Home About us Contact
|
Home About us Contact | ||
|
|
||
R
Kinds of R Terms modified by R Selected AbstractsStereospecificity and stereoselectivity of flobufen metabolic profile in male rats in vitro and in vivo: Phase I of biotransformationCHIRALITY, Issue 10 2001Vladimír Wsól Abstract Flobufen (F) is the original nonsteroidal antiinflammatory drug (NSAID) containing two enantiomers. The aim of this investigation was to elucidate the biotransformation pathway of F at chiral level in phase I of biotransformation. Stereoselectivity and stereospecificity of the respective enzymes were studied in male rats in vitro (microsomal and cytosolic fractions, hepatocytes suspension) and in vivo. The rac -F, (+)-R-F and (,)-S-F were used as substrates. Amounts of F enantiomers, 4-dihydroflobufen diastereoisomers (DHF) and other metabolites (M-17203, UM) were determined with a chiral HPLC method in two chromatographic runs on R,R-ULMO and allyl-terguride bonded columns. Stereoselective biotransformation of the two enantiomers of F was observed at all tested levels and significant bidirectional chiral inversion of enantiomers of F was observed in hepatocytes. Mean enantiomeric ratios of F concentrations (S-/R-), after rac -F incubations, ranging from 1.09 in cytosolic fraction to 18.23 in hepatocytes. Stereospecificity of the respective F reductases was also observed. (2R;4S)-DHF and (2S;4S)-DHF are the principal metabolites of F in microsomes and hepatocytes. Neither DHF diastereoisomers nor M-17203 were found in cytosolic fraction. Only the nonchiral metabolite, M-17203, was found in all urine and feces samples after oral administration of F. Chirality 13:754,759, 2001. © 2001 Wiley-Liss, Inc. [source] Cytomegalovirus prophylaxis with valganciclovir in African,American renal allograft recipients based on donor/recipient serostatusCLINICAL TRANSPLANTATION, Issue 2 2005Scott A Gruber Abstract:, There is a paucity of data examining the efficacy of valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis in kidney transplant patients, particularly with regard to utilization of a risk-stratified dosing regimen. Eighty adult African,American (AA) renal allograft recipients transplanted from November 3, 2001 to May 28, 2003 and followed for 22 ± 8 months received VGC once daily for 90 d post-transplant dosed according to donor/recipient (D/R) serostatus: high risk (D+/R,) received 900 mg (n = 12); moderate risk (D+/R+, D,/R+) received 450 mg (n = 60); and low risk (D,/R,) received no prophylaxis (n = 8). Thymoglobulin or basiliximab was used for induction, and mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus for maintenance immunosuppression. Only six patients (7.5%) developed symptomatic CMV infection diagnosed by pp65 antigenemia, three in the high-risk (25%) and three in the moderate-risk (5%) group (p = 0.02). All patients were on tacrolimus for at least 3 months prior to diagnosis. There were no cases of tissue-invasive disease, resistance to treatment, or recurrence. D+/R, serostatus was the only significant independent predictor for CMV infection using multivariate analysis (odds ratio 10.5; p = 0.04). Thymoglobulin induction was not associated with CMV infection. None of 43 patients who were exposed to sirolimus for >30 d developed CMV infection, vs. six of 37 who were not (p = 0.006). We conclude that VGC dosed according to D/R serostatus provides safe and effective CMV prophylaxis in AA renal allograft recipients. [source] Inheritance of resistance and cross resistance pattern in indoxacarb-resistant diamondback moth Plutella xylostella L.ENTOMOLOGICAL RESEARCH, Issue 1 2010Sarita NEHARE Abstract Leaf-dip assay of Plutella xylostella against indoxacarb showed that the concentration that produced 50% mortality (LC50) of indoxacarb ranged from 20.1 to 11.9 ppm, with highest in Nasik and lowest levels in Coimbatore strains. In selection studies, the LC50 of indoxacarb was 18.5 ppm at generation 1 (G1), which increased to 31.3-fold (167.8 ppm) resistance after ten exposed generations (G10) as compared to unexposed. The LC50 of quinalphos was 74.4 ppm, which increased to 10.0-fold (631.5 ppm) resistance after G10. The LC50 of cypermethrin resistant strain resulted in an 11.5-fold increase in resistance after G10. In P. xylostella, heritability (h2) after ten generations of selection was estimated at 0.4. The number of generations required for tenfold increase in LC50 (1/R) were 6.7. The response to indoxacarb selection in P. xylostella was 0.2 and the selection differential was estimated as 0.4. The phenotypic standard deviation was 0.2. Reciprocal crosses between indoxacarb-resistant and susceptible strains showed that the inheritance of indoxacarb resistance was autosomal. The degree of heritability (DLC) (0.4, 0.4) indicated incomplete recessive inheritance of indoxacarb resistance. [source] Granulation sensing of first-break ground wheat using a near-infrared reflectance spectrometer: studies with soft red winter wheats,JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 3 2003Melchor C Pasikatan Abstract A near-infrared reflectance spectrometer, previously evaluated as a granulation sensor for first-break ground wheat from six wheat classes and hard red winter (HRW) wheats, was further evaluated for soft red winter (SRW) wheats. Two sets of 35 wheat samples, representing seven cultivars of SRW wheat ground by an experimental roller mill at five roll gap settings (0.38, 0.51, 0.63, 0.75 and 0.88,mm), were used for calibration and validation. Partial least squares regression was applied to develop the granulation models using combinations of four data pretreatments (log(1/R), baseline correction, unit area normalisation and derivatives) and subregions of the 400,1700,nm wavelength range. Cumulative mass of size fraction was used as reference value. Models that corrected for path length effects (those that used unit area normalisation) predicted the bigger size fractions well. The model based on unit area normalisation/first derivative predicted 34 out of 35 validation spectra with standard errors of prediction of 3.53, 1.83, 1.43 and 1.30 for the >1041, >375, >240 and >136,µm size fractions respectively. Because of less variation in mass of each size fraction, SRW wheat granulation models performed better than the previously reported models for six wheat classes. However, because of SRW wheat flour's tendency to stick to the underside of sieves, the finest size fraction of these models did not perform as well as the HRW wheat models. © 2003 Society of Chemical Industry [source] Preliminary crystallographic study of the Streptococcus agalactiae sortases, sortase A and sortase C1ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 9 2010Baldeep Khare Sortases are cysteine transpeptidases that are essential for the assembly and anchoring of cell-surface adhesins in Gram-positive bacteria. In Streptococcus agalactiae (GBS), the pilin-specific sortase SrtC1 catalyzes the polymerization of pilins encoded by pilus island 1 (PI-1) and the housekeeping sortase SrtA is necessary for cell-wall anchoring of the resulting pilus polymers. These sortases are known to utilize different substrates for pilus polymerization and cell-wall anchoring; however, the structural correlates that dictate their substrate specificity have not yet been clearly defined. This report presents the expression, purification and crystallization of SrtC1 (SAG0647) and SrtA (SAG0961) from S. agalactiae strain 2603V/R. The GBS SrtC1 has been crystallized in three crystal forms and the GBS SrtA has been crystallized in one crystal form. [source] Severe Atrioventricular Decoupling, Uncoupling, and Ventriculoatrial Coupling During Enhanced Atrial Pacing: Incidence, Mechanisms, and Implications for Minimizing Right Ventricular Pacing in ICD PatientsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2008MICHAEL O. SWEENEY M.D. Background: Enhanced AAI/R pacing minimizes right ventricular pacing but may permit or induce AV decoupling (AV-DC) due to unrestricted AV intervals (AVIs). The purpose of this study was to characterize and quantify AVI behavior in a randomized trial of enhanced AAI/R pacing in ICD patients. Methods: One hundred twenty-one patients in the Marquis ICD MVPÔ Study, a randomized 1-month crossover comparison of cumulative% ventricular pacing (Cum%VP) in enhanced AAIR (MVP) vs DDD/R, were analyzed. AV-DC was defined as ,40% AVIs >300 ms; VA coupling (VA-C) was defined as%V-atrial pace (AP) intervals <300 ms. Dynamic AVI behavior and increases in Cum%VP due to AV block (AV uncoupling, AV-UC) were characterized using Holters with real-time ICD telemetry. Results: AV-DC occurred in 17 (14%) of patients. Baseline PR, amiodarone, nighttime, lower rate >60 beats/min, rate response, and Cum%AP were associated with longer AVIs. Logistic regression identified baseline PR (odds ratio [OR]= 1.024, 95% confidence interval [CI] 1.007,1.042; P = 0.005), and Cum%AP (OR = 1.089, 95% CI 1.027,1.154; P = 0.004) as predictors of AV-DC. AV-DC was associated with ,10-fold increases in both Cum%VP (13.6 ± 28.3% vs 1.2 ± 3.9%; P = 0.023) due to transient AV-UC) and VA-C (6.0 ± 17.5% vs 0.5 ± 1.2%, P = 0.028). AV coupling (<40% AVIs >300 ms) was preserved in 104 (86%) patients. Conclusions: AV-DC, VA-C, and AV-UC may be worsened or induced by enhanced AAI/R pacing. Conservative programming of lower rate and rate response should reduce the risk of AV-DC by reducing Cum%AP. [source] Multicenter, Prospective, Randomized Safety and Efficacy Study of a New Atrial-Based Managed Ventricular Pacing Mode (MVP) in Dual Chamber ICDsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2005MICHAEL O. SWEENEY M.D. Background: Ventricular desynchronization caused by right ventricular pacing may impair ventricular function and increase risk of heart failure (CHF), atrial fibrillation (AF), and death. Conventional DDD/R mode often results in high cumulative percentage ventricular pacing (Cum%VP). We hypothesized that a new managed ventricular pacing mode (MVP) would safely provide AAI/R pacing with ventricular monitoring and DDD/R during AV block (AVB) and reduce Cum%VP compared to DDD/R. Methods: MVP RAMware was downloaded in 181 patients with Marquis DR ICDs. Patients were initially randomized to either MVP or DDD/R for 1 month, then crossed over to the opposite mode for 1 month. ICD diagnostics were analyzed for cumulative percentage atrial pacing (Cum%AP), Cum%VP, and duration of DDD/R pacing for spontaneous AVB. Results: Baseline characteristics included age 66 ± 12 years, EF 36 ± 14%, and NYHA Class II,III 36%. Baseline PR interval was 190 ± 53 msec and programmed AV intervals (DDD/R) were 216 ± 50 (paced)/189 ± 53 (sensed) msec. Mean Cum%VP was significantly lower in MVP versus DDD/R (4.1 ± 16.3 vs 73.8 ± 32.5, P < 0.0001). The median absolute and relative reductions in Cum%VP during MVP were 85.0 and 99.9, respectively. Mean Cum%AP was not different between MVP versus DDD/R (48.7 ± 38.5 vs 47.3 ± 38.4, P = 0.83). During MVP overall time spent in AAI/R was 89.6% (intrinsic conduction), DDD/R 6.7% (intermittent AVB), and DDI/R 3.7% (AF). No adverse events were attributed to MVP. Conclusions: MVP safely achieves functional atrial pacing by limiting ventricular pacing to periods of intermittent AVB and AF in ICD patients, significantly reducing Cum%VP compared to DDD/R. MVP is a universal pacing mode that adapts to AVB and AF, providing both atrial pacing and ventricular pacing support when needed. [source] EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivityALLERGY, Issue 10 2007E. Ni, ankowska-Mogilnicka Abstract:, Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common causes of adverse drug reactions. Majority of them are of the hypersensitivity type. The two frequent clinical presentations of aspirin hypersensitivity are: aspirin-induced bronchial asthma/rhinosinusitis (AIA/R) and aspirin-induced urticaria/angioedema (AIU). The decisive diagnosis is based on provocation tests with aspirin, as the in vitro test does not hold diagnostic value as yet. Detailed protocols of oral, bronchial and nasal aspirin provocation tests are presented. Indications, contraindications for the tests, the rules of drug withdrawal and equipment are reviewed. Patient supervision and interpretations of the tests are proposed. [source] Effect of simplification from protease inhibitors to boosted atazanavir-based regimens in real-life conditionsHIV MEDICINE, Issue 9 2010R Rubio Background Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well-tolerated, once-daily protease inhibitor (PI). Few data are available on this agent as a treatment simplification option for patients taking other PIs. Objective The aim of the study was to determine the effectiveness and safety of ATV-containing regimens in patients who have simplified their antiretroviral treatment. Methods SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had undetectable HIV RNA on their current PI-containing therapy and who were switched to an ATV/r-based regimen. Patients underwent a routine physical examination, and data were collected on HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to treatment and patient satisfaction. Results A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29% had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median baseline CD4 count was 514 cells/,L. Median exposure to previous HIV therapy was 8 years, and 32% of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI replaced (62%) and tenofovir+lamivudine /emtricitabine the backbone most used during the study (29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral load. Hyperbilirubinaemia >3 mg/dL and increased alanine aminotransferase levels>200 IU/L were observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in total cholesterol, triglycerides and low-density lipoprotein cholesterol were ,13 mg/dL (,7%; P<0.0001), ,19 mg/dL (,13%; P<0.0001) and ,7 mg/dL (,6%; P=0.021), respectively. Conclusions In a real-world setting, switching from other PIs to ATV/r is a well-tolerated and safe option for improving the lipid profile and for retaining virological response in controlled pretreated patients. [source] Effects of nucleoside reverse transcriptase inhibitor backbone on the efficacy of first-line boosted highly active antiretroviral therapy based on protease inhibitors: meta-regression analysis of 12 clinical trials in 5168 patientsHIV MEDICINE, Issue 9 2009A Hill Objectives Tenofovir/emtricitabine (TDF/FTC) and abacavir/lamivudine (ABC/3TC) are widely used with ritonavir (RTV)-boosted protease inhibitors (PIs) as first-line highly active antiretroviral therapy (HAART), but there is conflicting evidence on their relative efficacy. The ACTG 5202 and BICOMBO trials suggested higher efficacy for TDF/FTC, whereas the HEAT trial showed no efficacy difference between the nucleoside reverse transcriptase inhibitor (NRTI) backbones. Methods A systematic MEDLINE search identified 21 treatment arms in 12 clinical trials of 5168 antiretroviral-naïve patients, where TDF/FTC (n=3399) or ABC/3TC (n=1769) was used with RTV-boosted PI. For each NRTI backbone and RTV-boosted PI, the percentage of patients with viral load <50 HIV-1 RNA copies/mL at week 48 by standardized Intent to Treat, Time to Loss of Virological Failure (ITT TLOVR) analysis were combined using inverse-variance weighting. The effect of baseline HIV RNA, CD4 cell count and choice of NRTI backbone were examined using a weighted analysis of covariance. Results Across all the trials, HIV RNA suppression rates were significantly higher for those with baseline viral load below 100 000 copies/mL (77.2%) vs. above 100 000 copies/mL (70.9%) (P=0.0005). For the trials of lopinavir/ritonavir (LPV/r), atazanavir/ritonavir (ATV/r) and fosamprenavir/ritonavir (FAPV/r) using either TDF/FTC or ABC/3TC, the HIV RNA responses were significantly lower when ABC/3TC was used, relative to TDF/FTC, for all patients (P=0.0015) and for patients with baseline viral load <100 000 copies/mL (70.1%vs. 80.6%, P=0.0161), and was borderline for those with viral load >100 000 copies/mL (67.5%vs. 71.5%, P=0.0523). Conclusions This systematic meta-regression analysis suggests higher efficacy for first-line use of a TDF/FTC NRTI backbone with boosted PIs, relative to use of ABC/3TC. However, this effect may be confounded by differences between the trials in terms of baseline characteristics, patient management or adherence. [source] Studies on amoebae and cysts associated with the isolation of Spongospora subterranea f.sp. subterranea in vitroPLANT PATHOLOGY, Issue 4 2001X.-S. Qu New evidence is presented to support the contention that the amoeba/cyst colonies isolated from surface-sterilized Spongospora subterranea f.sp. subterranea -infected potato tubers and spore balls have a saprophytic phase but are contaminants and not S. subterranea. Amoebae isolated from infected tissues and spore balls formed colonies associated with bacteria on 1% water agar at 18°C and encysted after 5,7 days. These cysts were morphologically distinct from the resting spores of S. subterranea and were formed singly or in a layer, unlike the spore ball (cystosorus) of S. subterranea. Amoebae, cysts and mixtures of amoebae and cysts in primary, secondary and tertiary subcultures failed to infect tomato roots. PCR amplification of DNA from amoebae, cysts and spore balls using the S. subterranea -specific primer pair SsF/R generated a 434-bp product from S. subterranea spore balls only and not from amoebae or cysts. When an amoeba/cyst-specific primer pair AmF/R was designed and used for PCR amplification, a single 411-bp product was generated from DNA of amoebae and cysts, but not from DNA of S. subterranea spore balls. These results are discussed in relation to earlier reports claiming the successful isolation of S. subterranea and other plasmodiophorids in vitro. [source] Characterization of non-covalent complexes of rutin with cyclodextrins by electrospray ionization tandem mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 6 2004Mingquan Guo Abstract Electrospray ionization tandem mass spectrometry (ESI-MSn) and the phase solubility method were used to characterize the gas-phase and solution-phase non-covalent complexes between rutin (R) and ,-, ,- and ,-cyclodextrins (CDs). The direct correlation between mass spectrometric results and solution-phase behavior is thus revealed. The order of the 1 : 1 association constants (Kc) of the complexes between R and the three CDs in solution calculated from solubility diagrams is in good agreement with the order of their relative peak intensities and relative collision-induced dissociation (CID) energies of the complexes under the same ESI-MSn condition in both the positive and negative ion modes. Not only the binding stoichiometry but also the relative stabilities and even binding sites of the CD,R complexes can be elucidated by ESI-MSn. The diagnostic fragmentation of CD,R complexes, with a significant contribution of covalent fragmentation of rutin leaving the quercetin (Q) moiety attached to the CDs, provides convincing evidence for the formation of inclusion complexes between R and CDs. The diagnostic fragment ions can be partly confirmed by the complexes between Q and CDs. The gas-phase stability order of the deprotonated CD,R complexes is ,-CD,R > ,-CD,R > ,-CD/R; ,-CD seems to bind R more strongly than the other CDs. Copyright © 2004 John Wiley & Sons, Ltd. [source] Kinetics of host immune responses and cytomegalovirus resistance in a liver transplant patientLIVER TRANSPLANTATION, Issue 10 2009Kirsten Schaffer Among solid organ transplant (SOT) recipients, donor-seropositive/recipient-seronegative (D+/R,) cytomegalovirus (CMV) status is associated with the highest risk of ganciclovir-resistant CMV disease, which has been reported for patients receiving oral ganciclovir but not valganciclovir prophylaxis. We report a case of CMV breakthrough infection in a D+/R, liver transplant patient while he was receiving oral valganciclovir. Forty samples collected over 6 months were analyzed for the CMV viral load, lymphocyte counts, cytokine levels, and lymphocyte differentiation status. Genotypic resistance testing of the viral UL97 gene was performed when the patient failed to respond. CMV viremia occurred on day 50 post-transplant, and 5 samples taken between days 50 and 85 showed the wild-type UL97 genotype. The appearance of deletion 594-595 was observed from day 114 post-transplant. Viral loads declined when foscarnet was commenced and remained below 10,000 copies/mL when the lymphocyte count was greater than 1000/,L (P = 0.02). T cell responses revealed significant expansion of CD8+ terminal effector memory cells. CD4+ cells were largely populations of naïve and central memory cells. Circulating interleukin 10 (IL-10) levels correlated with the viral load (P < 0.0001). Seroconversion occurred on day 230. The CMV viral load in combination with lymphocyte counts and IL-10 may be a predictive marker for the risk of development of resistant CMV disease in D+/R, SOT patients. Liver Transpl 15:1199,1203, 2009. © 2009 AASLD. [source] Primary CMV Infections Are Common in Kidney Transplant Recipients After 6 Months Valganciclovir ProphylaxisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010I. Helanterä Prolonging cytomegalovirus (CMV) prophylaxis in CMV seronegative recipients of a kidney from CMV seropositive donor (D+/R,) may reduce the incidence of late infections. We analyzed late-onset primary CMV infections after 6 months valganciclovir prophylaxis. Data from all CMV D+/R, kidney transplant recipients between January 2004 and December 2008 at our center were analyzed. Patients with a functioning graft at 6 months after transplantation who received 6 months of valganciclovir prophylaxis 900 mg once daily were included (N = 127). CMV was diagnosed with quantitative PCR. Prophylaxis was completed in 119 patients. Prophylaxis was stopped at 3,5 months due to leukopenia or gastrointestinal side effects in eight patients. Late-onset primary CMV infection developed in 47/127 (37%) patients median 244 days after transplantation (range 150,655) and median 67 days after the cessation of prophylaxis (range 1,475). Four infections were asymptomatic. In others, symptoms included fever (N = 28), gastrointestinal symptoms (nausea, vomiting, diarrhea) (N = 24), respiratory tract symptoms (N = 12), and hepatopathy (N = 6). Median peak viral load was 13500 copies/mL (range 400,2 831 000). Recurrent CMV infection developed in 9/47 (19%) patients. No significant risk factors for CMV infection were identified. Symptomatic primary CMV infections were commonly detected also after prolonged valganciclovir prophylaxis. [source] The Efficacy and Safety of 200 Days Valganciclovir Cytomegalovirus Prophylaxis in High-Risk Kidney Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010A. Humar Late-onset cytomegalovirus (CMV) disease is a significant problem with a standard 3-month prophylaxis regimen. This multicentre, double-blind, randomized controlled trial compared the efficacy and safety of 200 days' versus 100 days' valganciclovir prophylaxis (900 mg once daily) in 326 high-risk (D+/R,) kidney allograft recipients. Significantly fewer patients in the 200-day group versus the 100-day group developed confirmed CMV disease up to month 12 posttransplant (16.1% vs. 36.8%; p < 0.0001). Confirmed CMV viremia was also significantly lower in the 200-day group (37.4% vs. 50.9%; p = 0.015 at month 12). There was no significant difference in the rate of biopsy-proven acute rejection between the groups (11% vs. 17%, respectively, p = 0.114). Adverse events occurred at similar rates between the groups and the majority were rated mild-to-moderate in intensity and not related to study medication. In conclusion, this study demonstrates that extending valganciclovir prophylaxis (900 mg once daily) to 200 days significantly reduces the incidence of CMV disease and viremia through to 12 months compared with 100 days' prophylaxis, without significant additional safety concerns associated with longer treatment. The number needed to treat to avoid one additional patient with CMV disease up to 12 months posttransplant is approximately 5. [source] Clinical Predictors of Relapse after Treatment of Primary Gastrointestinal Cytomegalovirus Disease in Solid Organ Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010A. J. Eid Primary gastrointestinal cytomegalovirus (CMV) disease after solid organ transplantation (SOT) is difficult to treat and may relapse. Herein, we reviewed the clinical records of CMV D+/R, SOT recipients with biopsy-proven gastrointestinal CMV disease to determine predictors of relapse. The population consisted of 26 kidney (13 [50%]), liver (10 [38%]) and heart (3 [12%]) transplant recipients who developed gastrointestinal CMV disease at a median of 54 (interquartile range [IQR]: 40,70) days after stopping antiviral prophylaxis. Except for one patient, all received induction intravenous ganciclovir (mean ± SD, 33.8 ± 19.3 days) followed by valganciclovir (27.5 ± 13.3 days) in 18 patients. Ten patients further received valganciclovir maintenance therapy (41.6 ± 28.6 days). The median times to CMV PCR negativity in blood was 22.5 days (IQR: 16.5,30.7) and to normal endoscopic findings was 27.0 days (IQR: 21.0,33.5). CMV relapse, which occurred in seven (27%) patients, was significantly associated with extensive disease (p = 0.03). CMV seroconversion, viral load, treatment duration, maintenance therapy and endoscopic findings at the end of therapy were not significantly associated with CMV relapse. In conclusion, an extensive involvement of the gastrointestinal tract was significantly associated with CMV relapse. However, endoscopic evidence of resolution of gastrointestinal disease did not necessarily translate into a lower risk of CMV relapse. [source] Cell-Mediated Immunity to Predict Cytomegalovirus Disease in High-Risk Solid Organ Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009D. Kumar Late-onset cytomegalovirus (CMV) disease commonly occurs after discontinuation of antiviral prophylaxis. We determined the utility of testing CD8+ T-cell response against CMV as a predictor of late-onset CMV disease after a standard course of antiviral prophylaxis. Transplant patients at high-risk for CMV disease were enrolled. CD8+ T-cell-mediated immunity (CMI) was tested using the QuantiFERON-CMV assay at baseline, 1, 2 and 3 months posttransplant by measurement of interferon-, response to whole blood stimulation with a 21-peptide pool. The primary outcome was the ability of CMI testing to predict CMV disease in the first 6 months posttransplant. There were 108 evaluable patients (D+/R+ n = 39; D-/R+ n = 34; D+/R- n = 35) of whom 18 (16.7%) developed symptomatic CMV disease. At the end of prophylaxis, CMI was detectable in 38/108 (35.2%) patients (cutoff 0.1 IU/mL interferon-,). CMV disease occurred in 2/38 (5.3%) patients with a detectable interferon-, response versus 16/70 (22.9%) patients with a negative response; p = 0.038. In the subgroup of D+/R- patients, CMV disease occurred in 1/10 (10.0%) patients with a detectable interferon-, response (cutoff 0.1 IU/mL) versus 10/25 (40.0%) patients with a negative CMI, p = 0.12. Monitoring of CMI may be useful for predicting late-onset CMV disease. [source] Cost of prophylaxis in the management of cytomegalovirus infection in solid organ transplant recipientsCLINICAL TRANSPLANTATION, Issue 4 2007Federico Oppenheimer Abstract:, Background:, Limited economic data exist on the use of valganciclovir for the prevention of cytomegalovirus (CMV) infection and disease in solid organ transplant (SOT) recipients. We compared the economics of sequential i.v. and oral ganciclovir prophylaxis vs. oral valganciclovir prophylaxis alone in high-risk (D+/R,) SOT patients. Methods:, A cost-minimization analysis was performed from the perspective of the Spanish National Health System comparing the cost of sequential ganciclovir prophylaxis (induction with i.v. ganciclovir 10 mg/kg daily for 14 d followed by oral ganciclovir 1 g t.i.d. for 3 months) vs. oral valganciclovir prophylaxis (900 mg once daily for 100 d). Resource utilization data for both regimens were obtained from the literature and from clinical records of 83 patients in nine Spanish hospitals. Results were expressed as average cost per patient treated. Results:, The average cost per patient treated with sequential ganciclovir or valganciclovir prophylaxis was ,3715.51 and ,3295.90, respectively. The higher cost of ganciclovir therapy was due to concomitant administration of anti-CMV immunoglobulin (,313.73), drug administration costs (,401.45), catheter culture tests (,13.64) and adverse events associated with catheter use (,3.30). Following a sensitivity analysis, taking into account dose and duration of drug, concomitant medications and adverse events, costs for valganciclovir and sequential therapy were similar. Conclusions:, Valganciclovir prophylaxis is as economical as sequential ganciclovir prophylaxis in high-risk D+/R, SOT patients. In addition, the once-daily dosing regimen of valganciclovir is more convenient, and avoids the complications associated with catheter use. [source] Cytomegalovirus prophylaxis with valganciclovir in African,American renal allograft recipients based on donor/recipient serostatusCLINICAL TRANSPLANTATION, Issue 2 2005Scott A Gruber Abstract:, There is a paucity of data examining the efficacy of valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis in kidney transplant patients, particularly with regard to utilization of a risk-stratified dosing regimen. Eighty adult African,American (AA) renal allograft recipients transplanted from November 3, 2001 to May 28, 2003 and followed for 22 ± 8 months received VGC once daily for 90 d post-transplant dosed according to donor/recipient (D/R) serostatus: high risk (D+/R,) received 900 mg (n = 12); moderate risk (D+/R+, D,/R+) received 450 mg (n = 60); and low risk (D,/R,) received no prophylaxis (n = 8). Thymoglobulin or basiliximab was used for induction, and mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus for maintenance immunosuppression. Only six patients (7.5%) developed symptomatic CMV infection diagnosed by pp65 antigenemia, three in the high-risk (25%) and three in the moderate-risk (5%) group (p = 0.02). All patients were on tacrolimus for at least 3 months prior to diagnosis. There were no cases of tissue-invasive disease, resistance to treatment, or recurrence. D+/R, serostatus was the only significant independent predictor for CMV infection using multivariate analysis (odds ratio 10.5; p = 0.04). Thymoglobulin induction was not associated with CMV infection. None of 43 patients who were exposed to sirolimus for >30 d developed CMV infection, vs. six of 37 who were not (p = 0.006). We conclude that VGC dosed according to D/R serostatus provides safe and effective CMV prophylaxis in AA renal allograft recipients. [source] Severe Atrioventricular Decoupling, Uncoupling, and Ventriculoatrial Coupling During Enhanced Atrial Pacing: Incidence, Mechanisms, and Implications for Minimizing Right Ventricular Pacing in ICD PatientsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2008MICHAEL O. SWEENEY M.D. Background: Enhanced AAI/R pacing minimizes right ventricular pacing but may permit or induce AV decoupling (AV-DC) due to unrestricted AV intervals (AVIs). The purpose of this study was to characterize and quantify AVI behavior in a randomized trial of enhanced AAI/R pacing in ICD patients. Methods: One hundred twenty-one patients in the Marquis ICD MVPÔ Study, a randomized 1-month crossover comparison of cumulative% ventricular pacing (Cum%VP) in enhanced AAIR (MVP) vs DDD/R, were analyzed. AV-DC was defined as ,40% AVIs >300 ms; VA coupling (VA-C) was defined as%V-atrial pace (AP) intervals <300 ms. Dynamic AVI behavior and increases in Cum%VP due to AV block (AV uncoupling, AV-UC) were characterized using Holters with real-time ICD telemetry. Results: AV-DC occurred in 17 (14%) of patients. Baseline PR, amiodarone, nighttime, lower rate >60 beats/min, rate response, and Cum%AP were associated with longer AVIs. Logistic regression identified baseline PR (odds ratio [OR]= 1.024, 95% confidence interval [CI] 1.007,1.042; P = 0.005), and Cum%AP (OR = 1.089, 95% CI 1.027,1.154; P = 0.004) as predictors of AV-DC. AV-DC was associated with ,10-fold increases in both Cum%VP (13.6 ± 28.3% vs 1.2 ± 3.9%; P = 0.023) due to transient AV-UC) and VA-C (6.0 ± 17.5% vs 0.5 ± 1.2%, P = 0.028). AV coupling (<40% AVIs >300 ms) was preserved in 104 (86%) patients. Conclusions: AV-DC, VA-C, and AV-UC may be worsened or induced by enhanced AAI/R pacing. Conservative programming of lower rate and rate response should reduce the risk of AV-DC by reducing Cum%AP. [source] Multicenter, Prospective, Randomized Safety and Efficacy Study of a New Atrial-Based Managed Ventricular Pacing Mode (MVP) in Dual Chamber ICDsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2005MICHAEL O. SWEENEY M.D. Background: Ventricular desynchronization caused by right ventricular pacing may impair ventricular function and increase risk of heart failure (CHF), atrial fibrillation (AF), and death. Conventional DDD/R mode often results in high cumulative percentage ventricular pacing (Cum%VP). We hypothesized that a new managed ventricular pacing mode (MVP) would safely provide AAI/R pacing with ventricular monitoring and DDD/R during AV block (AVB) and reduce Cum%VP compared to DDD/R. Methods: MVP RAMware was downloaded in 181 patients with Marquis DR ICDs. Patients were initially randomized to either MVP or DDD/R for 1 month, then crossed over to the opposite mode for 1 month. ICD diagnostics were analyzed for cumulative percentage atrial pacing (Cum%AP), Cum%VP, and duration of DDD/R pacing for spontaneous AVB. Results: Baseline characteristics included age 66 ± 12 years, EF 36 ± 14%, and NYHA Class II,III 36%. Baseline PR interval was 190 ± 53 msec and programmed AV intervals (DDD/R) were 216 ± 50 (paced)/189 ± 53 (sensed) msec. Mean Cum%VP was significantly lower in MVP versus DDD/R (4.1 ± 16.3 vs 73.8 ± 32.5, P < 0.0001). The median absolute and relative reductions in Cum%VP during MVP were 85.0 and 99.9, respectively. Mean Cum%AP was not different between MVP versus DDD/R (48.7 ± 38.5 vs 47.3 ± 38.4, P = 0.83). During MVP overall time spent in AAI/R was 89.6% (intrinsic conduction), DDD/R 6.7% (intermittent AVB), and DDI/R 3.7% (AF). No adverse events were attributed to MVP. Conclusions: MVP safely achieves functional atrial pacing by limiting ventricular pacing to periods of intermittent AVB and AF in ICD patients, significantly reducing Cum%VP compared to DDD/R. MVP is a universal pacing mode that adapts to AVB and AF, providing both atrial pacing and ventricular pacing support when needed. [source] Rate coefficients for the OH + acetaldehyde (CH3CHO) reaction between 204 and 373 KINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 10 2008Lei Zhu The rate coefficient, k1, for the gas-phase reaction OH + CH3CHO (acetaldehyde) , products, was measured over the temperature range 204,373 K using pulsed laser photolytic production of OH coupled with its detection via laser-induced fluorescence. The CH3CHO concentration was measured using Fourier transform infrared spectroscopy, UV absorption at 184.9 nm and gas flow rates. The room temperature rate coefficient and Arrhenius expression obtained are k1(296 K) = (1.52 ± 0.15) × 10,11 cm3 molecule,1 s,1 and k1(T) = (5.32 ± 0.55) × 10,12 exp[(315 ± 40)/T] cm3 molecule,1 s,1. The rate coefficient for the reaction OH (, = 1) + CH3CHO, k7(T) (where k7 is the rate coefficient for the overall removal of OH (, = 1)), was determined over the temperature range 204,296 K and is given by k7(T) = (3.5 ± 1.4) × 10,12 exp[(500 ± 90)/T], where k7(296 K) = (1.9 ± 0.6) × 10,11 cm3 molecule,1 s,1. The quoted uncertainties are 2, (95% confidence level). The preexponential term and the room temperature rate coefficient include estimated systematic errors. k7 is slightly larger than k1 over the range of temperatures included in this study. The results from this study were found to be in good agreement with previously reported values of k1(T) for temperatures <298 K. An expression for k1(T), suitable for use in atmospheric models, in the NASA/JPL and IUPAC format, was determined by combining the present results with previously reported values and was found to be k1(298 K) = 1.5 × 10,11 cm3 molecule,1 s,1, f(298 K) = 1.1, E/R = 340 K, and , E/R (or g) = 20 K over the temperature range relevant to the atmosphere. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 635,646, 2008 [source] Role of Rac 1 and cAMP in endothelial barrier stabilization and thrombin-induced barrier breakdownJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2009Y. Baumer Barrier stabilizing effects of cAMP as well as of the small GTPase Rac 1 are well established. Moreover, it is generally believed that permeability-increasing mediators such as thrombin disrupt endothelial barrier functions primarily via activation of Rho A. In this study, we provide evidence that decrease of both cAMP levels and of Rac 1 activity contribute to thrombin-mediated barrier breakdown. Treatment of human dermal microvascular endothelial cells (HDMEC) with Rac 1-inhibitor NSC-23766 decreased transendothelial electrical resistance (TER) and caused intercellular gap formation. These effects were reversed by addition of forskolin/rolipram (F/R) to increase intracellular cAMP but not by the cAMP analogue 8-pCPT-2,-O-Methyl-cAMP (O-Me-cAMP) which primarily stimulates protein kinase A (PKA)-independent signaling via Epac/Rap 1. However, both F/R and O-Me-cAMP did not increase TER above control levels in the presence of NSC-23766 in contrast to experiments without Rac 1 inhibition. Because Rac 1 was required for maintenance of barrier functions as well as for cAMP-mediated barrier stabilization, we tested the role of Rac 1 and cAMP in thrombin-induced barrier breakdown. Thrombin-induced drop of TER and intercellular gap formation were paralleled by a rapid decrease of cAMP as revealed by fluorescence resonance energy transfer (FRET). The efficacy of F/R or O-Me-cAMP to block barrier-destabilizing effects of thrombin was comparable to Y27632-induced inhibition of Rho kinase but was blunted when Rac 1 was inactivated by NSC-23766. Taken together, these data indicate that decrease of cAMP and Rac 1 activity may be an important step in inflammatory barrier disruption. J. Cell. Physiol. 220: 716,726, 2009. © 2009 Wiley-Liss, Inc. [source] Effects of nucleoside reverse transcriptase inhibitor backbone on the efficacy of first-line boosted highly active antiretroviral therapy based on protease inhibitors: meta-regression analysis of 12 clinical trials in 5168 patientsHIV MEDICINE, Issue 9 2009A Hill Objectives Tenofovir/emtricitabine (TDF/FTC) and abacavir/lamivudine (ABC/3TC) are widely used with ritonavir (RTV)-boosted protease inhibitors (PIs) as first-line highly active antiretroviral therapy (HAART), but there is conflicting evidence on their relative efficacy. The ACTG 5202 and BICOMBO trials suggested higher efficacy for TDF/FTC, whereas the HEAT trial showed no efficacy difference between the nucleoside reverse transcriptase inhibitor (NRTI) backbones. Methods A systematic MEDLINE search identified 21 treatment arms in 12 clinical trials of 5168 antiretroviral-naïve patients, where TDF/FTC (n=3399) or ABC/3TC (n=1769) was used with RTV-boosted PI. For each NRTI backbone and RTV-boosted PI, the percentage of patients with viral load <50 HIV-1 RNA copies/mL at week 48 by standardized Intent to Treat, Time to Loss of Virological Failure (ITT TLOVR) analysis were combined using inverse-variance weighting. The effect of baseline HIV RNA, CD4 cell count and choice of NRTI backbone were examined using a weighted analysis of covariance. Results Across all the trials, HIV RNA suppression rates were significantly higher for those with baseline viral load below 100 000 copies/mL (77.2%) vs. above 100 000 copies/mL (70.9%) (P=0.0005). For the trials of lopinavir/ritonavir (LPV/r), atazanavir/ritonavir (ATV/r) and fosamprenavir/ritonavir (FAPV/r) using either TDF/FTC or ABC/3TC, the HIV RNA responses were significantly lower when ABC/3TC was used, relative to TDF/FTC, for all patients (P=0.0015) and for patients with baseline viral load <100 000 copies/mL (70.1%vs. 80.6%, P=0.0161), and was borderline for those with viral load >100 000 copies/mL (67.5%vs. 71.5%, P=0.0523). Conclusions This systematic meta-regression analysis suggests higher efficacy for first-line use of a TDF/FTC NRTI backbone with boosted PIs, relative to use of ABC/3TC. However, this effect may be confounded by differences between the trials in terms of baseline characteristics, patient management or adherence. [source] Hyperbaric oxygen therapy protects the liver from apoptosis caused by ischemia-reperfusion injury in ratsMICROSURGERY, Issue 7 2009José C. Chaves M.D., M.Sc. Purpose: The present paper aimed to investigate the role of hyperbaric oxygen treatment (HBO) and the apoptosis in rat liver ischemia-reperfusion injury (IRI). Methods: Thirty-seven male Wistar rats were subjected to 30 minutes of hepatic ischemia and 30 minutes of reperfusion and randomly distributed into six groups: G-I/R (n = 8), control without HBO; G-HBO/I (n = 8), HBO only during the ischemia period; G-HBO/R (n = 8), HBO only during the reperfusion period; G-HBO-I/R (n = 8), HBO during both the ischemia and reperfusion periods; G-Sh (n = 3), HBO without ischemia or reperfusion as sham group; G-C (n = 2) for control of current apoptosis expression on the normal liver tissue. HBO was carried out using a transparent, cylindrical acrylic chamber with a pressure of 2.0 ATA. Hepatic samples were stained for caspase-3 cleavage. Results: Apoptotic cells were identified in all groups. In the hepatic specimens of animals HBO-treated during ischemia (GHBO-I), there was a significant decrease (P < 0.001) in the number of cells undergoing apoptosis (1.62 ± 0.91). The apoptotic index showed no significant difference in the animals HBO-treated during ischemia/reperfusion (5.75 ± 1.28) compared with the G-I/R (3.5 ± 0.75), which had no HBO treatment. The apoptosis index (11.25 ± 1.90) was significantly higher (P < 0.01) in HBO-treated animals during the reperfusion period when compared with any of the other groups. Conclusion: A favorable effect was obtained when hyperbaric oxygen was administered early during ischemia. The hyperbaric oxygen in later periods of reperfusion was associated with a more severe apoptosis index. © 2009 Wiley-Liss, Inc. Microsurgery 2009. [source] Screening for G71R mutation of the UGT1A1 gene in the Javanese-Indonesian and Malay-Malaysian populationsPEDIATRICS INTERNATIONAL, Issue 5 2004Retno Sutomo AbstractBackground:,There are significant differences in the prevalence and severity of neonatal jaundice among various populations. Recently, it has been reported that a mutation of the UGT1A1 gene, glycine to arginine at codon 71 (G71R), is related to the development of neonatal jaundice in East Asian populations. However, whether the G71R mutation contributes to the high incidence of neonatal jaundice in different Asian populations remains unknown. The authors screened for this mutation in the Javanese-Indonesian and Malay-Malaysian populations. Methods:,One hundred and thirty-six subjects were enrolled in this study: 68 Javanese-Indonesian adults and 68 Malay-Malaysian newborns (32 with jaundice and 36 without jaundice). Denaturing high-performance liquid chromatography (DHPLC) was used to screen for the G71R mutation, and the results were confirmed by nucleotide sequencing analysis. Results:,With DHPLC, the authors easily and clearly detected seven subjects carrying the G71R mutation: two Javanese-Indonesian adults and five Malay-Malaysian newborns. In the 68 Javanese-Indonesian adults, the genotype distribution for G71R mutation was 66 G/G, two G/R and no R/R genotypes, and the mutated allele frequency was 0.015. In the 68 Malay-Malaysian newborns, genotype distribution for the mutation was 63 G/G, five G/R and no R/R genotypes, and the mutated allele frequency was 0.037. The genotype distributions did not differ significantly between the newborns with jaundice and those without jaundice. Conclusion:,The G71R mutation is present, but very rare, in Javanese-Indonesians and Malay-Malaysians. Thus, G71R mutation may not contribute to the high incidence of the neonatal jaundice in South-east Asian populations. DHPLC analysis is a very useful method for detecting the G71R mutation. [source] Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway,HEPATOLOGY, Issue 5 2010Nitika Arora Gupta Glucagon-like peptide 1 (GLP-1) is a naturally occurring peptide secreted by the L cells of the small intestine. GLP-1 functions as an incretin and stimulates glucose-mediated insulin production by pancreatic , cells. In this study, we demonstrate that exendin-4/GLP-1 has a cognate receptor on human hepatocytes and that exendin-4 has a direct effect on the reduction of hepatic steatosis in the absence of insulin. Both glucagon-like peptide 1 receptor (GLP/R) messenger RNA and protein were detected on primary human hepatocytes, and receptor was internalized in the presence of GLP-1. Exendin-4 increased the phosphorylation of 3-phosphoinositide-dependent kinase-1 (PDK-1), AKT, and protein kinase C , (PKC-,) in HepG2 and Huh7 cells. Small interfering RNA against GLP-1R abolished the effects on PDK-1 and PKC-,. Treatment with exendin-4 quantitatively reduced triglyceride stores compared with control-treated cells. Conclusion: This is the first report that the G protein,coupled receptor GLP-1R is present on human hepatocytes. Furthermore, it appears that exendin-4 has the same beneficial effects in vitro as those seen in our previously published in vivo study in ob/ob mice, directly reducing hepatocyte steatosis. Future use for human nonalcoholic fatty liver disease, either in combination with dietary manipulation or other pharmacotherapy, may be a significant advance in treatment of this common form of liver disease. (HEPATOLOGY 2010) [source] Temporal Dynamics of River Biofilm in Constant Flows: A Case Study in a Riverside Laboratory FlumeINTERNATIONAL REVIEW OF HYDROBIOLOGY, Issue 2 2010Stéphanie Boulêtreau Abstract A 15-week experiment was performed in a riverside laboratory flume (with diverted river water) to check variations of river biofilm structure (biomass, algal and bacterial compositions) and function (community gross primary production GPP and respiration) under constant flow while water quality went through natural temporal variations. One major suspended matter pulse coinciding with one river flood was recorded after 10 weeks of experiment. Epilithic biofilm first exhibited a 10-week typical pattern of biomass accrual reaching 33 g ash-free dry matter (AFDM) m,2 and 487 mg chlorophyll- a m,2 and then, experienced a shift to dominance of loss processes (loss of 60% AFDM and 80% chlorophyll- a) coinciding with the main suspended matter pulse. Algal diversity remained low and constant during the experiment: Fragilaria capucina and Encyonema minutum always contribute over 80% of cell counts. DGGE banding patterns discriminated between two groups that corresponded to samples before and after biomass loss, indicating major changes in the bacterial community composition. GPP/R remained high during the experiment, suggesting that photoautotrophic metabolism prevailed and detachment was not autogenic (i.e., due to algal senescence or driven by heterotrophic processes within the biofilm). Observational results suggested that silt deposition into the biofilm matrix could have triggered biomass loss. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Hypoxia-inducible factor and nuclear factor kappa-B activation in blood,brain barrier endothelium under hypoxic/reoxygenation stressJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Ken A. Witt Abstract This investigation focuses on transcription factor involvement in blood,brain barrier (BBB) endothelial cell-induced alterations under conditions of hypoxia and post-hypoxia/reoxygenation (H/R), using established in vivo/ex vivo and in vitro BBB models. Protein/DNA array analyses revealed a correlation in key transcription factor activation during hypoxia and H/R, including NF,B and hypoxia-inducible factor (HIF)1. Electrophoretic mobility shift assays confirmed NF,B and HIF1 binding activity ex vivo and in vitro, under conditions of hypoxia and H/R. Hypoxia- and H/R-treated BBB endothelium showed increased HIF1, protein expression in both cytoplasmic and nuclear fractions, in ex vivo and in vitro models. Co-immunoprecipitation of HIF1, and HIF1, was shown in the nuclear fraction under conditions of hypoxia and H/R in both models. Hypoxia- and H/R-treated BBB endothelium showed increased expression of NF,B-p65 protein in both cytoplasmic and nuclear fractions. Co-immunoprecipitation of NF,B-p65 with NF,B-p50 was shown in the nuclear fraction under conditions of hypoxia and H/R in the ex vivo model, and after H/R in the in vitro model. These data offer novel avenues in which to alter and/or investigate BBB activity across model systems and to further our understanding of upstream regulators during hypoxia and H/R. [source] Testing the locality of transport in self-gravitating accretion discsMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 2 2004G. Lodato ABSTRACT In this paper, we examine the issue of characterizing the transport associated with gravitational instabilities in relatively cold discs, discussing in particular the conditions under which it can be described within a local, viscous framework. We present the results of global, three-dimensional, smoothed particle hydrodynamics simulations of self-gravitating accretion discs, in which the disc is cooled using a simple parametrization for the cooling function. Our simulations show that the disc settles in a ,self-regulated' state, where the axisymmetric stability parameter Q, 1 and where transport and energy dissipation are dominated by self-gravity. We have computed the gravitational stress tensor and compared our results with expectations based on a local theory of transport. We find that, as long as the disc mass is smaller than 0.25M, and the aspect ratio H/R, 0.1, transport is determined locally, thus allowing for a viscous treatment of the disc evolution. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||