Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.493
Filtrar
1.
Food Chem Toxicol ; 135: 111051, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31837348

RESUMO

Excessive reactive oxygen radicals (ROS) produced by ionizing radiation (IR) can cause human body to serious oxidative damage, leading to oxidation-reduction (REDOX) system imbalance and immune system damage. Here, the radioprotection of EGCG was studied through a model of oxidative damage in 60Coγ radiation mice. Firstly, the weights and the main organs indexes of mice, including the liver index, spleen index and pancreas index, indicated preliminarily the safety and protection of EGCG. Then, the radioprotection of EGCG based on immune-regulation on radiation mice was further investigated. Results suggested that EGCG could prevent significantly the immune system damage caused by 60Coγ via increasing the immune organ index, inducing the transformation of spleen cells into T- and B-lymphocytes, and enhancing the macrophage phagocytosis, compared with model group. In addition, EGCG could also protect spleens of radiation mice from 60Coγ-induced the imbalance of REDOX system by enhancing the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), increasing the level of glutathione (GSH), suppressing lipid peroxidation (Malondialdehyde, MDA). The antioxidant enzymes activities of serum and livers were also increased markedly. Taken together, our results indicated that EGCG possessed the excellent potential to serve as a natural radioprotector against IR-induced damage.


Assuntos
Antioxidantes/metabolismo , Catequina/análogos & derivados , Radioisótopos de Cobalto/toxicidade , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Catequina/farmacologia , Masculino , Camundongos , Monócitos/imunologia , Monócitos/efeitos da radiação , Tamanho do Órgão/efeitos dos fármacos , Oxirredução , Lesões Experimentais por Radiação/imunologia , Lesões Experimentais por Radiação/metabolismo , Baço/efeitos dos fármacos , Baço/imunologia , Baço/efeitos da radiação
2.
Probl Radiac Med Radiobiol ; 24: 465-479, 2019 Dec.
Artigo em Inglês, Ucraniano | MEDLINE | ID: mdl-31841488

RESUMO

OBJECTIVE: to retrospectively characterize changes in the hepatobiliary system in liver cirrhosis (LC) in the clean-up workers of the Chornobyl NPP accident and to determine the factors of disease progression according to the expert materials of the Central Interagency Expert Commission on Establishing the Causal Relationship of the Diseases with the influence of factors of Chornobyl NPP accident. MATERIALS AND METHODS: Based on the data of 60 cases of the Central Interagency Expert Committee on establishing the causal link of diseases with the impact of the Chornobyl NPP accident, the factors of development, concomitant pathology and indicators of the hepatobiliary system status in 49 deceased and 11 alive clean-up workers with LC were investigated. RESULTS: A retrospective study of the morphological changes of the hepatobiliary system in the clean-up workers with LC showed that the main pathologic anatomical diagnosis in 37.8 % of cases was small-nodal LC, in 8.9 % - micromacronodular, in 4.4 % - large-nodal, in 2.2 % - primary biliary LC, in the other 40 % of cases - LC with uncer- tain nodal structure, as well as 2 (4.4 %) cases of fatty liver and 1 case (2.2 %) of portal cirrhosis against the back- ground of fatty liver. Pathomorphological changes were characterized by expressed growth of fibrous tissue with replacement of the liver parenchyma (fields of fibrosis), increase in size and impaired structure of the liver, thick- ening and tightening of its capsule, fibrotic changes in other organs - gastric mucosa, pancreas, spleen, lungs, heart. Histological examination revealed lobe structure abnormalities, false lobules, periportal fibrosis, lymphoid-lympho- cytic infiltration, diffuse fatty small-sized and large-drop dystrophy, and hepatocyte atrophy. Common inflammato- ry processes and fibrotic changes of other organs and systems: cardiovascular, urinary, bronchopulmonary, stomach, pancreas and spleen made the course of the LC more severe. The most frequent were cardiovascular diseases, signi- ficantly more frequent among the deceased than alive patients: hypertension - 67.3 % and 45.5 %, p < 0.05, coro- nary heart disease - 57.1 % and 18 %, p < 0.05. In most cases, the cause of death in the clean-up workers with LC was hepatic and cellular failure (53.3 %), which together with hepatic-renal failure (17.8 %) made 71.1 %. CONCLUSION: Changes in the hepatobiliary system of change in in the clean-up workers with LC were characterized by marked growth of fibrotic tissue with replacement of the parenchyma and impaired liver structure, fibrotic changes in other organs, diffuse fatty small and large droplet dystrophy and atrophy of hepatocytes. The severe course of the LC with the manifestation of the disease at the stage of decompensation was due to a vague clinical picture, lack of subjective symptoms of liver disease, slow, steadily progressing development, lack of or inadequate examination and treatment, a significant number of concomitant pathology of other organs and systems. The fac- tors of the development of LC in the clean-up workers were the long course of chronic liver disease, numerous con- comitant pathology, long stay in the accident zone, the effect of ionizing radiation, as well as the lack of dispensa- ry supervision and adequate treatment.


Assuntos
Doenças Cardiovasculares/patologia , Acidente Nuclear de Chernobyl , Socorristas , Fígado Gorduroso/patologia , Cirrose Hepática/patologia , Lesões por Radiação/patologia , Adulto , Ductos Biliares/patologia , Ductos Biliares/efeitos da radiação , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Progressão da Doença , Fígado Gorduroso/etiologia , Fígado Gorduroso/mortalidade , Fígado Gorduroso/fisiopatologia , Feminino , Mucosa Gástrica/patologia , Mucosa Gástrica/efeitos da radiação , Coração/fisiopatologia , Coração/efeitos da radiação , Humanos , Fígado/patologia , Fígado/efeitos da radiação , Cirrose Hepática/etiologia , Cirrose Hepática/mortalidade , Cirrose Hepática/fisiopatologia , Pulmão/patologia , Pulmão/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Pâncreas/efeitos da radiação , Exposição à Radiação/efeitos adversos , Lesões por Radiação/etiologia , Lesões por Radiação/mortalidade , Lesões por Radiação/fisiopatologia , Estudos Retrospectivos , Baço/patologia , Baço/efeitos da radiação , Análise de Sobrevida , Fatores de Tempo , Ucrânia
3.
Med Sci Monit ; 25: 8920-8927, 2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31760404

RESUMO

BACKGROUND Several factors found in foods are beneficial to human health and they may contribute to radiation protection. Taking food factors could be an easy way to reduce the effects of radiation after nuclear accidents, as well as secondary radiation risks after cancer radiotherapy or space missions. Here, diallyl disulfide (DADS), a component of garlic oil, was studied for its ability to mitigate radiation damage. MATERIAL AND METHODS We investigated the effects of DADS on micronucleus (MN) formation and apoptosis in HepG2 cells by use of 4-Gy X-ray irradiation. We also assessed the effects of DADS on radiation damage in vivo by evaluating MN formation in bone marrow cells in mice (BALB/c, 8-week-old females) after oral intake of DADS prior to irradiation with 4 Gy. Several tissue effects were also investigated. RESULTS The presence of DADS inhibited MN formation, whereas DADS had no influence on the radiation-induced inhibition of cell cycle progression in HepG2 cells. An increase in apoptosis in HepG2 cells was induced after irradiation, and this effect was stronger in the presence of DADS than in its absence. In mice, when DADS was administered daily for 3 days prior to irradiation, MN formation in irradiated mice was decreased. The decrease in MN formation in mice was greater with 0.5% DADS compared to 1% DADS. Moreover, an increase in spleen weight observed 3 weeks after irradiation was suppressed in mice administered DADS. CONCLUSIONS DADS is a potential radiation-protective agent that effectively mitigates DNA damage, and its effects in the spleen observed after irradiation may be related to inflammation and carcinogenesis.


Assuntos
Compostos Alílicos/farmacologia , Dissulfetos/farmacologia , Lesões por Radiação/prevenção & controle , Compostos Alílicos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Dissulfetos/metabolismo , Feminino , Células Hep G2/efeitos da radiação , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Protetores contra Radiação/farmacologia , Baço/efeitos da radiação
4.
Int Immunopharmacol ; 76: 105913, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31627170

RESUMO

Radiation exposure poses a significant threat to public health, which can lead to acute hematopoietic system and intestinal system injuries due to their higher radiation sensitivity. Hence, antioxidants and thiol-reducing agents could have a potential protective effect against this complication. The dithiol compound 1,4-dithiothreitol (DTT) has been used in biochemistry, peptide/protein chemistry and clinical medicine. However, the effect of DTT on ionizing radiation (IR)-induced hematopoietic injury and intestinal injury are unknown. The current investigation was designed to evaluate the effect of DTT as a safe and clinically applicable thiol-radioprotector in irradiated mice. DTT treatment improved the survival of irradiated mice and ameliorated whole body irradiation (WBI)-induced hematopoietic injury by attenuating myelosuppression and myeloid skewing, increasing self-renewal and differentiation of hematopoietic progenitor cells/hematopoietic stem cells (HPCs/HSCs). In addition, DTT treatment protected mice from abdominal irradiation (ABI)-induced changes in crypt-villus structures and function. Furthermore, treatment with DTT significantly enhanced the ABI-induced reduction in Olfm4 positive cells and offspring cells of Lgr5+ stem cells, including lysozyme+ Paneth cells and Ki67+ cells. Moreover, IR-induced DNA strand break damage, and the expression of proapoptotic-p53, Bax, Bak protein and antiapoptotic-Bcl-2 protein were reversed in DTT treated mice, and DTT also promoted small intestine repair after radiation exposure via the p53 intrinsic apoptotic pathway. In general, these results demonstrated the potential of DTT for protection against hematopoietic injury and intestinal injury after radiation exposure, suggesting DTT as a novel effective agent for radioprotection.


Assuntos
Síndrome Aguda da Radiação/tratamento farmacológico , Ditiotreitol/uso terapêutico , Lesões Experimentais por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Síndrome Aguda da Radiação/metabolismo , Animais , Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Ditiotreitol/farmacologia , Raios gama/efeitos adversos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos da radiação , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Intestino Delgado/efeitos da radiação , Masculino , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Lesões Experimentais por Radiação/metabolismo , Protetores contra Radiação/farmacologia , Baço/efeitos dos fármacos , Baço/efeitos da radiação , Timo/efeitos dos fármacos , Timo/efeitos da radiação , Proteína Supressora de Tumor p53/metabolismo , Irradiação Corporal Total
5.
J Radiat Res ; 60(6): 747-758, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31504707

RESUMO

This study examines the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the anti-cancer effects of fractionated X-ray irradiation of Ehrlich solid tumor-bearing mice. Swiss albino mice bearing tumors were exposed to the following: (i) Biobran treatment (40 mg/kg/day, intraperitoneal injections) beginning on day 11 post-tumor cell inoculation until day 30; (ii) ionizing radiation (Rad) 2 Gy at three consecutive doses on days 12, 14 and 16; or (iii) Biobran + Rad. Final tumor weight was suppressed by 46% for Biobran, 31% for Rad and 57% for the combined treatment (Biobran + Rad) relative to control untreated mice. Biobran and Rad also arrested the hypodiploid cells in the sub-G1-phase, signifying apoptosis by +102% and +85%, respectively, while the combined treatment induced apoptosis by +123%, with similar results in the degree of DNA fragmentation. Furthermore, Biobran + Rad upregulated the relative gene expression and protein level of p53 and Bax in tumor cells, down-regulated Bcl-2 expression, and increased the Bax/Bcl-2 ratio and caspase-3 activity, with the combined treatment greater than for either treatment alone. Additionally, the combined treatment modulated the decrease in body weight, the increase in liver and spleen weight, and the elevation of liver enzymes aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase to be within normal values. We conclude that Biobran enhances radiation therapy-induced tumor regression by potentiating apoptosis and minimizing toxicities related to radiation therapy, suggesting that Biobran may be useful in human cancer patients undergoing radiotherapy and warranting clinical trials.


Assuntos
Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/radioterapia , Xilanos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Peso Corporal/efeitos dos fármacos , Peso Corporal/efeitos da radiação , Carcinoma de Ehrlich/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Terapia Combinada , Dano ao DNA , Fragmentação do DNA/efeitos dos fármacos , Fragmentação do DNA/efeitos da radiação , Feminino , Regulação da Expressão Gênica , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Fígado/efeitos da radiação , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/efeitos da radiação , Baço/efeitos dos fármacos , Baço/patologia , Baço/efeitos da radiação , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Raios X , Xilanos/farmacologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
6.
Microb Pathog ; 136: 103672, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31442574

RESUMO

With the globe warming, chronic heat stress (CHS) has been considered to be a common hazard that could negatively affect pig's growth and reproduction performance. However, the effects of CHS on the immune functions of pigs were seldom reported, especially the cellular immune functions of intestinal mucosal system. In order to resolve this problem, a pig CHS model was built firstly and the effects of CHS on numbers of T cells in spleen and small intestines were observed. Exposure to a temperature of 39 °C, 4 h/d for 10d, the expression of heat stress protein 70 (HSP70) was increased dramatically. Under CHS condition, the numbers of CD3+ T cells were increased dramatically in both spleens and small intestines. Besides, the numbers of CD4+T cells and the value of CD4+/CD8+T cells in spleens were also significantly increased. The results highly revealed that CHS made the equilibrium state of immune function destroyed. Furthermore, CHS mainly promoted the expression of anti-apoptosis factor B cell lymphoma-2 (Bcl-2) and thus inhibited the apoptosis of lymphocytes in spleens and intestinal mucosa. This study demonstrates for the first time that CHS negatively affects the immune functions of both spleens and intestinal mucosal system in pigs through the inhibition of apoptosis. Our study can richer the data for study of mechanism of CHS and provide new knowledge for reference of making new strategy to control the disease induced by CHS.


Assuntos
Apoptose/efeitos da radiação , Resposta ao Choque Térmico , Mucosa Intestinal/imunologia , Mucosa Intestinal/efeitos da radiação , Baço/imunologia , Baço/efeitos da radiação , Animais , Temperatura Alta , Suínos , Fatores de Tempo
7.
Hum Exp Toxicol ; 38(10): 1195-1211, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31256688

RESUMO

The present study was premeditated to examine the radioprotective effects of aqueous Aloe vera gel extract against whole-body X-ray irradiation-induced hematological alterations and splenic tissue injury in mice. Healthy male balb/c mice were divided into four groups: group 1, control; group 2, A. vera (50 mg/kg body weight) administered per oral on alternate days for 30 days (15 times); group 3, X-ray exposure of 2 Gy (0.25 Gy twice a day for four consecutive days in the last week of the experimental protocol); and group 4, A. vera + X-ray. X-ray exposure caused alterations in histoarchitecture of spleen along with enhanced clastogenic damage as assessed by micronucleus formation and apoptotic index. Irradiation caused an elevation in proinflammatory cytokines like tumor necrosis factor and interleukin-6, total leucocyte counts, neutrophil counts and decreased platelet counts along with unaltered red blood cell counts and hemoglobin. Irradiation also caused an elevation in reactive oxygen species (ROS), lipid peroxidation (LPO) levels, lactate dehydrogenase activity and alterations in enzymatic and nonenzymatic antioxidant defense mechanism in plasma and spleen. However, administration of A. vera gel extract ameliorated X-ray irradiation-induced elevation in ROS/LPO levels, histopathological and clastogenic damage. It also modulated biochemical indices, inflammatory markers, and hematological parameters. These results collectively indicated that the A. vera gel extract offers protection against whole-body X-ray exposure by virtue of its antioxidant, anti-inflammatory and anti-apoptotic potential.


Assuntos
Apoptose/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Preparações de Plantas/farmacologia , Lesões Experimentais por Radiação/sangue , Lesões Experimentais por Radiação/prevenção & controle , Baço/efeitos dos fármacos , Administração Oral , Animais , Antioxidantes/metabolismo , Apoptose/efeitos da radiação , Contagem de Leucócitos , Leucócitos/efeitos da radiação , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Masculino , Camundongos Endogâmicos BALB C , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Contagem de Plaquetas , Lesões Experimentais por Radiação/patologia , Baço/patologia , Baço/efeitos da radiação , Irradiação Corporal Total
8.
Int J Radiat Biol ; 95(8): 1072-1084, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31140892

RESUMO

Purpose: Diagnostic radiation is an important part of patient care in the Intensive Care Unit; however, there is little data on the acute effects of exposure to these doses. We investigated pulmonary and splenic response 30 minutes, 4 hours or 24 hours after exposure to 2 mGy, 20 mGy, 200 mGy or 4 Gy whole-body X-radiation in a Sprague Dawley rat model. Materials and methods: Lung injury was assessed via respiratory mechanics, pulmonary edema, cellular, and proteinaceous fluid infiltrate and protein expression of oxidative stress markers. The radiation effect on the spleen was determined via proliferation, apoptosis and protein expression of oxidative stress markers. Results: All measurements of the lung did not differ from sham animals except for an increase in catalase after high dose exposure. Stimulated splenocyte proliferation increased after sham and low dose exposure, did not change after 200 mGy exposure and was significantly lower after 4 Gy exposure. The number of apoptotic cells increased 4 hours after 4 Gy exposure. There were fewer apoptotic cells after low dose exposure compared to sham. Both catalase and MnSOD were increased after 4 Gy exposure. Conclusion: There was no measured effect on pulmonary function while there was an impact to the spleen after low and high dose exposure.


Assuntos
Pulmão/efeitos da radiação , Baço/efeitos da radiação , Irradiação Corporal Total , Animais , Apoptose/efeitos da radiação , Proliferação de Células/efeitos da radiação , Relação Dose-Resposta à Radiação , Pulmão/patologia , Masculino , Estresse Oxidativo/efeitos da radiação , Doses de Radiação , Ratos , Mecânica Respiratória/efeitos da radiação , Baço/patologia
9.
Electromagn Biol Med ; 38(2): 177-183, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31017814

RESUMO

The study investigated the effect of extremely low-frequency electromagnetic fields (ELF-EMFs) exposure at different magnetic flux densities on genes expression of transcription factor Maf (c-Maf), signal transducer and activator of transcription 6 (STAT6), and retinoid-related orphan receptor alpha (RORα) in the spleen and thymus of rats. Eighty adult male rats were separated into four ELF-EMFs exposed and were exposed to magnetic flux densities of 1, 100, 500, and 2000 µT at a frequency of 50 Hz for 2 h daily for up to 60 d. All rats were intraperitoneally immunized on d 31, 44, and 58 of exposure. The experimental results showed that the expression levels of c-Maf, STAT6, and RORα in the thymus were not significantly changed at different magnetic flux densities. The expression levels of RORα and c-Maf were significantly downregulated at the densities of 1 and 100 µT, while the expression of STAT6 was only significantly decreased at the density of 100 µT. In conclusion, low magnetic flux densities of ELF-EMFs may reduce the expression levels of c-Maf, STAT6, and RORα genes in the spleen.


Assuntos
Campos Eletromagnéticos , Regulação da Expressão Gênica/efeitos da radiação , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Proteínas Proto-Oncogênicas c-maf/genética , Fator de Transcrição STAT6/genética , Baço/efeitos da radiação , Timo/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Masculino , Ratos , Ratos Wistar , Baço/metabolismo , Timo/metabolismo
10.
Environ Toxicol ; 34(7): 788-795, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30843661

RESUMO

The present study was to evaluate the radiomitigative effect of naringenin (NRG) on the modulation of ionizing radiation (IR)-induced spleen injury. Rats were exposed to 12 Gy (3Gy/two times/week). NRG (50mg/Kg), was orally given one hour after the first radiation dose, and daily continued during the irradiation period. Rats were sacrificed 1 day after the last dose of radiation. NRG showed a significant decrease of malondialdehyde, hydrogen peroxide with a significant elevation of superoxide dismutase, catalase and glutathione peroxidase activities and glutathione content. Moreover, NRG confirmed the intracellular defense mechanisms through activation of nuclear factor (erythroid-derived 2)-like2 (Nrf2) and haem oxygenase-1 (HO-1) levels and their protein expression. In addition, NRG deactivated the nuclear factor-κB (NF-κB) and reduced the pro-inflammatory cytokines. Further, NRG showed positive modulation in the haematological values (WBCs, RBCs, Hb, Hct% and PLt). In conclusion, these results suggested that NRG reversed the IR-induced redox-imbalance in the rat spleen.


Assuntos
Flavanonas/farmacologia , Heme Oxigenase-1/fisiologia , Fator 2 Relacionado a NF-E2/fisiologia , Estresse Oxidativo , Lesões por Radiação/prevenção & controle , Esplenopatias/prevenção & controle , Animais , Catalase/metabolismo , Raios gama/efeitos adversos , Glutationa/metabolismo , Heme Oxigenase-1/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio/metabolismo , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Estresse Oxidativo/efeitos da radiação , Lesões por Radiação/etiologia , Lesões por Radiação/metabolismo , Ratos , Ratos Wistar , Fatores de Risco , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/efeitos da radiação , Esplenopatias/etiologia , Esplenopatias/metabolismo , Superóxido Dismutase/metabolismo
11.
Med Oncol ; 36(2): 16, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30617767

RESUMO

Splenectomy before allogeneic stem cell transplantation (ASCT) for patients with myelofibrosis (MF) remains a matter of debate, and conflicting results have been reported to date. The procedure seems to fasten post-transplant hematological recovery, but it does not have an impact on survival. The role of pre-transplant splenic irradiation (SI) is much more difficult to evaluate. Forty-four patients (25 males and 19 females) with MF at median age of 49 years at diagnosis (range 14-67) underwent ASCT. The post-transplant outcome was compared between irradiated and non-irradiated patients. Eleven patients received irradiation before transplantation. Median dose of radiation was 1000 cGy (range 600-2400). There was no difference in median time to engraftment between patients with and without previous radiotherapy. Acute and chronic graft versus host disease (GVHD) occurred in 47% and 36% of patients, respectively. There was no difference in GVHD incidence between groups. Eight patients relapsed/progressed in irradiated group versus 17 in non-irradiated (70% vs. 51%; p = 0.3). Transformation to acute myeloid leukemia was observed in 3 patients: 2 in irradiated and 1 in non-irradiated group. In total, 22 patients died with no statistical difference in death rate between irradiated and non-irradiated subjects. The probability of overall survival after transplant for the entire cohort at 2 years was 54% (72% for irradiated and 48% for non-irradiated patients; p = 0.25). Splenic irradiation prior to ASCT for myelofibrosis has not beneficial effect on post-transplant outcome.


Assuntos
Mielofibrose Primária/terapia , Baço/efeitos da radiação , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/radioterapia , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
12.
Biochem Biophys Res Commun ; 510(1): 156-162, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30678810

RESUMO

Locally applied radiation to the tumor is reported to stimulate systemic immune response. During radiotherapy to the abdominal cancer, spleen often receives certain dose, though as an important immune organ, little is known about the impact of splenic irradiation (SI) on systemic immune and local tumor control. Through a mice model, we found that the combination of SI with tumor irradiation (TI) helped in local control. The analysis of the tumor infiltrating leucocytes demonstrated that SI plus TI brought more T cell aggregation in the tumor microenvironment (TME), which helped in tumor control. Increased T cell infiltration may be partly due to higher expression of T cell chemokine in the TME and more expression of CXCR3 on the T cells in the spleen after SI. SI produced more IL-1ß in the spleen, IL-1ß stimulated the expression of CXCR3 on the T cells, and enhanced their migration ability. Taken together, radiation to the spleen combined with TI helped in local control through promoting T cell infiltration, and may be a considerable means to enhance the immunomodulatory of radiotherapy.


Assuntos
Neoplasias/radioterapia , Baço/efeitos da radiação , Animais , Movimento Celular/imunologia , Quimiocinas/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Linfócitos do Interstício Tumoral/citologia , Linfócitos do Interstício Tumoral/fisiologia , Camundongos , Neoplasias/prevenção & controle , Receptores CXCR3/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Resultado do Tratamento , Microambiente Tumoral/imunologia
13.
Int J Radiat Biol ; 95(3): 286-297, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30496016

RESUMO

PURPOSE: Ionizing radiation is nowadays effectively used in cancer treatments. However, the effect of irradiation in immune-system cells is poorly understood and remains controversial. The aim of this work was to determine the effect of γ-irradiation in the structural and functional properties of mice splenic cells. MATERIALS AND METHODS: Structural traits of irradiated splenic cells were evaluated by Atomic Force Microscopy and Raman spectroscopy. Functional properties were measured by gene and protein expression by RT-qPCR and ELISA, respectively. The induced cytotoxic effect was evaluated by MTT assay and the phagocytic capability by flow cytometry. RESULTS: Membrane roughness and molecular composition of splenic adherent cells are not changed by irradiation doses exposure. An increase in transcription of pro-inflammatory cytokines was observed. While protein expression decreased in IL-2 dose-dependent, relevant differences were identified in the anti-inflammatory marker IL-10 at 27 Gy. An increase of cytotoxicity in irradiated cells at 7 Gy and 27 Gy doses was observed, while phagocytosis was slight increased at 7 Gy dose but not statistically significant. CONCLUSIONS: We have demonstrated that γ-irradiation affects the splenic cells and changes the cytokines profile toward a pro-inflammatory phenotype and a tendency to increase the cytotoxicity was found, which implies a stimulation of immune response induced by γ-irradiation.


Assuntos
Raios gama , Baço/citologia , Animais , Relação Dose-Resposta à Radiação , Regulação da Expressão Gênica/efeitos da radiação , Células HeLa , Humanos , Interleucina-10/metabolismo , Interleucina-2/metabolismo , Masculino , Camundongos , Fagocitose/efeitos da radiação , Baço/imunologia , Baço/metabolismo , Baço/efeitos da radiação
14.
Radiat Res ; 192(3): 241-250, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30430917

RESUMO

The purpose of the current study was to characterize the effects of simulated microgravity and radiation-induced changes in retina and retinal vasculature, and to assess the accompanying early changes in immune cells and hematological parameters. To better understand the effects of spaceflight, we used a combination of treatments designed to simulate both the radiation and low-gravity aspects of space conditions. To simulate the broad energy spectrum of a large solar particle event (SPE) and galactic cosmic ray (GCR) radiation, male C57BL/6J mice were exposed to whole-body irradiation using fully modulated beams of 150-MeV protons containing particles of energy from 0 to 150 MeV and a uniform dose-vs.-depth profile. The mice were also hindlimb-unloaded (HLU) by tail suspension. Mice were unloaded for 7 days, exposed to 50 cGy, unloaded for an additional 7 days and then sacrificed for tissue isolation at days 4 and 30 after the combined treatments. Increases in the number of apoptotic cells were observed in the endothelial cells of mice that received radiation alone or with HLU compared to controls at both days 4 and 30 (P < 0.05). Endothelial nitric oxide synthase (eNOS) levels were significantly elevated in the retina after irradiation only or combined with HLU compared to controls at the 30-day time point (P < 0.05). The most robust changes were observed in the combination group, suggesting a synergistic response to radiation and unloading. For hematopoietic parameters, our analysis indicated the main effects for time and radiation at day 4 after treatments (day 11 postirradiation) (P < 0.05), but a smaller influence of HLU for both white blood cell and lymphocyte counts. The group treated with both radiation and HLU showed greater than 50% reduction in lymphocyte counts compared to controls. Radiation-dependent differences were also noted in specific lymphocyte subpopulations (T, B, natural killer cells). This study shows indications of an early effect of low-dose radiation and spaceflight conditions on retina and immune populations.


Assuntos
Sistema Hematopoético/efeitos da radiação , Prótons/efeitos adversos , Retina/efeitos da radiação , Simulação de Ausência de Peso/efeitos adversos , Animais , Peso Corporal/efeitos da radiação , Contagem de Células , Relação Dose-Resposta à Radiação , Células Endoteliais/efeitos da radiação , Meio Ambiente Extraterreno , Linfócitos/citologia , Linfócitos/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III/metabolismo , Retina/citologia , Baço/efeitos da radiação , Fatores de Tempo
15.
Radiat Res ; 191(2): 162-175, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30520704

RESUMO

Over the last 50 years, a number of important physiological changes in humans who have traveled on spaceflights have been catalogued. Of major concern are the short- and long-term radiation-induced injuries to the hematopoietic system that may be induced by high-energy galactic cosmic rays encountered on interplanetary space missions. To collect data on the effects of space radiation on the human hematopoietic system in vivo, we used a humanized mouse model. In this study, we irradiated humanized mice with 0.4 Gy of 350 MeV/n 28Si ions, a dose that has been shown to induce tumors in tumor-prone mice and a reference dose that has a relative biological effectiveness of 1 (1 Gy of 250-kVp X rays). Cell counts, cell subset frequency and cytogenetic data were collected from bone marrow spleen and blood of irradiated and control mice at short-term (7, 30 and 60 days) and long-term ( 6 - 7 months) time points postirradiation. The data show a significant short-term effect on the human hematopoietic stem cell counts imparted by both high- and low-LET radiation exposure. The radiation effects on bone marrow, spleen and blood human cell counts and human cell subset frequency were complex but did not alter the functions of the hematopoietic system. The long-term data acquired from high-LET irradiated mice showed complete recovery of the human hematopoietic system in all hematopoietic compartments. The combined results demonstrate that, in spite of early perturbation, the longer term effects of high-LET radiation are not detrimental to human hematopoiesis in our system of study.


Assuntos
Radiação Cósmica , Hematopoese/efeitos da radiação , Células-Tronco Hematopoéticas/efeitos da radiação , Animais , Contagem de Células Sanguíneas , Medula Óssea/efeitos da radiação , Relação Dose-Resposta à Radiação , Humanos , Camundongos , Camundongos Endogâmicos NOD , Modelos Animais , Neoplasias Induzidas por Radiação/genética , Eficiência Biológica Relativa , Voo Espacial , Baço/efeitos da radiação
16.
Radiat Res ; 191(2): 176-188, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30566388

RESUMO

Nuclear factor-erythroid-2-related factor 2 transcription factor (Nrf2) is activated by reactive oxygen species (ROS) and binds to antioxidant response elements in the promoter regions of its target genes involved in redox regulation and antioxidative functions. In this study, we elucidated the relationship between radiation dose and the expression response of Nrf2 target genes involved in oxidative stress, such as heme oxygenase 1, ferritin heavy polypeptide 1 ( Fth1), NADPH dehydrogenase quinone 1, glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, glutathione reductase ( Gsr) and thioredoxin reductase 1 genes, in peripheral blood from X-ray irradiated mice. Whole-body radiation doses ranged from 0.5 to 3 Gy, and gene expressions were analyzed using reverse transcription quantitative polymerase chain reaction. A significant relationship was observed only for one gene: a statistically significant positive correlation between radiation dose and Fth1 mRNA expression was detected. However, Fth1 did not show any correlations with the biological damages induced by radiation tested in this study. Furthermore, while Gsr expression was significantly associated with spleen weight loss, splenic cell number reduction and bone marrow cell death apoptosis, no significant correlation was observed between Gsr expression and radiation dose. Together these results indicate that Nrf2 target gene expression is closely related to radiation dose and its level may reflect biological damages induced by ionizing radiation. These findings suggest the possibility for application of these target genes as a bio-dosimeter and/or damage marker in individuals exposed to ionizing radiation.


Assuntos
Regulação da Expressão Gênica/efeitos da radiação , Fator 2 Relacionado a NF-E2/genética , Radiação Ionizante , Animais , Células da Medula Óssea/efeitos da radiação , Morte Celular/efeitos da radiação , Relação Dose-Resposta à Radiação , Camundongos , Tamanho do Órgão/efeitos da radiação , Estresse Oxidativo/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/efeitos da radiação , Irradiação Corporal Total
17.
Phys Med ; 56: 41-49, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30527088

RESUMO

PURPOSE: Peptide receptor radionuclide therapy with 177Lu-DOTATATE has become a standard treatment modality in neuroendocrine tumours (NETs). No consensus has yet been reached however regarding the absorbed dose threshold for lesion response, the absorbed dose limit to organs-at-risk, and the optimal fractionation and activity to be administered. This is partly due to a lack of uniform and comparable dosimetry protocols. The present article details the development of an organ-at-risk dosimetry procedure, which could be implemented and used routinely in a clinical context. METHODS: Forty-seven patients with NETs underwent 177Lu-DOTATATE therapy. Three SPECT/CT images were acquired at 4, 24 and 144-192 h post-injection. Three blood samples were obtained together with the SPECT/CT acquisitions and 2 additional samples were obtained around 30 min and 1 h post-injection. A bi-exponential fit was used to compute the source organ time-integrated activity coefficients. Coefficients were introduced into OLINDA/EXM software to compute organ-at-risk absorbed doses. Median values for all patients were computed for absorbed dose coefficient D/A0 and for late effective half-life T1/2eff for kidneys, spleen and red marrow. RESULTS: Dosimetry resulted in a median[interquartile range] of 0.78[0.35], 1.07[0.58] and 0.028[0.010] Gy/GBq for D/A0 and of 55[9], 71[9] and 52[18] h for T1/2eff for kidneys, spleen and red marrow respectively. CONCLUSIONS: A dosimetry procedure for organs-at-risk in 177Lu-DOTATATE therapy based on serial SPECT/CT images and blood samples can be implemented routinely in a clinical context with limited patient burden. The results obtained were in accordance with those of other centres.


Assuntos
Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Órgãos em Risco , Radiometria/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/efeitos da radiação , Feminino , Humanos , Rim/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/uso terapêutico , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Baço/efeitos da radiação
18.
PLoS One ; 13(10): e0205211, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30356336

RESUMO

High levels of uranium (U) exist in soil, water, and air in the Southwestern United States due, in part, to waste generated from more than 160,000 abandoned hard rock mines located in this region. As a result, many people living in this region are chronically exposed to U at levels that have been linked to detrimental health outcomes. In an effort to establish a relevant in vivo mouse model for future U immunotoxicity studies, we evaluated the tissue distribution of U in immune organs; blood, bone marrow, spleen, and thymus, as well as femur bones, kidneys, and liver, following a 60-d drinking water exposure to uranyl acetate (UA) in male and female C57BL/6J mice. Following the 60-d exposure, there was low overall tissue retention of U (<0.01%) at both the 5 and the 50 ppm (mg/L) oral concentrations. In both male and female mice, there was limited U accumulation in immune organs. U only accumulated at low concentrations in the blood and bone marrow of male mice (0.6 and 16.8 ng/g, respectively). Consistent with previous reports, the predominant sites of U accumulation were the femur bones (350.1 and 399.0 ng/g, respectively) and kidneys (134.0 and 361.3 ng/g, respectively) of male and female mice. Findings from this study provide critical insights into the distribution and retention of U in lymphoid tissues following chronic drinking water exposure to U. This information will serve as a foundation for immunotoxicological assessments of U, alone and in combination with other metals.


Assuntos
Exposição Ambiental , Tecido Linfoide/efeitos da radiação , Compostos Organometálicos/administração & dosagem , Urânio/toxicidade , Animais , Sangue/efeitos da radiação , Medula Óssea/efeitos da radiação , Camundongos , Radiação , Sudoeste dos Estados Unidos , Baço/efeitos da radiação , Timo/efeitos da radiação
19.
In Vivo ; 32(6): 1519-1525, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30348711

RESUMO

AIM: Our study sought to identify dosimetric predictors of treatment-related lymphopenia during chemoradiotherapy for esophageal cancer. MATERIALS AND METHODS: Patients with esophageal cancer who had received definitive chemoradiotherapy at our Institution were retrospectively assessed. The absolute volume of the spleen, body, and bone marrow that had received 5, 10, 20, and 30 Gy and the mean splenic dose were recorded. RESULTS: Multivariate linear regression analysis revealed that docetaxel use and spleen dose-volume parameters (V5, V10, V20, V30, and mean splenic dose) were significant independent factors negatively influencing the absolute lymphocyte count at nadir. An increase of 1 Gy in mean splenic dose predicted a 2.9% decrease in nadir absolute lymphocyte count. Univariable logistic regression analysis showed that the mean splenic dose was a significant predictor of grade 4 lymphopenia. None of the body or bone marrow dose-volume parameters significantly predicted lymphopenia. CONCLUSION: Higher spleen dose-volume parameters were associated with severe lymphopenia during chemoradiotherapy.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/radioterapia , Linfopenia/epidemiologia , Idoso , Medula Óssea/patologia , Medula Óssea/efeitos da radiação , Quimiorradioterapia/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/patologia , Feminino , Humanos , Contagem de Linfócitos , Linfopenia/etiologia , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Baço/patologia , Baço/efeitos da radiação
20.
Phys Med ; 54: 1-14, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30336998

RESUMO

Prompt-gamma (PG) imaging has the potential for monitoring proton therapy in real time. Different approaches are investigated. We focus on developing multi-slat collimators to image PG quanta, aiming at optimizing collimator performance to detect deviations in treatment delivery. We investigated six different multi-slat configurations, which have either optimal (analytical) intrinsic spatial resolution at fixed efficiency, or otherwise; at different distances from the proton pencil-beam axis (15 cm-35 cm). We used Geant4 to simulate irradiations of the head (energy: 130 MeV) and pelvis (200 MeV) of an anthropomorphic phantom, with and without physiologic/morphologic or setup changes of clinical dosimetric relevance. The particles escaping the phantom were transported through each of these multi-slat configurations and the gamma counts profiles were recorded at the collimator exit. Median filtering was applied to the registered PG-profiles to mitigate the effects of septa shadowing and statistical fluctuations. Time-of-flight discrimination was used to enhance the signal-to-background ratio, which appeared crucial for 200 MeV irradiations. Visual detection of the artificially introduced changes was possible by comparing the PG to the depth-dose profiles. Moreover, 2 mm range shifts could be detected in the head irradiation case using a simple linear regression fit to the falloff of the PG-profile. The influence of changes in complex, patient-like dose distributions on the PG-profiles obtained with multi-slat collimation is first studied in this work, which further gives insight on collimator design optimization and highlights its potential and simplicity for detecting proton treatment deviations over a wide range of Bragg peak positions.


Assuntos
Imagens de Fantasmas , Terapia com Prótons/instrumentação , Cintilografia/instrumentação , Humanos , Método de Monte Carlo , Hipófise/diagnóstico por imagem , Hipófise/efeitos da radiação , Dosagem Radioterapêutica , Baço/diagnóstico por imagem , Baço/efeitos da radiação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA