bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin sensitizes endometrial cancer cells to chemotherapy by repressing glyoxalase I expression
Authors: Dong Lingling , Zhou Qian , Zhang Zhenbo , Zhu Yaping , Duan Tao , Feng Youji 
Published: April 2012

AbstractAim:  Metformin plays an important role in the inhibition of cancer cell growth and prolongs remission durations. It reverses progestin‐resistance in endometrial cancer cells by downregulating glyoxalase I (GloI) expression. This study aimed to investigate the effect of metformin on endometrial cancer cell chemotherapeutic sensitivity and explore the underlying molecular mechanisms.Material and Methods:  MTT assay was performed to determine the rate of cell death after cisplatin and paclitaxel with or without metformin. Western blot was carried out to analyze GloI expression. SiRNA‐targeting of GloI was used to knockdown GloI expression before further treatment with chemotherapeutic agents to examine the effect of GloI downregulation on chemotherapy‐induced cell killing. In addition, plasmid transfection was used to overexpress GloI and determine whether high GloI levels blocked metformin‐enhanced cell sensitivity to chemotherapy. PCR was used to analyze the efficiency of RNA interference and plasmid transfection.Results:  The addition of metformin enhanced the sensitivity of endometrial cells to cisplatin and paclitaxel, which was associated with reduced levels of GloI expression. Moreover, low‐dose chemotherapeutic drugs alone could not significantly reduce GloI expression, whereas the addition of metformin potently downregulated GloI protein levels. Cisplatin and paclitaxel markedly inhibited the proliferative ability of GloI‐depleted endometrial cancer cells. However, the overexpression of GloI abolished the effect of metformin‐enhanced cell sensitivity to chemotherapeutic drugs.Conclusion:  Metformin enhances the rate of cell‐killing induced by chemotherapeutic agents by repressing GloI expression.
Oxidative stress measured by carbonyl groups level in postmenopausal women after oral and transdermal hormone therapy
Authors: Polac Ireneusz , Borowiecka Marta , Wilamowska Agnieszka , Nowak Pawel 
Published: April 2012

AbstractAim:  Menopause is associated with an increased risk of cardiovascular disorders, which are accompanied by oxidative stress. Our study was undertaken to determine whether oxidative stress in menopausal women could be reduced after six months of oral or transdermal hormonal therapy.Material and Methods:  Carbonyl groups of proteins in blood plasma were estimated by sensitive ELISA method with anti‐DNP antibodies. In this method, protein samples diluted in phosphate‐buffered saline were adsorbed to wells of an ELISA plate and then reacted with dinitrophenylhydrazine (DNPH).Results:  Plasma protein carbonyl levels of postmenopausal women treated with o‐HT and t‐HT for six months (o‐HT: 1.785 ± 0.31 nmol/mg; t‐HT: 1.838 ± 0.33 nmol/mg) were lower when compared with the control group (2.232 ± 0.28 nmol/mg). There was no statistically significant difference in carbonyl levels between women after oral and transdermal HT (P = 0.149).Conclusion:  Hormonal therapy reduces the level of carbonyl protein, a marker of oxidative stress, suggesting potential protective effect.
Uterine tamponade using condom catheter balloon in the management of non‐traumatic postpartum hemorrhage
Authors: Rathore Asmita Muthal , Gupta Sonali , Manaktala Usha , Gupta Sangeeta , Dubey Chandan , Khan Mumtaz 
Published: April 2012

AbstractAim:  To study the efficacy and complications of uterine tamponade using condom catheter balloon in non‐traumatic postpartum hemorrhage (PPH).Material and Methods:  This prospective study was conducted in a tertiary care teaching hospital in India. Eighteen patients with non‐traumatic PPH not responding to medical management were included in the study. Uterine tamponade was achieved by a condom catheter balloon filled with saline and kept in situ for 8–48 h. The main outcome measures were success rate in controlling hemorrhage, time required to stop bleeding, subsequent morbidity and technical difficulties. Data was analyzed using appropriate statistical methods.Results:  The success rate of condom catheter balloon in controlling hemorrhage was 94%. The mean amount of fluid filled in the condom catheter balloon was 409 mL. The average time taken to control bleeding was 6.2 min. The mean duration for which condom catheter balloon was left in situ was 27.5 h. The average amount of blood loss was 1330 mL. Five patients (28%) had infective morbidity.Conclusion:  Condom catheter balloon is effective in controlling non‐traumatic PPH in 94% cases. It is effective, simple to use, easily available and is a cheap modality to manage non‐traumatic postpartum hemorrhage, especially in limited resource settings.
5′‐Ectonucleotidase‐knockout mice lack non‐REM sleep responses to sleep deprivation
Authors: Zielinski Mark R. , Taishi Ping , Clinton James M. , Krueger James M. 
Published: April 2012

AbstractAdenosine and extracellular adenosine triphosphate (ATP) have multiple physiological central nervous system actions including regulation of cerebral blood flow, inflammation and sleep. However, their exact sleep regulatory mechanisms remain unknown. Extracellular ATP and adenosine diphosphate are converted to adenosine monophosphate (AMP) by the enzyme ectonucleoside triphosphate diphosphohydrolase 1, also known as CD39, and extracellular AMP is in turn converted to adenosine by the 5′‐ectonuleotidase enzyme CD73. We investigated the role of CD73 in sleep regulation. Duration of spontaneous non‐rapid eye movement sleep (NREMS) was greater in CD73‐knockout (KO) mice than in C57BL/6 controls whether determined in our laboratory or by others. After sleep deprivation (SD), NREMS was enhanced in controls but not CD73‐KO mice. Interleukin‐1 beta (IL1β) enhanced NREMS in both strains, indicating that the CD73‐KO mice were capable of sleep responses. Electroencephalographic power spectra during NREMS in the 1.0–2.5 Hz frequency range was significantly enhanced after SD in both CD73‐KO and WT mice; the increases were significantly greater in the WT mice than in the CD73‐KO mice. Rapid eye movement sleep did not differ between strains in any of the experimental conditions. With the exception of CD73 mRNA, the effects of SD on various adenosine‐related mRNAs were small and similar in the two strains. These data suggest that sleep is regulated, in part, by extracellular adenosine derived from the actions of CD73.
The absence of voiding symptoms in men with a prostate‐specific antigen (PSA) concentration of ≥3.0 ng/mL is an independent risk factor for prostate cancer: results from the Gothenburg Randomized Screening Trial
Authors: Frånlund Maria , Carlsson Sigrid , Stranne Johan , Aus Gunnar , Hugosson Jonas 
Published: April 2012

Study Type – Prognostic (RCT)Level of Evidence 1bWhat's known on the subject? and What does the study add?There are only a few studies and no consensus concerning the relationship between LUTS and prostate cancer. This paper focuses on 2353 men with an elevated PSA level within the Gothenburg Randomized Screening Trial who underwent biopsy and answered questions regarding LUTS. The main conclusion was that the absence of voiding symptoms is an independent risk factor for prostate cancer detection.OBJECTIVE
To investigate whether men with obstructive voiding symptoms are at increased risk for being diagnosed with prostate cancer within the Gothenburg randomized population‐based prostate cancer screening trial.
SUBJECTS AND METHODS
In 1995, 20 000 men born between 1930 and 1944 were randomly selected from the population register and randomized to either a screening group (10 000), invited for total prostate‐specific antigen (tPSA) testing every second year until they reached an upper age‐limit pending between 67 and 71 years, or to a control group not invited (10 000).
Men with a PSA concentration of ≥3.0 ng/mL were offered further examination with prostate biopsies. Immediately before the physician's examination a self‐administered, study‐specific questionnaire was completed including one question concerning obstructive voiding symptoms.
Multivariate logistic regression modelling was used to estimate odds ratios (ORs) for associations of age, tPSA, free/total PSA (f/tPSA) ratio, prostate volume and the presence of voiding symptoms in prostate cancer risk. A P < 0.05 was considered statistically significant.
RESULTS
Between 1995 and 2010 there were 2590 men who had an elevated PSA concentration (≥3.0 ng/mL) at least once during the study. Of these, 2353 men (91%) accepted further clinical examination with transrectal ultrasonography (TRUS) and prostate biopsies. In all, 633/2353 men had prostate cancer (27%) on biopsy and 1720/2353 men (73%) had a benign pathology.
Men with prostate cancer reported a lower frequency of voiding symptoms (24% vs 31%, P < 0.001), independent of age and locally advanced tumours (T2b–T4). In the multivariate logistic regression model increasing age and tPSA were positively associated with prostate cancer while prostate volume, f/tPSA ratio and the presence of voiding symptoms were all inversely associated with the risk of detecting prostate cancer in a screening setting. This inverse association of voiding symptoms and prostate cancer detection was restricted to men with large prostates (>37.8 mL); 15% in men with voiding symptoms vs 22% in asymptomatic men (P < 0.001).
CONCLUSION
The presence of voiding symptoms should not be a decision tool for deciding which men with an elevated PSA concentration should be offered biopsies of the prostate.
Bland thrombus association with tumour thrombus in renal cell carcinoma: analysis of surgical significance and role of inferior vena caval interruption
Authors: Ayyathurai Rajinikanth , Garcia‐Roig Michael , Gorin Michael A. , González Javier , Manoharan Murugesan , Kava Bruce R. , Soloway Mark S. , Ciancio Gaetano 
Published: April 2012

Study Type – Therapy (case series)Level of Evidence 4What's known on the subject? and What does the study add?The surgical implications of renal cell carcinoma with coexisting bland and tumour thrombi of the inferior vena cava is not well described. In this study we review our experience managing these tumours. On multivariate analysis, we found that the presence of bland thrombus was associated with an increased need for surgical interruption of the inferior vena cava.OBJECTIVE
To study the role of interruption of the inferior vena cava (IVC) in patients with renal cell carcinoma (RCC) and associated bland and tumour thrombi.
METHODS
We reviewed 129 consecutive patients with the preoperative diagnosis of RCC with tumour thrombus who underwent radical nephrectomy and tumour thrombectomy in one academic institution between May 1997 and February 2011.
RESULTS
Percentages of patients with levels I, II, III and IV tumour thrombus were 29%, 13%, 48% and 9%, respectively.
The perioperative mortality rate was 2.3%. There were 29 (22%) perioperative complications recorded.
In all, 19 patients underwent surgical interruption of the IVC by ligation or segmental resection, including one level II, 14 level III and four level IV thrombi.
A total of 15 patients (12%) had bland thrombus associated with the tumour thrombus; four of these underwent intraoperative IVC filter placement and eight underwent surgical IVC interruption.
Advanced level of tumour thrombus was the only significant factor predicting association of bland thrombus (odds ratio [OR]= 2.09, 95% confidence interval [CI]: 1.082–4.037, P= 0.028).
On multivariate analysis, level of thrombus (OR = 3.1, 95% CI: 1.30–7.74, P= 0.011) and association of bland thrombus (OR = 9.07, 95% CI: 2.42–34.01, P= 0.001) were significant factors for IVC interruption.
CONCLUSIONS
Surgical interruption of the IVC is a feasible option in selected patients with chronic IVC obstruction. Association of bland thrombus with tumour thrombus should alert the surgical team to the potential for a challenging surgery.
Precise preoperative imaging to assess the degree of venous obstruction and to help with differentiation between bland and tumour thrombus is key to achieving a surgical outcome with minimal morbidity.
The correlation between size of renal cell carcinoma and its histopathological characteristics: a single center study of 1867 renal cell carcinoma cases
Authors: Zhang Cuijian , Li Xuesong , Hao Han , Yu Wei , He Zhisong , Zhou Liqun 
Published: April 2012

Study Type – Prognosis (case series)Level of Evidence 4What's known on the subject? and What does the study add?We had known from former studies of RCC that the risks of high grade tumours increased with tumour size and probability of localized tumour decreased with tumour size increasing. Our study had provided large and detailed data about pathologic features of RCC. We also examined the exactly changing of probabilities of different subtypes with diameter increasing and evaluated the effects of hemorrhage, necrosis and cystic degeneration on pathologic subtypes.OBJECTIVE
To investigate the correlation between tumour size and histopathological characteristics of renal cell carcinoma (RCC).
PATIENTS AND METHODS
A total of 1867 patients who underwent surgical operation between January 2002 and March 2010 due to RCC were included. According to 1997 WHO recommendation about Fuhrman nuclear grading of RCC which criteria we used, tumours were stratified by the largest pathologic diameter into 5 groups, the discrepancy of tumour grade between different groups and whether tumour size could predict histological subtype were analyzed.
RESULTS
The largest diameter (mean ±sd) of G1, G2, and G3 tumours were 3.27 ± 1.46 cm,4.87 ± 2.23 cm, and 7.39 ± 3.11 cm, respectively. The percentage of extracapsular extension tumours in 2 cm or less, 2.1 and 4.0 cm, 4.1 to 7 cm, 7.1 to 10 cm, and more than 10 cm group were 0.5%, 4.3%, 19.8%, 57.9%, and 91.9%, respectively. The distribution of G1 tumours shows a decreasing trend with the diameter becoming larger, while the G3 tumours shows an opposite trend (P < 0.05). Logistic regression analysis predicted that the odds of papillary, chromophobe, and other types vs clear cell decreased with increase in tumour size. If the tumour was complicated with hemorrhage or necrosis, the chance of being chromophobe was higher, while the probability of being papillary and chromophobe decreased when a tumour with cystic degeneration.
CONCLUSION
There was a significant correlation between tumour size and tumour grade and stage; Larger tumours were prone to have higher grade and stage, and the probability of being clear cell carcinoma grew higher as the tumour size increased.
Transient receptor potential vanilloid 1 mediates nerve growth factor‐induced bladder hyperactivity and noxious input
Authors: Frias Barbara , Charrua Ana , Avelino Antonio , Michel Martin C. , Cruz Francisco , Cruz Celia D. 
Published: April 2012

What's known on the subject? and What does the study add?The interaction between the TRPV1 and NGF systems has been addressed only in the context of acute somatic pain. The present study expands this view and indicates that this interaction remains operative and is important as a mechanism for chronic visceral pain and dysfunction. Moreover, it further stresses the need to develop more specific and effective TRPV1 antagonists for clinical use.OBJECTIVES
To explore the role of transient receptor potential vanilloid 1 (TRPV1) in the excitatory effects of chronic administration of nerve growth factor (NGF) on bladder‐generated sensory input and reflex activity.
To explore new therapeutic targets for bladder dysfunction.
MATERIALS AND METHODS
Wild‐type (WT) and TRPV1 knockout (KO) mice received daily intraperitoneal injections of NGF (1 µg/10 g) or saline for a period of 4 days, during which time thermal sensitivity was evaluated daily. On the 5th day, mice were anaesthetized and cystometries were performed. The frequency, amplitude and area under the curve (AUC) of bladder reflex contractions were determined.
c‐Fos expression was evaluated on L6 spinal cord sections of WT and TRPV1 KO mice treated with saline or chronic NGF by immunohistochemistry.
TrkA receptor staining intensity was determined in L6 spinal cord sections and respective dorsal root ganglia of WT and TRPV1 KO mice.
RESULTS
Repeated administration of NGF induced thermal hypersensitivity in WT but not in TRPV1 KO mice.
The frequency of bladder contractions of saline‐treated WT and TRPV1 KO mice was similar, the values respectively being 0.45 ± 0.12/min and 0.46 ± 0.16/min. Treatment with NGF enhanced bladder reflex activity in WT mice to 1.23 ± 0.41/min (P < 0.05). In NGF‐treated KO mice, the frequency of bladder contractions was 0.60 ± 0.05/min. Irrespective of treatment, no differences were observed in the amplitude of bladder contractions of WT and TRPV1 KO mice. The AUC was significantly increased in NGF‐treated WT‐mice, when compared with saline‐treated WT‐mice. No changes were found in AUC of saline‐treated and NGF‐treated TRPV1 KO mice.
Chronic administration of NGF resulted in a significant increase of spinal c‐Fos expression in WT mice (P < 0.05 vs KO animals), but not in TRPV1 KO animals.
TrkA expression was similar in WT and TRPV1 KO mice.
CONCLUSIONS
NGF‐induced bladder overactivity and noxious input depend on the interaction of NGF with TRPV1.
The lack of bladder overactivity in TRPV1 KO mice treated with NGF does not represent loss of TrkA expression.
TRPV1 is essential for NGF‐driven bladder dysfunction and represents a bottleneck target in bladder pathologies associated with NGF up‐regulation.
Exenatide plus metformin compared with metformin alone on β‐cell function in patients with Type 2 diabetes
Authors: Derosa G. , Franzetti I. G. , Querci F. , Carbone A. , Ciccarelli L. , Piccinni M. N. , Fogari E. , Maffioli P. 
Published: April 2012

Diabet. Med. 29, 1515–1523 (2012)AbstractAim  To quantify how much exenatide added to metformin improves β‐cell function, and to evaluate the impact on glycaemic control, insulin resistance and inflammation compared with metformin alone.Methods  A total of 174 patients with Type 2 diabetes with poor glycaemic control were instructed to take metformin for 8 ± 2 months, then they were randomly assigned to exenatide (5 μg twice a day for the first 4 weeks and forced titration to 10 μg twice a day thereafter) or placebo for 12 months. At 12 months we evaluated anthropometric measurements, glycaemic control, insulin resistance and β‐cell function variables, glucagon, adiponectin, high sensitivity‐C reactive protein and tumour necrosis factor‐α. Before and after 12 months, patients underwent a combined euglycaemic hyperinsulinaemic and hyperglycaemic clamp, with subsequent arginine stimulation.Results  Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA‐IR), and glucagon values and a greater increase in C‐peptide levels, homeostasis model assessment β‐cell function index (HOMA‐β) and adiponectin compared with placebo + metformin. Exenatide + metformin decreased waist and hip circumference, and reduced concentrations of high sensitivity‐C reactive protein and tumour necrosis factor‐α. Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C‐peptide response to glucose and C‐peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin.Conclusion  Exenatide is effective not only on glycaemic control, but also in protecting β‐cells and in reducing inflammation.
Voluntary Disclosure, Manipulation, and Real Effects
Authors: BEYER ANNE , GUTTMAN ILAN 
Published: April 2012

ABSTRACTWe study a model in which managers’ disclosure and investment decisions are both endogenous and managers can manipulate their voluntary reports through (suboptimal) investment, financing, or operating decisions. Managers are privately informed about the value of their firm and have incentives to voluntarily disclose information and manipulate their reports in order to obtain more favorable terms when issuing equity to finance a new profitable investment opportunity. The model shows that treating managers’ disclosure and investment decisions both as endogenous and allowing managers to manipulate their voluntary reports yields qualitatively different predictions from when the disclosure and investment decisions are considered separately and managers cannot engage in manipulation. The model predicts that managers’ disclosure strategy is sometimes characterized by two distinct nondisclosure intervals (contrary to traditional threshold equilibria of voluntary disclosure models) and that managers with intermediate news sometimes forego the new profitable investment opportunity. As such, the paper highlights the importance of considering the interdependencies between firms’ disclosure and investment decisions and provides new empirical predictions.
RATIONAL EXPECTATIONS UNDER CONDITIONS OF COSTLY INFORMATION
Authors: Darby Michael R. 
Published: April 2012

ABSTRACTThis paper analyzes optimal formation of rational expectations where information is costly to obtain to utilize. Under these conditions, expectations normally formed by an estimator will be intermediate between those based on all available information and those which are optimal extrapolative predictors.1 Since the costs of information are likely to vary less than the value of information, this model can explain systematic differences in expectations in markets, such as, labor, for which the value of accuracy of expectations differs between or among buyers and sellers. Similarly, expectations about the same variable may differ between markets where arbitrage is also costly.Section I extends a model due to Theil toanalyzetheeffectsofcostlyinformation. Illustrative applications are discussed in Section II.
Heterogeneous Expectations, Restrictions on Short Sales, and Equilibrium Asset Prices
Authors: JARROW ROBERT 
Published: April 2012

ABSTRACTUnder heterogeneous expectations, the mean–variance model of capital market equilibrium is employed to determine the effect restricting short sales has on equilibrium asset prices. Two equivalent markets differing only with respect to short sale restrictions are compared. It is shown that, in general, risky asset prices can either rise or fall due to short sale constraints. However, under a homogeneity of beliefs for the covariance matrix of future prices, short sale constraints will only increase risky asset prices.
Transaction Costs and the Pricing of Assets
Authors: MAYSHAR JORAM 
Published: April 2012

ABSTRACTThe existence of transaction costs explains why investors do not fully diversify their portfolios. This paper examines the implications of such limited diversification on equilibrium asset prices in the framework of the capital asset pricing model. In the pricing equation obtained here an asset's risk premium depends on a weighted average of its covariance with the market and its own variance.
Efficient Funds in a Financial Market with Options: a New Irrelevance Proposition
Authors: JOHN KOSE 
Published: April 2012

ABSTRACTUnder the same assumptions that Ross used to assert the existence of an efficient fund (on which a spanning set of options can be written) we prove that almost any portfolio is an efficient fund. From a constructive point of view, a randomly chosen vector of portfolio weights yields an efficient fund. When the Ross assumptions are relaxed, a limited notion of efficiency‐maximal efficiency‐is the best attainable. The maximally efficient funds are also everywhere dense in the portfolio space. Some implications are discussed and illustrative examples given.