Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 77
Filtrar
1.
Environ Pollut ; 348: 123906, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561036

RESUMO

Recently, there has been an increasing emphasis on examining the ecotoxicological effects of anthropogenic microparticles (MPs), especially microplastic particles, and related issues. Nevertheless, a notable deficiency exists in our understanding of the consequences on marine organisms, specifically in relation to microfibers and the combined influence of MPs and temperature. In this investigation, mysid shrimp (Americamysis bahia), an important species and prey item in estuarine and marine food webs, were subjected to four separate experimental trials involving fibers (cotton, nylon, polyester, hemp; 3 particles/ml; approximately 200 µm in length) or fragments (low-density Polyethylene: LDPE, polylactic acid: PLA, and their leachates; 5, 50, 200, 500 particles/ml; 1-20 µm). To consider the effects in the context of climate change, three different temperatures (22, 25, and 28 °C) were examined. Organismal growth and swimming behavior were measured following exposure to fragments and microfibers, and reactive oxygen species and particle uptake were investigated after microfiber exposure. To simulate the physical characteristics of MP exposure, such as microfibers obstructing the gills, we also assessed the post-fiber-exposure swimming behavior in an oxygen-depleted environment. Data revealed negligible fragment, but fiber exposure effects on growth. PLA leachate triggered higher activity at 25 °C and 28 °C; LDPE exposures led to decreased activity at 28 °C. Cotton exposures led to fewer behavioral differences compared to controls than other fiber types. The exposure to hemp fibers resulted in significant ROS increases at 28 °C. Microfibers were predominantly located within the gastric and upper gastrointestinal tract, suggesting extended periods of residence and the potential for obstructive phenomena over the longer term. The combination of increasing water temperatures, microplastic influx, and oxidative stress has the potential to pose risks to all components of marine and aquatic food webs.


Assuntos
Plásticos , Poluentes Químicos da Água , Animais , Microplásticos , Temperatura , Água , Polietileno , Brasil , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Crustáceos , Poliésteres
2.
Environ Pollut ; 334: 122116, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37394053

RESUMO

Tire tread particles (TTP) are environmentally prevalent microplastics and generate toxic aqueous leachate. We determined the total carbon and nitrogen leachate concentrations and chemical profiles from micron (∼32 µm) and centimeter (∼1 cm) TTP leachate over 12 days. Dissolved organic carbon (DOC) and total dissolved nitrogen (TDN) were used to measure the concentration of leached compounds. Nontargeted chemical analysis by comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOF-MS) was used to compare the chemical profiles of leachates. After leaching for 12 days, DOC was 4.0 times higher in the micron TTP leachate than in the centimeter TTP leachate, and TDN was 2.6 times higher. The total GC×GC/TOF-MS chromatographic feature peak area was 2.9 times greater in the micron TTP leachate than the centimeter TTP leachate, and similarly, the total relative abundance of 54 tentatively identified compounds was 3.3 times greater. We identified frequently measured tire-related chemicals, such as 6PPD, N-cyclohexyl-N'-phenylurea (CPU), and hexa(methoxymethyl)melamine (HMMM), but nearly 50% of detected chemicals were not previously reported in tire literature or lacked toxicity information. Overall, the results demonstrate that smaller TTP have a greater potential to leach chemicals into aquatic systems, but a significant portion of these chemicals are not well-studied and require further risk assessment.


Assuntos
Matéria Orgânica Dissolvida , Fenilenodiaminas , Plásticos , Poluentes Químicos da Água , Matéria Orgânica Dissolvida/análise , Matéria Orgânica Dissolvida/química , Matéria Orgânica Dissolvida/classificação , Cromatografia Gasosa-Espectrometria de Massas , Plásticos/análise , Plásticos/química , Plásticos/classificação , Tamanho da Partícula , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Poluentes Químicos da Água/classificação , Fenilenodiaminas/análise , Fenilenodiaminas/química , Fenilenodiaminas/classificação , Medição de Risco
3.
Chemosphere ; 296: 133934, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35176295

RESUMO

Synthetic rubber emissions from automobile tires are common in aquatic ecosystems. To assess potential impacts on exposed organisms, early life stages of the estuarine indicator species Inland Silverside (Menidia beryllina) and mysid shrimp (Americamysis bahia) were exposed to three tire particle (TP) concentrations at micro and nano size fractions (0.0038, 0.0378 and 3.778 mg/L in mass concentrations for micro size particles), and separately to leachate, across a 5-25 PSU salinity gradient. Following exposure, M. beryllina and A. bahia had significantly altered swimming behaviors, such as increased freezing, changes in positioning, and total distance moved, which could lead to an increased risk of predation and foraging challenges in the wild. Growth for both A. bahia and M. beryllina was reduced in a concentration-dependent manner when exposed to micro-TP, whereas M. beryllina also demonstrated reduced growth when exposed to nano-TP (except lowest concentration). TP internalization was dependent on the exposure salinity in both taxa. The presence of adverse effects in M. beryllina and A. bahia indicate that even at current environmental levels of tire-related pollution, which are expected to continue to increase, aquatic ecosystems may be experiencing negative impacts.


Assuntos
Ecossistema , Poluentes Químicos da Água , Animais , Crustáceos , Peixes , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
5.
Hum Mol Genet ; 27(4): 691-705, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29300972

RESUMO

UBTF (upstream binding transcription factor) exists as two isoforms; UBTF1 regulates rRNA transcription by RNA polymerase 1, whereas UBTF2 regulates mRNA transcription by RNA polymerase 2. Herein, we describe 4 patients with very similar patterns of neuroregression due to recurrent de novo mutations in UBTF (GRCh37/hg19, NC_000017.10: g.42290219C > T, NM_014233.3: c.628G > A) resulting in the same amino acid change in both UBTF1 and UBTF2 (p.Glu210Lys [p.E210K]). Disease onset in our cohort was at 2.5 to 3 years and characterized by slow progression of global motor, cognitive and behavioral dysfunction. Notable early features included hypotonia with a floppy gait, high-pitched dysarthria and hyperactivity. Later features included aphasia, dystonia, and spasticity. Speech and ambulatory ability were lost by the early teens. Magnetic resonance imaging showed progressive generalized cerebral atrophy (supratentorial > infratentorial) with involvement of both gray and white matter. Patient fibroblasts showed normal levels of UBTF transcripts, increased expression of pre-rRNA and 18S rRNA, nucleolar abnormalities, markedly increased numbers of DNA breaks, defective cell-cycle progression, and apoptosis. Expression of mutant human UBTF1 in Drosophila neurons was lethal. Although no loss-of-function variants are reported in the Exome Aggregation Consortium (ExAC) database and Ubtf-/- is early embryonic lethal in mice, Ubtf+/- mice displayed only mild motor and behavioral dysfunction in adulthood. Our data underscore the importance of including UBTF E210K in the differential diagnosis of neuroregression and suggest that mainly gain-of-function mechanisms contribute to the pathogenesis of the UBTF E210K neuroregression syndrome.


Assuntos
Mutação de Sentido Incorreto/genética , Proteínas Pol1 do Complexo de Iniciação de Transcrição/genética , Pré-Escolar , Disartria/genética , Feminino , Marcha Atáxica/genética , Humanos , Imageamento por Ressonância Magnética , Masculino , Hipotonia Muscular/genética , Linhagem , RNA Ribossômico 18S/genética
6.
Lupus ; 26(14): 1517-1527, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28467291

RESUMO

Background The abnormal biological activity of cytokines plays an important role in the pathophysiology of both systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Several studies have highlighted the association of vitamin D and certain pro-inflammatory cytokines with disease activity in SLE. However, there are limited data on the association of vitamin D and antiphospholipid antibodies (aPL) with various proinflammatory biomarkers in these patients and their relative impact on clinical outcomes. Methods The serum levels of several aPL, 25-hydroxy-vitamin D, pro-inflammatory cytokines including IFNα, IL-1ß, IL-6, IL-8, IP10, sCD40L, TNFα and VEGF were measured in 312 SLE patients from the Jamaican ( n = 45) and Hopkins ( n = 267) lupus cohorts using commercial Milliplex and ELISA assays. Oxidized LDL/ß2glycoprotein antigenic complexes (oxLß2Ag) and their associated antibodies were also measured in the Jamaican cohort. Healthy controls for oxidative marker and cytokine testing were used. Results Abnormally low vitamin D levels were present in 61.4% and 73.3% of Hopkins and Jamaican SLE patients, respectively. Median concentrations of IP10, TNFα, sCD40L and VEGF were elevated in both cohorts, oxLß2Ag and IL-6 were elevated in the Jamaican cohort, and IFNα, IL-1ß and IL-8 were the same or lower in both cohorts compared to controls. IP10 and VEGF were independent predictors of disease activity, aPL, IP10 and IL-6 were independent predictors of thrombosis and IL-8, and low vitamin D were independent predictors of pregnancy morbidity despite there being no association of vitamin D with pro-inflammatory cytokines. Conclusions Our results indicate that aPL-mediated pro-inflammatory cytokine production is likely a major mechanism of thrombus development in SLE patients. We provide presumptive evidence of the role IL-8 and hypovitaminosis D play in obstetric pathology in SLE but further studies are required to characterize the subtle complexities of vitamin D's relationship with cytokine production and disease activity in these patients.


Assuntos
Citocinas/sangue , Lúpus Eritematoso Sistêmico/fisiopatologia , Estresse Oxidativo , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antifosfolipídeos/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Mediadores da Inflamação/sangue , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Trombose/etiologia , Vitamina D/sangue , Adulto Jovem
8.
Free Radic Biol Med ; 99: 189-198, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27519268

RESUMO

BACKGROUND: Nitric oxide (NO) is an important vascular signalling molecule. NO is synthesised endogenously by endothelial nitric oxide synthase (eNOS). An alternate pathway is exogenous dietary nitrate, which can be converted to nitrite and then stored or further converted to NO and used immediately. Atherosclerosis is associated with endothelial dysfunction and subsequent lesion formation. This is thought to arise due to a reduction in the bioavailability and/or bioactivity of endogenous NO. AIM: To determine if dietary nitrate can protect against endothelial dysfunction and lesion formation in the ApoE-/- mouse fed a high fat diet (HFD). METHODS AND RESULTS: ApoE-/- fed a HFD were randomized to receive (i) high nitrate (10mmol/kg/day, n=12), (ii) moderate nitrate (1mmol/kg/day, n=8), (iii) low nitrate (0.1mmol/kg/day, n=8), or (iv) sodium chloride supplemented drinking water (control, n=10) for 10 weeks. A group of C57BL6 mice (n=6) received regular water and served as a healthy reference group. At 10 weeks, ACh-induced vessel relaxation was significantly impaired in ApoE-/- mice versus C57BL6. Mice supplemented with low or moderate nitrate showed significant improvements in ACh-induced vessel relaxation compared to ApoE-/- mice given the high nitrate or sodium chloride. Plaque collagen expression was increased and lipid deposition reduced following supplementation with low or moderate nitrate compared to sodium chloride, reflecting increased plaque stability with nitrate supplementation. Plasma nitrate and nitrite levels were significantly increased in all three groups fed the nitrate-supplemented water. CONCLUSION: Low and moderate dose nitrate significantly improved endothelial function and atherosclerotic plaque composition in ApoE-/- mice fed a HFD.


Assuntos
Apolipoproteínas E/genética , Aterosclerose/dietoterapia , Suplementos Nutricionais , Nitratos/administração & dosagem , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico/metabolismo , Placa Aterosclerótica/dietoterapia , Acetilcolina/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Apolipoproteínas E/deficiência , Aterosclerose/etiologia , Aterosclerose/genética , Aterosclerose/patologia , Colágeno/genética , Colágeno/metabolismo , Dieta Hiperlipídica/efeitos adversos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nitratos/sangue , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologia , Técnicas de Cultura de Tecidos , Vasodilatação/efeitos dos fármacos
9.
Br J Pharmacol ; 173(4): 752-65, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26103560

RESUMO

BACKGROUND AND PURPOSE: Inflammasomes are multimeric complexes that facilitate caspase-1-mediated processing of the pro-inflammatory cytokines IL-1ß and IL-18. Clinical hypertension is associated with renal inflammation and elevated circulating levels of IL-1ß and IL-18. Therefore, we investigated whether hypertension in mice is associated with increased expression and/or activation of the inflammasome in the kidney, and if inhibition of inflammasome activity reduces BP, markers of renal inflammation and fibrosis. EXPERIMENTAL APPROACH: Wild-type and inflammasome-deficient ASC(-/-) mice were uninephrectomized and received deoxycorticosterone acetate and saline to drink (1K/DOCA/salt). Control mice were uninephrectomized but received a placebo pellet and water. BP was measured by tail cuff; renal expression of inflammasome subunits and inflammatory markers was measured by real-time PCR and immunoblotting; macrophage and collagen accumulation was assessed by immunohistochemistry. KEY RESULTS: 1K/DOCA/salt-induced hypertension in mice was associated with increased renal mRNA expression of inflammasome subunits NLRP3, ASC and pro-caspase-1, and the cytokine, pro-IL-1ß, as well as protein levels of active caspase-1 and mature IL-1ß. Following treatment with 1K/DOCA/salt, ASC(-/-) mice displayed blunted pressor responses and were also protected from increases in renal expression of IL-6, IL-17A, CCL2, ICAM-1 and VCAM-1, and accumulation of macrophages and collagen. Finally, treatment with a novel inflammasome inhibitor, MCC950, reversed hypertension in 1K/DOCA/salt-treated mice. CONCLUSIONS AND IMPLICATIONS: Renal inflammation, fibrosis and elevated BP induced by 1K/DOCA/salt treatment are dependent on inflammasome activity, highlighting the inflammasome/IL-1ß pathway as a potential therapeutic target in hypertension.


Assuntos
Hipertensão/metabolismo , Inflamassomos/metabolismo , Nefropatias/metabolismo , Animais , Proteínas Reguladoras de Apoptose/deficiência , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Adaptadoras de Sinalização CARD , Desoxicorticosterona/administração & dosagem , Hipertensão/induzido quimicamente , Inflamassomos/antagonistas & inibidores , Nefropatias/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Sais/administração & dosagem
10.
J Food Sci ; 80(1): E84-92, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25471730

RESUMO

Composite "wet" alginate films were manufactured from alginate-carbohydrate solutions containing 5% alginate and 0.25% pectin, carrageenan (kappa or iota), potato starch (modified or unmodified), gellan gum, or cellulose (extracted or commercial). The "wet" alginate films were used as a model to understand co-extruded alginate sausage casings that are currently being used by several sausage manufacturers. The mechanical, optical, and microstructural properties of the calcium cross-linked composite films were explored. In addition, the water holding capacity and textural profile analysis properties of the alginate-carbohydrate gels were studied. The results indicate that the mechanical properties of "wet" alginate films/casings can be modified by adding various carbohydrates to them. Alginate films with pectin, carrageenan, and modified potato starch had significantly (P < 0.05) greater elongation values than pure alginate films. The alginate-pectin films also had greater (P < 0.05) tensile strengths than the pure alginate films. Alginate films with extracted cellulose, commercial cellulose, and modified potato starch had lower (P < 0.05) puncture force, distance, and work values than the alginate control films. Transmission electron microscopy images showed a very uniform alginate network in the control films. Several large cellulose fibers were visible in the films with extracted cellulose, while the cellulose fibers in the films with commercial cellulose were difficult to distinguish. Despite these apparent differences in cellulose fiber length, the 2 cellulose films had similar puncture and tensile properties.


Assuntos
Alginatos/química , Amido/química , Carragenina/química , Celulose/química , Manipulação de Alimentos , Géis/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Microscopia Eletrônica de Transmissão , Estrutura Molecular , Pectinas/química , Polissacarídeos Bacterianos/química , Solanum tuberosum/química , Resistência à Tração/fisiologia , Água/química
11.
Free Radic Res ; 49(2): 186-98, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25496431

RESUMO

Nicotinamide adenine dinucleotide phosphate oxidases (NOX) are enzymes that generate reactive oxygen species (ROS). NOX2 activity in the vascular wall is elevated in hypercholesterolemia, and contributes to oxidative stress and atherogenesis. Here we examined the role of another NOX isoform, NOX1, in atherogenesis in apolipoprotein E-knockout (APOE(-/-)) mice fed a Western diet for 14 weeks. Although NOX1 mRNA expression was unchanged in aortas from APOE(-/-) versus wild-type mice, expression of the NOX1-specific organizer, NOXO1, was diminished, consistent with an overall reduction in NOX1 activity in APOE(-/-) mice. To examine the impact of a further reduction in NOX1 activity, APOE(-/-) mice were crossed with NOX1(-/y) mice to generate NOX1(-/y)/APOE(-/-) double-knockouts. NOX1 deficiency in APOE(-/-) mice was associated with 30-50% higher plasma very-low-density lipoprotein (VLDL)/LDL and triglyceride levels (P < 0.01). Vascular ROS levels were also elevated by twofold in NOX1(-/y)/APOE(-/-) versus APOE(-/-) mice (P < 0.05), despite no changes in expression of other NOX subunits. Although en face analysis of the descending aorta revealed no differences in plaque area between NOX1(-/y)/APOE(-/-) and APOE(-/-) mice, intimal thickening in the aortic sinus was increased by 40% (P < 0.05) in the double-knockouts. Moreover, NOX1 deficiency was associated with a less stable plaque phenotype; aortic sinus lesions contained 60% less collagen (P < 0.01), 40% less smooth muscle (P < 0.01), and 2.5-fold higher levels of matrix metalloproteinase-9 (P < 0.001) than lesions in APOE(-/-) mice. Thus, these data, which suggest a protective role for NOX1 against hyperlipidemia and atherosclerosis in APOE(-/-) mice, highlight the complex and contrasting roles of different NOX isoforms (e.g., NOX2 versus NOX1) in vascular pathology.


Assuntos
Apolipoproteínas E/genética , Aterosclerose/genética , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , NADH NADPH Oxirredutases/genética , Triglicerídeos/sangue , Animais , Aterosclerose/sangue , Lipoproteínas LDL/genética , Lipoproteínas VLDL/genética , Camundongos , Camundongos Knockout , NADPH Oxidase 1 , Triglicerídeos/genética
12.
Clin Pharmacol Ther ; 96(4): 429-37, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24949994

RESUMO

Clindamycin is commonly prescribed to treat children with skin and skin-structure infections (including those caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)), yet little is known about its pharmacokinetics (PK) across pediatric age groups. A population PK analysis was performed in NONMEM using samples collected in an opportunistic study from children receiving i.v. clindamycin per standard of care. The final model was used to optimize pediatric dosing to match adult exposure proven effective against CA-MRSA. A total of 194 plasma PK samples collected from 125 children were included in the analysis. A one-compartment model described the data well. The final model included body weight and a sigmoidal maturation relationship between postmenstrual age (PMA) and clearance (CL): CL (l/h) = 13.7 × (weight/70)(0.75) × (PMA(3.1)/(43.6(3.1) + PMA(3.1))); V (l) = 61.8 × (weight/70). Maturation reached 50% of adult CL values at ~44 weeks PMA. Our findings support age-based dosing.


Assuntos
Antibacterianos/farmacocinética , Clindamicina/farmacocinética , Adolescente , Antibacterianos/administração & dosagem , Criança , Pré-Escolar , Clindamicina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Modelos Biológicos
13.
J Food Sci ; 79(4): E562-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24611902

RESUMO

In this study, the physical properties of "wet" alginate films gelled with various divalent cations (Ba(2+) , Ca(2+) , Mg(2+) , Sr(2+) , and Zn(2+) ) were explored. Additionally, the effect of adding NaCl to the alginate film-forming solution prior to gelling was evaluated. Aside from Mg(2+) , all of the divalent cations were able to produce workable "wet" alginate films. Films gelled with BaCl2 (without added NaCl) had the highest (P < 0.05) tensile strength and Young's modulus while films gelled with CaCl2 (alone) had the highest puncture strength. The Zn-alginate and Sr-alginate films had the highest elongation at break values. Adding NaCl to the alginate film-forming solution increased the viscosity of the solution. Films with added NaCl were less transparent and had lower tensile strength, elongation, and puncture strength than films formed without NaCl in the film-forming solution. ATR-FTIR results showed a slight shift in the asymmetric COO(-) vibrational peak of the alginate when the "wet" alginate films were gelled with Zn(2+) .


Assuntos
Alginatos/química , Cátions/química , Embalagem de Alimentos/métodos , Cloreto de Sódio/química , Estresse Mecânico , Resistência à Tração , Géis/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Oligoelementos/química , Viscosidade
14.
Public Health Genomics ; 17(2): 76-83, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24458016

RESUMO

BACKGROUND: Knowledge about hereditary colorectal cancer (CRC) can aid cancer screening and prevention in high-risk patients. Genetic testing, once conducted primarily at academic centers, is now routinely performed in a variety of clinics. Nonacademic physicians may not be aware of hereditary CRC standards of care. METHODS: From August to November 2012, a survey was administered to predominantly primary care physicians evaluating academic center affiliation, past training in genetics and knowledge regarding hereditary CRC. RESULTS: One hundred forty physicians completed the survey. Knowledge of hereditary CRC was neither associated with academic affiliation nor with training during medical school or residency, but with continuing medical education (CME) training. Those with CME training were more likely to know that screening could be enhanced for patients with a hereditary cancer risk (OR = 4.49, 95% CI = 1.40-14.38) and that an individual with hereditary CRC would have different screening recommendations (OR = 7.49, 95% CI = 1.37-40.81). Residency training and CME training were associated with more frequent hereditary risk assessment. CONCLUSION: Genetics training may be associated with physicians' knowledge and assessment of hereditary CRC. Training at the CME level in particular may be integral to the delivery of genetic services in clinical practice.


Assuntos
Centros Médicos Acadêmicos , Neoplasias Colorretais , Educação Médica/estatística & dados numéricos , Genética Médica/educação , Conhecimentos, Atitudes e Prática em Saúde , Médicos de Atenção Primária/educação , Padrões de Prática Médica/estatística & dados numéricos , Competência Clínica/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/prevenção & controle , Coleta de Dados , Detecção Precoce de Câncer/estatística & dados numéricos , Educação Médica Continuada/estatística & dados numéricos , Feminino , Testes Genéticos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco/estatística & dados numéricos , Estados Unidos
15.
Nitric Oxide ; 35: 72-8, 2013 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-24012721

RESUMO

Impaired platelet responsiveness to nitric oxide (NO resistance) is a common characteristic of many cardiovascular disease states and represents an independent risk factor for cardiac events and mortality. NO resistance reflects both scavenging of NO by superoxide (O2(-)), and impairment of the NO receptor, soluble guanylate cyclase (sGC). There is thus an urgent need for circumvention of NO resistance in order to improve clinical outcomes. Nitroxyl (HNO), like NO, produces vasodilator and anti-aggregatory effects, largely via sGC activation, but is not inactivated by O2(-). We tested the hypothesis that HNO circumvents NO resistance in human platelets. In 57 subjects with or without ischemic heart disease, platelet responses to the HNO donor isopropylamine NONOate (IPA/NO) and the NO donor sodium nitroprusside (SNP) were compared. While SNP (10µM) induced 29±3% (p<0.001) inhibition of platelet aggregation, IPA/NO (10µM) caused 75±4% inhibition (p<0.001). In NO-resistant subjects (n=28), the IPA/NO:SNP response ratio was markedly increased (p<0.01), consistent with partial circumvention of NO resistance. Similarly, cGMP accumulation in platelets was greater (p<0.001) with IPA/NO than with SNP stimulation. The NO scavenger carboxy-PTIO (CPTIO, 200µM) inhibited SNP and IPA/NO responses by 92±7% and 17±4% respectively (p<0.001 for differential inhibition), suggesting that effects of IPA/NO are only partially NO-mediated. ODQ (10µM) inhibited IPA/NO responses by 36±8% (p<0.001), consistent with a contribution of sGC/haem to IPA/NO inhibition of aggregation. There was no significant relationship between whole blood ROS content and IPA/NO responses. Thus the HNO donor IPA/NO substantially circumvents platelet NO resistance while acting, at least partially, as a haem-mediated sGC activator.


Assuntos
Plaquetas/efeitos dos fármacos , Óxido Nítrico/metabolismo , Óxidos de Nitrogênio/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Plaquetas/metabolismo , Estudos de Casos e Controles , GMP Cíclico/metabolismo , Feminino , Humanos , Hidrazinas/farmacologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica , Nitroprussiato/farmacologia , Oxirredução
16.
Regul Toxicol Pharmacol ; 63(3): 426-32, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22668749

RESUMO

Global regulatory agencies require bioinformatic sequence analysis as part of their safety evaluation for transgenic crops. Analysis typically focuses on encoded proteins and adjacent endogenous flanking sequences. Recently, regulatory expectations have expanded to include all reading frames of the inserted DNA. The intent is to provide biologically relevant results that can be used in the overall assessment of safety. This paper evaluates the relevance of assessing the allergenic potential of all DNA reading frames found in common food genes using methods considered for the analysis of T-DNA sequences used in transgenic crops. FASTA and BLASTX algorithms were used to compare genes from maize, rice, soybean, cucumber, melon, watermelon, and tomato using international regulatory guidance. Results show that BLASTX for maize yielded 7254 alignments that exceeded allergen similarity thresholds and 210,772 alignments that matched eight or more consecutive amino acids with an allergen; other crops produced similar results. This analysis suggests that each nontransgenic crop has a much greater potential for allergenic risk than what has been observed clinically. We demonstrate that a meaningful safety assessment is unlikely to be provided by using methods with inherently high frequencies of false positive alignments when broadly applied to all reading frames of DNA sequence.


Assuntos
Antígenos de Plantas/genética , Produtos Agrícolas/genética , DNA Bacteriano/genética , Proteínas de Plantas/genética , Homologia de Sequência de Aminoácidos , Sequência de Aminoácidos , Biologia Computacional , Bases de Dados de Proteínas , Dados de Sequência Molecular , Plantas Geneticamente Modificadas , Alinhamento de Sequência
17.
J Appl Microbiol ; 104(5): 1442-8, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18194254

RESUMO

AIM: To determine the stability and variability in concentration of spore suspensions of Bacillus anthracis (BA) spore suspensions by comparing different methods of enumeration and to detect changes, if any, under different storage conditions. METHODS AND RESULTS: Plate and microscope counts were compared to measuring the genomic equivalents based on DNA content BA spore suspensions. We developed chemical methods to extract spore DNA and extra-spore (ES) DNA. DNA mass was determined by gel electrophoresis and QPCR assays were developed using the markers on the chromosome (rpoB) and the pXO1 plasmid (pag). The plate counts and microscope counts were very stable (for up to 900 days). The effect of freezing and the presence of additives in samples were tested for up to 300 days, and the results indicated that the additives tested and freezing did not decrease the viability or microscope counts. CONCLUSIONS: Bacillus anthracis spore suspensions can be stored for long periods of time without significant loss of viability or clumping. The content of ES DNA was variable and changed with time. SIGNIFICANT AND IMPACT OF THE STUDY: The study shows that BA spore suspensions can be developed for reference materials providing a uniform basis for comparing detection equipment and results from different laboratories.


Assuntos
Bacillus anthracis/fisiologia , Preservação Biológica , Esporos Bacterianos , Antraz/microbiologia , Bacillus anthracis/genética , Técnicas Bacteriológicas , Primers do DNA/genética , DNA Bacteriano/análise , Viabilidade Microbiana , Reação em Cadeia da Polimerase/métodos
18.
J Laryngol Otol ; 121(6): 571-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17134537

RESUMO

AIM: To establish the diagnostic accuracy and adequacy of fine needle aspiration cytology (FNAC) within a regional cancer network, and to determine what service improvements may be required to allow successful implementation of an FNAC-based, 'one-stop' head and neck clinic, as proposed by the current National Institute for Clinical Excellence guidelines. MATERIALS AND METHODS: The Sussex cancer network serves a population of 1,200,000 and contains five hospitals within three acute trusts. In 2004, an audit was undertaken retrospectively to examine the diagnostic adequacy and accuracy of head and neck FNAC across the network. Comparisons were then made with the results of subsequent relevant surgery. For the purposes of the audit, FNAC was subdivided into three main groups: salivary gland, thyroid gland and neck node. As part of the data analysis, we also noted the clinical source of the FNAC and whether it was performed blind or under image guidance. RESULTS: In 2004, 712 FNAC procedures were undertaken in 647 patients, 276 of whom underwent subsequent surgery. Fine needle aspiration cytology was non-diagnostic in 52 per cent of patients in the neck node group, in 50 per cent in the salivary gland group and in 30 per cent in the thyroid group. With these non-diagnostic results removed, statistical analysis was performed on data from those patients who had undergone both FNAC and subsequent surgery. This gave a sensitivity of 89 per cent and a specificity of 57 per cent in the neck node group, a sensitivity of 64 per cent and specificity of 100 per cent in the salivary gland group, and a sensitivity of 62 per cent and specificity of 86 per cent in the thyroid group. Diagnostic problems with FNAC were noted, particularly in the differentiation of reactive nodal hyperplasia from lymphoma and in diagnosing follicular thyroid lesions. Ultrasound guidance was used in 50 per cent of the thyroid FNAC procedures but in only a minority of patients in the neck node and salivary gland groups. CONCLUSION: This audit demonstrated widespread diagnostic difficulties associated with head and neck FNAC in a large patient sample. It is likely that these problems will be mirrored in other cancer networks. In order for one-stop head and neck clinics to succeed, the non-diagnostic rate of FNAC in particular must be minimised. There are strategies to enable this, depending on local resources, including increased access to cytologists or cytology technicians, diagnostic ultrasound, image guidance for FNAC and the use of ultrasound-guided core biopsy.


Assuntos
Biópsia por Agulha Fina/normas , Institutos de Câncer/organização & administração , Erros de Diagnóstico/estatística & dados numéricos , Neoplasias de Cabeça e Pescoço/diagnóstico , Biópsia por Agulha Fina/métodos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Auditoria Médica , Estudos Retrospectivos , Sensibilidade e Especificidade
19.
Lupus ; 14(11): 914-7, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16335586

RESUMO

Antiphospholipid syndrome in association with vasculitis is highlighted in this report. The combination of thrombotic and inflammatory processes resulted in endocarditis, aneurysm formation and thrombosis. To our knowledge this is the first presentation of a large vessel aneurysm in these conditions. Anticoagulation and immunosuppression are the treatment modalities of choice.


Assuntos
Aneurisma/etiologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Endocardite/etiologia , Poliarterite Nodosa/complicações , Poliarterite Nodosa/diagnóstico , Aneurisma/patologia , Angiografia , Endocardite/diagnóstico , Humanos , Masculino , Artérias Mesentéricas , Pessoa de Meia-Idade , Artéria Ulnar/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...