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1.
Sci Rep ; 11(1): 2809, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531581

RESUMO

Accurate prognostic biomarkers in early-stage melanoma are urgently needed to stratify patients for clinical trials of adjuvant therapy. We applied a previously developed open source deep learning algorithm to detect tumor-infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&E) images of early-stage melanomas. We tested whether automated digital (TIL) analysis (ADTA) improved accuracy of prediction of disease specific survival (DSS) based on current pathology standards. ADTA was applied to a training cohort (n = 80) and a cutoff value was defined based on a Receiver Operating Curve. ADTA was then applied to a validation cohort (n = 145) and the previously determined cutoff value was used to stratify high and low risk patients, as demonstrated by Kaplan-Meier analysis (p ≤ 0.001). Multivariable Cox proportional hazards analysis was performed using ADTA, depth, and ulceration as co-variables and showed that ADTA contributed to DSS prediction (HR: 4.18, CI 1.51-11.58, p = 0.006). ADTA provides an effective and attainable assessment of TILs and should be further evaluated in larger studies for inclusion in staging algorithms.

2.
Clin Cancer Res ; 26(5): 1126-1134, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31636101

RESUMO

PURPOSE: Biomarkers for disease-specific survival (DSS) in early-stage melanoma are needed to select patients for adjuvant immunotherapy and accelerate clinical trial design. We present a pathology-based computational method using a deep neural network architecture for DSS prediction. EXPERIMENTAL DESIGN: The model was trained on 108 patients from four institutions and tested on 104 patients from Yale School of Medicine (YSM, New Haven, CT). A receiver operating characteristic (ROC) curve was generated on the basis of vote aggregation of individual image sequences, an optimized cutoff was selected, and the computational model was tested on a third independent population of 51 patients from Geisinger Health Systems (GHS). RESULTS: Area under the curve (AUC) in the YSM patients was 0.905 (P < 0.0001). AUC in the GHS patients was 0.880 (P < 0.0001). Using the cutoff selected in the YSM cohort, the computational model predicted DSS in the GHS cohort based on Kaplan-Meier (KM) analysis (P < 0.0001). CONCLUSIONS: The novel method presented is applicable to digital images, obviating the need for sample shipment and manipulation and representing a practical advance over current genetic and IHC-based methods.

3.
Am J Clin Dermatol ; 21(1): 1-11, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31602560

RESUMO

Immunotherapy has revolutionized the treatment of melanoma. Targeting of the immune checkpoints cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 has led to improved survival in a subset of patients. Unfortunately, the use of immune checkpoint inhibitors is associated with significant side effects and many patients do not respond to treatment. Thus, there is an urgent need both for prognostic biomarkers to estimate risk and for predictive biomarkers to determine which patients are likely to respond to therapy. In this review, prognostic and predictive biomarkers that are an active area of research are outlined. Of note, certain transcriptomic signatures are already used in the clinic, albeit not routinely, to prognosticate patients. In the predictive setting, programmed cell death protein ligand 1 expression has been shown to correlate with benefit but is not precise enough to be used as an exclusionary biomarker. Future investigation will need to focus on biomarkers that are easily reproducible, cost effective, and accurate. The use of readily available clinical material, such as serum or hematoxylin and eosin-stained images, may offer one such path forward.


Assuntos
Biomarcadores Tumorais/metabolismo , Imunoterapia/métodos , Melanoma/tratamento farmacológico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacologia , Humanos , Imunoterapia/efeitos adversos , Melanoma/imunologia , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento
4.
J Trace Elem Med Biol ; 46: 32-38, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29413108

RESUMO

BACKGROUND AND OBJECTIVES: Exposure to cadmium (Cd) has been associated with aberrant zinc and copper homeostasis. This study investigated if Cd exposure impairs renal reabsorption of metals. METHODS: Renal tubular reabsorption of metals were calculated from urine to serum metal ratios and analyzed for an independent association with Cd exposure levels, using data from 100 men and 100 women, aged 16-60 years. RESULTS: The smoking prevalence was 30% in men and 0% in women. The male and female means (SD) for urine Cd were 0.54 (0.43) and 0.62 (0.43) µg/g creatinine. The mean (SD) for fractional zinc reabsorption was 77.2 (23) % in men and 87.7 (13.3) % in women, while the copper reabsorption was 100% in both men and women. Lower zinc reabsorption levels were associated with higher Cd exposure (P<0.001), higher serum copper to zinc ratios (P=0.007) and higher tubular impairment levels (P=0.024). Reduced zinc reabsorption was particularly severe in smokers as those with high Cd exposure had 44.9% and 37.2% (P<0.001) lower zinc reabsorption than those with low and moderate exposures. The mean zinc reabsorption in male non-smokers with high Cd exposure was 25.8% (P<0.001) and 18.2% (P=0.003) lower than those with low and moderate exposures, while the corresponding figure for female non-smokers was 17% (P<0.001), and 12.8% (P=0.013), respectively. CONCLUSIONS: This is the first report demonstrating Cd-dose dependent reduction in renal zinc reabsorption and high serum copper to zinc ratios.


Assuntos
Cádmio/toxicidade , Cobre/sangue , Cobre/urina , Poluentes Ambientais/toxicidade , Zinco/sangue , Zinco/urina , Adolescente , Adulto , Cádmio/sangue , Cádmio/urina , Proteínas de Transporte/metabolismo , Creatinina/metabolismo , Poluentes Ambientais/sangue , Poluentes Ambientais/urina , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Medição de Risco , Adulto Jovem
5.
Proc Natl Acad Sci U S A ; 110(16): 6448-52, 2013 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-23576718

RESUMO

In 2011, Lake Erie experienced the largest harmful algal bloom in its recorded history, with a peak intensity over three times greater than any previously observed bloom. Here we show that long-term trends in agricultural practices are consistent with increasing phosphorus loading to the western basin of the lake, and that these trends, coupled with meteorological conditions in spring 2011, produced record-breaking nutrient loads. An extended period of weak lake circulation then led to abnormally long residence times that incubated the bloom, and warm and quiescent conditions after bloom onset allowed algae to remain near the top of the water column and prevented flushing of nutrients from the system. We further find that all of these factors are consistent with expected future conditions. If a scientifically guided management plan to mitigate these impacts is not implemented, we can therefore expect this bloom to be a harbinger of future blooms in Lake Erie.


Assuntos
Mudança Climática , Eutrofização/fisiologia , Lagos/microbiologia , Modelos Biológicos , Fósforo/análise , Poluentes Químicos da Água/análise , Agricultura/métodos , Conservação dos Recursos Naturais/métodos , Great Lakes Region , Lagos/análise , Chuva , Temperatura , Movimentos da Água , Vento
6.
Tohoku J Exp Med ; 228(4): 267-88, 2012 12.
Artigo em Inglês | MEDLINE | ID: mdl-23117262

RESUMO

Many decades after an outbreak of severe cadmium poisoning, known as Itai-itai disease, cadmium continues to pose a significant threat to human health worldwide. This review provides an update on the effects of this environmental toxicant cadmium, observed in numerous populations despite modest exposure levels. In addition, it describes the current knowledge on the link between heme catabolism and glycolysis. It examines novel functions of heme oxygenase-2 (HO-2) that protect against type 2-diabetes and obesity, which have emerged from diabetic/obese phenotypes of the HO-2 knockout mouse model. Increased cancer susceptibility in type-2 diabetes has been noted in several large cohorts. This is a cause for concern, given the high prevalence of type-2 diabetes worldwide. A lifetime exposure to cadmium is associated with pre-diabetes, diabetes, and overall cancer mortality with sex-related differences in specific types of cancer. Liver and kidney are target organs for the toxic effects of cadmium. These two organs are central to the maintenance of blood glucose levels. Further, inhibition of gluconeogenesis is a known effect of heme, while cadmium has the propensity to alter heme catabolism. This raises the possibility that cadmium may mimic certain HO-2 deficiency conditions, resulting in diabetic symptoms. Intriguingly, evidence has emerged from a recent study to suggest the potential interaction and co-regulation of HO-2 with the key regulator of glycolysis: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4). HO-2 could thus be critical to a metabolic switch to cancer-prone cells because the enzyme PFKFB and glycolysis are metabolic requirements for cell proliferation and resistance to apoptosis.


Assuntos
Cádmio/metabolismo , Diabetes Mellitus Tipo 2/enzimologia , Suscetibilidade a Doenças/enzimologia , Heme Oxigenase (Desciclizante)/metabolismo , Neoplasias/enzimologia , Animais , Glicemia/metabolismo , Cádmio/efeitos adversos , Diabetes Mellitus Tipo 2/sangue , Suscetibilidade a Doenças/sangue , Humanos , Neoplasias/sangue
7.
Horm Cancer ; 3(5-6): 205-17, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22833172

RESUMO

Clinical studies have shown that progestins increase breast cancer risk in hormone replacement therapy, while we and others have previously reported that progestins stimulate invasive properties in progesterone receptor (PR)-rich human breast cancer cell lines. Based on others' reports that omega-3 fatty acids inhibit metastatic properties of breast cancer, we have reviewed the literature for possible connections between omega-3 fatty-acid-driven pathways and progestin-stimulated pathways in an attempt to suggest theoretical mechanisms for possible omega-3 fatty acid inhibition of progestin stimulation of breast cancer invasion. We also present some data suggesting that fatty acids regulate progestin stimulation of invasive properties in PR-rich T47D human breast cancer cells, and that an appropriate concentration of the omega-3 fatty acid eicosapentaenoic acid inhibits progestin stimulation of invasive properties. It is hoped that focus on the inter-relationship between pathways by which omega-3 fatty acids inhibit and progestins stimulate breast cancer invasive properties will lead to further in vitro, in vivo, and clinical studies testing the hypothesis that omega-3 fatty acids can inhibit progestin stimulation of invasive properties in breast cancer, and ameliorate harmful effects of progestins which occur in combined progestin-estrogen hormone replacement therapy.


Assuntos
Neoplasias da Mama/patologia , Ácidos Graxos Ômega-3/farmacologia , Progestinas/efeitos adversos , Animais , Neoplasias da Mama/metabolismo , Interações Medicamentosas , Feminino , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Invasividade Neoplásica , Receptores de Progesterona/metabolismo
8.
Arch Phys Med Rehabil ; 92(1): 146-60, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21187217

RESUMO

OBJECTIVE: To systematically review the research findings regarding the associations between psychosocial factors and adjustment to chronic pain in persons with physical disabilities. DATA SOURCES: A key word literature search was conducted using articles listed in PubMed, PsychInfo, and CINAHL up to March 2010, and manual searches were made of all retrieved articles to identify published articles that met the review inclusion criteria. STUDY SELECTION: To be included in the review, articles needed to (1) be written in English, (2) include adults with a physical disability who report having pain, (3) include at least 1 measure of a psychosocial predictor domain, (4) include at least 1 criterion measure of pain or patient functioning, and (5) report the results of associations between the psychosocial factors and criterion measures used in the study. Twenty-nine studies met the inclusion criteria. DATA EXTRACTION: Three reviewers tabulated study details and findings. DATA SYNTHESIS: The disability groups studied included spinal cord injury (SCI), acquired amputation, cerebral palsy (CP), multiple sclerosis (MS), and muscular dystrophy (MD). Psychosocial factors were shown to be significantly associated with pain and dysfunction in all disability groups. The psychosocial factors most closely associated with pain and dysfunction across the samples included (1) catastrophizing cognitions; (2) task persistence, guarding, and resting coping responses; and (3) perceived social support and solicitous responding social factors. Pain-related beliefs were more strongly associated with pain and dysfunction in the SCI, CP, MS, and MD groups than in the acquired amputation group. CONCLUSIONS: The findings support the importance of psychosocial factors as significant predictors of pain and functioning in persons with physical disabilities. Clinical trials to test the efficacy of psychosocial treatments for pain and dysfunction are warranted, as are studies to determine whether psychosocial factors have a causal influence on pain and adjustment in these populations.


Assuntos
Pessoas com Deficiência/psicologia , Pessoas com Deficiência/reabilitação , Dor/psicologia , Atividades Cotidianas , Adaptação Psicológica , Doença Crônica , Humanos , Saúde Mental , Apoio Social , Fatores Socioeconômicos
9.
Toxicon ; 56(5): 668-73, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19538985

RESUMO

Ciguatera is a food poisoning identified as the principal risk factor in the consumption of tropical fish in Oceania. The syndrome, which follows ingestion of ciguatoxin-contaminated ciguateric fishes, is characterised by an array of gastrointestinal and neurological features. In this report we examine forensic samples associated with a human fatality using a (3)H-brevetoxin binding assay and reversed-phase HPLC/MS and HPLC/MS/MS. Three Pacific ciguatoxins (P-CTX) were detected in the implicated fish flesh sample by LC-MS/MS, implicating multiple P-CTXs in the fatal case. Additionally, ciguatoxin was identified in a liver sample obtained at post-mortem. The level of ciguatoxin detected (0.14 ppb P-CTX-1 equivalents by binding assay) indicated that at least 10% of the ingested P-CTX-1 remained in the human liver 6 days after the toxic fish was consumed. This study confirms the potential of tropical reef fish to accumulate sufficient P-CTX to be lethal to humans, especially if the liver and viscera are consumed as part of the meal.


Assuntos
Intoxicação por Ciguatera/mortalidade , Animais , Cromatografia Líquida de Alta Pressão , Humanos , Espectrometria de Massas/métodos , Oceano Pacífico , Ensaio Radioligante
10.
Water Sci Technol ; 60(4): 1003-12, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19700839

RESUMO

Estrogenic endocrine disrupting compounds (e-EDCs) are present in treated sewage and there is concern about estrogenicity of potable recycled water. However e-EDCs are also present in other environmental media and intake from water needs to be considered in relation to these other sources. The concentrations of 13 e-EDCs in foodstuffs and drinking water are reviewed, their predicted concentrations in recycled water are estimated, and the daily estrogenic intake as 17beta-estradiol equivalent (EEq) based on both in vitro and in vivo potencies is calculated as 1.39 and 9.65 microg EEq/d, respectively. Dietary intake accounts for more than 99.8% of that total, and more than 84.2% is due to phytosterols. Drinking 2 L of recycled water per day is expected to add 0.001 to 0.016 microg EEq/d based on in vitro and in vivo potencies, respectively. Exposure to e-EDCs in recycled water is therefore likely to be insignificant compared to current dietary intakes.


Assuntos
Conservação dos Recursos Naturais , Disruptores Endócrinos/análise , Exposição Ambiental/análise , Estrogênios/análise , Água/química , Dieta , Comportamento Alimentar , Alimentos , Abastecimento de Água/análise
11.
J Steroid Biochem Mol Biol ; 117(1-3): 23-30, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19563893

RESUMO

Superoxide dismutase (SOD) occurs in two intracellular forms in mammals, copper-zinc SOD (CuZnSOD), found in the cytoplasm, mitochondria and nucleus, and manganese superoxide dismutase (MnSOD), in mitochondria. Changes in MnSOD expression (as compared to normal cells) have been reported in several forms of cancer, and these changes have been associated with regulation of cell proliferation, cell death, and metastasis. We have found that progestins stimulate MnSOD in T47D human breast cancer cells in a time and physiological concentration-dependent manner, exhibiting specificity for progestins and inhibition by the antiprogestin RU486. Progestin stimulation occurs at the level of mRNA, protein, and enzyme activity. Cycloheximide inhibits stimulation at the mRNA level, suggesting that progestin induction of MnSOD mRNA depends on synthesis of protein. Experiments with the MEK inhibitor UO126 suggest involvement of the MAP kinase signal transduction pathway. Finally, MnSOD-directed siRNA lowers progestin-stimulated MnSOD and inhibits progestin stimulation of migration and invasion, suggesting that up-regulation of MnSOD may be involved in the mechanism of progestin stimulation of invasive properties. To our knowledge, this is the first characterization of progestin stimulation of MnSOD in human breast cancer cells.


Assuntos
Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Congêneres da Progesterona/farmacologia , Superóxido Dismutase/metabolismo , Sequência de Bases , Neoplasias da Mama/etiologia , Butadienos/farmacologia , Linhagem Celular Tumoral , Primers do DNA/genética , Feminino , Antagonistas de Hormônios/farmacologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mifepristona/farmacologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/fisiopatologia , Nitrilos/farmacologia , Promegestona/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , RNA Interferente Pequeno/genética , Receptores de Progesterona/metabolismo , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/genética
12.
Exp Eye Res ; 87(6): 587-93, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18948096

RESUMO

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly. Risk factors include old age, female gender, obesity, smoking, low dietary intakes of antioxidants and increased exposure to the toxic metal cadmium (Cd(2+)). Supplementation with high-dose zinc (80 mg) provides some protection, but the mechanism(s) underlying such protection has not been fully elucidated. The present study had a focus on the human retinal pigment epithelial (RPE) cell line ARPE-19 in an attempt to demonstrate a reduction in intracellular Cd(2+) effect associated with heme oxygenase-1 (HO-1) expression by co-exposure with zinc (Zn(2+)) or manganese (Mn(2+)), which is known to be a more potent inhibitor of Cd(2+) uptake than Zn(2+). Our results indicated that co-exposure of 10 microM Cd(2+) with 5 microM Mn(2+) reduced the intracellular Cd(2+) effect by 50-60%, possibly by limiting the amounts of Cd(2+) entering cells through Mn(2+) transporter protein (ZIP8). A similar reduction in a Cd(2+) effect was achieved by co-exposure with 20 microM Zn(2+) while co-exposure with 5 and 10 microM Zn(2+) ions was ineffective. Mn(2+) ions as low as 2.5 microM were found to cause an increase in HO-1 mRNA expression levels in ARPE-19 cells, demonstrating for the first time that Mn(2+) is an inducer of HO-1. Mn(2+) ions at 1 microM induced HO-1 mRNA expression in the HEK293 human embryonic kidney cells. In contrast, Zn(2+) in 5, 10 or 20 microM concentrations did not induce expression of HO-1 in ARPE-19 cells or any other cells tested. These data suggest the superiority of Mn(2+) over Zn(2+) in preventing Cd(2+) uptake and accumulation in RPE to toxic levels. Further, induction of HO-1 by Mn(2+) could provide RPE with some resistance to enhanced oxidative stress arising from Cd(2+) accumulation in RPE as HO-1 is one of the frontline cellular antioxidant defense mechanisms.


Assuntos
Cádmio/antagonistas & inibidores , Manganês/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Zinco/farmacologia , Cádmio/farmacocinética , Cádmio/farmacologia , Linhagem Celular , Relação Dose-Resposta a Droga , Perfilação da Expressão Gênica/métodos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Genótipo , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , Células Tumorais Cultivadas
13.
Biochem Biophys Res Commun ; 377(3): 878-83, 2008 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-18957281

RESUMO

Prostaglandin (PG) D(2) exerts multiple actions through interaction with distinct receptors, DP1 and DP2. We have shown that PGD(2) induces the expression of heme oxygenase-1 (HO-1) in the retinal pigment epithelium (RPE) that is essential for survival of photoreceptors. HO-1 is a key enzyme in physiological heme degradation. Here, we explored the mechanism for the PGD(2)-mediated induction of HO-1 expression using ARPE-19 human RPE cells. ARPE-19 cells secrete PGD(2) and express DP2 mRNA, but not DP1 mRNA. Treatment with a DP2 agonist, 15(R)-15-methyl-PGD(2) or DK-PGD(2), increased HO-1 mRNA expression, and pretreatment with a DP2 antagonist, CAY10471, decreased the magnitude of the PGD(2)-mediated HO-1 induction. By contrast, either DP1 agonist or antagonist caused only marginal influence on HO-1 expression. Moreover, transient expression assays showed the DP2 agonist activated the HO-1-gene promoter in the enhancer-dependent manner. Thus, PGD(2) induces HO-1 mRNA expression through DP2 receptor, linking the PGD(2)-DP2 signaling with heme homeostasis.


Assuntos
Heme Oxigenase-1/biossíntese , Prostaglandina D2/fisiologia , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Epitélio Pigmentado da Retina/enzimologia , Cádmio/farmacologia , Carbazóis/farmacologia , Linhagem Celular , Heme/metabolismo , Homeostase , Humanos , Regiões Promotoras Genéticas/efeitos dos fármacos , Prostaglandina D2/farmacologia , RNA Mensageiro/biossíntese , Receptores Imunológicos/agonistas , Receptores Imunológicos/antagonistas & inibidores , Receptores de Prostaglandina/agonistas , Receptores de Prostaglandina/antagonistas & inibidores , Epitélio Pigmentado da Retina/efeitos dos fármacos , Sulfonamidas/farmacologia
14.
J Photochem Photobiol B ; 93(2): 88-93, 2008 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-18755599

RESUMO

Vitamin D deficiency is a major health concern worldwide. Very little is understood regarding its production in the human body by exposure to UV radiation. In particular, we have no means of predicting how much vitamin D (cholecalciferol) will be produced in the skin after exposure to sunlight. Using a refined in vitro model, we found that there is a nonlinear relationship between UV dose and cholecalciferol synthesis. Two minimal erythemal doses (MED) of UV radiation produced 1.84 microg/mL of cholecalciferol whereas 4 MED produced 2.81 microg/mL. We also found that the production of cholecalciferol is restricted by the initial concentration of its precursor (7-dehydrocholesterol, 7-DHC). For example, using an initial concentration of 7-DHC of 102 microg/mL, the resultant cholecalciferol production was 1.05 microg/mL after receiving 4 MED exposure. Under the same exposure conditions, an initial concentration of 305 microg/mL yielded 2.81 g/mL of cholecalciferol. The data presented in this paper has important implications for humans, including: (1) increasing UV exposure does not result in a proportionate increase in the amount of cholecalciferol that is produced; and (2) the initial concentration of 7-DHC in the skin may impact the amount of cholecalciferol that can be synthesized. When translating these results to population groups, we will discuss how the sun exposure message needs to be carefully formulated to account for such considerations.


Assuntos
Colecalciferol/biossíntese , Colecalciferol/efeitos da radiação , Cromatografia Líquida de Alta Pressão , Desidrocolesteróis/metabolismo , Desidrocolesteróis/efeitos da radiação , Relação Dose-Resposta à Radiação , Humanos , Técnicas In Vitro , Modelos Biológicos , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta
16.
Conserv Biol ; 22(2): 338-50, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18402583

RESUMO

The mandate to increase endangered salmon populations in the Columbia River Basin of North America has created a complex, controversial resource-management issue. We constructed an integrated assessment model as a tool for analyzing biological-economic trade-offs in recovery of Snake River spring- and summer-run chinook salmon (Oncorhynchus tshawytscha). We merged 3 frameworks: a salmon-passage model to predict migration and survival of smolts; an age-structured matrix model to predict long-term population growth rates of salmon stocks; and a cost-effectiveness analysis to determine a set of least-cost management alternatives for achieving particular population growth rates. We assessed 6 individual salmon-management measures and 76 management alternatives composed of one or more measures. To reflect uncertainty, results were derived for different assumptions of effectiveness of smolt transport around dams. Removal of an estuarine predator, the Caspian Tern (Sterna caspia), was cost-effective and generally increased long-term population growth rates regardless of transport effectiveness. Elimination of adult salmon harvest had a similar effect over a range of its cost estimates. The specific management alternatives in the cost-effective set depended on assumptions about transport effectiveness. On the basis of recent estimates of smolt transport effectiveness, alternatives that discontinued transportation or breached dams were prevalent in the cost-effective set, whereas alternatives that maximized transportation dominated if transport effectiveness was relatively high. More generally, the analysis eliminated 80-90% of management alternatives from the cost-effective set. Application of our results to salmon management is limited by data availability and model assumptions, but these limitations can help guide research that addresses critical uncertainties and information. Our results thus demonstrate that linking biology and economics through integrated models can provide valuable tools for science-based policy and management.


Assuntos
Conservação dos Recursos Naturais/métodos , Pesqueiros/economia , Pesqueiros/métodos , Modelos Teóricos , Salmão/fisiologia , Migração Animal/fisiologia , Animais , Noroeste dos Estados Unidos , Dinâmica Populacional , Rios , Análise de Sobrevida
17.
J Toxicol Environ Health A ; 70(19): 1578-83, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17763075

RESUMO

Managing public concerns relating to chemical exposures can consume substantial public health resources, particularly as the scientific basis around these issues is often contentious. Toxicology remains underrecognized as a public health discipline in Australia, although Australian toxicologists are making significant contributions from academia, government, and the commercial sector toward assessing the level of risk and protecting the community from environmental hazards. Internationally, the growth of environmental toxicology and the promotion of sound science in risk assessment as a basis for making regulatory decisions have been, to some extent, driven by the outcomes of the 1992 UNCED Conference on Sustainable Development (Rio Summit) and its Chapter 19 Agenda 21 activities. The promotion of safe chemical management practices and the need for global strengthening of capabilities in toxicology are among the initiatives of the Intergovernmental Forum on Chemical Safety (IFCS), which was formed after the Rio Summit to manage these programs. This article describes some of the initiatives in capacity building that marked the development of environmental toxicology in Australia since 1992 in response to these international environmental health initiatives.


Assuntos
Saúde Ambiental/organização & administração , Toxicologia/organização & administração , Austrália , Congressos como Assunto , Conservação dos Recursos Naturais , Monitoramento Ambiental/métodos , Órgãos Governamentais , Pesquisas sobre Serviços de Saúde , Humanos , Administração em Saúde Pública , Alocação de Recursos/métodos , Medição de Risco/métodos
18.
J Toxicol Environ Health A ; 70(19): 1694-9, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17763088

RESUMO

Out of 247 traditional Chinese medicines (TCM) investigated, a proportion were contaminated with arsenic (5-15%), lead (approximately 5%), and mercury (approximately 65%). Some preparations exceeded the tolerable daily intake (TDI) for males and females for arsenic (4 and 5 products, respectively), lead (1 and 2 products), and mercury (5 and 7 products). These exceedances were as high as 2760-fold, which posed a potential danger to public health. As many users are known to self-prescribe, there is a substantial risk of poisoning from the consumption of these contaminated TCM.


Assuntos
Arsênico/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Chumbo/isolamento & purificação , Mercúrio/isolamento & purificação , Adulto , Arsênico/toxicidade , Criança , Feminino , Inquéritos Epidemiológicos , Humanos , Chumbo/toxicidade , Masculino , Concentração Máxima Permitida , Mercúrio/toxicidade , Modelos Estatísticos , Medição de Risco/métodos
19.
Toxicol Appl Pharmacol ; 224(1): 89-97, 2007 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-17707874

RESUMO

Arsenicals are proven carcinogens in humans and it imposes significant health impacts on both humans and animals. Recently monomethylarsonous acid (MMA(III)), the toxic metabolite of arsenic has been identified in human urine and believed to be more acutely toxic than arsenite and arsenate. Arsenic also affects the activity of a number of haem biosynthesis enzymes. As a part of 2-year arsenic carcinogenicity study, young female C57BL/6J mice were given drinking water containing 0, 100, 250 and 500 microg/L arsenic as MMA(III)ad libitum. 24 h urine samples were collected at 0, 1, 2, 4, 8 weeks and every 8 weeks for up to 104 weeks. Urinary arsenic speciation and porphyrins were measured using HPLC-ICP-MS and HPLC with fluorescence detection respectively. DMA(V) was a major urinary metabolite detected. Significant dose-response relationship was observed between control and treatment groups after 1, 4, 24, 32, 48, 56, 88, 96 and 104 weeks. The level of uroporphyrin in 250 and 500 microg As/L group is significantly different from the control group after 4, 8, 16, 32, 56, 72, 80, 96 and 104 weeks. Coproporphyrin I level in 500 microAs/L group is significantly different from control group after 8, 24, 32, 40, 56, 72, 80, 88 and 104 weeks. After 4 weeks the level of coproporphyrin III concentration significantly increased in all the treatment groups compared to the control except week 16 and 48. Our results show urinary DMA(V) and porphyrin profile can be used as an early warning biomarker for chronic MMA(III) exposure before the onset of cancer.


Assuntos
Arsênico/urina , Compostos Organometálicos/toxicidade , Porfirinas/urina , Animais , Biomarcadores , Biomarcadores Tumorais , Cromatografia Líquida de Alta Pressão , Coproporfirinas/urina , Relação Dose-Resposta a Droga , Feminino , Metilação , Camundongos , Camundongos Endogâmicos C57BL , Espectrometria de Massas por Ionização por Electrospray , Uroporfirinas/urina
20.
Br J Psychiatry ; 190: 475-83, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17541106

RESUMO

BACKGROUND: There has been no comprehensive investigation of psychological health in Australia's Korean War veteran population, and few researchers are investigating the health of coalition Korean War veterans into old age. AIMS: To investigate the association between war service, anxiety, post-traumatic stress disorder (PTSD) and depression in Australia's 7525 surviving male Korean War veterans and a community comparison group. METHOD: A survey was conducted using a self-report postal questionnaire which included the PTSD Checklist, the Hospital Anxiety and Depression scale and the Combat Exposure Scale. RESULTS: Post-traumatic stress disorder (OR 6.63, P<0.001), anxiety (OR 5.74, P<0.001) and depression (OR 5.45, P<0.001) were more prevalent in veterans than in the comparison group. These disorders were strongly associated with heavy combat and low rank. CONCLUSIONS: Effective intervention is necessary to reduce the considerable psychological morbidity experienced by Korean War veterans. Attention to risk factors and early intervention will be necessary to prevent similar long-term psychological morbidity in veterans of more recent conflicts.


Assuntos
Ansiedade/psicologia , Transtorno Depressivo/etiologia , Guerra da Coreia , Transtornos de Estresse Pós-Traumáticos/psicologia , Veteranos/psicologia , Idoso , Idoso de 80 Anos ou mais , Austrália , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Fatores de Tempo
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