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1.
Cancer Causes Control ; 34(11): 949-961, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37341814

RESUMO

PURPOSE: To assess whether androgens play a role in explaining the sex related differences in the incidence of colorectal cancer (CRC). METHODS: A nationwide matched cohort study was conducted employing the Prostate Cancer data Base Sweden (PCBaSe) 4.0 during the study period 2006-2016. Prostate cancer (PC) patients receiving androgen deprivation therapy (ADT) were treated as exposed. Prostate cancer-free men from the general population were randomly selected and matched to the index case by birth year and county of residence, forming the unexposed group. All were followed until a diagnosis of CRC, death, emigration, or end of the study period. The risk of CRC among ADT exposed PC patients compared to unexposed cancer-free men was calculated using a flexible parametric survival model and expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: There was an increased risk of CRC among ADT exposed PC patients compared to unexposed cancer-free men (HR 1.27 [95% CI 1.15-1.41]), in particular an increased risk of adenocarcinoma of the colon (HR 1.33 [95% CI 1.17-1.51]) and more specifically an increased risk of adenocarcinoma of the distal colon (HR 1.53 [95% CI 1.26-1.85]). Examination of latency effects yielded significantly decreased HRs over time for CRC (p = 0.049 for trend). CONCLUSIONS: This population-based study found an increased risk of CRC among PC patients exposed to ADT, specifically adenocarcinoma of the distal colon, which indicates an increased association between ADT (PC + ADT) and CRC but not a positive dose-response trend questioning a true causal effect.


Assuntos
Adenocarcinoma , Neoplasias Colorretais , Neoplasias da Próstata , Masculino , Humanos , Estudos de Coortes , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/epidemiologia , Antagonistas de Androgênios/efeitos adversos , Androgênios , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/epidemiologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/epidemiologia
2.
Pediatr Radiol ; 52(12): 2278-2289, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35536415

RESUMO

Phosphate has extensive physiological roles including energy metabolism, genetic function, signal transduction and membrane integrity. Regarding the skeleton, not only do phosphate and calcium form the mineral component of the skeleton, but phosphate is also essential in regulating function of skeletal cells. Although our understanding of phosphate homeostasis has lagged behind and remains less than that for calcium, considerable advances have been made since the recognition of fibroblast growth factor-23 (FGF23) as a bone-derived phosphaturic hormone that is a major regulator of phosphate homeostasis. In this two-part review of disorders of phosphate homeostasis in children, part 1 covers the basics of mineral ion homeostasis and the roles of phosphate in skeletal biology. Part 1 includes phosphate-related disorders of mineralization for which overall circulating mineral ion homeostasis remains normal. Part 2 covers hypophosphatemic and hyperphosphatemic disorders, emphasizing, but not limited to, those related to increased and decreased FGF23 signaling, respectively.


Assuntos
Cálcio , Fosfatos , Criança , Humanos , Cálcio/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Homeostase/fisiologia , Minerais , Fosfatos/metabolismo
3.
Pediatr Radiol ; 52(12): 2290-2305, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35536416

RESUMO

Phosphorus, predominantly in the form of inorganic phosphate PO4-3, has many essential physiological functions. In the skeleton, phosphate and calcium form the mineral component and phosphate is also essential in regulating function of skeletal cells. Considerable advances have been made in our understanding of phosphate homeostasis since the recognition of fibroblast growth factor-23 (FGF23) as a bone-derived phosphaturic hormone. This second part of a two-part review of disorders of phosphate homeostasis in children covers hypophosphatemic and hyperphosphatemic disorders that are of interest to the pediatric radiologist, emphasizing, but not limited to, those related to abnormalities of FGF23 signaling.


Assuntos
Hipofosfatemia , Criança , Humanos , Hipofosfatemia/diagnóstico por imagem , Fatores de Crescimento de Fibroblastos/fisiologia , Homeostase/fisiologia , Fosfatos , Osso e Ossos
4.
Ecotoxicology ; 30(4): 560-574, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33770305

RESUMO

Rats and mice can damage food and agricultural products as well as transmit diseases, thereby requiring control of their numbers. Application of Second Generation Anticoagulant Rodenticides (SGARs) often reduces rodent numbers locally. However, predators eating rodents, including non-target species, that have consumed SGARs may be secondarily exposed and potentially lethally poisoned. Here we study whether SGARs may have contributed to the widespread population declines of a rodent-eating raptor, the Common Kestrel (Falco tinnunculus) in the UK. We show that 161 (66.8%) of the 241 Kestrels submitted for ecotoxicology tests between 1997 and 2012 had detectable levels of at least one SGAR in their livers. Adult Kestrels had significantly higher prevalence of SGARs than juveniles, suggesting accumulation of SGARs through time. The prevalence and concentrations of individual SGARs in Kestrels were significantly higher in England than in Scotland. SGAR prevalence in Kestrels were positively associated with some land cover types, primarily arable cereals and broad-leaved woodland, and negatively associated with mainly mean elevation, probably reflecting variation in SGAR usage across land cover types. By using volunteer-collected data on national Kestrel abundance 1997-2012, we show that there is a negative correlation between the Kestrel population index in a specific year and the concentration of bromadialone as well as the total SGAR concentration in the same year. Although correlative, this is the first study to provide evidence for a potential population-limiting effect of SGARs on a raptor.


Assuntos
Falconiformes , Aves Predatórias , Rodenticidas , Animais , Anticoagulantes , Inglaterra , Camundongos , Ratos , Rodenticidas/toxicidade
5.
Environ Sci Technol ; 54(14): 8938-8948, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32551599

RESUMO

Environmental contaminants and parasites are ubiquitous stressors that can affect animal physiology and derive from similar dietary sources (co-exposure). To unravel their interactions in wildlife, it is thus essential to quantify their concurring drivers. Here, the relationship between blood contaminant residues (11 trace elements and 17 perfluoroalkyl substances) and nonlethally quantified gastrointestinal parasite loads was tested while accounting for intrinsic (sex, age, and mass) and extrinsic factors (trophic ecology inferred from stable isotope analyses and biologging) in European shags Phalacrocorax aristotelis. Shags had high mercury (range 0.65-3.21 µg g-1 wet weight, ww) and extremely high perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) residues (3.46-53 and 4.48-44 ng g-1 ww, respectively). Males had higher concentrations of arsenic, mercury, PFOA, and PFNA than females, while the opposite was true for selenium, perfluorododecanoic acid (PFDoA), and perfluooctane sulfonic acid (PFOS). Individual parasite loads (Contracaecum rudolphii) were higher in males than in females. Females targeted pelagic-feeding prey, while males relied on both pelagic- and benthic-feeding organisms. Parasite loads were not related to trophic ecology in either sex, suggesting no substantial dietary co-exposure with contaminants. In females, parasite loads increased strongly with decreasing selenium:mercury molar ratios. Females may be more susceptible to the interactive effects of contaminants and parasites on physiology, with potential fitness consequences.


Assuntos
Poluentes Ambientais , Fluorocarbonos , Mercúrio , Parasitos , Selênio , Animais , Aves , Ecologia , Feminino , Fluorocarbonos/análise , Masculino
6.
Arch Environ Contam Toxicol ; 76(3): 394-404, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30564852

RESUMO

We examined how coastal mercury contamination varied spatially and temporally across the Iberian Peninsula by measuring mercury concentrations in the eggs of the sentinel biomonitor yellow-legged gull (Larus michahellis). Samples were collected from eight colonies that ranged from the Atlantic across the south and northern areas of the Mediterranean. We also measured Hg residues in eggs of the one of the most endangered gull species in the world, the Audouin's gull (Larus audouinii) from the Ebro Delta, where colonies of yellow-legged and Audouin's gull co-occur. Fresh eggs were collected in 2009 and 2016 and samples were pooled from each colony for analysis. Mercury concentrations in yellow-legged gulls ranged between 0.4 and 2.8 mg/kg dry weight (dw); although there were no significant differences in concentrations between sampling periods, significant differences were found between colonies. Higher concentrations were associated with northern Mediterranean colonies (Columbretes and Ebro Delta), likely due to proximity to emission sources, circulatory marine currents and diet composition. Mercury concentrations in yellow-legged gull eggs were lower than those reported to result in impaired hatching. Residues in Audouin's gull eggs from the Ebro Delta were significantly higher (4.0-5.6 mg/kg dw) than those in yellow-legged gull from the same location, probably associated with dietary differences. Mercury levels in Audouin's gull were ten times above the benchmark suggested to reduce nest success by 10%. Overall, these results raise concern for adverse health impacts in this protected seabird species and further investigation in Audouin's gull eggs from the Ebro Delta is recommended.


Assuntos
Charadriiformes/crescimento & desenvolvimento , Monitoramento Ambiental/métodos , Poluentes Ambientais/análise , Mercúrio/análise , Óvulo/química , Animais , Oceano Atlântico , Mar Mediterrâneo , Portugal , Espanha , Análise Espaço-Temporal
7.
J Magn Reson Imaging ; 47(4): 936-947, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28801960

RESUMO

PURPOSE: To implement quantitative Dixon magnetic resonance imaging (MRI) methods for brown adipose tissue (BAT) characterization at inactive and cold-activated states in normal weight, overweight, and obese subjects. The hypotheses are that MRI characteristics of BAT would differentiate between nonobese and obese subjects, and activation of BAT in response to thermal challenges that are detected by MRI would be correlated with BAT activity measured by positron emission tomography / computed tomography (PET/CT). MATERIALS AND METHODS: Fifteen male subjects (20.7 ± 1.5 years old) including six normal weight, five overweight, and four obese subjects participated in the study. A multiecho Dixon MRI sequence was performed on a 1.5T scanner. MRI was acquired under thermoneutral, nonshivering thermogenesis, and subsequent warm-up conditions. Fat fraction (FF), R2*, and the number of double bonds (ndb) were measured by solving an optimization problem that fits in- and out-of-phase MR signal intensities to the fat-water interference models. Imaging acquisition and postprocessing were performed by two MRI physicists. In each subject, Dixon MRI measurements of FF, R2*, and ndb were calculated for each voxel within all BAT regions of interest (ROIs) under each thermal condition. Mean FF, R2*, and ndb were compared between nonobese (ie, normal-weight/overweight) and obese subjects using the two-sample t-test. Receiver operating characteristic (ROC) analyses were performed to differentiate nonobese vs. obese subjects. BAT MRI measurement changes in response to thermal condition changes were compared with hypermetabolic BAT volume/activity measured by PET/CT using the Pearson's correlation. In addition, BAT MRI measurements were compared with body adiposity using the Pearson's correlation. P < 0.05 was considered statistically significant. RESULTS: Obese subjects showed higher FF and lower R2* than nonobese subjects under all three thermal conditions (P < 0.01). ROC analyses demonstrated that FF and R2* were excellent predictors for the differentiation of nonobese from obese subjects (100% specificity and 100% sensitivity). FF changes under thermal challenges were correlated with hypermetabolic BAT volume (r = -0.55, P = 0.04 during activation, and r = 0.72, P = 0.003 during deactivation), and with BAT activity (r = 0.69, P = 0.006 during deactivation), as measured by PET/CT. FF and R2* under all three thermal conditions were highly correlated with body adiposity (P ≤ 0.002). CONCLUSION: MRI characteristics of BAT differentiated between nonobese and obese subjects in both inactivated and activated states. BAT activation detected by Dixon MRI in response to thermal challenges were correlated with glucose uptake of metabolically active BAT. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:936-947.


Assuntos
Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Sobrepeso/diagnóstico por imagem , Sobrepeso/fisiopatologia , Termogênese/fisiologia , Adulto , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Obesidade/diagnóstico por imagem , Obesidade/fisiopatologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sensibilidade e Especificidade , Adulto Jovem
8.
Environ Sci Technol ; 51(15): 8672-8681, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28636345

RESUMO

Organochlorine (OC) pesticides pose a significant environmental risk to wildlife and humans and have been associated with Alzheimer's disease (AD). This study aims to spectroscopically analyze brains from free-flying birds and link the results to OC exposure and consequent amyloid aggregation. As long-lived apex predators, predatory birds represent a sentinel species similar to humans. Therefore, the results have implications for both species and may also add to our understanding of the role OC pesticides play in the development of AD. Brains of wild Sparrowhawks were analyzed using ATR-FTIR and Raman spectroscopy and Congo red staining; results were correlated with OC pesticide concentrations in livers. Effects of OC exposure were sex- and age-dependent and associated alterations were seen in lipids and protein secondary structure. A shift from α-helix to ß-sheet conformation of proteins indicated that concentrations of OC pesticides >7.18 µg/g may lead to cerebral amyloid aggregation.


Assuntos
Proteínas Amiloidogênicas/efeitos dos fármacos , Aves , Encéfalo/patologia , Hidrocarbonetos Clorados/toxicidade , Praguicidas/toxicidade , Animais , Fígado
9.
Pediatr Radiol ; 46(5): 591-600, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26886911

RESUMO

This paper addresses significant misconceptions regarding the etiology of fractures in infants and young children in cases of suspected child abuse. This consensus statement, supported by the Child Abuse Committee and endorsed by the Board of Directors of the Society for Pediatric Radiology, synthesizes the relevant scientific data distinguishing clinical, radiologic and laboratory findings of metabolic disease from findings in abusive injury. This paper discusses medically established epidemiology and etiologies of childhood fractures in infants and young children. The authors also review the body of evidence on the role of vitamin D in bone health and the relationship between vitamin D and fractures. Finally, the authors discuss how courts should properly assess, use, and limit medical evidence and medical opinion testimony in criminal and civil child abuse cases to accomplish optimal care and protection of the children in these cases.


Assuntos
Maus-Tratos Infantis/diagnóstico , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/etiologia , Deficiência de Vitamina D/complicações , Criança , Pré-Escolar , Consenso , Feminino , Medicina Legal , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco
10.
Pediatr Blood Cancer ; 62(11): 2007-10, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26011159

RESUMO

Neuroblastoma in patients with congenital central hypoventilation syndrome (CCHS) as part of a neurocristopathy syndrome is a rare finding and has only been associated with paired-like homeobox 2b (PHOX2B) non-polyalanine-repeat-expansion mutations. To the best of our knowledge, we report the first case of a child with CCHS and Hirschsprung disease who had a PHOX2B polyalanine-repeat-expansion mutation (PARM) (genotype 20/33) and developed high-risk neuroblastoma. We further describe his treatment including chemotherapy and therapeutic I(131) -metaiodobenzylguanidine. This case highlights the need to consider neuroblastoma in patients with CCHS and the longest PHOX2B PARMs and to individualize treatment based on co-morbidities.


Assuntos
Proteínas de Homeodomínio/genética , Neuroblastoma , Síndrome de Hipoventilação por Obesidade , Peptídeos/genética , Fatores de Transcrição/genética , Expansão das Repetições de Trinucleotídeos , Adulto , Humanos , Masculino , Neuroblastoma/genética , Neuroblastoma/patologia , Neuroblastoma/terapia , Síndrome de Hipoventilação por Obesidade/genética , Síndrome de Hipoventilação por Obesidade/patologia , Síndrome de Hipoventilação por Obesidade/terapia
11.
Gen Comp Endocrinol ; 214: 47-55, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25776461

RESUMO

This study investigated the feasibility of measuring corticosterone in feathers from cryo-archived raptor specimens, in order to provide a retrospective assessment of the activity of the stress axis in relation to contaminant burden. Feather samples were taken from sparrowhawk Accipiter nisus, kestrel Falco tinnunculus, buzzard Buteo buteo, barn owl Tyto alba, and tawny owl Strix aluco and the variation in feather CORT concentrations with respect to species, age, sex, feather position, and body condition was assessed. In sparrowhawks only, variation in feather CORT content was compared with hepatic metal concentrations. For individuals, CORT concentration (pgmm(-1)) in adjacent primary flight feathers (P5 and P6), and left and right wing primaries (P5), was statistically indistinguishable. The lowest concentrations of CORT were found in sparrowhawk feathers and CORT concentrations did not vary systematically with age or sex for any species. Significant relationships between feather CORT content and condition were observed in only tawny owl and kestrel. In sparrowhawks, feather CORT concentration was found to be positively related to the hepatic concentrations of five metals (Cd, Mn, Co, Cu, Mo) and the metalloid As. There was also a negative relationship between measures of condition and total hepatic metal concentration in males. The results suggest that some factors affecting CORT uptake by feathers remain to be resolved but feather CORT content from archived specimens has the potential to provide a simple effects biomarker for exposure to environmental contaminants.


Assuntos
Aves/metabolismo , Corticosterona/metabolismo , Poluição Ambiental/análise , Plumas/metabolismo , Fígado/metabolismo , Metais/metabolismo , Animais , Aves/crescimento & desenvolvimento , Índice de Massa Corporal , Plumas/crescimento & desenvolvimento , Feminino , Masculino , Radioimunoensaio
12.
Pediatr Radiol ; 45(11): 1682-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26092667

RESUMO

BACKGROUND: Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. OBJECTIVE: To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. MATERIALS AND METHODS: Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. RESULTS: MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). CONCLUSION: This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.


Assuntos
Tecido Adiposo Marrom/patologia , Adiposidade , Imagem de Difusão por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos , Obesidade/patologia , Obesidade Infantil/patologia , Adolescente , Criança , Feminino , Humanos , Masculino , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
13.
Am J Med Genet A ; 164A(6): 1545-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24668887

RESUMO

Hyperphosphatemic familial tumoral calcinosis (HFTC) is characterized by enhanced renal phosphate absorption, hyperphosphatemia, and tumor-like extraosseous calcifications due to inactivating mutations in FGF23 or associated proteins. Surgical excision is needed when low phosphate diet and phosphate binders are ineffective. Sporadic reports have supported acetazolamide use. We report on a 7-year-old African American boy who presented with severe HFTC requiring numerous surgical excisions. Tumors continued to appear and others reoccurred despite phosphate restriction and sevelamer carbonate. At the age of 9.5 years, acetazolamide (40 mg/kg/day) was added and resulted in mild metabolic acidosis (bicarbonate 25.3 mEq/L vs. 21.4 mEq/L, P < 0.001; serum pH 7.38 vs. 7.31, P = 0.013, pre- and post-acetazolamide, respectively) but no change in tubular reabsorption of phosphate (TRP) (96.9% vs. 95.9%, P = 0.34) or serum phosphate (6.6 mg/dl vs. 6.9 mg/dl, P = 0.52 pre- and post-acetazolamide, respectively). Following the initiation of acetazolamide therapy, the patient experienced significant improvement in disease course as indicated by resolution of localized bone pain, cessation of tumor formation, and no tumor recurrence. Despite mild metabolic acidosis, our patient had improved linear growth and did not develop any other side effects related to therapy. Intact FGF23 remained abnormally low throughout disease course, while C-terminal FGF23 increased with acetazolamide. We conclude that acetazolamide can control severe HFTC by inducing mild metabolic acidosis despite no change in serum phosphate or TRP. This effect may be exerted though improved calcium-phosphate complex solubility and increased FGF23 locally.


Assuntos
Acetazolamida/uso terapêutico , Calcinose/tratamento farmacológico , Inibidores da Anidrase Carbônica/uso terapêutico , Fatores de Crescimento de Fibroblastos/genética , Hiperostose Cortical Congênita/tratamento farmacológico , Hiperfosfatemia/tratamento farmacológico , Acidose/induzido quimicamente , Negro ou Afro-Americano/genética , Calcinose/cirurgia , Quelantes/uso terapêutico , Criança , Fator de Crescimento de Fibroblastos 23 , Humanos , Hiperostose Cortical Congênita/cirurgia , Hiperfosfatemia/cirurgia , Masculino , Fosfatos/sangue , Poliaminas/uso terapêutico , Sevelamer
14.
Analyst ; 139(5): 896-905, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24162371

RESUMO

Nanoparticles appear to induce toxic effects through a variety of mechanisms including generation of reactive oxygen species (ROS), physical contact with the cell membrane and indirect catalysis due to remnants from manufacture. The development and subsequent increasing usage of nanomaterials has highlighted a growing need to characterize and assess the toxicity of nanoparticles, particularly those that may have detrimental health effects such as carbon-based nanomaterials (CBNs). Due to interactions of nanoparticles with some reagents, many traditional toxicity tests are unsuitable for use with CBNs. Infrared (IR) spectroscopy is a non-destructive, high throughput technique, which is unhindered by such problems. We explored the application of IR spectroscopy to investigate the effects of CBNs on Gram-negative (Pseudomonas fluorescens) and Gram-positive (Mycobacterium vanbaalenii PYR-1) bacteria. Two types of IR spectroscopy were compared: attenuated total reflection Fourier-transform infrared (ATR-FTIR) and synchrotron radiation-based FTIR (SR-FTIR) spectroscopy. This showed that Gram-positive and Gram-negative bacteria exhibit differing alterations when exposed to CBNs. Gram-positive bacteria appear more resistant to these agents and this may be due to the protection afforded by their more sturdy cell wall. Markers of exposure also vary according to Gram status; Amide II was consistently altered in Gram-negative bacteria and carbohydrate altered in Gram-positive bacteria. ATR-FTIR and SR-FTIR spectroscopy could both be applied to extract biochemical alterations induced by each CBN that were consistent across the two bacterial species; these may represent potential biomarkers of nanoparticle-induced alterations. Vibrational spectroscopy approaches may provide a novel means of fingerprinting the effects of CBNs in target cells.


Assuntos
Bactérias Gram-Negativas/química , Bactérias Gram-Positivas/química , Nanoestruturas/análise , Nanoestruturas/toxicidade , Espectroscopia de Infravermelho com Transformada de Fourier/normas , Síncrotrons/normas , Animais , Bovinos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Soroalbumina Bovina , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Testes de Toxicidade/métodos , Testes de Toxicidade/normas
15.
Environ Sci Technol ; 48(15): 8433-45, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24968307

RESUMO

Despite a long history of successful use, routine application of some anticoagulant rodenticides (ARs) may be at a crossroad due to new regulatory guidelines intended to mitigate risk. An adverse outcome pathway for ARs was developed to identify information gaps and end points to assess the effectiveness of regulations. This framework describes chemical properties of ARs, established macromolecular interactions by inhibition of vitamin K epoxide reductase, cellular responses including altered clotting factor processing and coagulopathy, organ level effects such as hemorrhage, organism responses with linkages to reduced fitness and mortality, and potential consequences to predator populations. Risk assessments have led to restrictions affecting use of some second-generation ARs (SGARs) in North America. While the European regulatory community highlighted significant or unacceptable risk of ARs to nontarget wildlife, use of SGARs in most EU member states remains authorized due to public health concerns and the absence of safe alternatives. For purposes of conservation and restoration of island habitats, SGARs remain a mainstay for eradication of invasive species. There are significant data gaps related to exposure pathways, comparative species sensitivity, consequences of sublethal effects, potential hazards of greater AR residues in genetically resistant prey, effects of low-level exposure to multiple rodenticides, and quantitative data on the magnitude of nontarget wildlife mortality.


Assuntos
Anticoagulantes/toxicidade , Rodenticidas/toxicidade , Animais , Europa (Continente) , Cadeia Alimentar , América do Norte , Medição de Risco
16.
J Neurooncol ; 113(2): 285-91, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23508296

RESUMO

This study investigates the outcome of children <10 years old with newly-diagnosed ependymoma treated on the prospective multinational "Head Start" III clinical trial. Between April 2004 and July 2009, 19 children with newly-diagnosed ependymoma were enrolled. All children were to receive five induction chemotherapy cycles followed by one consolidation cycle of myelo-ablative chemotherapy and autologous hematopoietic cell rescue. Children between 6 and 10 years of age or with residual tumor prior to consolidation were to receive irradiation thereafter. Median age of 19 children (8 female) was 20 months at diagnosis. Median follow up was 44 months. The primary site was infratentorial in 11 and supratentorial in 8 patients. Gross total resection was achieved in 10 patients. After induction chemotherapy, all three supratentorial ependymoma patients with residual disease achieved a complete response (CR), while only one of six infratentorial patients with residual disease achieved CR. Three infratentorial patients developed progressive disease during induction chemotherapy. All four infratentorial patients with residual disease who underwent autologous hematopoietic cell transplant, failed to achieve CR. Four patients received focal irradiation following chemotherapy. The 3-year event free survival (EFS) and overall survival (OS) for supratentorial ependymoma were 86 ± 13 % and 100 % respectively. The 3-year EFS and OS for infratentorial ependymoma were 27 ± 13 % and 73 ± 13 % respectively. The role of intensive induction and consolidation chemotherapy in deferring irradiation should be investigated further in children with supratentorial ependymoma with residual disease following surgery. This approach appears ineffective in children with infratentorial ependymoma in the absence of irradiation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/mortalidade , Ependimoma/mortalidade , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ependimoma/diagnóstico , Ependimoma/terapia , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Prognóstico , Estudos Prospectivos , Dosagem Radioterapêutica , Taxa de Sobrevida , Vincristina/administração & dosagem
17.
Biol Lett ; 9(4): 20130492, 2013 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-23804293

RESUMO

The use of human and veterinary pharmaceuticals is increasing. Over the past decade, there has been a proliferation of research into potential environmental impacts of pharmaceuticals in the environment. A Royal Society-supported seminar brought together experts from diverse scientific fields to discuss the risks posed by pharmaceuticals to wildlife. Recent analytical advances have revealed that pharmaceuticals are entering habitats via water, sewage, manure and animal carcases, and dispersing through food chains. Pharmaceuticals are designed to alter physiology at low doses and so can be particularly potent contaminants. The near extinction of Asian vultures following exposure to diclofenac is the key example where exposure to a pharmaceutical caused a population-level impact on non-target wildlife. However, more subtle changes to behaviour and physiology are rarely studied and poorly understood. Grand challenges for the future include developing more realistic exposure assessments for wildlife, assessing the impacts of mixtures of pharmaceuticals in combination with other environmental stressors and estimating the risks from pharmaceutical manufacturing and usage in developing countries. We concluded that an integration of diverse approaches is required to predict 'unexpected' risks; specifically, ecologically relevant, often long-term and non-lethal, consequences of pharmaceuticals in the environment for wildlife and ecosystems.


Assuntos
Exposição Ambiental , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Preparações Farmacêuticas/metabolismo , Vertebrados/metabolismo , Animais , Animais Selvagens/metabolismo , Conservação dos Recursos Naturais , Monitoramento Ambiental , Cadeia Alimentar , Humanos
18.
Pediatr Radiol ; 43(2): 140-51, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23208530

RESUMO

Rickets is characterized by impaired mineralization and ossification of the growth plates of growing children caused by a variety of disorders, the most frequent of which is nutritional deficiency of vitamin D. Despite ample knowledge of its etiology and the availability of cost-effective methods of preventing it, vitamin D deficiency rickets remains a significant problem in developing and developed countries. This two-part review covers the history, etiology, pathophysiology and clinical and radiographical findings of vitamin D deficiency rickets. Other less frequent causes of rickets and some of the disorders entering into the differential diagnoses of rickets are also considered. Controversial issues surrounding vitamin D deficiency include determination of what constitutes vitamin D sufficiency and the potential relationship between low levels of vitamin D metabolites in many individuals and unexplained fractures in infants.


Assuntos
Osso e Ossos/fisiopatologia , Raquitismo/diagnóstico , Raquitismo/fisiopatologia , Vitamina D/metabolismo , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Masculino
19.
Pediatr Radiol ; 43(2): 152-72, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23179485

RESUMO

This is the continuation of a two-part review of rickets. This part emphasizes the specific pathophysiology, clinical features, pathoanatomy and radiographic findings of vitamin D deficiency rickets. Other forms of rickets, differential diagnostic considerations and the potential relationship between low levels of vitamin D metabolites and unexplained fractures in infants are also discussed.


Assuntos
Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Raquitismo/complicações , Raquitismo/diagnóstico por imagem , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Masculino , Radiografia
20.
Environ Sci Technol ; 46(24): 13504-11, 2012 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-23171278

RESUMO

PBDE contamination in terrestrial biota is poorly characterized, and robust data on temporal trends are scarce. We measured temporal (1985-2007) and spatial trends in PBDE contamination in the eggs of the sparrowhawk (Accipiter nisus), a sentinel for the terrestrial environment. Five BDEs were the most abundant (BDE 99 > 47 > 153 > 100 > 154). Their concentrations, and that of the sum PBDEs (ΣPBDE), increased from the mid-1980s, peaking in the midlate 1990s at levels that were sustained until the end of the study. This and the predominance of BDE99 contrast with patterns in piscivorous species and suggest sparrowhawks, and perhaps terrestrial species more widely, may be relatively poor metabolizers of penta-BDEs. BDE 196, 197, 201, and 203 concentrations increased linearly through the study, indicating increasing contamination possibly from the presence of these congeners in, and/or debromination of, deca-BDE formulations. Variation in egg ΣPBDE concentration was not explained by % urban land cover, human population density or % of arable land in proximity to the nest site, or by land use. Overall, egg ΣPBDE concentrations (34-2281 ng/g wet weight) were some of the highest reported in birds from Europe. We found no relationship between ΣPBDE concentrations and eggshell thickness.


Assuntos
Ecossistema , Monitoramento Ambiental , Éteres Difenil Halogenados/análise , Óvulo/metabolismo , Animais , Falconiformes , Éteres Difenil Halogenados/toxicidade , Humanos , Modelos Lineares , Fatores de Tempo , Reino Unido
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