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2.
Environ Monit Assess ; 195(11): 1354, 2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37864721

RESUMO

The Canada-Alberta Oil Sands Monitoring (OSM) Program began long-term surface water quality monitoring on the lower Athabasca River in 2012. Sampling of low level, bio-accumulative polycyclic aromatic compounds (PACs) targeted a suite of parent and alkylated compounds in the Athabasca River (AR) mainstem using semi-permeable membrane devices (SPMDs). Samples were collected along a gradient from upstream reference near Athabasca, Alberta, through exposure to the Athabasca oil sands deposit (AOSD), various tributary inflows, and mining activities within the OSMA, to downstream recovery near Wood Buffalo National Park (WBNP) and reference on the Slave River. The program adapted over the years, shifting in response to program review and environmental events. The AOSD chemical fingerprint was present in samples collected within the AOSD, through the oil sands mineable area (OSMA), downstream to recovery from 2013 to 2019. PACs were dominated by alkylated phenanthrenes/anthracenes (PAs) and dibenzothiophenes (Ds), with elevated levels of alkylated fluorenes (Fs), naphthalenes (Ns), fluoranthenes/pyrenes (FlPys) and benzo[a]anthracenes/chrysenes (BaACs), increasing in concentration from C1 < C2 < C3 < C4. Concentrations of these petrogenic PACs were at their highest within the OSMA and downstream of tributaries. The AOSD fingerprint was absent from sites located outside of the influence of the AOSD and downstream of the Peace-Athabasca Delta on the Slave River. PAC concentrations in the AR increased with mainstem discharge and loadings from tributaries, were moderated by the PAD, and diluted by the Peace River. This work bolsters the baseline PAC information previously reported for the Athabasca River and waters downstream, reporting 7 years of data, from all sites within the mainstem monitoring program, and exploring potential regional and hydrological drivers of these between sites and over time.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Compostos Policíclicos , Poluentes Químicos da Água , Campos de Petróleo e Gás , Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos/análise , Compostos Orgânicos , Alberta , Antracenos , Poluentes Químicos da Água/análise
3.
Can J Microbiol ; 67(11): 813-826, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34171204

RESUMO

Microbial communities are an important aspect of overall riverine ecology; however, appreciation of the effects of anthropogenic activities on unique riverine microbial niches, and how the collection of these samples affects the observed diversity and community profile is lacking. We analyzed prokaryotic and eukaryotic communities from surface water, biofilms, and suspended load niches along a gradient of oil sands-related contamination in the Athabasca River (Alberta, Canada), with suspended load or particle-associated communities collected either via Kenney Sampler or centrifugation manifold. At the phylum level, different niche communities were highly similar to each other and across locations. However, there were significant differences in the abundance of specific genera among the different niches and across sampling locations. A generalized linear model revealed that use of the Kenney Sampler resulted in more diverse bacterial and eukaryotic suspended load community than centrifugal collection, though suspended load communities collected by any means remained stably diverse across locations. Although there was an influence of water quality parameters on community composition, all sampled sites support diverse bacterial and eukaryotic communities regardless of the degree of contamination, highlighting the need to look beyond ecological diversity as a means of assessing ecological perturbations, and consider collecting samples from multiple niche environments.


Assuntos
Rios , Poluentes Químicos da Água , Alberta , Monitoramento Ambiental , Eucariotos/genética , Mineração , Campos de Petróleo e Gás , Poluentes Químicos da Água/análise
4.
Front Microbiol ; 11: 267, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32174897

RESUMO

Manufactured Zn oxide nanoparticle (ZnO-NP) are extensively used world-wide in personal care and industrial products and are important contaminants of aquatic environments. To understand the overall impact of ZnO-NP contamination on aquatic ecosystems, investigation of their toxicity on aquatic biofilms is of particular consequence, given biofilms are known sinks for NP contaminants. In order to assess alterations in the functional activity of river microbial biofilm communities as a result of environmentally-relevant ZnO-NP exposure, biofilms were exposed to ionic zinc salt or ZnOPs that were uncoated (hydrophilic), coated with silane (hydrophobic) or stearic acid (lipophilic), at a total concentration of 188 µg l-1 Zn. ICP-MS analyses of biofilms indicated ZnO-NP concentrated in the biofilms, with hydrophilic, hydrophobic, and lipophilic treatments reaching 0.310, 0.250, and 0.220 µg Zn cm-2 of biofilm, respectively, while scanning transmission X-ray microspectroscopy (STXM) analyses of biofilms confirmed that Zn was extensively- and differentially-sorbed to biofilm material. Microbial community composition, based on taxonomic affiliation of mRNA sequences and enumeration of protozoa and micrometazoa, was not affected by these treatments, and the total transcriptional response of biofilms to all experimental exposures was not indicative of a global toxic-response, as cellular processes involved in general cell maintenance and housekeeping were abundantly transcribed. Transcripts related to major biological processes, including photosynthesis, energy metabolism, nitrogen metabolism, lipid metabolism, membrane transport, antibiotic resistance and xenobiotic degradation, were differentially expressed in Zn-exposures relative to controls. Notably, transcripts involved in nitrogen fixation and photosynthesis were decreased in abundance in response to Zn-exposure, while transcripts related to lipid degradation and motility-chemotaxis were increased, suggesting a potential role of Zn in biofilm dissolution. ZnO-NP and ionic Zn exposures elicited generally overlapping transcriptional responses, however hydrophilic and hydrophobic ZnO-NPs induced a more distinct effect than that of lipophilic ZnO-NPs, which had an effect similar to that of low ionic Zn exposure. While the physical coating of ZnO-NP may not induce specific toxicity observable at a community level, alteration of ecologically important processes of photosynthesis and nitrogen cycling are an important potential consequence of exposure to ionic Zn and Zn oxides.

5.
Environ Pollut ; 256: 113515, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31706760

RESUMO

Cerium oxide (CeO2) nanoparticles are used as in-fuel catalysts and in manufacturing processes, creating a potential for release to aquatic environments. Exposures at 1 and 10 µg/L CeO2-nanoparticles were made to assess effects during the development of river biofilm communities. Scanning transmission x-ray microscopy (STXM) indicated extensive sorption of nanoparticles to the community and co-localization with lipid moieties. Following 8 weeks of development, polycarbonate coupons were removed from the reactors and used for molecular analyses, denaturing gradient gel electrophoresis analysis (DGGE-16S rRNA) and 16S rRNA amplicon sequencing. Microscopic imaging of the biofilm communities (bacterial, photosynthetic biomass, exopolymer composition, thickness, protozoan numbers), as well as carbon substrate utilization fingerprinting was performed. There was a trend toward reduced photosynthetic biomass, but no significant effects of CeO2 exposure were found on photosynthetic and bacterial biomass or biofilm thickness. Sole carbon source utilization analyses indicated increased utilization of 10 carbon sources in the carbohydrate, carboxylic acid and amino acids categories related to CeO2 exposures; however, predominantly, no significant effects (p < 0.05) were detected. Measures of microbial diversity, lectin binding affinities of exopolymeric substances and results of DGGE analyses, indicated significant changes to community composition (p < 0.05) with CeO2 exposure. Increased binding of the lectin Canavalia ensiformis was observed, consistent with changes in bacterial-associated polymers. Whereas, no significant changes were observed in binding to residues associated with algal and cyanobacterial exopolymers. 16S rRNA amplicon sequencing of community DNA indicated changes in diversity and shifts in community composition; however, these did not trend with increasing CeO2 exposure. Counting of protozoans in the biofilm communities indicated no significant effects on this trophic level. Thus, based on biomass and functional measures, CeO2 nanoparticles did not appear to have significant effects; however, there was evidence of selection pressure resulting in significant changes in microbial community composition.


Assuntos
Biofilmes/crescimento & desenvolvimento , Cério/toxicidade , Nanopartículas/toxicidade , Rios/microbiologia , Biomassa , Cianobactérias/metabolismo , Monitoramento Ambiental , RNA Ribossômico 16S
6.
Environ Toxicol Chem ; 38(11): 2414-2425, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31365141

RESUMO

Studies of the South Saskatchewan River confirmed that N,N-diethyl-m-toluamide (DEET) is ubiquitous at 10 to 20 ng/L, whereas in effluent-dominated Wascana Creek, levels of 100 to 450 ng/L were observed. Effects of DEET exposure were assessed in microbial communities using a wide variety of measures. Communities developed in rotating annular reactors with either 100 or 500 ng/L DEET, verified using gas chromatography-mass spectrometry analyses. Microscale analyses indicated that both DEET concentrations resulted in significant (p < 0.05) declines in photosynthetic biomass, whereas bacterial biomass was unaffected. There was no detectable effect of DEET on the levels of chlorophyll a. However, pigment analyses indicated substantial shifts in algal-cyanobacterial community structure, with reductions of green algae and some cyanobacterial groups at 500 ng/L DEET. Protozoan/micrometazoan grazers increased in communities exposed to 500 ng/L, but not 100 ng/L, DEET. Based on thymidine incorporation or utilization of carbon sources, DEET had no significant effects on metabolic activities. Fluorescent lectin-binding analyses showed significant (p < 0.05) changes in glycoconjugate composition at both DEET concentrations, consistent with altered community structure. Principal component cluster analyses of denaturing gradient gel electrophoresis indicated that DEET exposure at either concentration significantly changed the bacterial community (p < 0.05). Analyses based on 16S ribosomal RNA of community composition confirmed changes with DEET exposure, increasing detectable beta-proteobacteria, whereas actinobacteria and acidimicrobia became undetectable. Further, cyanobacteria in the subclass Oscillatoriophycideae were similarly not detected. Thus, DEET can alter microbial community structure and function, supporting the need for further evaluation of its effects in aquatic habitats. Environ Toxicol Chem 2019;38:2414-2425. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.


Assuntos
DEET/toxicidade , Exposição Ambiental/análise , Microbiota/efeitos dos fármacos , Rios/química , Poluentes Químicos da Água/toxicidade , Animais , Biofilmes/efeitos dos fármacos , Biomassa , Carbono/metabolismo , Clorofila A/metabolismo , Clorófitas/efeitos dos fármacos , Cianobactérias/efeitos dos fármacos , Processamento de Imagem Assistida por Computador , Fotossíntese/efeitos dos fármacos , Análise de Componente Principal , RNA Ribossômico 16S/genética , Saskatchewan
7.
Infancy ; 24(2): 210-227, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32677198

RESUMO

Parental reflective functioning (PRF) is a robust predictor of parenting sensitivity and secure infant attachment, but its assessment requires extensive resources, limiting its integration into research and clinical practice. The Mini-Parent Reflective Functioning Interview (Mini-PRFI) assesses the parent's capacity to mentalize for his/her 6-month-old infant (rated using the PRF coding system; Slade et al., 2004, PRF coding system and Slade REF, Unpublished protocol, New York, NY: The City University of New York). In the current study, we examined whether Mini-PRFI scores were associated with theoretically related constructs; to establish a point of comparison, we evaluated links between Mini-PRFI scores alongside RF assessed from the Adult Attachment Interview (AAI). Mother-infant dyads (N = 88) completed the AAI before the birth of the infant, the Mini-PRFI and an interaction task (rated for insensitive parental behavior) when infants were 6 months old, as well as the Strange Situation Procedure when infants were 16 months old. Mini-PRFI scores were strongly positively associated with AAI RF and negatively associated with maternal insensitivity. Mini-PRFI scores predicted infant attachment organization (secure/insecure, organized/disorganized) at 16 months, and this effect was mediated by parenting insensitivity. These findings suggest that the Mini-PRFI predicts theoretically related attachment constructs, demonstrating the promise of the Mini-PRFI to increase the accessibility of interview-based PRF measurements to clinicians and researchers.

8.
Genome Announc ; 5(39)2017 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-28963222

RESUMO

The genetic basis for biofilm formation among nontyphoidal salmonellae (NTS) remains poorly understood. This draft genome submission provides initial insights on the genetic differences between biofilm-forming and non-biofilm-forming clinical and environmental NTS serovars.

9.
Philos Trans A Math Phys Eng Sci ; 375(2101)2017 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-28739969

RESUMO

The Lewis acids Ga(C6F5)3, In(C6F5)3 and Ga(C6Cl5)3 are prepared and their Lewis acidity has been probed experimentally and computationally. The species Ga(C6F5)3 and In(C6F5)3 in conjunction with phosphine donors are shown to heterolytically split H2 and catalyse the hydrogenation of an imine. In addition, frustrated Lewis pairs (FLPs) derived from Ga(C6F5)3 and In(C6F5)3 and phosphines react with diphenyldisulfide to phosphoniumgallates or indates of the form [tBu3PSPh][PhSE(C6F5)3] and [tBu3PSPh][(µ-SPh)(E(C6F5)3)2] (E = Ga, In). The potential of the FLPs based on Ga(C6F5)3, In(C6F5)3 and Ga(C6Cl5)3 and phosphines is also shown in reactions with phenylacetylene to give pure or mixtures of the products [tBu3PH][PhCCE(C6X5)3] and R3P(Ph)C=C(H)E(C6X5)3 A number of these species are crystallographically characterized. The implications for the use of these species in FLP chemistry are considered.This article is part of the themed issue 'Frustrated Lewis pair chemistry'.

10.
PLoS One ; 10(5): e0128130, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26020522

RESUMO

Mitochondria, long known as the cell powerhouses, also regulate redox signaling and arbitrate cell survival. The organelles are now appreciated to exert additional critical roles in cell state transition from a pluripotent to a differentiated state through balancing glycolytic and respiratory metabolism. These metabolic adaptations were recently shown to be concomitant with mitochondrial morphology changes and are thus possibly regulated by contingencies of mitochondrial dynamics. In this context, we examined, for the first time, mitochondrial network plasticity during the transition from proliferating neural progenitors to post-mitotic differentiating neurons. We found that mitochondria underwent morphological reshaping in the developing neural tube of chick and mouse embryos. In the proliferating population, mitochondria in the mitotic cells lying at the apical side were very small and round, while they appeared thick and short in interphase cells. In differentiating neurons, mitochondria were reorganized into a thin, dense network. This reshaping of the mitochondrial network was not specific of a subtype of progenitors or neurons, suggesting that this is a general event accompanying neurogenesis in the spinal cord. Our data shed new light on the various changes occurring in the mitochondrial network during neurogenesis and suggest that mitochondrial dynamics could play a role in the neurogenic process.


Assuntos
Diferenciação Celular/fisiologia , Mitocôndrias/metabolismo , Rede Nervosa/embriologia , Células-Tronco Neurais/metabolismo , Neurogênese/fisiologia , Neurônios/metabolismo , Medula Espinal/embriologia , Animais , Embrião de Galinha , Células HeLa , Humanos , Camundongos , Rede Nervosa/citologia , Células-Tronco Neurais/citologia , Neurônios/citologia , Medula Espinal/citologia
11.
Appl Environ Microbiol ; 79(23): 7398-412, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24056457

RESUMO

Sediments from the Athabasca River and its tributaries naturally contain bitumen at various concentrations, but the impacts of this variation on the ecology of the river are unknown. Here, we used controlled rotating biofilm reactors in which we recirculated diluted sediments containing various concentrations of bituminous compounds taken from the Athabasca River and three tributaries. Biofilms exposed to sediments having low and high concentrations of bituminous compounds were compared. The latter were 29% thinner, had a different extracellular polysaccharide composition, 67% less bacterial biomass per µm2, 68% less cyanobacterial biomass per µm2, 64% less algal biomass per µm2, 13% fewer protozoa per cm2, were 21% less productive, and had a 33% reduced content in chlorophyll a per mm2 and a 20% reduction in the expression of photosynthetic genes, but they had a 23% increase in the expression of aromatic hydrocarbon degradation genes. Within the Bacteria, differences in community composition were also observed, with relatively more Alphaproteobacteria and Betaproteobacteria and less Cyanobacteria, Bacteroidetes, and Firmicutes in biofilms exposed to high concentrations of bituminous compounds. Altogether, our results suggest that biofilms that develop in the presence of higher concentrations of bituminous compounds are less productive and have lower biomass, linked to a decrease in the activities and abundance of photosynthetic organisms likely due to inhibitory effects. However, within this general inhibition, some specific microbial taxa and functional genes are stimulated because they are less sensitive to the inhibitory effects of bituminous compounds or can degrade and utilize some bitumen-associated compounds.


Assuntos
Biofilmes/efeitos dos fármacos , Biota/efeitos dos fármacos , Células Eucarióticas/efeitos dos fármacos , Hidrocarbonetos/toxicidade , Células Procarióticas/efeitos dos fármacos , Rios/microbiologia , Rios/parasitologia
12.
Hum Mol Genet ; 22(22): 4451-9, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23814039

RESUMO

Hypertension, the most frequently diagnosed clinical condition world-wide, predisposes individuals to morbidity and mortality, yet its underlying pathological etiologies are poorly understood. So far, a large number of quantitative trait loci (QTLs) have been identified in both humans and animal models, but how they function together in determining overall blood pressure (BP) in physiological settings is unknown. Here, we systematically and comprehensively performed pair-wise comparisons of individual QTLs to create a global picture of their functionality in an inbred rat model. Rather than each of numerous QTLs contributing to infinitesimal BP increments, a modularized pattern arises: two epistatic 'blocks' constitute basic functional 'units' for nearly all QTLs, designated as epistatic module 1 (EM1) and EM2. This modularization dictates the magnitude and scope of BP effects. Any EM1 member can contribute to BP additively to that of EM2, but not to those of the same module. Members of each EM display epistatic hierarchy, which seems to reflect a related functional pathway. Rat homologues of 11 human BP QTLs belong to either EM1 or EM2. Unique insights emerge into the novel genetic mechanism and hierarchy determining BP in the Dahl salt-sensitive SS/Jr (DSS) rat model that implicate a portion of human QTLs. Elucidating the pathways underlying EM1 and EM2 may reveal the genetic regulation of BP.


Assuntos
Pressão Sanguínea/genética , Epistasia Genética , Homeostase/genética , Locos de Características Quantitativas , Animais , Animais Congênicos , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Hipertensão/genética , Hipertensão/fisiopatologia , Ratos , Ratos Endogâmicos Dahl , Ratos Endogâmicos Lew
13.
Ann Pharmacother ; 47(3): 324-32, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23482734

RESUMO

BACKGROUND: As rates of polypharmacy rise and medication regimens become more complex, the risk of potential cytochrome P450 (CYP)-mediated drug-drug interactions (DDIs) is a growing clinical concern for older adults. OBJECTIVE: To determine the prevalence of potential CYP-mediated DDIs in older hospitalized adults with polypharmacy and analyze the relationship between the number of drugs dispensed and the probability of these interactions in this high-risk population. METHODS: A prospective 16-week cohort study was conducted among consecutive new patients aged 65 years and older with polypharmacy (>5 drugs) admitted to a community hospital. The medication profiles of these patients were analyzed with a new multidrug cytochrome-specific software program. The prevalence of potential CYP-mediated DDIs was determined, with the probability calculated as a function of the number of medications dispensed using multivariate Poisson regression adjusted for age and sex. Comparative performance of the software program and a standard 2-drug alert program for detecting these DDIs was evaluated using the Wilcoxon-Mann-Whitney rank-sum test. Pharmacists' decisions to recommend medication adjustment based on the probability of CYP-mediated DDIs were recorded. RESULTS: The prevalence of potential CYP-mediated DDIs detected among 275 older adults with polypharmacy was 80%. The probability of at least 1 CYP-mediated DDI was 50% for persons taking 5-9 drugs, 81% with 10-14 drugs, 92% with 15-19 drugs, and 100% with 20 or more drugs. Addition of each medication to a 5-drug regimen conferred a 12% increased risk of a potential CYP-mediated DDI after adjustment for age and sex (OR 1.12; 95% CI 1.09-1.14). The multidrug software identified a median increase of 3 (95% CI 2.5-3.5) potential CYP-mediated DDIs per patient, compared to use of the standard 2-drug alert software. Pharmacists targeted patients for medication adjustment or close clinical monitoring in 23% of cases. CONCLUSIONS: The prevalence of potential CYP-mediated DDIs is high in geriatric patients with polypharmacy. The risk of DDIs increases as a function of the number of medications dispensed. Pharmacists' decision to intervene for potential CYP-mediated DDIs depends on clinical judgment in addition to the output from drug alert software programs, but may be facilitated by a single multicomponent, multidrug potential CYP-mediated DDI assessment.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Interações Medicamentosas , Polimedicação , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Hospitais Comunitários/estatística & dados numéricos , Humanos , Masculino , Prevalência , Estudos Prospectivos , Risco
14.
J Hypertens ; 31(5): 927-35, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23442991

RESUMO

OBJECTIVES: Diastolic dysfunction often represents the onset of diastolic heart failure (DHF). We previously showed in principle that diastolic function in Dahl salt-sensitive rats (DSS) can be genetically determined by quantitative trait loci (QTLs) that also modulate blood pressure (BP). METHODS: We analyzed cardiac phenotypes of four 'single' congenic strains by echocardiography, in which a specific DSS chromosome segment was replaced by its normotensive Lewis homologue. RESULTS: Two of the strains permanently lowered BP, and but attenuated diastolic dysfunction only in rats at 10 weeks of age, not at 15 weeks fed on a 2% NaCl diet starting from 8 weeks of age. We then combined multiple QTLs by integrating several 'single' congenic strains. As a result, BP was greatly reduced. Cardiac dysfunction and LV hypertrophy were continuously improved from 10 to 15 weeks, although the degree and timing of the improvement varied among different congenic combinations. CONCLUSION: Distinct QTLs exist that simultaneously modulate BP and diastolic function. These QTLs, in combination, synergistically lowered BP and permanently alleviated or reversed diastolic dysfunction. The genes that are contained in the congenic strains affecting diastolic function are not known for their specific influence on BP. Novel long-term strategies of prognosis, diagnosis and therapy for hypertensive DHF appear from this work.


Assuntos
Pressão Sanguínea/genética , Diástole/genética , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/genética , Locos de Características Quantitativas , Animais , Diástole/fisiologia , Dineínas/genética , Masculino , Ratos , Ratos Endogâmicos Dahl
15.
J Pharm Pharm Sci ; 16(5): 665-75, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24393550

RESUMO

PURPOSE: The purpose of this study was to develop an artificial neural network (ANN) model to predict drug removal during dialysis based on drug properties and dialysis conditions. Nine antihypertensive drugs were chosen as model for this study. METHODS: Drugs were dissolved in a physiologic buffer and dialysed in vitro in different dialysis conditions (UFRmin/UFRmax, with/without BSA). Samples were taken at regular intervals and frozen at -20ºC until analysis. Extraction methods were developed for drugs that were dialysed with BSA in the buffer. Drug concentrations were quantified by high performance liquid chromatography (HPLC) or mass spectrometry (LC/MS/MS). Dialysis clearances (CLDs) were calculated using the obtained drug concentrations. An ANOVA with Scheffe's pairwise adjustments was performed on the collected data in order to investigate the impact of drug plasma protein binding and ultrafiltration rate (UFR) on CLD. The software Neurosolutions was used to build ANNs that would be able to predict drug CLD (output). The inputs consisted of dialysis UFR and the herein drug properties: molecular weight (MW), logD and plasma protein binding. RESULTS: Observed CLDs were very high for the majority of the drugs studied. The addition of BSA in the physiologic buffer statistically significantly decreased CLD for carvedilol (p= 0.002) and labetalol (p<0.001), but made no significant difference for atenolol (p= 0.100). In contrast, varying UFR does not significantly affect CLD (p>0.025). Multiple ANNs were built and compared, the best model was a Jordan and Elman network which showed learning stability and good predictive results (MSEtesting = 129). CONCLUSION: In this study, we have developed an ANN-model which is able to predict drug removal during dialysis. Since experimental determination of all existing drug CLDs is not realistic, ANNs represent a promising tool for the prediction of drug CLD using drug properties and dialysis conditions.


Assuntos
Antagonistas Adrenérgicos beta/farmacocinética , Inibidores da Enzima Conversora de Angiotensina/farmacocinética , Anti-Hipertensivos/farmacocinética , Redes Neurais de Computação , Diálise Renal , Humanos , Membranas Artificiais , Soroalbumina Bovina/metabolismo
16.
J Pharm Pharm Sci ; 16(5): 657-64, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24393549

RESUMO

PURPOSE: In order to update our data on drug dialyzability using the high-permeability dialysis membranes, atenolol elimination by an in vitro dialysis model was compared to that observed in six patients during high-permeability hemodialysis (HD), and the predictive value of the model was evaluated. METHODS: Atenolol clearance was evaluated in six patients undergoing chronic HD. They were considered as eligible candidates if they were between 18 and 80 years of age, had a body mass index between 19 and 30 kg/m2, underwent HD and were taking atenolol on a regular basis in oral tablet form for at least 1 month before the study started. Atenolol clearance was also evaluated in three in vitro dialysis sessions with high-permeability polysulfone membrane. Atenolol was dissolved in 6 L of Krebs-Henseleit buffer with bovine serum albumin. Dialysis parameters were set to mirror as much as possible the patients' parameters (flow rate: 300 mL/min, dialyzate flow: 500 mL/min). After sample collection, drug concentrations were measured with high performance liquid chromatography. The comparison between in vivo and in vitro atenolol elimination kinetics was performed by drawing the curve fittings of concentrations vs. time on SigmaPlot 12, and adding a 95% prediction interval to each elimination curve fitting. RESULTS: Mean dialysis clearance of atenolol in vitro and in vivo was 198 ± 4 and 235 ± 53 mL/min, respectively. Atenolol was significantly removed within the study time period in both in vitro and in vivo experiments. By the end of in vitro dialysis, atenolol remaining in the drug reservoir was less than 2% of initial arterial concentration. CONCLUSION: Our study has indicated that atenolol is almost entirely cleared during high-permeability hemodialysis. Furthermore, the in vitro prediction interval of the drug elimination curve fitting could forecast its in vivo elimination especially at the end of dialysis.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Atenolol/farmacocinética , Modelos Biológicos , Diálise Renal , Antagonistas de Receptores Adrenérgicos beta 1/sangue , Adulto , Idoso , Atenolol/sangue , Feminino , Humanos , Masculino , Membranas Artificiais , Pessoa de Meia-Idade , Permeabilidade
17.
Environ Toxicol Chem ; 31(3): 508-17, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22180277

RESUMO

The authors examined effects of three common contaminants, caffeine (CF), acetaminophen (AC), and diclofenac (DF), as well as their mixtures on the development, functioning, and biodiversity of river biofilm communities. Biofilms were cultivated in rotating annular reactors. Treatments included AC, CF, DF, AC + CF, AC + DF, CF + DF, AC + CF + DF at 5 µg/L, and their molar equivalent as carbon and nutrients. Incubations using ¹4C-labeled AC, DF, and CF indicated that 90% of the CF, 80% of the AC, and less than 2% of the DF were converted to CO2. Digital imaging revealed a variety of effects on algal, cyanobacterial, and bacterial biomass. Algal biomass was unaffected by AC or CF in combination with DF but significantly reduced by all other treatments. Cyanobacterial biomass was influenced only by the AC + DF application. All treatments other than AC resulted in a significant decrease in bacterial biomass. Diclofenac or DF + CF and DF + AC resulted in increases in micrometazoan grazing. The denaturing gradient gel electrophoresis of Eubacterial community DNA, evaluated by principal component analysis and analysis of similarity, indicated that relative to the control, all treatments had effects on microbial community structure (r = 0.47, p < 0.001). However, the AC + CF + DF treatment was not significantly different from its molar equivalent carbon and nutrient additions. The Archaeal community differed significantly in its response to these exposures based on community analyses, confirming a need to integrate these organisms into ecotoxicological studies.


Assuntos
Acetaminofen/toxicidade , Biofilmes/efeitos dos fármacos , Cafeína/toxicidade , Diclofenaco/toxicidade , Rios/microbiologia , Microbiologia da Água , Poluentes Químicos da Água/toxicidade , Archaea/classificação , Archaea/efeitos dos fármacos , Archaea/crescimento & desenvolvimento , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Biodiversidade , Biofilmes/crescimento & desenvolvimento , Biomassa , Carbono/farmacologia , Cianobactérias/classificação , Cianobactérias/efeitos dos fármacos , Cianobactérias/crescimento & desenvolvimento , Rios/química
18.
J Hypertens ; 30(1): 81-6, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22124177

RESUMO

OBJECTIVES: The discovery of causative genes leading to hypertension in animal models can reveal new mechanistic insights into blood pressure (BP) regulations. Previously, we isolated segments that harbor BP quantitative trait loci (QTLs) on rat chromosome 10 as defined by congenic strains made from crosses of inbred hypertensive Dahl salt-sensitive (DSS) and normotensive Lewis rats. The aim of the current study was to identify hypertension-causing genes for each QTL. METHODS: Molecular analysis was performed. RESULTS: A systematic and comprehensive molecular analysis divulged particular genes that carry nonconserved mutations. Specifically, the proline rich 11 gene is likely responsible for C10QTL5. C10QTL1 is one of five genes, namely Benzodiazepine receptor associated protein 1, Loc689764, myotubularin related protein 4, protein phosphatase 1E, PP2C domain containing and ring finger protein 43. Loc100363423 with no known function is a candidate for C10QTL3. The ATP-binding cassette, subfamily A (ABC1), member 8a gene is probably responsible for C10QTL2. CONCLUSIONS: Primary genes initiating polygenic hypertension are those not known to be involved in BP modulation. Novel pathways towards BP homeostasis appear to underlie the functionality of C10QTL5, C10QTL1 and C10QTL3 and C10QTL2. Moreover, these genes may become innovative targets for the diagnosis and therapeutics of essential hypertension.


Assuntos
Predisposição Genética para Doença , Hipertensão/genética , Animais , Sequência de Bases , Pressão Sanguínea , Primers do DNA , Homeostase , Humanos , Hipertensão/fisiopatologia , Mutação , Locos de Características Quantitativas , Ratos , Ratos Endogâmicos Dahl , Ratos Endogâmicos Lew , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
J Phys Chem A ; 115(48): 14006-12, 2011 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-22029260

RESUMO

Bare metal anions K(-), Rb(-), Cs(-), Fe(-), Co(-), Ni(-), Cu(-), and Ag(-), generated by electrospray ionization of the corresponding oxalate or tricarballylate solutions, were allowed to react with methyl and ethyl chloride, methyl bromide, nitromethane, and acetonitrile in the collision hexapole of a triple-quadrupole mass spectrometer. Observed reactions include (a) the formation of halide, nitride, and cyanide anions, which was shown to be likely due to the insertion of the metal into the C-X, C-N, and C-C bonds, (b) transfer of H(+) from the organic molecule, which is demonstrated to most likely be due to the simple transfer of a proton to form neutral metal hydride, and (c) in the case of nitromethane, direct electron transfer to form the nitromethane radical anion. Interestingly, Co(-) was the only metal anion to transfer an electron to acetonitrile. Differences in the reactions are related to the differences in electron affinity of the metals and the Δ(acid)H° of the metals and organic substrates. Density functional theory calculations at the B3-LYP/6-311++G(3df,2p)//B3-LYP/6-31+G(d) level of theory shed light on the relative energetics of these processes and the mechanisms by which they take place.


Assuntos
Ânions/química , Físico-Química , Gases/química , Metais/química , Prótons , Acetonitrilas/química , Transporte de Elétrons , Elétrons , Cloreto de Etil/química , Metano/análogos & derivados , Metano/química , Cloreto de Metila/química , Nitroparafinas/química , Oxalatos/química , Teoria Quântica , Soluções , Espectrometria de Massas por Ionização por Electrospray , Termodinâmica , Ácidos Tricarboxílicos/química
20.
Int J Phytoremediation ; 13(7): 674-80, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21972494

RESUMO

Salt-impacted soils resulting from oilfield brine spills are increasingly becoming a significant problem in oil-producing areas of Canada such as Alberta and Saskatchewan. The native halophyte Atriplex patula is being considered a potential species for phytoremediation of brine-impacted sites in these hemiboreal climactic zones. The objective of this study was to investigate the optimal seeding conditions under field conditions (with no irrigation) of A. patula for phytoremediation of salt from a brine-impacted site. Atriplex patula was identified in preliminary greenhouse trials to have one of the highest salt accumulations in relation to plant yields. Different seeding methods of A. patula were assessed in an attempt to achieve reproducible growth of this species. While plant yields for A. patula were improved on compacted soil by approximately 30-50%, growth was uneven with regard to density and height. The uneven growth may be due to seed quality and low precipitation during the field season, while improvements in plant yield on compact soil might be due to a lack of competition with other species.


Assuntos
Atriplex/crescimento & desenvolvimento , Plantas Tolerantes a Sal/crescimento & desenvolvimento , Alberta , Atriplex/fisiologia , Biodegradação Ambiental , Biomassa , Hordeum/crescimento & desenvolvimento , Salinidade , Plantas Tolerantes a Sal/fisiologia , Sais , Estações do Ano , Sementes/crescimento & desenvolvimento , Solo/análise , Poluentes do Solo , Água/fisiologia
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