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1.
Anal Chem ; 95(13): 5610-5617, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36961989

RESUMO

Antigen tests to detect SARS-CoV-2 have emerged as a promising rapid diagnostic method for COVID-19, but they are unable to differentiate between variants of concern (VOCs). Here, we report a rapid point-of-care test (POC-T), termed CoVariant-SPOT, that uses a set of antibodies that are either tolerant or intolerant to spike protein mutations to identify the likely SARS-CoV-2 strain concurrent with COVID-19 diagnosis using antibodies targeting the nucleocapsid protein. All reagents are incorporated into a portable, multiplexed, and sensitive diagnostic platform built upon a nonfouling polymer brush. To validate CoVariant-SPOT, we tested recombinant SARS-CoV-2 proteins, inactivated viruses, and nasopharyngeal swab samples from COVID-19 positive and negative individuals and showed that CoVariant-SPOT can readily distinguish between two VOCs: Delta and Omicron. We believe that CoVariant-SPOT can serve as a valuable adjunct to next-generation sequencing to rapidly identify variants using a scalable and deployable POC-T, thereby enhancing community surveillance efforts worldwide and informing treatment selection.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Teste para COVID-19 , Anticorpos
2.
Curr Opin Urol ; 30(1): 9-16, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31652164

RESUMO

PURPOSE OF REVIEW: Prostate cancer is a high prevalence malignancy whose management is a major challenge for clinicians worldwide. Molecular imaging, and in particular PET with computed tomography (PET/CT), is increasingly gaining importance in the work up and management of all prostate cancer patients. PET/CT remains, however, an expensive imaging modality and currently not reimbursed. RECENT FINDINGS: Although other PET tracers are available and have gained institutional recognition from regulatory agencies, prostate-specific membrane agents (PSMA)-based PET/CT tracers have demonstrated the highest sensitivity and specificity for prostate cancer, outperforming any other PET radioligand to date. Regardless of the clinical scenario (staging, biochemical recurrence, therapy response assessment in advanced prostate cancer) PSMA PET/CT scans have become common practice in countries allowing for use outside of controlled clinical trials because of the overwhelming evidence demonstrating the extremely high sensitivity of this imaging modality in identifying prostate cancer lesions. This evidence can make PSMA PET/CT appealing for clinicians and lead to unnecessary scanning with limited supporting evidence. SUMMARY: Our aim is to provide an update on the most recent literature available on PET-based imaging for prostate cancer and particularly PSMA PET/CT, offering an expert opinion on the data collected to provide clinicians with guidance on appropriateness and efficacy of PET-based imaging, in order to maximize clinical benefits and avoid waste of resources.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Humanos , Masculino , Imagem Molecular , Tomografia por Emissão de Pósitrons , Próstata/patologia , Neoplasias da Próstata/patologia
3.
J Org Chem ; 79(21): 10153-69, 2014 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-25265243

RESUMO

We report details of the synthesis of a series of bi- and trichromophores. These compounds contain mixtures of chromophores that have zwitterionic (ZWI) and neutral ground state (NGS) components covalently attached to each other. The neutral ground state moieties are based on dyes with aniline donors--such as Disperse Red 1--whereas the zwitterionic components are derived from chromophores with pro-aromatic donors such as 1,4-dihydropyridinylidene. By combining both ZWI and NGS components, we aim to develop novel compounds for nonlinear optics in which there is an enhancement of the overall hyperpolarizability coupled with a decrease in the net dipole moment. Thus, this approach should eliminate the electrostatic effects that result when only one type of chromophore is used, and so reduce the likelihood of undesirable aggregation occurring. This, in turn, should enable us to realize organic materials with large macroscopic optical nonlinearities. An analysis of the UV-vis results suggests that there is a strong dependence on solvent polarity that determines whether the embedded constituents should be treated as discrete elements; in low polarity solvents, there appear to be strong intramolecular interactions occurring, particularly when a 1,4-quinolinylidene-based donor is used in the ZWI component.

4.
Neuromodulation ; 17(6): 599-615; discussion 615, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25112892

RESUMO

INTRODUCTION: The International Neuromodulation Society (INS) has determined that there is a need to provide an expert consensus that defines the appropriate use of neuromodulation technologies for appropriate patients. The Neuromodulation Appropriateness Consensus Committee (NACC) was formed to give guidance to current practice and insight into future developments. METHODS: The INS executive board selected members of the international scientific community to analyze scientific evidence for current and future innovations and to use clinical experience to fill in any gaps in information. The NACC used PubMed and Google Scholar to obtain current evidence in the field and used clinical and research experience to give a more complete picture of the innovations in the field. RESULTS: The NACC has determined that currently approved neurostimulation techniques and technologies have expanded our ability to treat patients in a more effective and specific fashion. Despite these advances, the NACC has identified several additional promising technologies and potential applications for neurostimulation that could move this field forward and expand the applicability of neuromodulation. CONCLUSIONS: The NACC concludes that the field of neurostimulation is an evolving and rapidly changing one that will lead to improved patient access, safety, and outcomes.


Assuntos
Dor Crônica/terapia , Terapia por Estimulação Elétrica , Manejo da Dor/métodos , Animais , Doenças Cardiovasculares/terapia , Terapia por Estimulação Elétrica/efeitos adversos , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/métodos , Terapia por Estimulação Elétrica/normas , Eletrodos Implantados/efeitos adversos , Eletrodos Implantados/normas , Medicina Baseada em Evidências , Humanos , Transtornos Mentais/terapia , Camundongos , Neuronavegação , Optogenética/instrumentação , Optogenética/métodos , Manejo da Dor/efeitos adversos , Transplante de Células-Tronco , Telemedicina/métodos , Estimulação Magnética Transcraniana/instrumentação , Estimulação Magnética Transcraniana/métodos , Estimulação Magnética Transcraniana/normas
5.
Neuromodulation ; 17(6): 571-97; discussion 597-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25112891

RESUMO

INTRODUCTION: The International Neuromodulation Society (INS) has determined that there is a need for guidance regarding safety and risk reduction for implantable neurostimulation devices. The INS convened an international committee of experts in the field to explore the evidence and clinical experience regarding safety, risks, and steps to risk reduction to improve outcomes. METHODS: The Neuromodulation Appropriateness Consensus Committee (NACC) reviewed the world literature in English by searching MEDLINE, PubMed, and Google Scholar to evaluate the evidence for ways to reduce risks of neurostimulation therapies. This evidence, obtained from the relevant literature, and clinical experience obtained from the convened consensus panel were used to make final recommendations on improving safety and reducing risks. RESULTS: The NACC determined that the ability to reduce risk associated with the use of neurostimulation devices is a valuable goal and possible with best practice. The NACC has recommended several practice modifications that will lead to improved care. The NACC also sets out the minimum training standards necessary to become an implanting physician. CONCLUSIONS: The NACC has identified the possibility of improving patient care and safety through practice modification. We recommend that all implanting physicians review this guidance and consider adapting their practice accordingly.


Assuntos
Dor Crônica/terapia , Terapia por Estimulação Elétrica/efeitos adversos , Manejo da Dor/métodos , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/métodos , Eletrodos Implantados/efeitos adversos , Segurança de Equipamentos , Medicina Baseada em Evidências , Hematoma/etiologia , Humanos , Neurocirurgia/educação , Manejo da Dor/efeitos adversos , Educação de Pacientes como Assunto , Seleção de Pacientes , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/prevenção & controle , Comportamento de Redução do Risco , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/prevenção & controle , Estimulação da Medula Espinal/efeitos adversos , Estimulação da Medula Espinal/instrumentação , Estimulação da Medula Espinal/métodos , Infecção dos Ferimentos/etiologia , Infecção dos Ferimentos/prevenção & controle
6.
PLoS One ; 19(6): e0304690, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861513

RESUMO

BACKGROUND: Antimicrobial overprescription is common for lower respiratory tract infections (LRTI), as viral and bacterial infections generally present with similar clinical features. Overprescription is associated with downstream antimicrobial resistance. This study aims to identify the prevalence and predictors of antibiotic prescription among patients hospitalized with viral LRTI. METHODS: A prospective cohort study was conducted among patients aged ≥1 year hospitalized with viral LRTI in a tertiary care hospital in Southern Province, Sri Lanka from 2018-2021. Demographic, clinical, and laboratory data were recorded. Nasopharyngeal and blood samples were collected for multiplex polymerase chain reaction testing for 21 respiratory pathogens and procalcitonin (PCT) detection, respectively. Demographic and clinical features associated with antibiotic prescription were identified using Chi Square and t-tests; significant variables (p<0.05) were further included in multivariable logistic regression models. The potential impact of biomarker testing on antibiotic prescription was simulated using standard c-reactive protein (CRP) and PCT cut-offs. RESULTS: Of 1217 patients enrolled, 438 (36.0%) had ≥1 respiratory virus detected, with 48.4% of these patients being male and 30.8% children. Influenza A (39.3%) and human rhinovirus/ enterovirus (28.3%) were most commonly detected. A total of 114 (84.4%) children and 266 (87.8%) adults with respiratory viruses were treated with antibiotics. Among children, neutrophil percentage (median 63.6% vs 47.6%, p = 0.04) was positively associated with antibiotic prescription. Among adults, headache (60.6% vs 35.1%, p = 0.003), crepitations/crackles (55.3% vs 21.6%, p<0.001), rhonchi/wheezing (42.9% vs 18.9%, p = 0.005), and chest x-ray opacities (27.4% vs 8.1%, p = 0.01) were associated with antibiotic prescription. Access to CRP and procalcitonin test results could have potentially decreased inappropriate antibiotic prescription in this study by 89.5% and 83.3%, respectively. CONCLUSIONS: High proportions of viral detection and antibiotic prescription were observed among a large inpatient cohort with LRTI. Increased access to point-of-care biomarker testing may improve antimicrobial prescription.


Assuntos
Antibacterianos , Infecções Respiratórias , Humanos , Masculino , Feminino , Sri Lanka/epidemiologia , Antibacterianos/uso terapêutico , Criança , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Adulto , Adolescente , Pré-Escolar , Pessoa de Meia-Idade , Estudos Prospectivos , Prevalência , Lactente , Hospitalização , Adulto Jovem , Pró-Calcitonina/sangue , Idoso , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-24427012

RESUMO

The title compound, C21H13N3O, crystallizes with two independent molecules with similar conformations per asymmetric unit. The dihydrofuran rings are essentially planar with maximum deviations of 0.017 (1) and 0.006 (1) Šfor the O atoms. The dihedral angles between the di-hydro-furan ring and the attached phenyl rings are 79.90 (6) and 82.07 (6)° in one mol-ecule and 79.36 (6) and 72.26 (6)° in the other. In the crystal, the molecules are linked by weak C-H⋯π and C-H⋯N inter-actions similar to those in other closely related crystals. The replacement of appended methyl by phenyl groups has not significantly affected the dihydrofuran ring structure or the crystal packing interactions.

8.
J Spinal Cord Med ; 46(3): 501-507, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-33798025

RESUMO

Context/Objective: Magnetic resonance imaging (MRI) indices of spinal cord damage are predictive of future motor function after spinal cord injury (SCI): hyperintensity length, midsagittal tissue bridges, and Brain and Spinal Injury Center (BASIC) scores. Whether these indices are predictive of outdoor walking after SCI is unknown. The primary purpose was to see if these MRI indices predict the ability to walk outdoors one-year after SCI. The secondary purpose was to determine if MRI indices provide additional predictive value if initial lower extremity motor scores are available.Design: Retrospective. Clinical T2-weighted MRIs were used to quantify spinal cord damage. Three MRI indices were calculated: midsagittal ventral tissue bridges, hyperintensity length, BASIC scores.Setting: Academic hospital.Participants: 129 participants with cervical SCI.Interventions: Inpatient rehabilitation.Outcomes Measures: One year after SCI, participants self-reported their outdoor walking ability.Results: Midsagittal ventral tissue bridges, hyperintensity length, and BASIC scores significantly correlated with outdoor walking ability (R = 0.34, P < 0.001; R = -0.25, P < 0.01; Rs = -0.35, P < 001, respectively). Using midsagittal ventral tissue bridges and hyperintensity length, the final adjusted R2 for model 1 = 0.19. For model 2, the adjusted R2 using motor scores alone = 0.81 and MRI variables were non-significant. All five participants with observable intramedullary hemorrhage reported they were unable to walk one block outdoors.Conclusions: The MRI indices were significant predictors of outdoor walking ability, but when motor scores were available, this was the strongest predictor and neither midsagittal tissue bridges nor hyperintensity length contributed additional value. MRI indices may be a quick and convenient supplement to physical examination when motor testing is unavailable.


Assuntos
Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/complicações , Estudos Retrospectivos , Caminhada , Imageamento por Ressonância Magnética/métodos , Exame Físico , Medula Espinal/patologia
9.
Trials ; 23(1): 777, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104702

RESUMO

BACKGROUND: In Australia, tobacco smoking rates have declined but inequalities remain with significantly higher smoking prevalence among low-socioeconomic populations. Clinical trial data suggest vaporized nicotine products (VNPs) aid smoking cessation. Most VNP trials have used refillable tank systems, but newer generation (pod) devices now comprise the largest market share yet have limited clinical trial evidence on safety and effectiveness. This study evaluates the effectiveness, safety and cost-effectiveness of VNPs (pod and tank device) compared with nicotine replacement therapy ([NRT]-gum or lozenge) for smoking cessation. METHODS: This is a two-arm, open-label, superiority, parallel group, randomized controlled trial (RCT) with allocation concealment and blinded outcome assessment. The RCT is conducted at the National Drug and Alcohol Research Centre at the University of New South Wales, Sydney, Australia. Participants are people who smoke daily, are interested in quitting and receive a government pension or allowance (N = 1058). Participants will be randomized (1:1 ratio) to receive 8 weeks of free: VNPs, with pod (40 mg/mL nicotine salt) and tank device (18 mg/mL freebase nicotine) in mixed flavours; or NRT (gum or lozenge; 4 mg). All participants will receive daily text message behavioural support for 5 weeks. Assessments will be undertaken by telephone at baseline, with three follow-up calls (two check-in calls within the first month and final follow-up at 7 months post randomization) to ascertain smoking status, treatment adherence and adverse events. The primary outcome is 6-month continuous abstinence verified by carbon monoxide breath test of ≤5ppm at 7-month follow-up. Safety and cost-effectiveness of VNPs versus NRT will also be evaluated. DISCUSSION: Further data are required to strengthen certainty of evidence for VNPs aiding smoking cessation, particularly for newer generation pod devices. To our knowledge, this trial is the first to offer choice of VNPs and no comparative effectiveness trial data exists for new pod devices. If effective, the findings can inform wider implementation of VNPs to aid smoking cessation in a priority group. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621000076875. Registered on 29 January 2021.  https://www.anzctr.org.au.


Assuntos
Alcoolismo , Abandono do Hábito de Fumar , Austrália , Análise Custo-Benefício , Humanos , Nicotina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Abandono do Hábito de Fumar/métodos , Classe Social , Nicotiana , Dispositivos para o Abandono do Uso de Tabaco/efeitos adversos , Resultado do Tratamento
10.
Cell Genom ; 2(11)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36465279

RESUMO

During pandemics, individuals exhibit differences in risk and clinical outcomes. Here, we developed single-cell high-throughput human in vitro susceptibility testing (scHi-HOST), a method for rapidly identifying genetic variants that confer resistance and susceptibility. We applied this method to influenza A virus (IAV), the cause of four pandemics since the start of the 20th century. scHi-HOST leverages single-cell RNA sequencing (scRNA-seq) to simultaneously assign genetic identity to cells in mixed infections of cell lines of European, African, and Asian origin, reveal associated genetic variants for viral burden, and identify expression quantitative trait loci. Integration of scHi-HOST with human challenge and experimental validation demonstrated that a missense variant in endoplasmic reticulum aminopeptidase 1 (ERAP1; rs27895) increased IAV burden in cells and human volunteers. rs27895 exhibits population differentiation, likely contributing to greater permissivity of cells from African populations to IAV. scHi-HOST is a broadly applicable method and resource for decoding infectious-disease genetics.

11.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 11): o3046-7, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22220058

RESUMO

The title mol-ecule, C(35)H(25)N(3)O(3), packs utilizing C-H⋯π attractive inter-actions causing the identical 4-benzyl-oxyphenyl groups to pack with different conformational angles. This difference is consistent with the variable inter-planar dihedral angles found in closely related structures.

12.
Minerva Urol Nephrol ; 73(1): 32-41, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32550630

RESUMO

INTRODUCTION: Prostate specific membrane antigen (PSMA) positron emission tomography (PET) with computed tomography (CT) is a promising molecular imaging technique for prostate cancer (PCa). Although not yet included in international guidelines, PSMA PET/CT is commonly used in clinical practice to stage patients with newly diagnosed PCa. This review focuses on the most up-to-date literature on staging high-risk prostate cancer with PSMA PET/CT. EVIDENCE ACQUISITION: An online based literature research encompassing original studies, reviews and meta-analysis was performed in the month of November of 2019. The most relevant and impactful research was then extracted based on the expertise of the authors, with the specific focus of highlighting the clinical impact and appropriateness of PSMA PET/CT in staging PCa. EVIDENCE SYNTHESIS: The use of PSMA PET/CT is appropriate in all high-risk patients with newly diagnosed PCa as it will often have a significant clinical impact. Although preliminary findings are promising, there is still a scarcity of data regarding the performance of PSMA PET/CT vs. other modalities in defining disease within the prostate gland. There is good evidence suggesting that PSMA PET/CT may be superior to every other imaging modality in assessing loco-regional and distant metastatic disease. CONCLUSIONS: PSMA PET/CT has the potential to become a gold standard in staging high risk prostate cancer, providing clinicians with accurate information on the extent of disease within the prostate and the presence of loco-regional and distant metastatic disease within a single scan.


Assuntos
Estadiamento de Neoplasias/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Antígeno Prostático Específico/química , Neoplasias da Próstata/diagnóstico , Humanos , Masculino
13.
Sci Adv ; 7(49): eabl7682, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34860546

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are concerning in the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a rapid test, termed CoVariant-SCAN, that detects neutralizing antibodies (nAbs) capable of blocking interactions between the angiotensin-converting enzyme 2 receptor and the spike protein of wild-type (WT) SARS-CoV-2 and three other variants: B.1.1.7, B.1.351, and P.1. Using CoVariant-SCAN, we assessed neutralization/blocking of monoclonal antibodies and plasma from COVID-19­positive and vaccinated individuals. For several monoclonal antibodies and most plasma samples, neutralization against B.1.351 and P.1 variants is diminished relative to WT, while B.1.1.7 is largely cross-neutralized. We also showed that we can rapidly adapt the platform to detect nAbs against an additional variant­B.1.617.2 (Delta)­without reengineering or reoptimizing the assay. Results using CoVariant-SCAN are consistent with live virus neutralization assays and demonstrate that this easy-to-deploy test could be used to rapidly assess nAb response against multiple SARS-CoV-2 variants.

14.
Sci Adv ; 7(26)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34172447

RESUMO

Highly sensitive, specific, and point-of-care (POC) serological assays are an essential tool to manage coronavirus disease 2019 (COVID-19). Here, we report on a microfluidic POC test that can profile the antibody response against multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens-spike S1 (S1), nucleocapsid (N), and the receptor binding domain (RBD)-simultaneously from 60 µl of blood, plasma, or serum. We assessed the levels of antibodies in plasma samples from 31 individuals (with longitudinal sampling) with severe COVID-19, 41 healthy individuals, and 18 individuals with seasonal coronavirus infections. This POC assay achieved high sensitivity and specificity, tracked seroconversion, and showed good concordance with a live virus microneutralization assay. We can also detect a prognostic biomarker of severity, IP-10 (interferon-γ-induced protein 10), on the same chip. Because our test requires minimal user intervention and is read by a handheld detector, it can be globally deployed to combat COVID-19.


Assuntos
Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Testes Imediatos , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/virologia , Teste Sorológico para COVID-19/instrumentação , Humanos , Reprodutibilidade dos Testes , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo
15.
Comp Biochem Physiol B Biochem Mol Biol ; 151(3): 336-48, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18761099

RESUMO

There has been recent public concern regarding the impacts of environmental pollution on populations of otters. Population level impacts have been seen with otter (Lutra lutra) populations in Europe due to polychlorinated biphenyls, and with some segments of the Prince William Sound, AK, sea otter (Enhydra lutris) population following the Exxon Valdez oil spill. Despite public interest in these animals and their ecological significance, there are few tools that allow for the study of otter's response to contaminant exposure. Cytochrome p450 1A (CYP1A) performs the first step in metabolizing many xenobiotics, including many polychlorinated biphenyls and polycyclic aromatic hydrocarbons. CYP1A induction is a frequently used biomarker of exposure to these compounds. Despite the potential importance of this gene in ecological risk assessment, the complete coding sequence has not been published for any otter species. This study's objective was to isolate the gene for CYP1A1 and CYP1A2 in sea otters using a series of PCR-based approaches. The coding sequences from CYP1A1 and CYP1A2 from sea otters were identified and published in GenBank. Both CYP1A sequences are homologous to those obtained from marine mammals and other carnivores. These sequences will be useful as tools for researchers assessing contaminant exposure in mustelid populations.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Lontras/metabolismo , Animais , Sequência de Bases , Biomarcadores/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Dados de Sequência Molecular , Lontras/genética , Especificidade da Espécie , Poluentes Químicos da Água
16.
CJEM ; 8(2): 123-5, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17175875

RESUMO

A 33-year-old woman presented to a community emergency department with a 4-day history of monocular orbital pain, photophobia and pain on extraocular movement. Findings included chemosis, conjunctival injection and restricted extraocular movements causing strabismus. She was diagnosed with orbital cellulitis during her initial emergency department visit and treated with intravenous antibiotics. On her second ED visit later the same day, a diagnosis of orbital pseudotumour was made after computed tomography revealed inflammation of the sclera, optic nerve, muscle and adipose tissue within the orbit. Antibiotics were discontinued and tapering steroids were initiated, with prompt resolution of symptoms.


Assuntos
Celulite (Flegmão)/etiologia , Pseudotumor Orbitário/diagnóstico , Corticosteroides/uso terapêutico , Adulto , Celulite (Flegmão)/tratamento farmacológico , Feminino , Humanos , Pseudotumor Orbitário/tratamento farmacológico , Tomografia Computadorizada por Raios X
17.
Mar Pollut Bull ; 50(7): 705-23, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15946701

RESUMO

The relationships among cytochrome P450 induction in marine wildlife species, levels of fluorescent aromatic compounds (FAC) in their bile, the chemical composition of the inducing compounds, the significance of the exposure pathway, and any resulting injury, as a consequence of exposure to crude oil following a spill, are reviewed. Fish collected after oil spills often show increases in cytochrome P450 system activity, cytochrome P4501A (CYP1A) and bile fluorescent aromatic compounds (FAC), that are correlated with exposure to polycyclic aromatic hydrocarbons (PAH) in the oil. There is also some evidence for increases in bile FAC and induction of cytochrome P450 in marine birds and mammals after oil spills. However, when observed, increases in these exposure indicators are transitory and generally decrease to background levels within one year after the exposure. Laboratory studies have shown induction of cytochrome P450 systems occurs after exposure of fish to crude oil in water, sediment or food. Most of the PAH found in crude oil (dominantly 2- and 3-ring PAH) are not strong inducers of cytochrome P450. Exposure to the 4-ring chrysenes or the photooxidized products of the PAH may account for the cytochrome P450 responses in fish collected from oil-spill sites. The contribution of non-spill background PAH, particularly combustion-derived (pyrogenic) PAH, to bile FAC and cytochrome P450 system responses can be confounding and needs to be considered when evaluating oil spill effects. The ubiquity of pyrogenic PAH makes it important to fully characterize all sources of PAH, including PAH from natural resources, e.g. retene, in oil spill studies. In addition, such parameters as species, sex, age, ambient temperature and season need to be taken into account. While increases in fish bile FAC and cytochrome P450 system responses, can together, be sensitive general indicators of PAH exposure after an oil spill, there is little unequivocal evidence to suggest a linkage to higher order biological effects, e.g. toxicity, lesions, reproductive failure.


Assuntos
Bile/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Petróleo/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Animais Selvagens/imunologia , Bile/efeitos dos fármacos , Desastres , Exposição Ambiental , Peixes/metabolismo , Oceanos e Mares , Espectrometria de Fluorescência/métodos
18.
Environ Health Perspect ; 112(5): 511-5, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15064153

RESUMO

Structural differences were identified in gill DNA from two groups of English sole collected from Puget Sound, Washington, in October 2000. One group was from the industrialized Duwamish River (DR) in Seattle and the other from relatively clean Quartermaster Harbor (QMH). Chemical markers of sediment contamination [e.g., polynuclear aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs)] established that the DR was substantially more contaminated than QMH. The levels of these chemicals in the sediments of both sites were consistent with levels of cytochrome P450 1A (CYP1A) expression in the gills of English sole from the same sites. Structural differences in gill DNA between the groups were evinced via statistical models of Fourier transform-infrared (FT-IR) spectra. Marked structural damage was found in the gill DNA of the DR fish as reflected in differences in base functional groups (e.g., C-O and NH2) and conformational properties (e.g., arising from perturbations in vertical base stacking interactions). These DNA differences were used to discriminate between the two fish groups through principal components analysis of mean FT-IR spectra. In addition, logistic regression analysis allowed for the development of a "DNA damage index" to assess the effects of contaminants on the gill. The evidence implies that environmental chemicals contribute to the DNA changes in the gill. The damaged DNA is a promising marker for identifying, through gill biopsies, contaminant effects on fish.


Assuntos
DNA/efeitos dos fármacos , Linguado/genética , Brânquias/efeitos dos fármacos , Dibenzodioxinas Policloradas/análogos & derivados , Poluentes Químicos da Água/toxicidade , Animais , Benzofuranos/análise , Citocromo P-450 CYP1A1/metabolismo , DNA/química , Linguado/anatomia & histologia , Sedimentos Geológicos/química , Brânquias/metabolismo , Brânquias/patologia , Modelos Logísticos , Bifenilos Policlorados/análise , Dibenzodioxinas Policloradas/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Polímeros/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Washington , Poluentes Químicos da Água/análise
19.
Environ Toxicol Chem ; 21(8): 1618-27, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12152761

RESUMO

The Delaware River-Bay system, USA, was the subject of a study by the National Oceanic and Atmospheric Administration that involved chemical and biological analyses, including the use of the biomarker P450 human reporter gene system (HRGS) to document the occurrence and distribution of cytochrome P450 (CYP) 1A1-inducing compounds. Sediment extracts from 81 locations along the Delaware River, Delaware Bay and immediate coastline were tested by utilizing HRGS as an inexpensive screening test, and were also analyzed for polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls, with selected stations analyzed for dioxins and furans. Benthic community degradation has been observed when benzo[a]pyrene equivalents (BaPEq) exceeded 60 microg/g. The average levels of BaPEq for the largely industrialized upper, middle, and lower regions of the Delaware River were 107, 62, and 5 microg/g, respectively, excluding outliers. Tributaries leading into river averaged 21 microg/g BaPEq, whereas the central Bay and open coast had relatively low values (2.0 and 0.5 microg/g BaPEq, respectively). The HRGS values were highly correlated with total PAHs measured in the same sediment samples (r2 = 0.81). Overall, contamination levels consistently decreased from the upper and middle river sites as collection locations progressed down through the lower river and bay to the coast. Thus, despite the relatively high contaminant load in the river system, Delaware Bay and the immediate coastline seem to have relatively low levels of contaminants, and, therefore, impacts on the benthic organisms in the bay and coast would not be expected from these findings.


Assuntos
Biomarcadores/análise , Citocromo P-450 CYP1A1/análise , Citocromo P-450 CYP1A1/biossíntese , Genes Reporter/genética , Sedimentos Geológicos/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , Animais , Bioensaio/métodos , Delaware , Monitoramento Ambiental , Indução Enzimática , Humanos , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Poluentes Químicos da Água/farmacologia
20.
Environ Toxicol Chem ; 22(9): 1945-55, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12959519

RESUMO

Six toxicity assays were compared to determine their efficacy in assessing toxicity dynamics during a wetland bioremediation study. The toxicity bioassays used were the Microtox 100% elutriate test, Microtox Solid Phase Test (SPT), amphipod assay, P450 reporter gene system, Toxi-ChromoPad test and a Salmonella/microsome assay. Oiled sediments were analyzed for toxicity in the petroleum biostimulation experiment conducted along the San Jacinto River, near Houston (TX, USA). The bioassays were evaluated for their ability to measure acute toxicity, chronic toxicity, and the mutagenic potential of amended oiled plots as compared to oiled and unoiled control plots. Amendments were diammonium phosphate alone or in combination with potassium nitrate, which served as an alternate electron acceptor. With exception of the Toxi-ChromoPad and Salmonella tests, the bioassays exhibited a significant increase in toxicity after oil application. Microtox bioassays detected significant sediment toxicity up to 29 d after oil and amendment application. The Microtox solid phase test results correlated strongly with gas chromatography-mass spectrometry analyses of total target saturate and aromatic hydrocarbons. The amphipod assay detected initial toxicity with a decline to day 70, followed by a significant increase in toxicity on day 140 in plots receiving nutrient amendments, which may be in response to excessive nutrient application. Low levels of enzyme induction were observed with the P450 reporter gene system assay in all oiled sediments throughout the study, suggesting low but persistent levels of polycyclic aromatic hydrocarbons. Of the six tests, the two Microtox tests and the amphipod test showed the most potential in evaluating petroleum toxicity in wetland sediments.


Assuntos
Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Hidrocarbonetos Aromáticos/toxicidade , Petróleo , Anfípodes , Animais , Biodegradação Ambiental , Bioensaio/métodos , Sistema Enzimático do Citocromo P-450/biossíntese , Cromatografia Gasosa-Espectrometria de Massas , Genes Reporter , Hidrocarbonetos Aromáticos/análise , Microssomos , Salmonella , Testes de Toxicidade/métodos , Vibrio/genética
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