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1.
Sci Total Environ ; 852: 158383, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36057302

RESUMO

In addition to obvious negative effects on water quality in eutrophic aquatic ecosystems, recent work suggests that cyanobacterial harmful algal blooms (CHABs) also impact air quality via emissions carrying cyanobacterial cells and cyanotoxins. However, the environmental controls on CHAB-derived aerosol and its potential public health impacts remain largely unknown. Accordingly, the aims of this study were to 1) investigate the occurrence of microcystins (MC) and putatively toxic cyanobacterial communities in particulate matter ≤ 2.5 µm in diameter (PM2.5), 2) elucidate environmental conditions promoting their aerosolization, and 3) identify associations between CHABs and PM2.5 concentrations in the airshed of the Chowan River-Albemarle Sound, an oligohaline, eutrophic estuary in eastern North Carolina, USA. In summer 2020, during peak CHAB season, continuous PM2.5 samples and interval water samples were collected at two distinctive sites for targeted analyses of cyanobacterial community composition and MC concentration. Supporting air and water quality measurements were made in parallel to contextualize findings and permit statistical analyses of environmental factors driving changes in CHAB-derived aerosol. MC concentrations were low throughout the study, but a CHAB dominated by Dolichospermum occurred from late June to early August. Several aquatic CHAB genera recovered from Chowan River surface water were identified in PM2.5 during multiple time points, including Anabaena, Aphanizomenon, Dolichospermum, Microcystis, and Pseudanabaena. Cyanobacterial enrichment in PM2.5 was indistinctive between subspecies, but at one site during the early bloom, we observed the simultaneous enrichment of several cyanobacterial genera in PM2.5. In association with the CHAB, the median PM2.5 mass concentration increased to 8.97 µg m-3 (IQR = 5.15), significantly above the non-bloom background of 5.35 µg m-3 (IQR = 3.70) (W = 1835, p < 0.001). Results underscore the need for highly resolved temporal measurements to conclusively investigate the role that CHABs play in regional air quality and respiratory health risk.


Assuntos
Cianobactérias , Microcistinas , Microcistinas/análise , Estuários , Lagos/microbiologia , Ecossistema , Proliferação Nociva de Algas , Material Particulado/análise
2.
Health (London) ; 26(5): 663-678, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34674571

RESUMO

The lifestyle model, which attributes etiological power and moral responsibility to the individual, is dominant in health promotion discourse. While sociologists rightly critique this model's individualistic outlook, there has been insufficient distinction between the two anti-individualistic models that commonly inform their work: the well-known "sociological model" and the culturally influential but under-conceptualized model tentatively called the "finitude model." Not only is there insufficient awareness of the different etiological causes (inequality and human fragility) and political orientations (redistribution and recognition) underlying the sociological and finitude models, but there is also insufficient recognition of how the finitude model may inform illness explanation. To raise awareness about the existence and analytical utility of the finitude model, I elucidate its core assumptions through a brief review of some influential texts in late-modern health politics. Further, I illustrate the empirical utility of the notion of the finitude model by analyzing how it is used to explain illness in Arthur Frank's and Kathlyn Conway's influential cancer memoirs. Thematic analysis of the memoirs produces two major findings. First, Frank and Conway rely on the finitude model to claim victimhood and blame the blamers. Second, they seem unaware of the double-edged character of such a model, which tends to downplay how social inequality shapes health. My analysis reveals the one-sidedness of both the finitude and sociological models, and that any illness explanation therefore needs to integrate both anti-individualistic models to challenge the lifestyle model successfully.


Assuntos
Estilo de Vida , Neoplasias , Humanos
3.
Toxins (Basel) ; 13(2)2021 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-33498948

RESUMO

Microcystins are common freshwater cyanobacterial toxins that affect liver function. The toxicities of five microcystin congeners (microcystin-LA (MCLA), MCLR, MCLY, MCRR, and MCYR) commonly observed in harmful algal blooms (HABs) were evaluated in BALB/c mice after a single oral administration of doses ranging from those that were no observed adverse effect levels (NOAELs) to lowest observed adverse effect levels (LOAELs). Animals were monitored for changes in behavior and appearance, and euthanized 24 h after dosing. Test endpoints included clinical changes, necropsy observations, and serum indicators of hepatic toxicity and general homeostasis. Doses were 0.5-7 mg/kg MCLA, 0.5-11 mg/kg MCLR, 1-7 mg/kg MCLY, 7-22 mg/kg MCRR, and 3-11 mg/kg MCYR. MCLA at 3 mg/kg elevated liver/body weight ratio and liver score, ALT, AST, and GLDH, indicating hepatic toxicity, reduced serum glucose and highly elevated total serum bilirubin. MCLR and MCLY induced similar effects with LOAELs of 5 mg/kg, although a greater extent and severity of effects were observed in MCLR animals. MCRR exposure at 22 mg/kg was associated with reduced serum glucose. MCYR induced scattered liver effects at 7 mg/kg and reduced serum glucose levels at 5 mg/kg. The results indicate significant differences in congener-induced toxicity after microcystin exposure.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fígado/efeitos dos fármacos , Toxinas Marinhas/toxicidade , Microcistinas/toxicidade , Administração Oral , Animais , Bilirrubina/sangue , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cianobactérias/metabolismo , Relação Dose-Resposta a Droga , Feminino , Proliferação Nociva de Algas , Fígado/metabolismo , Fígado/patologia , Masculino , Toxinas Marinhas/administração & dosagem , Camundongos Endogâmicos BALB C , Microcistinas/administração & dosagem , Nível de Efeito Adverso não Observado
4.
Toxicology ; 441: 152529, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32590024

RESUMO

1,1,2,2-tetrafluoro-2-[1,1,1,2,3,3-hexafluoro-3-(1,1,2,2-tetrafluoroethoxy)propan-2-yl]oxyethane-1-sulfonic acid (PFESA-BP2) was first detected in 2012 in the Cape Fear River downstream of an industrial manufacturing facility. It was later detected in the finished drinking water of municipalities using the Cape Fear River for their water supply. No toxicology data exist for this contaminant despite known human exposure. To address this data gap, mice were dosed with PFESA-BP2 at 0, 0.04, 0.4, 3, and 6 mg/kg-day for 7 days by oral gavage. As an investigative study, the final dose groups evolved from an original dose of 3 mg/kg which produced liver enlargement and elevated liver enzymes. The dose range was extended to explore a no effect level. PFESA-BP2 was detected in the sera and liver of all treated mice. Treatment with PFESA-BP2 significantly increased the size of the liver for all mice at 3 and 6 mg/kg-day. At the 6 mg/kg-day dose, the liver more than doubled in size compared to the control group. Male mice treated with 3 and 6 mg/kg-day and females treated with 6 mg/kg-day demonstrated significantly elevated serum markers of liver injury including alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), and liver/body weight percent. The percent of PFESA-BP2 in serum relative to the amount administered was similar in male and female mice, ranged from 9 to 13 %, and was not related to dose. The percent accumulation in the liver of the mice varied by sex (higher in males), ranged from 30 to 65 %, and correlated positively with increasing dose level.


Assuntos
Hidrocarbonetos Fluorados/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Relação Dose-Resposta a Droga , Feminino , Hidrocarbonetos Fluorados/sangue , Hidrocarbonetos Fluorados/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Tamanho do Órgão/efeitos dos fármacos , Poluentes Químicos da Água/sangue , Poluentes Químicos da Água/farmacocinética
5.
Toxins (Basel) ; 12(6)2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32570788

RESUMO

Microcystins (MCs) are common cyanobacterial toxins that occur in freshwaters worldwide. Only two of the >200 MC variants have been tested for potential toxicity after oral exposure. This paper reports on the toxicity of 10 different MC congeners identified in algal blooms, microcystin-LR (MCLR), MCLA, MCLF, MCLW, MCLY, MCRR, [Asp3]MCRR, [Asp3,Dhb7]MCRR, MCWR, and MCYR after single administrations to BALB/c mice. In a preliminary MCLR dose-response study of 3 to 9 mg/kg doses, ≥5 mg/kg induced clinical changes, increased serum levels of ALT, AST, and GLDH, liver congestion, increased liver/body weight ratios, and reduced serum glucose and total protein. Based on the extent of these effects, the 10 congeners were administered as single 7 mg/kg oral doses and toxicity evaluated. The greatest toxicity was observed with MCLA and MCLR including a high percentage of moribundity. In addition to eliciting effects similar to those listed above for MCLR, MCLA also induced serum alterations indicative of jaundice. MCLY, and MCYR induced changes like those noted with MCLR, but to lesser extents. MCLW and MCLF exhibited some serum and morphological changes associated with hepatic toxicity, while there were few indications of toxicity after exposures to MCRR, [Asp3]MCRR, [Asp3,Dhb7]MCRR, or MCWR. These data illustrate a wide spectrum of hepatic effects and different potencies of these MC congeners.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fígado/efeitos dos fármacos , Microcistinas/toxicidade , Testes de Toxicidade Aguda , Administração Oral , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Relação Dose-Resposta a Droga , Feminino , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos BALB C , Microcistinas/administração & dosagem
6.
Cancer Invest ; 37(2): 67-72, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873889

RESUMO

There has been controversy about the presence and potential role of aquaporin-4 (AQP4) in glioblastoma (GBM). We analyzed tissue from 22 patients with newly-diagnosed GBM as well as matching tissue from 17 of these cases who underwent repeat resection for suspected recurrence and performed immunohistochemical analysis for AQP-4 expression. While some degree of AQP4 expression was detected in all 22 cases (39 samples), there was no clear relationship between staining pattern and disease status (active versus inactive GBM) between baseline and time of repeat biopsy. In addition, there was no clear relationship between AQP4 expression and degree of edema.


Assuntos
Aquaporina 4/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Adulto , Idoso , Biópsia , Neoplasias Encefálicas/patologia , Quimiorradioterapia/métodos , Progressão da Doença , Edema/metabolismo , Edema/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Glioblastoma/patologia , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
7.
CNS Neurosci Ther ; 24(3): 187-192, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29285884

RESUMO

INTRODUCTION: Superficial siderosis is a rare, neurodegenerative disease caused by toxic accumulation of hemosiderin on the surface of the brain and the spinal cord, most commonly from chronic subarachnoid hemorrhage. AIMS: The aim of this study was to assess the clinical and radiological outcomes of superficial siderosis patients using deferiprone, a cell permeant iron chelator. Subjects obtained pre- and post-treatment brain MRIs and weekly laboratory tests. Osirix software was used to develop a method of quantifying hemosiderin deposition. Three-dimensional whole brain images of gradient echo images were rendered and compared by dividing the mean T2 hyperintensity to the maximal cerebrospinal fluid signal. RESULTS: A total of 38 subjects completed the study, of which clinical and radiological data were available for 30. The average age was 64 years (range 37-86), 53% were male, 94% were white. Nineteen subjects (63%) reported either no progression of disease or an improvement in at least one neurological domain, with 40% of patients reporting a stabilization in hearing function and 30% reporting stable or improved coordination and walking. By MRI, there was an overall mean increase in T2 hyperintensity of the whole brain of 1%-13% over the 2-year time period in half of patients, indicating a reduction hemosiderosis. There were no cases of agranulocytosis, and declines of white blood cells counts and neutrophils averaged <10%. Fatigue was the most common side effect. CONCLUSION: This is the first long-term prospective study of superficial siderosis on the iron chelator, deferiprone. MRI quantification of hemosiderin appears to demonstrate a measurable reduction in half of patients and this correlated with a stabilized or improving disease course. A future placebo-controlled trial is necessary to determine whether deferiprone is an effective therapy for superficial siderosis.


Assuntos
Deferiprona/uso terapêutico , Hemossiderose/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Feminino , Hemossiderose/diagnóstico por imagem , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/diagnóstico por imagem , Estudos Prospectivos
8.
Mult Scler J Exp Transl Clin ; 3(4): 2055217317740145, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29270309

RESUMO

BACKGROUND: Dalfampridine has the potential to be effective in patients with transverse myelitis (TM) as this rare disorder shares some clinical and pathogenic similarities with multiple sclerosis. METHODS: This is a randomized, double-blind, placebo-controlled crossover study of dalfampridine extended-release (D-ER, Ampyra®). Sixteen adult study participants with monophasic TM confirmed by MRI were enrolled if their baseline timed 25-foot walking speed was between 5 and 60 seconds. Participants were randomized to receive 10 mg twice-daily doses of either D-ER or placebo control for eight weeks, then crossed over to the second arm of placebo or dalfampridine for eight weeks. The primary outcome measure was the timed 25-foot walk. RESULTS: Of 16 enrolled participants, three withdrew and 13 completed the trial. Among the 13 completers, nine individuals showed an average timed walk that was faster in the D-ER arm compared to the placebo arm, but only four participants met the stricter statistical threshold to be classified as a responder. Analyses of secondary clinical outcome measures including strength, balance assessments, spasticity, and Expanded Disability Status Scale (EDSS) score showed trends toward improvement with D-ER. CONCLUSIONS: D-ER may be beneficial in TM to improve walking speed and other neurological functions.

9.
J Vis Exp ; (99): e52249, 2015 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-26068024

RESUMO

The rat optic nerve is a useful model for stem cell regeneration research. Direct injection into the rat optic nerve allows delivery into the central nervous system in a minimally-invasive surgery without bone removal. This technique describes an approach to visualization and direct injection of the optic nerve following minor fascial dissection from the orbital ridge, using a conjunctival traction suture to gently pull the eye down and out. Representative examples of an injected optic nerve show successful injection of dyed beads.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos/veterinária , Procedimentos Neurocirúrgicos/veterinária , Nervo Óptico/cirurgia , Transplante de Células-Tronco/veterinária , Animais , Injeções/veterinária , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Neurocirúrgicos/métodos , Ratos , Transplante de Células-Tronco/métodos
10.
Acta Neuropathol Commun ; 3: 28, 2015 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-25990016

RESUMO

INTRODUCTION: Neuromyelitis Optica (NMO) is an autoimmune disease primarily targeting the spinal cord and optic nerve leading to paralysis and blindness. The discovery of an antibody against the astrocytic water channel, aquaporin-4 (AQP4), in the majority of patients, has led to the presumption that the antibody was necessary for disease pathogenesis. The potential role of T cells in the central nervous system, however, has not been thoroughly examined. RESULTS: We generated an anti-AQP4 antibody seronegative model of NMO using pathogenic AQP4-reactive T cells in mice by immunizing AQP4 null mice with peptides corresponding to the second extracellular loop of AQP4, loop C. When polarized to a Th17 phenotype and transferred to wild-type mice, these cells caused tail and limb weakness. Histology showed demyelination and T cell infiltration in the spinal cord, optic nerve and brain. Animals receiving cells re-stimulated in culture with non-specific proteins resulted in no behavioral disease, indicating that specific targeting of AQP4 is essential for this phenotype. CONCLUSIONS: In summary, we show that AQP4-reactive T cells are sufficient to trigger an NMO-like disease in mice, independent of antibodies, indicating that pathogenic AQP4-reactive T cells may play a similar role in humans.


Assuntos
Aquaporina 4/imunologia , Imunoglobulina G/imunologia , Neuromielite Óptica/imunologia , Neuromielite Óptica/patologia , Linfócitos T/imunologia , Animais , Formação de Anticorpos/imunologia , Aquaporina 4/genética , Encéfalo/patologia , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Nervo Óptico/patologia , Peptídeos/imunologia , Medula Espinal/patologia , Linfócitos T/citologia
11.
BMC Neurol ; 13: 104, 2013 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-23927715

RESUMO

BACKGROUND: Neuromyelitis optica (NMO) is a devastating inflammatory disorder of the optic nerves and spinal cord characterized by frequently recurring exacerbations of humoral inflammation. NMO is associated with the highly specific NMO-IgG biomarker, an antibody that binds the aquaporin-4 water channel. Aquaporin-4 is present on glial endfeet in the central nervous system (CNS). In humans, the NMO-IgG portends more frequent exacerbations and a worse long-term clinical outcome. METHODS: We tested the longer-term outcome of mice with EAE injected with NMO-IgG and followed them for 60 days. Clinical exams and pathology of the spinal cord and optic nerves were compared to mice that received control human IgG. RESULTS: Passively transferred human NMO-IgG leads to more severe neurology disability over two months after onset of disease. Clinical worsening is associated with an increased concentration of large demyelinating lesions primarily to subpial AQP4-rich regions of the spinal cord. CONCLUSIONS: NMO-IgG is pathogenic in the context of EAE in mice.


Assuntos
Encefalomielite Autoimune Experimental/sangue , Encefalomielite Autoimune Experimental/imunologia , Imunoglobulina G/sangue , Neuromielite Óptica/imunologia , Animais , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos Ly/imunologia , Antígenos Ly/metabolismo , Aquaporina 4/imunologia , Aquaporina 4/metabolismo , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/imunologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/etiologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Bainha de Mielina/metabolismo , Bainha de Mielina/patologia , Glicoproteína Mielina-Oligodendrócito/toxicidade , Nervo Óptico/metabolismo , Nervo Óptico/patologia , Fragmentos de Peptídeos/toxicidade , Medula Espinal/metabolismo , Medula Espinal/patologia , Fatores de Tempo
12.
Neuropharmacology ; 49(5): 703-14, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16019039

RESUMO

Our goals were to identify biochemical markers for transient global ischemia-induced delayed neuronal death and test possible drug therapies against this neuronal damage. Four-vessel occlusion (4-VO) for 20 min was used as a rat model. The temporal expression profiles of three glutamate transporters (GLT-1, GLAST and EAAC1) were evaluated in the CA1 region of the hippocampus and the striatum. The protein levels of the GLT-1 were significantly down-regulated between 3 and 6 h after ischemia-reperfusion in the CA1 region and striatum, returned to the control (2-VO) levels 24 h after reperfusion and remained unchanged for up to 7 days. The levels of GLAST in the CA1 region and striatum, and EAAC1 in the CA1 region did not change after ischemia from 1 h to 7 days. Pretreatment with group III metabotropic glutamate receptor antagonist s-alpha-MCPA (20 microg/5 microl) 30 min prior to 4-VO significantly restored the GLT-1 levels in the CA1 region caused by global ischemia at both 3 and 6 h after reperfusion. The loss of pyramidal neurons in the CA1 region due to ischemia-reperfusion could also be prevented by intraventricular pretreatment with s-alpha-MCPA. The current findings pinpoint the significance of GLT-1 during ischemia/reperfusion and suggest a potential application of group III metabotropic glutamate receptor antagonist against ischemic/hypoxic neuronal damage.


Assuntos
Transportador 2 de Aminoácido Excitatório/biossíntese , Hipocampo/metabolismo , Ataque Isquêmico Transitório/metabolismo , Neostriado/metabolismo , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Ácido 2-Metil-4-clorofenoxiacético/farmacologia , Sistema X-AG de Transporte de Aminoácidos/biossíntese , Animais , Western Blotting , Regulação para Baixo/efeitos dos fármacos , Transportador 1 de Aminoácido Excitatório , Transportador 3 de Aminoácido Excitatório , Proteínas de Transporte de Glutamato da Membrana Plasmática , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Neostriado/citologia , Neostriado/efeitos dos fármacos , Células Piramidais/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Simportadores/biossíntese
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