ALP) activity, matrix mineralization and gene expression pattern were determined. Pravastatin did not affect cell differentiation. Simvastatin and lovastatin enhanced bone morphogenetic protein 2 (BMP‐2) mRNA levels. In contrast, ALP activity and mRNA levels were suppressed by statins, as well as the DNA content and cell activity (MTT). An increase in apoptotic events was observed at high concentrations of statins, along with high Ca‐45 incorporation. Lower concentrations of statins did not increase apoptotic staining, but also failed to induce calcification. When statin‐induced calcification did occur, the morphology of the deposits was very different from the conventional nodule formation; the calcium was laid down along the membranes of the rounded cells suggesting it was as a result of cell death. Our results indicate that statins are not able to differentiate human MSCs into osteoblasts and that high concentrations of statins (>1 μM) have a cytotoxic effect.
Retracted:Advanced glycation endproduct (AGE) accumulation and AGE receptor (RAGE) up‐regulation contribute to the onset of diabetic cardiomyopathy
Authors: Ma Heng , Li Shi‐Yan , Xu Peisheng , Babcock Sara A. , Dolence E. Kurt , Brownlee Michael , Li Ji , Ren Jun 
Published: October 2008

AbstractDiabetic cardiomyopathy is manifested by compromised systolic and diastolic function. This study was designed to examine the role of advanced glycation endproduct (AGE) and AGE receptor (RAGE) in diabetic cardiomyopathy. Heart function was assessed in isolated control and streptozotocin‐induced diabetic hearts followingin vivoRAGE gene knockdown using RNA interference. Cardiomyocyte mechanical properties were evaluated including peak shortening (PS), time‐to‐PS (TPS) and time‐to‐90% relengthening (TR90). RAGE was assayed by RT‐PCR and immunoblot. Diabetes significantly enhanced cardiac MG, AGE and RAGE levels accompanied with colocalization of AGE and RAGE in cardiomyocytes. Diabetes‐elicited increase in RAGE was inhibited byin vivosiRNA interference. The AGE formation inhibitor benfotiamine significantly attenuated diabetes‐induced elevation in MG, AGE, RAGE and collagen cross‐linking without affecting hypertriglyceridaemia and hypercholesterolaemia in diabetes. Diabetes markedly decreased LV contractility, as evidenced by reduced ±dP/dt and LV developed pressure (LVDP), which were protected by RAGE gene knockdown. In addition, MG‐derived AGE (MG‐AGE) up‐regulated cardiac RAGE mRNA and triggered cardiomyocyte contractile dysfunction reminiscent of diabetic cardiomyopathy. The MG‐AGE‐elicited prolongation of TPS and TR90was ablated by an anti‐RAGE antibody in cardiomyocytes. Interestingly, MG‐AGE‐induced cardiomyocyte dysfunction was associated with mitochondrial membrane potential (MMP) depolarization and reduced GSK‐3β inactivation in control cardiomyocytes, similar to those fromin vivodiabetes. Treatment with siRNA‐RAGE ablated diabetes‐induced MMP depolarization and GSK‐3β inactivation. Collectively, our result implicated a role of AGE‐RAGE in the pathogenesis of diabetic cardiomyopathy.
E10A, an adenovirus carrying human endostatin gene, in combination with docetaxel treatment inhibits prostate cancer growth and metastases
Authors: Zhao Peng , Luo Rongcheng , Wu Jiangxue , Xie Fajun , Li Hongli , Xiao Xia , Fu Liwu , Zhu Xiaofeng , Liu Ranyi , Zhu Yinghui , Liang Zhihui , Huang Wenlin 
Published: October 2008

AbstractE10A, a replication‐defective adenovirus carrying human endostatin gene, has finished Phase I clinical trials for solid cancers. We assessed whether the combination of E10A with docetaxel would enhance antiangiogenic activities and inhibit prostate cancer growth and metastases. Combination use of conditioned medium from prostate cancer cells infected by E10A and docetaxel exerted synergistic inhibition of HUVECs proliferation, migration and tube formation, compared with either agent alone. In prostate cancer s.c. xenograft models, combined therapy resulted in significant tumour growth inhibition and survival improvement. The antitumoural effect was tightly correlated with a remarkable decrease in tumour cell proliferation, microvessel, especially immature vasculature and significant increase in apoptosis induction. Systemic administration of E10A and docetaxel also effectively inhibited orthotopic growth and metastases of prostate cancer and achieved better in vivo antiangiogenic effects than either agent alone. Our data indicate that E10A in combination with docetaxel exert enhanced antiangiogenic activities and inhibit prostate cancer growth and metastases. Therefore, this approach may be an effective treatment for advanced prostate cancer and deserves more extensive investigation.
Transcriptional regulation of survivin by c‐Myc in BCR/ABL‐transformed cells: implications in anti‐leukaemic strategy
Authors: Fang Zhi Hong , Dong Chun Lan , Chen Zhong , Zhou Bin , Liu Na , Lan Hai Feng , Liang Lu , Liao Wen Bin , Zhang Lei , Han Zhong Chao 
Published: October 2008

AbstractBCR/ABL can cause chronic myelogenous leukaemia (CML) in part by altering the transcription of specific genes with growth‐ and/or survival‐promoting functions. Recently, BCR/ABL has been shown to activate survivin, an important regulator of cell growth and survival, but the precise molecular mechanisms behind its expression and consequences thereof in CML cells remain unclear. Here, we reported that BCR/ABL promotes survivin expression and its cytoplasmic accumulation. The increase of survivin was largely controlled at the transcriptional level through a mechanism mediated by JAK2/PI3K signal pathways that activated c‐Myc, leading to transactivation of survivin promoter. Dynamic down‐regulation of survivin was a key event involved in imatinib‐induced cell death while forced expression of survivin partially counteracted imatinib's effect on cell survival. Additionally, shRNA‐mediated silencing of survivin or c‐Myc eradicated colony formation of K562 cells in semi‐solid culture system, implying an essential role for this transcriptional network in BCR/ABL‐mediated cell transformation and survival. Finally, interruption of c‐Myc activity by 10058‐F4 exerted an anti‐leukaemia effect with a synergistic interaction with imatinib and overcame the anti‐apoptosis rescued by IL‐3 supplement. In conclusion, we have identified JAK2/PI3K‐mediated and c‐Myc‐dependent transactivation of survivin as a novel pathway in the transcriptional network orchestrated by BCR/ABL. These results suggest that the interference with this circuitry might be a potential utility for CML treatment.
Ginkgolide B preconditioning protects neurons against ischaemia‐induced apoptosis
Authors: Wu Xiaomei , Qian Zhongming , Ke Ya , Du Fang , Zhu Li 
Published: October 2008

AbstractIschaemic preconditioning (IP) has been reported to protect the brain against subsequent lethal ischaemia, but it has not been used clinically to prevent ischaemic injury because of safety concerns. The aim of the present study was to see whether Ginkgolide B (GB) is capable of preconditioning as IP to protect neurons against ischaemic injury; if so, which mechanism is involved. Cultured mouse cortical neurons at day 8 were pre‐treated with GB (120 μmol/l) for 24 hrs or exposed to short‐term ischaemia (1 hr) followed by 24‐hr normal culture to induce IP before being treated with severe ischaemia (5 hrs). GB and IP significantly increased cell viability, expression of hypoxia‐inducible factor‐1 alpha (HIF‐1α), erythropoietin (EPO), phosphorylated Bad at serine 136 (136p‐Bad) and phosphorylated glycogen synthase kinase‐ 3β at serine 9 (p‐GSK‐3β), and decreased the percentage of apoptotic cells and the level of active caspase‐3 in severely ischaemic neurons. Moreover, LY294002 that is a specific inhibitor of phosphatidylinositol 3‐kinase (PI3K) significantly reduced the enhanced expression of HIF‐1α, EPO and 136p‐Bad induced by GB and IP. These results suggest that GB, like IP in neurons, is capable of preconditioning against ischaemia‐induced apoptosis, the mechanism of which may involve the PI3K signalling pathway.
Recent aspects of medical care of malignant melanoma
Authors: Terheyden Patrick , Tilgen Wolfgang , Hauschild Axel 
Published: October 2008

SummaryRecent developments in the epidemiology, diagnosis and therapy of malignant melanoma are reviewed, with particular attention paid to established standards of care. When melanoma metastases are inoperable, they respond poorly to the various chemotherapy strategies, so that additional improvements are critically needed. Cytotoxic T‐lymphocyte antigen‐4 antibodies, multikinase inhibitors, anti‐apoptotic strategies and several other approaches are in progress in Phase III trials both as monotherapy as well as in combination with standard chemotherapy.
The effect of fermented apple diet supplementation on the growth performance and meat quality in finishing pigs
Authors: LEE Sung Dae , KIM Hoi Yun , JUNG Hyun Jung , JI Sang Yun , CHOWDAPPA Rekha , HA Ji Hee , SONG Young Min , PARK Jun Cheol , MOON Hong Kil , KIM In Cheul 
Published: October 2008

ABSTRACTThe objective of the present study was to investigate the effect of fermented apple diet (FAD) supplementation on the growth performance and meat quality in finishing Berkshires. The FAD was made from dropped apple mixed with rice bran and barley bran. Until 81 ± 1 kg live weight at 133 ± 1 days, the animals were fed a growing diet, after which experimental samples were fixed at 0, 2, 4 and 6% FAD as C, T1, T2 and T3 in the finishing diets. Growth performance, ADG, ADFI and feed efficiency were improved in T1 than other groups. In carcass parameters, carcass weight was higher (P < 0.05) in T1 than in other groups. In meat quality, moisture and crude protein contents decreased (P < 0.05) by addition of FAD. pH24 and WHC were higher (P < 0.05) in T1 than other groups. In sensory evaluation, marbling of fresh meat and tenderness, juiciness, flavor and overall acceptability of cooked meat were improved by the addition of FAD. According to the results of our experiment, FAD can be used for improvement of meat quality parameters.
Relationships between physical and structural properties of intramuscular connective tissue and toughness of raw pork
Authors: NISHIMURA Takanori , FANG Suhong , WAKAMATSU Jun‐ichi , TAKAHASHI Koui 
Published: October 2008

ABSTRACTWe studied the relationships between the shear‐force value and physical and structural properties of the intramuscular connective tissue (IMCT) in six classes of porcine skeletal muscle to elucidate the contribution of IMCT to toughness of raw pork. The shear‐force value of raw pork correlated significantly with that of the IMCT model prepared from each class of skeletal muscle (P < 0.05). The correlation suggested that the variable toughness of pork was caused by the mechanical strength of the endomysium and perimysium. The thickness of the secondary perimysium correlated significantly with the shear‐force value of raw pork (P < 0.05) and with that of the IMCT model (P < 0.05). The shear‐force value of raw pork correlated significantly with the total amount of collagen (P < 0.05) but not with the heat‐solubility of collagen. We concluded therefore that the thickness of the secondary perimysium determines the mechanical strength of IMCT and contributes to toughness in raw pork.
The evaluation of the curd forming ability of milk replacers
Authors: OKADA Keiji , KATO Junro , MIYAZAKI Tamako , IKUTA Kentaro , NAITO Yoshihisa , YASUDA Jun 
Published: October 2008

ABSTRACTInadequate milk curd formation in the abomasum of newborn calves causes malnutrition and diarrhea. In order to define the factors of inadequate curd formation, we compared the curd forming ability among 9 kinds of milk replacers, bulk milk (raw milk), and skim milk both in vitro and in vivo. When rennet was added, the raw milk and one milk replacer formed firm curds. The rest of the milk replacers and skim milk did not form any curd. When a solution of HCl was added, raw milk, three milk replacers and skim milk formed the curd at pH 4.5, but the other milk replacers did not. When HCl was added following the rennet, raw milk, one milk replacer and skim milk formed the curd. In vivo, raw milk, two milk replacers and skim milk showed good curd formation whereas the other milk replacers showed poor curd formation inside the abomasums of the calves. This study showed that most of the milk replacers sold in Japan could not form the curd with rennet.
Chronic Administration of Ketamine Elicits Antidepressant‐Like Effects in Rats without Affecting Hippocampal Brain‐Derived Neurotrophic Factor Protein Levels
Authors: Garcia Lêda S. , Comim Clarissa M. , Valvassori Samira S. , Réus Gislaine Z. , Andreazza Ana Cristina , Stertz Laura , Fries Gabriel R. , Gavioli Elaine Cristina , Kapczinski Flavio , Quevedo João 
Published: October 2008

Abstract:  A growing body of evidence has pointed to the blockade of the N‐methyl‐d‐aspartate (NMDA) receptor signaling as a potential therapeutic target for the treatment of major depression. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with ketamine and imipramine in rats. To this aim, rats were 14 days treated once a day with ketamine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open‐field tests. Ketamine and imipramine, at the all doses tested, reduced immobility time, and increased both climbing and swimming time of rats compared to the saline group, without affecting spontaneous locomotor activity. Brain‐derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine‐ and ketamine‐treated rats by ELISA sandwich assay. Chronic administration of both drugs, ketamine and imipramine, did not modify BDNF protein levels in the rat hippocampus. In conclusion, our findings demonstrate for the first time that chronic administration of acute inactive doses of ketamine (5 mg/kg) becomes active after chronic treatment, while no signs of tolerance to the behavioural effects of ketamine were observed after chronic administration of acute active doses (10 and 15 mg/kg). Finally, these findings further support the hypothesis that NMDA receptor could be a new pharmacological target for the treatment of mood disorders.
Increased Hepatotoxicity and Cardiac Fibrosis in Cocaine‐Treated Butyrylcholinesterase Knockout Mice
Authors: Duysen Ellen G. , Li Bin , Carlson Michaela , Li Yi‐Fan , Wieseler Stacy , Hinrichs Steven H. , Lockridge Oksana 
Published: October 2008

Abstract: In mice, cocaine is detoxified to inactive products by butyrylcholinesterase (BChE) and carboxylesterase. In human beings, cocaine detoxification is primarily by BChE. The focus of this investigation was to elucidate the importance of BChE in reducing pathophysiological effects following cocaine exposure. Previous studies examining the effects of cocaine on BChE deficient animals relied on chemical inhibition of BChE with tetraisopropyl pyrophosphoramide (iso‐OMPA). The creation of the BChE knockout mouse has provided a model for studying pathological effects of cocaine in mice free of chemical confounders. We hypothesized that mice with low or no BChE activity would have reduced cocaine metabolism, leading to hepatotoxicity and cardiomyopathy. A high‐resolutionin vivoimaging system recorded cardiac and respiratory function following treatment with a carboxylesterase inhibitor and a high dose of cocaine (100 mg/kg, intraperitoneally). The BChE−/− mice demonstrated depressed respiration through 12 hr after dosing and abnormal respiratory patterns consisting of a pause at full inspiration (apneusis), whereas BChE+/+ mice had recovered normal respiration rates by 30 min. after dosing and exhibited no apneusis. Liver and cardiac histology sections were analysed following a 20 mg/kg intraperitoneally dose of cocaine administered daily for 7 days. BChE–/– mice treated for 7 days with the chronic low dose showed significant hepatotoxicity and cardiac perivascular fibrosis compared to BChE+/+ mice. The observed functional changes following acute high‐dose and chronic low‐dose cocaine in BChE−/− and +/− mice warrants further investigation into the possibility of increased cocaine toxicity in human beings with BChE deficiency.
Antihyperlipidaemic Effect of Gymnema montanum: A Study on Lipid Profile and Fatty Acid Composition in Experimental Diabetes
Authors: Ramkumar Kunga Mohan , Vijayakumar Ramasamy Subramaniam , Ponmanickam Ponnirul , Velayuthaprabhu Shanmugan , Archunan Govindaraju , Rajaguru Palanisamy 
Published: October 2008

Abstract:   In the present study, the antihyperlipidaemic efficacy of ethanol extract of Gymnema montanum leaves was investigated in alloxan‐induced diabetic rats and the effect was compared to standard hypoglycaemic drug, glibenclamide. Male adult albino Wistar rats were injected with freshly prepared solution of alloxan monohydrate (150 mg/kg body weight) to induce diabetes. After 2 weeks, the rats with moderate diabetes were administered G. montanum leaves (200 mg/kg body weight) for 21 days by gastric lavage, after which serum, liver and kidney samples were analysed for lipid profile, lipoprotein changes and fatty acid composition. While the alloxan‐induced diabetic rats showed a significant increase in the levels of cholesterol, triglycerides and free fatty acids, the levels in the animals treated with G. montanum leaves were considerably reduced and restored to near normal values. Antihyperlipidaemic effects of G. montanum leaves were found to be comparable with that of glibenclamide. Similarly, G. montanum leaves treatment resulted in reversal of alterations observed in the plasma lipoproteins (high‐density lipoprotein, low‐density lipoprotein and very high‐density lipoprotein‐cholesterol) and fatty acid composition in serum, liver and kidney of alloxan‐induced rats. Our study suggests that phytochemicals present in G. montanum may play an important role in suppressing the elevated lipid profile in diabetes and may be useful for the prevention and/or early treatment of diabetes‐associated hyperlipidaemia.
Lack of Information Underlies Women's Perceptions of Erectile Dysfunction (ED) Drugs in Japan
Authors: Mita Koji , Kakehashi Masayuki , Hasegawa Yasuhisa , Inoue Yoji , Shigeta Masanobu , Matsubara Akio , Usui Tsuguru 
Published: October 2008

ABSTRACT

Introduction
Some Japanese women are known to have negative attitudes toward erectile dysfunction (ED) drugs, but the environment underlying these perceptions is unclear.

Aim
To reveal the underlying environment that shapes women's perceptions of ED drugs in Japan.

Methods
A web-based questionnaire was conducted through an Internet-based market research company. A total of 2,593 women in five age groups (20s, 30s, 40s, 50s, and 60s or older) were randomly invited to participate in this study, with an almost equal number in each age group. The questionnaire contained 30 items related to individual background and sexual information, concerns about the image of ED drugs, ED drug-related perceptions, and attitude toward sexual information media.

Main Outcome Measures
The women's attitude and the independent predictors that affect their partner's use of ED drugs were clarified.

Results
Answers were obtained from 1,077 women, of whom 35.4% (n = 381) had a negative image of ED drugs. Although 69.5% (n = 749) agreed that a sexual relationship with a male partner was important, only 26.7% (n = 288) agreed that this remained important if ED drugs were used. However, 56.7% (n = 611) and 57.7% (n = 621) of respondents, respectively, answered that they would allow their partner's use of ED drugs if they imagined that they understood the safety and effectiveness of ED drugs and that their quality of life was improved by their partner's use of the drugs. Lack of information about ED drugs was a significant predictor for acceptance of a partner's use of ED drugs among women with a negative image of ED drugs, since they were more likely to accept the use of these drugs if they were convinced about their safety and effectiveness or positive effect on quality of life.

Conclusion
Lack of information about ED drugs may influence the perception of women in Japan regarding these drugs.
The Sexual Lives of Residents and Fellows in Graduate Medical Education Programs: A Single Institution Survey
Authors: Ferguson Genoa G. , Nelson Christian J. , Brandes Steven B. , Shindel Alan W. 
Published: October 2008

ABSTRACT

Introduction
The prevalence of sexual problems among resident physicians has not been investigated.

Aim
To explore the sexual behavior of residents and fellows in training and to determine the incidence of sexual dysfunction in this population.

Methods
Residents and fellows at our institution were invited to complete a demographic questionnaire, as well as two to three gender-specific validated instruments for the assessment of human sexuality.

Main Outcome Measures
The validated survey instruments selected were the International Index of Erectile Function (IIEF), the Index of Premature Ejaculation (IPE), and the Self-Esteem and Relationship Quality (SEAR) survey for male residents, and the Female Sexual Function Index (FSFI) and the Index of Sex Life (ISL) for female residents. Results were compared with established normative data and validated cut-off scores that were available. Pearson correlation coefficient was used to assess for relationships between variables.

Results
There were 180 responses (83 female, 97 male, mean age 29 years), for a response rate of 20%. Among men, 90%, 67%, and 98% were in a relationship, married, and heterosexual, respectively. Among women, the same numbers were 80%, 55%, and 96%, respectively. Based on validated cut-off scores for the IIEF and FSFI, 13% of men reported ED (3% reported mild ED, 4% reported moderate ED, and 6% reported severe ED) and 60% of women were classified as “at high risk” for sexual problems, with desire disorders the most prevalent and orgasmic disorders the second most prevalent. There were significant gender differences with respect to the associations between sexual and relationship problems.

Conclusion
Sexual problems may be prevalent among residents in training, particularly female residents. Additional, larger studies that assess other quality of life measures and query sexual partners of residents are needed.