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Selected AbstractsCerebral oxygenation decreases during exercise in humans with beta-adrenergic blockadeACTA PHYSIOLOGICA, Issue 3 2009T. Seifert Abstract Aim:, Beta-blockers reduce exercise capacity by attenuated increase in cardiac output, but it remains unknown whether performance also relates to attenuated cerebral oxygenation. Methods:, Acting as their own controls, eight healthy subjects performed a continuous incremental cycle test to exhaustion with or without administration of the non-selective beta-blocker propranolol. Changes in cerebral blood flow velocity were measured with transcranial Doppler ultrasound and those in cerebral oxygenation were evaluated using near-infrared spectroscopy and the calculated cerebral mitochondrial oxygen tension derived from arterial to internal jugular venous concentration differences. Results:, Arterial lactate and cardiac output increased to 15.3 ± 4.2 mm and 20.8 ± 1.5 L min,1 respectively (mean ± SD). Frontal lobe oxygenation remained unaffected but the calculated cerebral mitochondrial oxygen tension decreased by 29 ± 7 mmHg (P < 0.05). Propranolol reduced resting heart rate (58 ± 6 vs. 69 ± 8 beats min,1) and at exercise exhaustion, cardiac output (16.6 ± 3.6 L min,1) and arterial lactate (9.4 ± 3.7 mm) were attenuated with a reduction in exercise capacity from 239 ± 42 to 209 ± 31 W (all P < 0.05). Propranolol also attenuated the increase in cerebral blood flow velocity and frontal lobe oxygenation (P < 0.05) whereas the cerebral mitochondrial oxygen tension decreased to a similar degree as during control exercise (delta 28 ± 10 mmHg; P < 0.05). Conclusion:, Propranolol attenuated the increase in cardiac output of consequence for cerebral perfusion and oxygenation. We suggest that a decrease in cerebral oxygenation limits exercise capacity. [source] Folate deficiency in human peripheral blood lymphocytes induces chromosome 8 aneuploidy but this effect is not modified by riboflavinENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2010Juan Ni Abstract Chromosome 8 aneuploidy is a common event in certain cancers but whether folate (F) deficiency induces chromosome 8 aneuploidy is not known. Furthermore the impact of riboflavin (R) deficiency, which may alter activity of a key enzyme in folate metabolism, on these events is unknown. Therefore, the aim of our research was to test the following hypotheses: (a) F deficiency induces chromosome 8 aneuploidy; (b) chromosome 8 aneuploidy is affected by F deficiency to a similar degree as chromosome 17 and (c) R deficiency aggravates the risk of aneuploidy caused by F deficiency. These hypotheses were tested in long-term cultures of lymphocytes from twenty female healthy volunteers (aged 30,48 years). Lymphocytes were cultured in each of the four possible combinations of low (L) and high (H) F (LF, 20 nmol/L, HF 200 nmol/L, respectively) and L and H R (LR 1 nmol/L, HR 500 nmol/L, respectively) media (LFLR, LFHR, HFLR, HFHR) for 9 days. Chromosomes 8 and 17 aneuploidy was measured in mononucleated (MONO) and cytokinesis-blocked binucleated (BN) cells using dual-color fluorescence in situ hybridization (FISH) with fluorescent centromeric probes specific for chromosomes 8 and 17. Culture in LF media (LFLR or LFHR) induced significant and similar increases in frequencies of aneuploidy of chromosomes 8 and 17 (P < 0.001) relative to culture in HF media (HFLR or HFHR). There was no significant effect of R concentration on aneuploidy frequency for either chromosome. We conclude that F deficiency is a possible cause of chromosome 8 aneuploidy. Environ. Mol. Mutagen. 2010. © 2009 Wiley-Liss, Inc. [source] Hearing loss in Fabry disease: data from the Fabry Outcome SurveyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2006S. Hegemann Abstract Background, Hearing loss is a common symptom in Fabry disease, but neither its natural course nor its aetiology has been defined precisely. The aim of this study was to provide a detailed epidemiological description of hearing impairment in patients in the Fabry Outcome Survey (FOS), which is the largest available database of Fabry patients. Materials and methods, Questionnaires were completed by 566 Fabry patients, of whom 316 reported ear-related symptoms. Pure-tone audiograms from 86 patients, performed before starting enzyme replacement therapy, were analysed and compared with age- and sex-specific normal values (International Organization for Standardization, ISO 7029). Results, When compared to an age-matched population (ISO 7029), 74% of patients had a threshold elevated above the 95th centile in at least one tested frequency. All frequencies were affected to a similar degree. However, only 14 patients (16%) were clinically affected by hearing impairment according to the age-independent World Health Organization (WHO) classification (mean threshold at 0·5, 1 and 2 kHz worse than 25 dB). Hearing loss was sensorineural in 63 patients (73%) of whom 7 patients (8%) had also a conductive component. One patient had a purely conductive hearing loss. Episodes of sudden hearing loss seemed to occur more frequently than in the general population. Men were affected earlier and more severely than women. Conclusions, Hearing in Fabry disease is significantly worse than in an age-matched general population but leads to clinically relevant hearing impairment in only 16% of cases. It resembles accelerated presbycusis with an additional Fabry-specific strial-type hearing loss. [source] Effect of two oral doses of 17,-estradiol associated with dydrogesterone on thrombin generation in healthy menopausal women: a randomized double-blind placebo-controlled studyFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2010Alexandra Rousseau Abstract Oral hormone therapy is associated with an increased risk of venous thrombosis. Drug agencies recommend the use of the lowest efficient dose to treat menopausal symptoms for a better risk/ratio profile, although this profile has not been totally investigated yet. The aim of the study was to compare the effect of the standard dose of 17,-estradiol to a lower one on thrombin generation (TG). In a 2-month study, healthy menopausal women were randomized to receive daily 1mg or 2 mg of 17,-estradiol (E1, n = 24 and E2, n = 26; respectively) with 10 mg dydrogesterone or placebo (PL, n = 22). Plasma levels factors VII, X, VIII and II were assessed before and after treatment as well as Tissue factor triggered TG, which allows the investigation of the different phases of coagulation process. The peak of thrombin was higher in hormone therapy groups (E1: 42.39 ± 50.23 nm, E2: 31.08 ± 85.86 nm vs. 10.52 ± 40.63 nm in PL, P = 0.002 and P = 0.01). Time to reach the peak was also shortened (PL: 0.26 ± 0.69 min vs. E1: ,0.26 ± 0.80 min, E2: ,0.55 ± 0.79 min, P <10,3 for both comparisons) and mean rate index of the propagation phase of TG was significantly increased. Among the studied clotting factors, only the levels of FVII were significantly increased after treatment administration. The two doses of 17,-estradiol induced in a similar degree an acceleration of the initiation and propagation phase of tissue factor triggered thrombin generation and a significant increase of FVII coagulant activity. [source] Spatial Effects in Website Adoption by Firms in European RegionsGROWTH AND CHANGE, Issue 1 2009MARGARITA BILLON ABSTRACT The purpose of this paper is to provide empirical evidence on the neighboring effects of Internet adoption as measured by the percentage of firms with their own website in the European regions. This is the first study that explicitly analyzes the role played by spatial effects to explain website adoption for the European case. A set of instruments and techniques commonly used in the spatial econometrics framework is employed to test the hypothesis that proximity matters when explaining Internet adoption by firms. Results show that firms in physically adjacent regions register a similar degree of Internet adoption, confirming the presence in this context of positive spatial dependence. Nevertheless, the spatial effects detected are mainly constrained by national borders. Gross domestic product (GDP) per capita, population density, sectoral composition, and education are positively related to geographic distribution of Internet adoption in the enlarged European Union. In addition, regional disparities in Internet adoption were found to be less important than territorial inequalities in GDP per capita. [source] Aging does not reduce the hepatocyte proliferative response of mice to the primary mitogen TCPOBOPHEPATOLOGY, Issue 4 2004Giovanna M. Ledda-Columbano It has been shown that the magnitude of DNA synthesis and the time at which maximal DNA synthesis occurs after two-thirds partial hepatectomy (PH) is greatly reduced in the liver of aged rodents compared to young animals. This reduction could represent an intrinsic defect in proliferation or a more specialized change in the response to PH. We therefore evaluated the proliferative capacity of hepatocytes in aged animals, following treatment with primary liver mitogens. We show that treatment of 12-month-old CD-1 mice with the hepatomitogen 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) caused an increase in hepatocyte proliferation similar to that seen in young (8-week-old) mice. The labeling index was 82% in the livers of aged mice versus 76% in young animals. Histological observation demonstrated that the number of hepatocytes entering mitoses was similar in both groups; the mitotic indices were 2.5 per thousand and 2.7 per thousand, respectively. Additional experiments showed that the timing of DNA synthesis and M phase were nearly identical in both aged and young mice. Stimulation of hepatocyte DNA synthesis was associated with increased expression of several cell cycle-associated proteins (cyclin D1, cyclin A, cyclin B1, E2F, pRb, and p107); all were comparable in aged mice and young mice. TCPOBOP treatment also increased expression of the Forkhead Box transcription factor m1b (Foxm 1b) to a similar degree in both groups. In conclusion, hepatocytes retain their proliferative capacity in old age despite impaired liver regeneration. These findings suggest that therapeutic use of mitogens would alleviate the reduction in hepatocyte proliferation observed in the elderly. (Hepatology 2000;40:981,988). [source] Alcoholic fatty liver differentially induces a neutrophil-chemokine and hepatic necrosis after ischemia-reperfusion in ratHEPATOLOGY, Issue 2 2000Shinwa Yamada M.D. Primary graft nonfunction of steatotic liver allograft is one of the factors causing shortage of donor livers. Ischemia/reperfusion (I/R) injury is an important contributory factor to primary graft nonfunction. In this study, we investigated the complex chain of events from transcription factor activation to necrosis through cytokine induction and apoptosis in steatotic rat liver after warm I/R. Rats with alcoholic or nonalcoholic fatty liver were subjected to hepatic warm I/R and compared with control rats. Rats fed an ethanol diet for 6 to 8 weeks developed severe hepatic necrosis accompanied by increased neutrophil recruitment after I/R, compared with rats with nonalcoholic fatty liver or control. Hepatic apoptosis as assessed by DNA fragmentation at 4 hours after I/R, however, increased to a similar degree in each of the 2 fatty liver models compared with the control. Alcoholic fatty liver exposed to I/R showed a rapid increase in nuclear factor-,B (NF-,B) binding activity at 1 hour after I/R, which preceded an increased expression of tumor necrosis factor , (TNF-,) and cytokine-induced neutrophil chemoattractant-1 (CINC-1). In contrast, nonalcoholic fatty liver did not show such potentiation of either NF-,B activation or cytokine induction after I/R. Our results have indicated that alcoholic fatty liver may differentially induce CINC-1 production and hepatic necrosis after I/R. Furthermore, our results suggest that apoptosis per se does not always lead to necrosis in the liver following I/R. [source] Financial Reporting Regulation: The Case of Converging Canadian and International Accounting and Auditing Standards,/LA RÉGLEMENTATION DE L'INFORMATION FINANCIÈRE: LA CONVERGENCE DES NORMES CANADIENNES ET INTERNATIONALES DE COMPTABILITÉ ET DE VÉRIFICATIONACCOUNTING PERSPECTIVES, Issue 1 2008Kathryn Bewley ABSTRACT This paper provides a descriptive analysis of the differences between existing Canadian accounting and auditing standards and the corresponding international standards that Canadian standard-setters have decided to converge them with, at the time of the decisions to converge. The descriptive analysis is based on two reconciliation documents published by the standard-setting boards of the Canadian Institute of Chartered Accountants. The main contributions of the paper are to outline and analyze the differences systematically in the context of prior research on financial reporting regulation and the impact of internationalization of accounting and auditing standards, and to identify key areas of difference that are likely to have the greatest impact on preparers, auditors, and users of Canadian financial statements. The results do not indicate that Canada is moving to a significantly more or less restrictive accounting measurement regime, but it appears that there will be greater disclosure detail required under international accounting standards than under existing Canadian standards. The key accounting difference relates to appraisal values for tangible and intangible assets that are permitted in international standards but not currently in their Canadian counterparts. The findings for auditing standards suggest that international and Canadian auditing standards impose a similar set of requirements on the audit function, and provide a similar degree of detailed application guidance. Differences in standards for the auditor's report and for management's written representations to the auditor are the most significant changes for audit practice in Canada. RÉSUMÉ L'auteure présente une analyse descriptive des éléments qui différencient les normes canadiennes de comptabilité et de vérification existantes et les normes internationales correspondantes vers lesquelles les normes canadiennes devraient converger, selon la position adoptée par les normalisateurs canadiens au moment de trancher la question. L'analyse descriptive se fonde sur deux documents de conciliation publiés par les conseils de normalisation de l'Institut Canadien des Comptables Agréés. Le principal apport de la présente étude est double: elle propose une description et une analyse systématiques des différences entre les normes dans le contexte des recherches précédentes sur la réglementation de l'information financière et l'incidence de l'internationalisation des normes de comptabilité et de vérification, et elle recense les principales sphères dans lesquelles les normes présentent des différences susceptibles d'avoir les conséquences les plus importantes pour les auteurs de l'information, les vérificateurs et les utilisateurs des états financiers canadiens. Selon les résultats de l'étude, le régime de mesure comptable vers lequel s'oriente le Canada ne présente pas un caractère qui serait plus ou moins restrictif, mais tout indique que les exigences en ce qui a trait au détail de l'information à fournir seront plus grandes sous le régime des normes comptables internationales que sous celui des normes canadiennes existantes. La principale différence relevée au chapitre de la comptabilité se rapporte aux valeurs d'expertise des actifs corporels et incorporels qui sont permises dans les normes internationales mais ne le sont pas dans les normes canadiennes actuelles. Quant à la vérification, il semble que les normes internationales et canadiennes imposent à la fonction de vérification un ensemble d'exigences similaires et contiennent des directives d'application d'une précision analogue. Les différences dans les normes relatives au rapport du vérificateur et aux déclarations écrites de la direction sont les changements les plus importants pour l'exercice de la vérification au Canada. [source] Evaluation of molecular forms of prostate-specific antigen and human kallikrein 2 in predicting biochemical failure after radical prostatectomyINTERNATIONAL JOURNAL OF CANCER, Issue 3 2009Sven Wenske Abstract Most pretreatment risk-assessment models to predict biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer rely on total prostate-specific antigen (PSA), clinical stage, and biopsy Gleason grade. We investigated whether free PSA (fPSA) and human glandular kallikrein-2 (hK2) would enhance the predictive accuracy of this standard model. Preoperative serum samples and complete clinical data were available for 1,356 patients who underwent RP for localized prostate cancer from 1993 to 2005. A case-control design was used, and conditional logistic regression models were used to evaluate the association between preoperative predictors and BCR after RP. We constructed multivariable models with fPSA and hK2 as additional preoperative predictors to the base model. Predictive accuracy was assessed with the area under the ROC curve (AUC). There were 146 BCR cases; the median follow up for patients without BCR was 3.2 years. Overall, 436 controls were matched to 146 BCR cases. The AUC of the base model was 0.786 in the entire cohort; adding fPSA and hK2 to this model enhanced the AUC to 0.798 (p = 0.053), an effect largely driven by fPSA. In the subgroup of men with total PSA ,10 ng/ml (48% of cases), adding fPSA and hK2 enhanced the AUC of the base model to a similar degree (from 0.720 to 0.726, p = 0.2). fPSA is routinely measured during prostate cancer detection. We suggest that the role of fPSA in aiding preoperative prediction should be investigated in further cohorts. © 2008 Wiley-Liss, Inc. [source] Evidence for heritable predisposition to epigenetic silencing of MLH1INTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Huiping Chen Abstract Epigenetic silencing of MLH1 is the most common cause of defective DNA mismatch repair in endometrial and colorectal cancers. We hypothesized that variation in the MLH1 gene might contribute to the risk for MLH1 methylation and epigenetic silencing. We undertook a case-control study to test for the association between MLH1 variants and abnormal MLH1 methylation. Eight MLH1 SNPs were typed in the normal DNA from women with endometrial carcinoma. For these studies, the cases were women whose cancers exhibited MLH1 methylation (N = 98) and the controls were women whose cancers had no MLH1 methylation (N = 219). One MLH1 SNP, rs1800734, located in the MLH1 CpG island at ,93 from the translation start site, was significantly associated with MLH1 methylation as were age at diagnosis and patient body mass index. In validation experiments, a similar-sized cohort of colorectal carcinoma patients (N = 387) showed a similar degree of association with the ,93 SNP; a smaller cohort of endometrial carcinomas (N = 181) showed no association. Combining all 3 cohorts showed an odds ratio of 1.61 (95% CI: 1.20,2.16) for the AA or AG vs. GG genotype at the ,93 SNP. Identification of risk alleles for MLH1 methylation could shed light on mechanisms of epigenetic silencing and may ultimately lead to new approaches to the prevention or treatment of malignancies associated with MLH1 inactivation. © 2007 Wiley-Liss, Inc. [source] Prospective cohort study comparing sequential organ failure assessment and acute physiology, age, chronic health evaluation III scoring systems for hospital mortality prediction in critically ill cirrhotic patientsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2006Y-C Chen Summary The aim of the study was to evaluate the usefulness of sequential organ failure assessment (SOFA) and acute physiology, age, chronic health evaluation III (APACHE III) scoring systems obtained on the first day of intensive care unit (ICU) admission in predicting hospital mortality in critically ill cirrhotic patients. The study enrolled 102 cirrhotic patients consecutively admitted to ICU during a 1-year period. Twenty-five demographic, clinical and laboratory variables were analysed as predicators of survival. Information considered necessary to calculate the Child,Pugh, SOFA and APACHE III scores on the first day of ICU admission was also gathered. Overall hospital mortality was 68.6%. Multiple logistic regression analysis revealed that mean arterial pressure, SOFA and APACHE III scores were significantly related to prognosis. Goodness-of-fit was good for the SOFA and APACHE III models. Both predictive models displayed a similar degree of the best Youden index (0.68) and overall correctness (84%) of prediction. The SOFA and APACHE III models displayed good areas under the receiver,operating characteristic curve (0.917 ± 0.028 and 0.912 ± 0.029, respectively). Finally, a strong and significant positive correlation exists between SOFA and APACHE III scores for individual patients (r2 = 0.628, p < 0.001). This investigation confirms the grave prognosis for cirrhotic patients admitted to ICU. Both SOFA and APACHE III scores are excellent tools to predict the hospital mortality in critically ill cirrhotic patients. The overall predictive accuracy of SOFA and APACHE III is superior to that of Child,Pugh system. The role of these scoring systems in describing the dynamic aspects of clinical courses and allocating ICU resources needs to be clarified. [source] The Logic of Access to the European Parliament: Business Lobbying in the Committee on Economic and Monetary AffairsJCMS: JOURNAL OF COMMON MARKET STUDIES, Issue 3 2004Pieter Bouwen This article is an attempt to test empirically a theory of access that investigates the logic behind the lobbying behaviour of business interests in the European Parliament. The theoretical framework tries to explain the degree of access of different organizational forms of business interest representation (companies, associations and consultants) to the supranational assembly in terms of a theory of the supply and demand of ,access goods'. On the basis of 14 exploratory and 27 semi-structured interviews, the hypotheses are checked in the Committee on Economic and Monetary Affairs (ECON) of the European Parliament. Surprisingly, European and national associations enjoy a similar degree of access to the Parliament. Individual companies and consultants have a much lower degree of access than the two collective forms of interest representation. In the conclusion, these results are analysed in the light of the existing literature on party cohesion and coalition formation in the European Parliament. [source] Re-induction of obese body weight occurs more rapidly and at lower caloric intake in beaglesJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3 2010D. Nagaoka Summary For the purpose of investigating the mechanism of obesity-induction/re-induction including weight-cycling in beagles, a study was conducted using commercially available dog food combined with human food to mimic at home-snacking and diet-supplementation behaviours. Adult female beagles, which had free access to water and exercise, were used (n = 9). All dogs were initially offered two times their daily calculated number of calories using a dry extruded diet plus blend of canola and soybean oils and allowed to eat ad libitum. After 3 weeks, Pecan shortbread cookies were added to the diet mixture. Obesity was induced during a 19-week period with 1875,2250 kcal/day consumed, on average, during this period. The dogs were then subjected to a weight-loss regimen while consuming 490,730 kcal/day. After weight loss, a similar degree of obesity was re-induced for 17 weeks even though dogs consumed only 1125,1250 kcal/day. Body weight, body condition scores, kcal consumption and food efficiency were recorded. Results indicated that less time and fewer kcal were required to re-induce the same degree of obesity compared with the initial obesity induction. Human snack foods appeared to stimulate appetite and thus contribute to the obese state. Food efficiency was also increased during the obesity-reinduction period compared with the induction period. This information may help pet owners better understand the need to limit table scraps and human-type food snacks in dogs prone to obesity as well as weight maintenance after weight loss. [source] Sublethal effects of chlorfluazuron on reproductivity and viability of Spodoptera litura (F. ) (Lep., Noctuidae)JOURNAL OF APPLIED ENTOMOLOGY, Issue 5-6 2000F. Perveen To clarify the sublethal effects of chlorfluazuron on reproductivity and viability of common cutworm, Spodoptera litura, some experiments were conducted under laboratory conditions. The LD50 was found to be 12.0 ng/larva when evaluated up to pupation and 9.9 ng/larva up to adult emergence. At lethal dosages the development of different instars, moulting to pupae and emergence into adults were found to be more affected. Reduction in the body weight was also observed in the larvae and pupae when treated with a sublethal dose (LD30 : 3.75 ng/larva) and in the adults when treated with sublethal doses (LD10 : 1.00 ng/larva; LD30 : 3.75 ng/larva) as newly moulted fifth instar larvae of S. litura, although the number of matings per female and life span of adult females and males remained unaffected by the same treatments. When sublethal doses were applied only to females or only to males, or both sexes, the average fecundity reduction was up to 35,44%. When only females were treated with sublethal doses, fertility was reduced by 49,58%; when only males were treated fertility was reduced by 65,81% and when both sexes were treated, fertility was reduced by 68,83%. Hatchability was reduced by 22,26% when only females were treated, by 44,66% when only males were treated and by 45,72% when both sexes were treated with LD10 or LD30 doses as newly moulted fifth instars. The results from these observations suggest that the fecundity was reduced to a similar degree when only females or only males or both sexes were treated with LD10 or LD30 doses as newly moulted fifth instars. However the fertility and hatchability were affected more when only males were treated with LD10 and much more when treated with LD30. Currently, work is in progress to find out the main reasons for the sublethal effects of chlorfluazuron on reproductivity and viability. [source] Study of epoxy toughened by in situ formed rubber nanoparticlesJOURNAL OF APPLIED POLYMER SCIENCE, Issue 1 2008Jun Ma Abstract The effect of rubber nanoparticles on mechanical properties and fracture toughness was investigated. Rubber nanoparticles of 2,3 nm were in situ synthesized in epoxy taking advantage of the reaction of an oligomer diamine with epoxy. The chemical reaction was verified by gel permeation chromatography (GPC) and 1HNMR, and the microstructure was characterized by transmission electron microscope. The rubber nanoparticles caused much less Young's modulus deterioration but toughened epoxy to a similar degree in comparison with their peer liquid rubber that formed microscale particles during curing. Fifteen wt % of rubber nanoparticles increased fracture energy from 140 to 840 J/m2 with Young's modulus loss from 2.85 to 2.49 GPa. The toughening mechanism might be the stress relaxation of the matrix epoxy leading to larger plastic work absorbed at the crack tip; there is no particle cavitation or deformation; neither crack deflection nor particle bridging were observed. The compound containing rubber nanoparticles demonstrates Newtonian liquid behavior with increasing shear rate; it shows lower initial viscosity at low shear rate than neat epoxy; this provides supplementary evidence to NMR and GPC result. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Differential effects of dihalogenated and trihalogenated acetates in the liver of B6C3F1 miceJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2001J. Kato-Weinstein Abstract Haloacetates are produced in the chlorination of drinking water in the range 10,100 ,g l,1. As bromide concentrations increase, brominated haloacetates such as bromodichloroacetate (BDCA), bromochloroacetate (BCA) and dibromoacetate (DBA) appear at higher concentrations than the chlorinated haloacetates: dichloroacetate (DCA) or trichloroacetate (TCA). Both DCA and TCA differ in their hepatic effects; TCA produces peroxisome proliferation as measured by increases in cyanide-insensitive acyl CoA oxidase activity, whereas DCA increases glycogen concentrations. In order to determine whether the brominated haloacetates DBA, BCA and BDCA resemble DCA or TCA more closely, mice were administered DBA, BCA and BDCA in the drinking water at concentrations of 0.2,3 g l,1. Both BCA and DBA caused liver glycogen accumulation to a similar degree as DCA (12 weeks). The accumulation of glycogen occurred in cells scattered throughout the acinus in a pattern very similar to that observed in control mice. In contrast, TCA and low concentrations of BDCA (0.3 g l,1) reduced liver glycogen content, especially in the central lobular region. The high concentration of BDCA (3 g l,1) produced a pattern of glycogen distribution similar to that in DCA-treated and control mice. This effect with a high concentration of BDCA may be attributable to the metabolism of BDCA to DCA. All dihaloacetates reduced serum insulin levels. Conversely, trihaloacetates had no significant effects on serum insulin levels. Dibromoacetate was the only brominated haloacetate that consistently increased acyl-CoA oxidase activity and rates of cell replication in the liver. These results further distinguish the effects of the dihaloacetates from those of peroxisome proliferators like TCA. Copyright © 2001 John Wiley & Sons, Ltd. [source] Tuning compounds for electrospray ionization/in-source collision-induced dissociation and mass spectra library searchingJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 9 2001Wolfgang Weinmann Abstract Tuning compounds for positive and negative electrospray ionization (ESI) were tested for the tuning of in-source collision-induced dissociation (ESI/CID) with three types of SCIEX API instruments (API 365, 2000 and 3000) in the single-quadrupole mode. The vacuum interfaces of these instruments differ slightly in geometry, but the principles of ionization and solvent evaporation by nebulizer and curtain gases, orifice and skimmer are identical. For comparison of in-source CID, breakdown curves of haloperidol, paracetamol, metronidazole and metamizole were acquired by increasing the orifice voltages. The API 2000 and 3000 required higher orifice voltages than did the API 365 to induce a similar degree of fragmentation of the protonated or deprotonated molecules to characteristic fragment ions. This increase of orifice voltage could be demonstrated with each of the four compounds tested by a shift of the maxima of the breakdown curves to higher orifice voltages. A procedure with three collision energy (CE) levels for drug identification with a mass spectra library set up with an API 365 therefore required an adjustment of the orifice voltages to higher values when being transferred to an API 2000 or API 3000. The corresponding orifice voltages for the three instruments were 20/50/80 V (API 365), 30/90/130 V (API 2000) and 40/80/120 V (API 3000). However, a change in orifice voltage of ±10 V (with the API 2000 and 3000) hardly influenced the fit values of a library search for each single CE level. For adjusting orifice voltages with different instruments, a tuning procedure with haloperidol and paracetamol is presented. With this tuning procedure an ESI/CID mass spectra library set up for API 365 and API 150 could also be used for drug identification with an API 2000 and an API 3000 with good library search results. Copyright © 2001 John Wiley & Sons, Ltd. [source] All CVB serotypes and clinical isolates induce irreversible cytopathic effects in primary cardiomyocytesJOURNAL OF MEDICAL VIROLOGY, Issue 2 2005Jeonghyun Ahn Abstract Coxsackievirus B3 (CVB3) has been identified as a major causative agent of acute and chronic myocarditis, but the involvement of other CVB serotypes in myocarditis has not been investigated. To dissect the pathological properties of different CVB serotypes toward primary cardiomyocytes, we tested their effects on primary cardiomyocyte cultures from neonatal rats. Morphological abnormalities were examined by both light and fluorescence microscopy after Hoechst 33342 staining, and loss of cell viability was estimated by MTT assay. All six CVB serotypes showed a similar degree of severe toxicity toward primary cardiomyocytes. CVB clinical isolates had cytopathic effects (CPEs) similar to those of their respective CVB reference strains. Within 1,2 days of infection with multiplicities of infection MOI 50, the cells began to experience morphological changes including cell shrinkage, rounding-up, and slight nuclear condensation. The irreversible loss of cell viability was readily observed within 3,5 days following virus infection. These results suggest that all six CVB serotypes induce direct, irreversible toxicity towards cardiomyocytes, which eventually leads to the death of infected cells. These findings indicate that the variations in CVB serotype are not the limiting factor determining the susceptibility of cardiomyocytes to CVB infection. J. Med. Virol. 75:290,294, 2005. © 2004 Wiley-Liss, Inc. [source] Sex Differences in the Distribution and Abundance of Androgen Receptor mRNA-Containing Cells in the Preoptic Area and Hypothalamus of the Ram and EweJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2004C. J. Scott Abstract Rams and ewes show a negative-feedback response to peripheral treatment with testosterone, with both sexes having a similar degree of suppression in luteinizing hormone (LH) secretion during the breeding season. At least part of the action of testosterone to suppress gonadotropin-releasing hormone/LH secretion is exerted via interaction with an androgen receptor. The distribution of androgen receptor-containing cells in the hypothalamus has been described for the ram, but similar studies have not been performed in the ewe. In the present study, we tested the hypothesis that levels of androgen receptor mRNA expression in the preoptic area and hypothalamus would be similar in rams and ewes. Perfusion-fixed brain tissue was obtained from adult Romney Marsh ewes (luteal phase) and rams during the breeding season (n = 4/sex). Androgen receptor mRNA expression was quantified in hypothalamic sections by in situ hybridization using an 35S-labelled riboprobe and image analysis. Hybridizing cells were found in the medial preoptic area, bed nucleus of the stria terminalis, anterior hypothalamic area, ventromedial nucleus, arcuate nucleus and premamillary nucleus. The level of androgen receptor mRNA expression was higher in rams than ewes in the rostral preoptic area, caudal preoptic area and rostral portion of the bed nucleus of the stria terminalis, with no sex difference in other regions. The preoptic area and bed nucleus of the stria terminalis are important for reproductive behaviour and the sex differences in androgen receptor mRNA expression at these levels may relate to this. The high level of androgen receptor mRNA expression in the basal hypothalamus, with no sex difference, is consistent with the role of this region in the regulation of gonadotropin secretion. [source] Alcohol and Cognitive Function: Assessment in Everyday Life and Laboratory Settings Using Mobile PhonesALCOHOLISM, Issue 12 2009Brian Tiplady Background:, Mobile phone (cellphone) technology makes it practicable to assess cognitive function in a natural setting. We assessed this method and compared impairment of performance due to alcohol in everyday life with measurements made in the laboratory. Methods:, Thirty-eight volunteers (20 male, aged 18,54 years) took part in the everyday study, completing assessments twice a day for 14 days following requests sent by text messages to the mobile phone. Twenty-six of them (12 male, aged 19,54) took part in a subsequent two-period crossover lab study comparing alcohol with no alcohol (placebo). Results:, Everyday entries with 5 or more units of alcohol consumed in the past 6 hours (inferred mean blood alcohol concentration 95 ml/100 ml) showed higher scores for errors in tests of attention and working memory compared with entries with no alcohol consumed that day. Response times were impaired for only 1 test, sustained attention to response. The laboratory comparison of alcohol (mean blood alcohol concentration 124 mg/100 ml) with placebo showed impairment to both reaction time and error scores for all tests. A similar degree of subjective drunkenness was reported in both settings. Conclusions:, We found that mobile phones allowed practical research on cognitive performance in an everyday life setting. Alcohol impaired function in both laboratory and everyday life settings at relevant doses of alcohol. [source] Radiation-grafted ion-exchange membranes: Influence of the initial matrix on the synthesis and structureJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 17 2001Nadia Walsby Abstract A series of commercial fluoropolymer films was irradiated with an electron beam, grafted with styrene, and sulfonated. The influence of the initial fluoropolymer on the grafting yields and the properties of the grafted and sulfonated membranes were investigated. The same synthesis procedure can be followed for most fluoropolymers and samples with a similar degree of grafting, and a homogenous polystyrene distribution can be prepared by varying the absorbed dose. The main difference among different fluoropolymer-based membranes is the water uptake from liquid water that has a roughly linear dependence on the crystallinity of the sample. The more amorphous the initial material, the greater the water uptake. Mechanical properties of the membranes at 50% relative humidity differ less than those of the starting materials and are comparable to those of Nafion® 105. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3008,3017, 2001 [source] Supercritical fluid extraction of ecdysterone from the roots of Achyranthes bidentata BL.JOURNAL OF SEPARATION SCIENCE, JSS, Issue 8 2008Yizhe Zheng Abstract Ecdysterone has been found in a great many plants and animals and has some valuable pharmaceutical properties. The present study was conducted to investigate optimal conditions for the extraction of the compound by supercritical fluid extraction from the roots of Achyranthes bidentata BL. An orthogonal array design (OAD), OA9(34), was employed as a chemometric method for optimization of the extraction of ecdysterone from the herbal medicine. Four parameters, namely, pressure and temperature of the supercritical fluid, the dynamic extraction time, and the flow rate of dimethyl sulfoxide, were studied and optimized by a three-level OAD. Determinations of the extracts were performed by high-performance liquid chromatography. The effects of the parameters were studied using analysis of variance. The results shown that the yield of ecdysterone could be influenced by the four parameters to a similar degree. The yield for DMSO-modified supercritical CO2 was in the range from 0.65 to 1.03 mg/g under the selected conditions. In comparison with methanol-modified supercritical CO2 and Soxhlet extraction, a higher yield was obtained when DMSO-modified supercritical CO2 was used. [source] Metabolic and histological features of non-alcoholic fatty liver disease patients with different serum alanine aminotransferase levelsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009V. W.-S. Summary Background, Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. Serum alanine aminotransferase (ALT) level is commonly performed to monitor NAFLD patients, but its clinical relevance is unclear. Aim, To evaluate the metabolic and histological features of NAFLD patients with different ALT levels. Methods, A total of 173 consecutive patients with biopsy-proven NAFLD were studied. Patients with persistently normal ALT and those with abnormal ALT were compared. Results, Patients with persistently normal ALT had lower steatosis grade than patients with abnormal ALT, but they had similar degree of lobular inflammation, ballooning and fibrosis. Among 19 patients with ALT below 0.5 times the upper limit of normal (ULN) at the time of liver biopsies, 8 (42%) and 3 (16%) had steatohepatitis and significant fibrosis respectively. The within-patient coefficient of variance was similarly high in patients with simple steatosis and steatohepatitis (33.5). Age and glucose, but not ALT, were independent factors associated with significant fibrosis. Discussion, Metabolic factors, but not ALT, are associated with histological severity. Patients with ALT < 0.5 × ULN may still have non-alcoholic steatohepatitis (NASH) and significant fibrosis. Evaluation of NAFLD patients should be based on metabolic risk factors, but not ALT level. [source] The efficiency of laser for the treatment of Ehlers,Danlos syndromeLASERS IN SURGERY AND MEDICINE, Issue 2 2005Daniel F. Mueller MD Abstract Background and Objectives A 61-year-old woman presented herself with extensive elastosis of the facial skin caused by Ehlers,Danlos syndrome (EDS). Study Design/Materials and Methods Two laser skin resurfacings reduced the wrinkles significantly better than the two preceding conventional facelifts. For the first time, we have been able to compare two treatments with different laser systems on the same patient. The first treatment was performed with a high energy pulsed CO2 laser, which has been in use for 8 years. The second treatment was performed by us using the latest technology CO2/erbium:YAG combination laser. Results/Conclusion Resulting in a similar degree of wrinkle reduction, the treatment with the combination laser markedly reduced the duration of the healing process and erythema phase. Lasers Surg. Med. 36:76,78, 2005. © 2005 Wiley-Liss, Inc. [source] Dysfunction of oesophageal motility in Helicobacter pylori -infected patients with reflux oesophagitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2001J. C. Y. Wu Background: Helicobacter pylori infection has been suggested to be protective against gastro-oesophageal reflux disease. However, a significant proportion of patients with gastro-oesophageal reflux disease are infected by H. pylori. Aim: To study oesophageal motor function in H. pylori -infected patients with reflux oesophagitis. Methods: Patients with erosive reflux oesophagitis were recruited prospectively for stationary oesophageal manometry and 24-h ambulatory oesophageal pH monitoring. H. pylori status was determined by biopsy urease test. Non-reflux volunteers were recruited as controls. Results: Seventy-four patients with erosive oesophagitis (34 H. pylori -positive, 40 H. pylori -negative) and 48 non-reflux patient controls (22 H. pylori -positive, 26 H. pylori -negative) were recruited. There was no difference in severity of oesophagitis (median grade, 1; P=0.53) or oesophageal acid exposure (total percentage time oesophageal pH < 4, 7.6% vs. 6.8%; P=0.57) between H. pylori -positive and H. pylori -negative groups. Compared to H. pylori -negative patients, H. pylori -positive patients had significantly lower basal lower oesophageal sphincter pressure (12.2 mmHg vs. 15.3 mmHg; P=0.03) and amplitude of distal peristalsis (56.9 mmHg vs. 68.4 mmHg; P=0.03). Ineffective oesophageal motility (14% vs. 7%; P=0.02) and failed oesophageal peristalsis were also significantly more prevalent in H. pylori -positive patients. Conclusions: Among patients with a similar degree of reflux oesophagitis, H. pylori -infected patients have more severe oesophageal dysmotility and lower oesophageal sphincter dysfunction. Oesophageal motor dysfunction probably plays a dominant role in the development of gastro-oesophageal reflux disease in patients with H. pylori infection. [source] Hyperglycemia Stimulates a Sustained Increase in Hydraulic Conductivity In Vivo without Any Change in Reflection CoefficientMICROCIRCULATION, Issue 7 2007RACHEL M. PERRIN ABSTRACT Objective: Increased microvascular permeability contributes to the development of diabetic microvascular complications and diabetic vasculopathy is correlated with blood glucose levels. The mechanisms underlying increased permeability, however, are poorly understood. Methods: The Landis-Michel technique was used to measure water permeability (hydraulic conductivity, Lp) and macromolecular permeability (reflection coefficient, ,) of exchange capillaries in frogs and rats. Results: Dialysed normoglycemic plasma from diabetic patients had no effect on Lp. The same plasma with 20 mM glucose increased hydraulic conductivity from (mean ± SEM × 10,7 cm · s,1· cm H2O,1) 5.73 ± 2.01 to 13.09 ± 2.67 (P < .01). Nondiabetic control plasma did not affect Lp, but addition of 20 mM glucose increased Lp to a similar degree. The effect of glucose alone was examined. Glucose at 20 mM increased Lp, from 2.82 ± 0.61 to 4.71 ± 1.35 × 10, 7 cm · s, 1· cm H2O,1 (P = .002, n = 13). A similar increase was seen in rat mesenteric microvessels, from 1.04 ± 0.40 in control perfusions to 2.18 ± 0.56, P < .05. The microvascular macromolecular reflection coefficient in all the above experiments was unaltered. The use of specific inhibitors indicated that the glucose-induced increased Lp did not appear to be mediated through protein kinase C (PKC), free radical generation, glucose metabolism, or albumin glycation. Conclusions: These data suggest that hyperglycemia induced increased apparent protein permeability may be secondary to a glucose-mediated change in macromolecular convective flux rather than any change in protein permeability per se. The authors speculate that the increased microvascular permeability to water in vivo is mediated by direct interaction of glucose with the endothelial cells (perhaps with the glycocalyx). [source] Excessive dopamine neuron loss in progressive supranuclear palsyMOVEMENT DISORDERS, Issue 4 2008Karen E. Murphy BSc(Hons) Abstract Progressive supranuclear palsy (PSP) and Parkinson's disease (PD) differ in their response to dopaminergic replacement therapies, despite having a similar degree of neuronal degeneration in the dopaminergic substantia nigra. We observed more widespread dopamine neuron loss in the extranigral A10 midbrain cell groups in PSP compared with PD. These cell groups innervate subcortical and cortical regions and may be required for adequate response to levodopa therapy. © 2007 Movement Disorder Society [source] Post inflammatory damage to the enteric nervous system in diverticular disease and its relationship to symptomsNEUROGASTROENTEROLOGY & MOTILITY, Issue 8 2009J. Simpson Abstract:, Some patients with colonic diverticula suffer recurrent abdominal pain and exhibit visceral hypersensitivity, though the mechanism is unclear. Prior diverticulitis increases the risk of being symptomatic while experimental colitis in animals increases expression of neuropeptides within the enteric nervous system (ENS) which may mediate visceral hypersensitivity. Our aim was to determine the expression of neuropeptides within the ENS in diverticulitis (study 1) and in patients with symptomatic disease (study 2). Study 1 , Nerves in colonic resection specimens with either acute diverticulitis (AD, n = 16) or chronic diverticulitis (CD, n = 16) were assessed for neuropeptide expression recording % area staining with protein gene product (PGP9.5), substance P (SP), neuropeptide K (NPK), pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP) and galanin. Study 2 , Seventeen symptomatic and 15 asymptomatic patients with colonic diverticula underwent flexible sigmoidoscopy and multiple peridiverticular mucosal biopsies. Study 1, Neural tissue, as assessed by PGP staining was increased to a similar degree in circular muscle in both AD and CD. The CD specimens showed significant increases in the immunoreactivity of SP, NPK and galanin in both mucosal and circular muscle layer compared with controls. Study 2 , Mucosal histology was normal and PGP9.5 staining was similar between groups however patients with symptomatic diverticular disease demonstrated significantly higher levels of SP, NPK, VIP, PACAP and galanin within the mucosal plexus. Patients with symptomatic diverticular disease exhibit increased neuropeptides in mucosal biopsies which may reflect resolved prior inflammation, as it parallels the changes seen in acute and chronic diverticulitis. [source] Impact of urodynamic based incontinence diagnosis on quality of life in women,,NEUROUROLOGY AND URODYNAMICS, Issue 3 2009Alexandra L. Haessler Abstract Aims To characterize the effect of urodynamic diagnosis on degree of incontinence related bother and health related quality of life in a large, multi-ethnic population of women. Methods Effects of multichannel urodynamic diagnosis, urethral competency, and other patient characteristics on abbreviated Urogenital Distress Inventory (UDI6) and Incontinence Impact Questionnaire (IIQ7) composite scores were analyzed retrospectively. Results Six hundred eleven patients were included. Mean UDI6 and IIQ7 scores were significantly higher among patients with mixed incontinence, detrusor overactivity, urinary stress incontinence with overactive bladder, and negative studies compared to those with stress incontinence without OAB. The relative composite UDI6 and IIQ7 mean scores did not significantly differ between the mixed incontinence, detrusor overactivity, stress incontinence with OAB and negative study groups. UDI6 and IIQ7 scores were significantly higher among stress incontinent patients with intrinsic sphincter deficiency, but similar among mixed incontinent patients with intrinsic sphincter deficiency. Conclusion Urodynamic diagnoses of detrusor overactivity, mixed incontinence, and stress incontinence with overactive bladder are associated with significantly worse incontinence related bother and health related quality of life when compared to those with stress incontinence without OAB. These conditions appear to have similar degree of impact on incontinence related bother and quality of life. Patients presenting with symptoms of incontinence can suffer a similar compromise in quality of life despite a negative MCUD study. Neurourol. Urodynam. 28:183,187, 2009. © 2008 Wiley-Liss, Inc. [source] Crown development in a pioneer tree, Rhus trichocarpa, in relation to the structure and growth of individual branchesNEW PHYTOLOGIST, Issue 4 2006Noriyuki Osada Summary ,,Based on an allometric reconstruction, the structure and biomass-allocation patterns of branches and current-year shoots were investigated in branches of various heights in the pioneer tree Rhus trichocarpa, to evaluate how crown development is achieved and limited in association with height. Path analysis was conducted to explore the effects of light availability, basal height and size of individual branches on branch structure and growth. ,,Branch angle was affected by basal height, whereas branch mass was influenced primarily by light availability. This result suggests that branch structure is strongly constrained by basal height, and that trees mediate such constraints under different light environments. ,,Previous-year leaf area and light availability showed positive effects on current-year stem mass. In contrast, branch basal height and mass negatively affected current-year stem mass. Moreover, the length of stems of a given diameter decreased with increasing branch height. Therefore the cost of biomass investment for a unit growth in length is greater for branches of larger size and at upper positions. ,,Vertical growth rate in length decreased with increasing height. Height-dependent changes in stem allometry and angle influenced the reduction in vertical growth rate to a similar degree. [source] | ||||||||||||||||||||||||||||||||||||||||