Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.101
Filtrar
1.
Br J Radiol ; 93(1107): 20190919, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32003576

RESUMO

OBJECTIVE: Monte Carlo (MC) simulations substantially improve the accuracy of predicted doses. This study aims to determine and quantify the uncertainties of setting up such a MC system. METHODS: Doses simulated with two Geant4-based MC calculation codes, but independently tuned to the same beam data, have been compared. Different methods of MC modelling of a pre-absorber have been employed, either modifying the beam source parameters (descriptive) or adding the pre-absorber as a physical component (physical). RESULTS: After the independent beam modelling of both systems in water (resulting in excellent range agreement) range differences of up to 3.6/4.8 mm (1.5% of total range) in bone/brain-like tissues were found, which resulted from the use of different mean water ionisation potentials during the energy tuning process. When repeating using a common definition of water, ranges in bone/brain agreed within 0.1 mm and gamma-analysis (global 1%,1mm) showed excellent agreement (>93%) for all patient fields. However, due to a lack of modelling of proton fluence loss in the descriptive pre-absorber, differences of 7% in absolute dose between the pre-absorber definitions were found. CONCLUSION: This study quantifies the influence of using different water ionisation potentials during the MC beam modelling process. Furthermore, when using a descriptive pre-absorber model, additional Faraday cup or ionisation chamber measurements with pre-absorber are necessary. ADVANCES IN KNOWLEDGE: This is the first study quantifying the uncertainties caused by the MC beam modelling process for proton pencil beam scanning, and a more detailed beam modelling process for MC simulations is proposed to minimise the influence of critical parameters.


Assuntos
Método de Monte Carlo , Terapia com Prótons/métodos , Incerteza , Absorção de Radiação , Ar , Osso e Ossos/efeitos da radiação , Encéfalo/efeitos da radiação , Humanos , Hipofracionamento da Dose de Radiação , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Água
2.
Cancer Radiother ; 24(1): 53-59, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32046915

RESUMO

PUPOSE: To compare dosimetric plans for the treatments of oligobrains metastases (2-6) using mono-isocentric arc therapy and multi-isocentric volumetric modulated arc therapy (VMAT). MATERIAL AND METHODS: A total of sixteen patients with multiple brain metastases were selected. Prescription dose was between 24 and 15Gy depending on the tumor size. For every patient,arctherapy and VMAT plans were generated respectively, with Elements Multiple Brain Mets SRS version 2.0 (BrainLab) and Eclipse SRS Treatment Planning Systeme version 15.5. The conformity index (CI), homogeinity index (HI), gradient index (GI), dose volume histogram for each organs at risk, total Monitor Units were evaluated. RESULTS: For coverage of the PTV, mono-isocentric plans showed a better CI and a better GI than multi-isocentric plans, respectively CI of 1.18±0.11 vs 1.41±0.20 (P<0.01), and GI of 3.55±0.59 vs 4.03±1.20 (P<0.01). Homogeneity index was not better with mono-isocentric plans, with respectively HI 24.32±3.87 vs 14.05±4.46 (P=1). For organs at risk, there were no statistical differences between mono and multi-isocentric plans for both eyes, both lenses, both optic nerves, chiasma, brainstem, and hippocampi.V12Gy and V10Gy of normal brain were statistically lower with mono-isocentric plans than with multi-isocentric plans, respectivellyV12Gy of 3.06Gy 95%CI [2.25;3.86]vs 5.18Gy 95%CI [3.43;6.93] (P<0,01) and V10Gy 4.66Gy 95%CI [3.33;5.98] vs7.30Gy 95%CI [4.73;9.87] (P<0.03). Total number of MU was significantly lower with mono-isocentric plans than with multi-isocentric plans, respectively 6668±1463 vs 12403±4941 (P<0.01), then treatment time was lower with mono-isocentric plans. CONCLUSION: Mono-isocentric plans had a better conformity index and gradient index than multi-isocentric plans for the treatment of multiple brain metastases. Moreover, mono-isocentric techniques gave fewer doses to normal brain and used less monitor units than multi-isocentric techniques.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/efeitos da radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador
3.
Cancer Radiother ; 24(1): 1-10, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31992516

RESUMO

PURPOSE: The purpose of this prospective dosimetric study was to assess the dose distribution regarding the brain areas implied in cognitive functions using two approaches: volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT). PATIENTS AND METHODS: Thirty-seven patients were treated using a dual-arc VMAT approach for supratentorial glioblastoma between 2016 and 2018. The total dose of 60Gy in 30 daily fractions was administered to the planning target volume (PTV). The brain structures that play an important role in cognitive physiology, such as the hippocampi, corpus callosum, cerebellum, subventricular zones (SVZ), were delineated. For each patient, a new treatment plan in HT was determined by a second medical physicist in a blindly fashion according to the same dose constraints and priorities. Statistical analyses were performed using the Wilcoxon-signed rank test. RESULTS: Conformity indexes remained similar with both techniques. The mean values were 0.96 (0.19-1.00) for VMAT and 0.98 (range, 0.84-1.00) for HT, respectively (P=0.73). Significant D50% reductions were observed with VMAT compared to HT: 14.6Gy (3.8-28.0) versus 17.4Gy (12.1-25.0) for the normal brain (P=0.014); 32.5Gy (10.3-60.0) versus 35.6Gy (17.1-58.0) for the corpus callosum (P=0.038); 8.1Gy (0.4-34.0) versus 12.8Gy (0.8-27.0) for the cerebellum (P<0.001), respectively. CONCLUSION: The VMAT approach seemed to improve the sparing of the key brain areas implied in cognitive functions without jeopardizing PTV coverage.


Assuntos
Neoplasias Encefálicas/radioterapia , Encéfalo/efeitos da radiação , Glioblastoma/radioterapia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão , Órgãos em Risco , Estudos Prospectivos
4.
J Photochem Photobiol B ; 204: 111775, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31935591

RESUMO

Wogonin (5,7-dihydroxy-8-methoxy flavone), an active component isolated from the root of Scutellaria baicalensis Georgi. Neurotoxic effects of γ irradiation have been established in humans and animals. The current study was designed to evaluate whether wogonin could restrain γ irradiation-induced neurotoxicity in rats and to explore the underlying mechanisms. Rats were divided into five groups, 10 rats each. Group 1 was orally administered distilled water and served as control. Group 2 received an oral daily dose of wogonin (30 mg/kg). Rats in group 3 were exposed to a whole-body single dose of γ-irradiation. Animals in group 4 received an oral daily dose of wogonin (30 mg/kg) for 15 days then exposed to a whole-body single dose of γ-irradiation. In group 5, rats were exposed to a whole-body single dose of γ-irradiation then were orally administered a daily dose of wogonin (30 mg/kg) for 15 days. There were significant increases in malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and Interleukin 6 (IL-6) levels and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA and protein expression. Whereas significant decreases in reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) level as well as nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA and protein expression in the irradiated group when compared with the relevant control. The cerebral cortex of irradiated rats showed vacuolization and nuclear pyknosis in the neuronal cells and focal gliosis. Wogonin administration pre- or post-irradiation significantly ameliorated all these previous effects. Wogonin had antioxidant and anti-inflammatory effects and ameliorated the histopathological changes in the brain.


Assuntos
Encéfalo/efeitos dos fármacos , Flavanonas/farmacologia , Raios gama , Fármacos Neuroprotetores/farmacologia , Administração Oral , Animais , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Medicamentos de Ervas Chinesas/farmacologia , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
6.
Int J Cancer ; 146(6): 1479-1489, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31583684

RESUMO

Patients with melanoma brain metastases (MBM) still have a very poor prognosis. Several treatment modalities have been investigated in an attempt to improve the management of MBM. This review aimed to evaluate the impact of current treatments for MBM on patient- and tumor-related outcomes, and to provide treatment recommendations for this patient population. A literature search in the databases PubMed, Embase, Web of Science and Cochrane was conducted up to January 8, 2019. Original articles published since 2010 describing patient- and tumor-related outcomes of adult MBM patients treated with clearly defined systemic therapy were included. Information on basic trial demographics, treatment under investigation and outcomes (overall and progression-free survival, local and distant control and toxicity) were extracted. We identified 96 eligible articles, comprising 95 studies. A large variety of treatment options for MBM were investigated, either used alone or as combined modality therapy. Combined modality therapy was investigated in 71% of the studies and resulted in increased survival and better distant/local control than monotherapy, especially with targeted therapy or immunotherapy. However, neurotoxic side-effects also occurred more frequently. Timing appeared to be an important determinant, with the best results when radiotherapy was given before or during systemic therapy. Improved tumor control and prolonged survival can be achieved by combining radiotherapy with immunotherapy or targeted therapy. However, more randomized controlled trials or prospective studies are warranted to generate proper evidence that can be used to change the standard of care for patients with MBM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/terapia , Quimiorradioterapia/métodos , Melanoma/terapia , Neoplasias Cutâneas/patologia , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/normas , Humanos , Melanoma/mortalidade , Melanoma/secundário , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Síndromes Neurotóxicas/etiologia , Guias de Prática Clínica como Assunto , Prognóstico , Intervalo Livre de Progressão , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia
7.
Gen Comp Endocrinol ; 285: 113266, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31493394

RESUMO

In the present study, the effects of photic environments, such as background color (white and black) and chromatic lights (blue, green, and red), on body color and gene expressions of melanin-concentrating hormone (mch) in the brain and proopiomelanocortin (pomc) in the pituitary, as well as the roles of the eyes and brain as mediators of ambient light to these genes, were examined in goldfish (Carassius auratus). Body color of goldfish exposed to fluorescent light (FL) under white background (WBG) was paler than those under black background (BBG). Gene expression levels for mch and pomc were reciprocally different depending on background color; under WBG, mRNA levels of mch and pomc were high and low, respectively, while under BBG, these levels were reversed. mch and pomc mRNA expressions of the fish exposed to chromatic light from LED were primarily similar to those exposed to FL, while blue light stimulated the expressions of mch and pomc. Ophthalmectomized goldfish exposed to FL or blue light showed minimum expression levels of mch gene, suggesting that eyes are the major mediator of ambient light for mch gene expression. Contrastingly, mRNA expressions of pomc in ophthalmectomized goldfish exposed to FL were different from those of intact goldfish. These results suggest that eyes play a functional role in mediating ambient light to regulate pomc gene expression. Since ophthalmectomy caused an increase in pomc mRNA contents in the fish exposed to blue light, we suggest that the brain is an additional mediator to regulate pomc gene expression.


Assuntos
Regulação da Expressão Gênica , Carpa Dourada/genética , Hormônios Hipotalâmicos/genética , Luz , Melaninas/genética , Pigmentação/genética , Pigmentação/efeitos da radiação , Hormônios Hipofisários/genética , Pró-Opiomelanocortina/genética , Animais , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Cor , Regulação da Expressão Gênica/efeitos da radiação , Hormônios Hipotalâmicos/metabolismo , Melaninas/metabolismo , Hipófise/metabolismo , Hipófise/efeitos da radiação , Hormônios Hipofisários/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
8.
Pak J Pharm Sci ; 32(4): 1589-1597, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31608878

RESUMO

The current study was designed to estimate the effect of υ-radiation on male rats pretreated with Levetiracetam (LEV) and/or Oxcarbazepine (OXC). Poly-treatment of rats with LEV, OXC and υ-radiation showed a significant elevation in the activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and isoenzyme creatinine kinase-MB (CK-MB) along with, an increase in the level of creatinine, urea, cardiac troponin (cTnI) and glutamate. These increases were associated with a decrease in acetylcholine (Ach) and υ-aminobutyric acid (GABA) levels. The data further revealed a significant increase of the apoptotic mediators tumor necrosis factor alpha (TNF-α) and brain caspase3 as well as, alterations in the oxidative stress parameters. The Results of the histopathological examination of liver, kidney, heart and brain tissues indicated coincidence with those recorded by the biochemical analysis. It seems promising to conclude that the exposure to υ-radiation intensified the deleterious and detrimental effect of dual treatment of LEV and OXC in rats.


Assuntos
Anticonvulsivantes/farmacologia , Raios gama/efeitos adversos , Levetiracetam/efeitos adversos , Oxcarbazepina/efeitos adversos , Acetilcolina/metabolismo , Alanina Transaminase/sangue , Animais , Anticonvulsivantes/efeitos adversos , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Quimioterapia Combinada , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Rim/efeitos da radiação , Levetiracetam/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/efeitos da radiação , Masculino , Malondialdeído/metabolismo , Neurotransmissores/metabolismo , Oxcarbazepina/farmacologia , Ratos
9.
Turk Neurosurg ; 29(6): 887-900, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31608966

RESUMO

AIM: To investigate the potential protective effects of melatonin on the chronic radiation emitted by third generation mobile phones on the brain. MATERIAL AND METHODS: A total of 24 male Wistar albino rats were divided into four equal groups. Throughout a 90-day experiment, no application was performed on the control group. The second group was exposed to 2100 MHz radiation for 30 minutes. Subcutaneous melatonin was injected into the third group. Subcutaneous melatonin injection was applied 40 minutes before radiation and then the fourth group was exposed to radiation for 30 minutes. At the end of the experiment, brain (cerebrum and cerebellum) tissues were taken from the subjects. Histochemical, immunohistochemical, ultrastructural and western blot analyses were applied. In addition to brain weight, Purkinje cells’ number, immunohistochemical H Score analyses and the results of the Western blot were examined statistically. RESULTS: With the application of radiation, neuronal edema, relatively-decreased numbers of neurons on hippocampal CA1 and CA3 regions, displacement of the Purkinje neurons and dark neurons findings were observed as a result of histochemical stainings. Radiation also activated the NMDA-receptor 2B/Calpain-1/Caspase-12 pathway, NMDA-receptor 2B and Calpain-1 with the findings being supported by western blot analyses. Pre-increased protein synthesis before apoptosis was identified by electron microscopy. CONCLUSION: Mobile phone radiation caused certain (ultra) structural changes on the brain and activated the NMDA-receptor 2B/ Calpain-1/Caspase-12 pathway; in addition, melatonin was found to be effective, but insufficient in demonstrating the protective effects.


Assuntos
Encéfalo/metabolismo , Calpaína/metabolismo , Caspase 12/metabolismo , Radiação Eletromagnética , Melatonina/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Encéfalo/efeitos dos fármacos , Encéfalo/efeitos da radiação , Calpaína/efeitos da radiação , Caspase 12/efeitos da radiação , Telefone Celular , Masculino , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação
10.
Elife ; 82019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613218

RESUMO

In Drosophila, ~150 neurons expressing molecular clock proteins regulate circadian behavior. Sixteen of these neurons secrete the neuropeptide Pdf and have been called 'master pacemakers' because they are essential for circadian rhythms. A subset of Pdf+ neurons (the morning oscillator) regulates morning activity and communicates with other non-Pdf+ neurons, including a subset called the evening oscillator. It has been assumed that the molecular clock in Pdf+ neurons is required for these functions. To test this, we developed and validated Gal4-UAS based CRISPR tools for cell-specific disruption of key molecular clock components, period and timeless. While loss of the molecular clock in both the morning and evening oscillators eliminates circadian locomotor activity, the molecular clock in either oscillator alone is sufficient to rescue circadian locomotor activity in the absence of the other. This suggests that clock neurons do not act in a hierarchy but as a distributed network to regulate circadian activity.


Assuntos
Relógios Circadianos/genética , Ritmo Circadiano/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Neurônios/metabolismo , Neuropeptídeos/genética , Proteínas Circadianas Period/genética , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Sistemas CRISPR-Cas , Comunicação Celular , Linhagem da Célula/genética , Relógios Circadianos/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Escuridão , Proteínas de Drosophila/deficiência , Drosophila melanogaster/metabolismo , Drosophila melanogaster/efeitos da radiação , Retroalimentação Fisiológica , Edição de Genes , Regulação da Expressão Gênica , Transdução de Sinal Luminoso/genética , Locomoção/genética , Locomoção/efeitos da radiação , Rede Nervosa/metabolismo , Rede Nervosa/efeitos da radiação , Neurônios/citologia , Neurônios/efeitos da radiação , Neuropeptídeos/deficiência , Proteínas Circadianas Period/deficiência , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética
11.
Elife ; 82019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613223

RESUMO

Animal circadian rhythms persist in constant darkness and are driven by intracellular transcription-translation feedback loops. Although these cellular oscillators communicate, isolated mammalian cellular clocks continue to tick away in darkness without intercellular communication. To investigate these issues in Drosophila, we assayed behavior as well as molecular rhythms within individual brain clock neurons while blocking communication within the ca. 150 neuron clock network. We also generated CRISPR-mediated neuron-specific circadian clock knockouts. The results point to two key clock neuron groups: loss of the clock within both regions but neither one alone has a strong behavioral phenotype in darkness; communication between these regions also contributes to circadian period determination. Under these dark conditions, the clock within one region persists without network communication. The clock within the famous PDF-expressing s-LNv neurons however was strongly dependent on network communication, likely because clock gene expression within these vulnerable sLNvs depends on neuronal firing or light.


Assuntos
Encéfalo/metabolismo , Relógios Circadianos/genética , Ritmo Circadiano/genética , Drosophila melanogaster/genética , Regulação da Expressão Gênica , Transdução de Sinal Luminoso/genética , Neurônios/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina Básica/deficiência , Fatores de Transcrição de Zíper de Leucina Básica/genética , Encéfalo/citologia , Encéfalo/efeitos da radiação , Sistemas CRISPR-Cas , Comunicação Celular , Linhagem da Célula/genética , Relógios Circadianos/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Escuridão , Proteínas de Drosophila/deficiência , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Drosophila melanogaster/efeitos da radiação , Retroalimentação Fisiológica , Edição de Genes , Rede Nervosa/metabolismo , Rede Nervosa/efeitos da radiação , Neurônios/citologia , Neurônios/efeitos da radiação , Neuropeptídeos/deficiência , Neuropeptídeos/genética , Proteínas Circadianas Period/deficiência , Proteínas Circadianas Period/genética , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética
12.
Radiat Res ; 192(6): 668-679, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31618121

RESUMO

Radiation therapy is one of the pillars of cancer treatment, with approximately one half of all cancer patients receiving it as part of their standard of care. Emerging evidence indicates that the biological effects of radiation are not limited to targeted cells. The radiation-induced bystander effect (RIBE) refers to the plethora of biological phenomena occurring in nonirradiated cells as a result of signal transmission from an irradiated cell. Experimental evidence has linked RIBE to numerous hallmarks of cancer including resisting cell death, tumor immune evasion, genomic instability, deregulated cellular energetics, tumor-promoting inflammation and sustained proliferative signaling as well as enhanced radioresistance, thus highlighting the potential role of RIBE events in patient treatment response. The mechanisms underlying RIBE events in vivo are poorly understood. However, elucidating the molecular mechanisms involved in their manifestation may reveal novel therapeutic targets to improve radiation response in cancer patients.


Assuntos
Efeito Espectador/efeitos da radiação , Dano ao DNA , Instabilidade Genômica , Neoplasias/radioterapia , Lesões por Radiação , Radioterapia/efeitos adversos , Animais , Apoptose , Encéfalo/efeitos da radiação , Morte Celular , Proliferação de Células , Humanos , Inflamação , Camundongos , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias/fisiopatologia , Neovascularização Patológica , Transdução de Sinais
13.
Nature ; 574(7777): 254-258, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31534216

RESUMO

Group 3 innate lymphoid cells (ILC3s) are major regulators of inflammation, infection, microbiota composition and metabolism1. ILC3s and neuronal cells have been shown to interact at discrete mucosal locations to steer mucosal defence2,3. Nevertheless, it is unclear whether neuroimmune circuits operate at an organismal level, integrating extrinsic environmental signals to orchestrate ILC3 responses. Here we show that light-entrained and brain-tuned circadian circuits regulate enteric ILC3s, intestinal homeostasis, gut defence and host lipid metabolism in mice. We found that enteric ILC3s display circadian expression of clock genes and ILC3-related transcription factors. ILC3-autonomous ablation of the circadian regulator Arntl led to disrupted gut ILC3 homeostasis, impaired epithelial reactivity, a deregulated microbiome, increased susceptibility to bowel infection and disrupted lipid metabolism. Loss of ILC3-intrinsic Arntl shaped the gut 'postcode receptors' of ILC3s. Strikingly, light-dark cycles, feeding rhythms and microbial cues differentially regulated ILC3 clocks, with light signals being the major entraining cues of ILC3s. Accordingly, surgically or genetically induced deregulation of brain rhythmicity led to disrupted circadian ILC3 oscillations, a deregulated microbiome and altered lipid metabolism. Our work reveals a circadian circuitry that translates environmental light cues into enteric ILC3s, shaping intestinal health, metabolism and organismal homeostasis.


Assuntos
Encéfalo/efeitos da radiação , Ritmo Circadiano/efeitos da radiação , Homeostase/efeitos da radiação , Intestinos/imunologia , Intestinos/efeitos da radiação , Luz , Linfócitos/imunologia , Linfócitos/efeitos da radiação , Fatores de Transcrição ARNTL/deficiência , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Animais , Relógios Biológicos/genética , Relógios Biológicos/efeitos da radiação , Encéfalo/fisiologia , Ritmo Circadiano/genética , Ritmo Circadiano/imunologia , Ritmo Circadiano/fisiologia , Sinais (Psicologia) , Comportamento Alimentar/efeitos da radiação , Feminino , Microbioma Gastrointestinal/efeitos da radiação , Imunidade Inata/efeitos da radiação , Intestinos/citologia , Metabolismo dos Lipídeos , Linfócitos/metabolismo , Masculino , Camundongos , Fotoperíodo
14.
Ann Afr Med ; 18(3): 127-131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417012

RESUMO

Background: Brain metastasis is a dreaded complication that significantly reduces the quality of life in breast cancer patients. The treatment options are limited by the inability of many chemotherapeutic agents to cross the blood-brain barrier. Surgery also has a limited role, except in few selected patients with oligometastasis. Therefore, whole-brain radiotherapy (WBRT) remains the available option that gives a gratifying result. However, the benefit of this treatment modality in our resource-poor environment needs to be investigated. Materials and Methods: The data of breast cancer patients with brain metastasis who were treated with WBRT using cobalt-60 equipment between 2005 and 2009 were retrospectively collected from the departmental medical record unit. The information extracted included biodata, presenting symptoms, imaging modality for confirmation of brain metastasis, treatment records, performance status pre-WBRT and 4 weeks post-WBRT, and other supportive treatments. Results: A total of 52 female patients were reviewed between 2005 and 2009. The mean age of patients was 44.7 years. The common clinical features on presentation were headache, nausea, and visual impairment in 30.8% of patients with the WHO performance status score ranging between 2 and 4. Patients with more than three brain deposits accounted for 71.2% of all the brain metastases. The mean radiation dose used for WBRT was 30 Gy in 10 fractions, and total responses recorded were 86.5% with 53.8% complete improvement in patients' performance status 4 weeks after WBRT treatment. Conclusion: WBRT is an effective treatment modality for patients with brain metastasis in our resource-poor environment. However, improvement of patients' performance status declined with advancing age.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Encéfalo/patologia , Neoplasias da Mama/radioterapia , Irradiação Craniana/métodos , Cuidados Paliativos/métodos , Adulto , Idoso , Encéfalo/efeitos da radiação , Neoplasias da Mama/patologia , Fracionamento da Dose de Radiação , Feminino , Hospitais Universitários , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Nigéria , Dosagem Radioterapêutica , Assistência Terminal , Resultado do Tratamento
15.
Radiat Oncol ; 14(1): 144, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409408

RESUMO

PURPOSE: Despite the success of fractionation in clinical practice to spare healthy tissue, it remains common for mouse models used to study the efficacy of radiation therapy to use minimal or no fractionation. The goal of our study was to create a fractionated mouse model of radiation necrosis that we could compare to our single fraction model. METHODS: Precision X-Ray's X-Rad 320 cabinet irradiator was used to irradiate the cerebrum of mice with four different fractionation schemes, while a 7 T Bruker magnetic resonance imaging (MRI) scanner using T2 and post-contrast T1 imaging was used to track the development of radiation necrosis over the span of six weeks. RESULTS: All four fractionation schemes with single fraction equivalent doses (SFED) less than 50 Gy for the commonly accepted alpha/beta ratio (α/ß) value of 2-3 Gy produced radiation necrosis comparable to what would be achieved with single fraction doses of 80 and 90 Gy. This is surprising when previous work using single fractions of 50 Gy produced no visible radiation necrosis, with the results of this study showing fractionation not sparing brain tissue as much as expected. CONCLUSION: Further interpretation of these results must take into consideration other studies which have shown a lack of sparing when fractionation has been incorporated, as well as consider factors such as the use of large doses per fraction, the time between fractions, and the limitations of using a murine model to analyze the human condition.


Assuntos
Encéfalo/patologia , Modelos Animais de Doenças , Fracionamento da Dose de Radiação , Lesões Experimentais por Radiação/patologia , Animais , Encéfalo/efeitos da radiação , Feminino , Imagem por Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Necrose , Lesões Experimentais por Radiação/etiologia
16.
Environ Sci Pollut Res Int ; 26(30): 30693-30710, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31463749

RESUMO

The primary objective of mobile phone technology is to achieve communication with any person at any place and time. In the modern era, it is impossible to ignore the usefulness of mobile phone technology in cases of emergency as many lives have been saved. However, the biological effects they may have on humans and other animals have been largely ignored and not been evaluated comprehensively. One of the reasons for this is the speedy uncontrollable growth of this technology which has surpassed our researching ability. Initiated with the first generation, the mobile telephony currently reaches to its fifth generation without being screened extensively for any biological effects that they may have on humans or on other animals. Mounting evidences suggest possible non-thermal biological effects of radiofrequency electromagnetic radiation (RF-EMR) on brain and behavior. Behavioral studies have particularly concentrated on the effects of RF-EMR on learning, memory, anxiety, and locomotion. The literature analysis on behavioral effects of RF-EMR demonstrates complex picture with conflicting observations. Nonetheless, numerous reports suggest a possible behavioral effect of RF-EMR. The scientific findings about this issue are presented in the current review. The possible neural and molecular mechanisms for the behavioral effects have been proposed in the light of available evidences from the literature.


Assuntos
Ansiedade/etiologia , Encéfalo/efeitos da radiação , Telefone Celular , Campos Eletromagnéticos/efeitos adversos , Memória/efeitos da radiação , Ondas de Rádio , Animais , Barreira Hematoencefálica/efeitos da radiação , Encéfalo/fisiopatologia , Radiação Eletromagnética , Humanos , Aprendizagem/efeitos da radiação , Locomoção/efeitos da radiação
17.
Genes (Basel) ; 10(9)2019 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-31450566

RESUMO

Brain and nervous system cancers in children represent the second most common neoplasia after leukemia. Radiotherapy plays a significant role in cancer treatment; however, the use of such therapy is not without devastating side effects. The impact of radiation-induced damage to the brain is multifactorial, but the damage to neural stem cell populations seems to play a key role. The brain contains pools of regenerative neural stem cells that reside in specialized neurogenic niches and can generate new neurons. In this review, we describe the advances in radiotherapy techniques that protect neural stem cell compartments, and subsequently limit and prevent the occurrence and development of side effects. We also summarize the current knowledge about neural stem cells and the molecular mechanisms underlying changes in neural stem cell niches after brain radiotherapy. Strategies used to minimize radiation-related damages, as well as new challenges in the treatment of brain tumors are also discussed.


Assuntos
Neoplasias Encefálicas/radioterapia , Células-Tronco Neurais/efeitos da radiação , Radioterapia/métodos , Animais , Encéfalo/citologia , Encéfalo/efeitos da radiação , Humanos , Células-Tronco Neurais/citologia , Neurogênese , Radioterapia/efeitos adversos
18.
Int J Radiat Oncol Biol Phys ; 105(2): 394-399, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31283978

RESUMO

PURPOSE: To compare normal tissue dosimetry between hippocampal-avoidance whole brain radiation therapy (HA-WBRT) and stereotactic radiosurgery (SRS) in patients with 10 to 30 brain metastases, and to describe a novel SRS strategy we term Spatially Partitioned Adaptive RadiosurgEry (SPARE). METHODS AND MATERIALS: A retrospective review identified SRS treatment plans with >10 brain metastases located >5 mm from the hippocampi. Our Gamma Knife Icon (GKI) SPARE (GKI-Spr) technique treats multiple metastases with single-fraction SRS partitioned over consecutive days while limiting the total treatment time to ≤60 minutes per day. Hippocampal and normal brain dosimetry were compared among GKI-Spr, single-fraction single-day GKI (GKI-Sfr), and 30 Gy in 10 fractions HA-WBRT. Dose metrics were converted to equivalent dose in 2 Gy fractions. RESULTS: Ten cases were analyzed. Compared with HA-WBRT, GKI-Spr significantly reduced the median equivalent dose in 2 Gy fractions hippocampal maximum point dose, mean dose, and dose to 40% of the hippocampi (D40%) by 86%, 93%, and 93%, respectively, and similarly for GKI-Sfr by 81%, 92%, and 91%, respectively. The normal brain median mean dose was reduced by 95% with GKI-Spr and 94% with GKI-Sfr. Compared with GKI-Sfr, GKI-Spr further reduced all normal brain and hippocampal dose metrics (P ≤ .014). CONCLUSIONS: GKI yields superior hippocampal and normal brain dosimetry compared with HA-WBRT, and GKI-Spr results in further dosimetric advantages.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana/métodos , Hipocampo/efeitos da radiação , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/efeitos da radiação , Radiocirurgia/métodos , Algoritmos , Encéfalo/efeitos da radiação , Humanos , Dosagem Radioterapêutica , Estudos Retrospectivos
19.
Int J Radiat Biol ; 95(11): 1547-1551, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31290704

RESUMO

Purpose: This study evaluated if Toxoplasma gondii infection and the drug-associated infection modifies the brain radiopharmaceutical Ethylene Cystine Diethylester Dihydrochloride (99mTc-ECD) biodistribution in mice.Materials and methods: A total of 18 mice were divided into 3 groups. Control group (C) received distilled water and 99mTc-ECD; Infected group (I) received T. gondii strain and 99mTc-ECD; Infected and Treated group (IT), in addition to infection, received association of Pyrimethamine and Sulfadiazine and 99mTc-ECD. The T. gondii strain used in this study was TgCkRrRN3. Forty minutes after administration of the 99mTc-ECD, all animals were euthanized, and blood and brain samples were isolated. The counting of the radioactivity percentage per gram of tissue (%ATI/g) was calculated, and statistical analysis was performed by t-test, with a level of significance of p < .05.Results: There was a significant increase in %ATI/g between groups C and I on brain (0.35 ± 0.02 and 0.45 ± 0.04; p = .041) and on blood (0.80 ± 0.09 and 1.14 ± 0.31; p = .049). A significant decrease in %ATI/g occurred between groups C and IT on blood (0.80 ± 0.09 and 0.54 ± 0.08; p = .001) and on brain (0.35 ± 0.02 and 0.22 ± 0.04; p = .049).Conclusions: Combined therapy of anti-Toxoplasma drugs in infected mice reduced the uptake of 99mTc-ECD, probably due to its binding to plasma proteins.


Assuntos
Encéfalo/parasitologia , Encéfalo/efeitos da radiação , Cisteína/análogos & derivados , Compostos de Organotecnécio/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Toxoplasma , Toxoplasmose/tratamento farmacológico , Toxoplasmose/parasitologia , Animais , Antiprotozoários/uso terapêutico , Encéfalo/metabolismo , Cisteína/farmacocinética , Masculino , Camundongos , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Distribuição Tecidual
20.
J Radiat Res ; 60(4): 466-475, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31197311

RESUMO

The effective dose (HE) and organ or tissue equivalent dose (HT) for use in brain computed tomography (CT) examinations with various body weights were evaluated. Thermoluminescent dosimeters (TLD-100H) were inserted into Rando and five anthropomorphic phantoms. These phantoms were made of polymethylmethacrylate (PMMA), according to the specifications of ICRU 48, with masses from 10 to 90 kg. Brain CT examinations were conducted, scanning the maxillae from the external auditory meatus to the parietal bone using a 128-slice multi-detector CT (MDCT) scanner. To reduce errors, three independent trials were conducted. Calculated HE,TLD, based on the weighting factor recommended by ICRP 103, was 1.72 ± 0.28 mSv, which slightly exceeds the HE,DLP of 1.70 mSv, that was calculated from the dose-length product (DLP) of the Rando phantom. This experiment yielded HE,TLD values of ICRP 103 from the highest 1.85 ± 0.28 (90 kg) to the lowest 1.47 ± 0.22 (10 kg) mSv. HE,TLD (mSv) = 5.45×10-3 W(kg) + 1.361, with an R2 of 0.87667. Using the DLP protocol, HE,DLP was estimated from CTDIvol that was recorded directly from the console display of the CT unit and multiplied by the conversion coefficient (k) recommended by the ICRP 103. Finally, the experimental results obtained herein are compared with those in the literature. Physicians should choose and adjust protocols to prevent the exposure of patients to unnecessary radiation, satisfying the as low as reasonably achievable (ALARA) principle. These findings will be valuable to patients, physicians, radiologists and the public.


Assuntos
Peso Corporal , Encéfalo/efeitos da radiação , Imagens de Fantasmas , Algoritmos , Antropometria , Calibragem , Feminino , Humanos , Masculino , Doses de Radiação , Dosimetria Termoluminescente , Tomografia Computadorizada por Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA