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1.
Science ; 262(5131): 229-33, 1993 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-17841870

RESUMO

X-ray absorption spectroscopy (XAS) of Fe(2+) in Fe(2)SiO(4) liquid at 1575 kelvin and 10(-4) gigapascal (1 bar) shows that the Fe(2+) -O bond length is 1.98 +/- 0.02 angstroms compared with approximately 2.22 angstroms in crystalline Fe(2)SiO(4) (fayalite) at the melting point (1478 kelvin), which indicates a decrease in average Fe(2+) coordination number from six in fayalite to four in the liquid. Anharmonicity in the liquid was accounted for using a data analysis procedure. This reduction in coordination number is similar to that observed on the melting of certain ionic salts. These results are used to develop a model of the medium-range structural environment of Fe(2+) in olivine-composition melts, which helps explain some of the properties of Fe(2)SiO(4) liquid, including density, viscosity, and the partitioning of iron and nickel between silicate melts and crystalline olivines. Some of the implications of this model for silicate melts in the Earth's crust and mantle are discussed.

2.
Exp Hematol ; 22(6): 510-6, 1994 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8187847

RESUMO

The aims of this study were to determine the radiosensitivities of murine thymic and splenic CD4+ and CD8+ lymphocytes and to evaluate the regeneration of these cells in a model of radiation-induced hematopoietic and immune suppression. CD4+ and CD8+ cells were quantitated using two-color flow-cytometric analysis. Cells obtained from C3H/HeN mice 24 hours after exposure to 0.25-8.0 Gy (0.4 Gy/min) 60Co were used to determine D0 values. Thymic CD4+ cells contained a radiosensitive subpopulation with a D0 of 0.97 +/- 0.05 Gy and a radioresistant subpopulation that survived exposures up to 8.0 Gy. CD8+ cells also contained a radiosensitive subpopulation with a D0 of 1.24 +/- 0.05 Gy and a radioresistant subpopulation with a D0 of 3.93 +/- 2.01 Gy. Double-positive thymic CD4+/CD8+ cells were uniformly radiosensitive, with a D0 of 1.03 +/- 0.28 Gy. Multiple T lymphocyte subpopulations based on radiosensitivity and CD4/CD8 antigen expression were also observed in the spleen. When mice were exposed to a sublethal 6.5-Gy radiation dose and recovery of T lymphocyte subsets was monitored, the relative radioresistance of CD4+ cells resulted in a selective enrichment of these cells among the surviving thymocytes and splenic lymphocytes. This relative enrichment of CD4+ cells became even more prominent 7 days after irradiation, when atrophy of the organs was greatest. Similar, although less dramatic, effects were observed for CD8+ cells. These studies demonstrate that (1) multiple T lymphocyte subpopulations can be identified based on radiosensitivity and CD4/CD8 antigen expression; (2) both CD4+ and CD8+ cells contain radioresistant subpopulations, with the CD4+ subpopulation being more resistant than the CD8+ subpopulation; and (3) although the number of radioresistant CD4+ cells is quite small, they persist in increased proportions during the periods preceding and corresponding to postirradiation hematopoietic recovery.


Assuntos
Subpopulações de Linfócitos T/efeitos da radiação , Animais , Relação CD4-CD8 , Relação Dose-Resposta à Radiação , Feminino , Raios gama , Camundongos , Camundongos Endogâmicos C3H , Baço/citologia , Timo/citologia
3.
Arch Ophthalmol ; 108(9): 1245-7, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2400344

RESUMO

The natural course of early diabetic retinopathy in young subjects with insulin-dependent diabetes mellitus was evaluated during 693 patient visits for 259 subjects during a mean of 2.4 years. Diabetic retinopathy is considered a progressive disease among people with insulin-dependent diabetes mellitus (type I). Improvement of early retinopathy has not been recognized as a part of the natural course. In our experience, 25% of observations in subjects with early diabetic retinopathy (grades 2 and 3) showed improvement. Thus, 28 of 174 observations of diabetic retinopathy improved from grade 2 to grade 1, and 34 of 79 observations improved from grade 3 to grades 2 or 1. Markov chains indicate that 25% of observations of diabetic retinopathy will change from grade 1 to grade 5 or 6 in 17.0 years and 25% will change from grade 2 to grade 5 or 6 in 16.0 years. Future studies of diabetic retinopathy should consider a matrix of estimated transition probabilities, depending on the population, to judge probabilities of transition between states of retinopathy.


Assuntos
Retinopatia Diabética/etiologia , Cadeias de Markov , Probabilidade , Adolescente , Adulto , Diabetes Mellitus Tipo 1/complicações , Retinopatia Diabética/classificação , Feminino , Humanos , Masculino , Prognóstico
4.
Arch Ophthalmol ; 108(12): 1733-5, 1990 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2256845

RESUMO

Vitreous fluorophotometry was performed on 240 eyes of 120 young subjects who had insulin-dependent diabetes mellitus (type I) and various grades of retinopathy. The concentration of fluorescein was measured in the anterior chamber and posterior vitreous 1 hour after intravenous injection of fluorescein. There was a significant association (P less than .001) between the grade of retinopathy and the level of posterior vitreous leakage. The amount of posterior vitreous leakage in each eye also had a significant association with borderline elevation of diastolic blood pressure. Subjects with excessive posterior vitreous leakage had significantly higher levels of urinary microalbumin excretion. In a multiple linear regression analysis for posterior vitreous leakage, retinal grade consistently entered the model at a significant level (P less than or equal to .00001 to .003). Blood pressure also entered the model for posterior vitreous leakage at a significant level for retinal grades of the right and left eyes and of the worst eye. These results demonstrate an association between leakage of retinal and renal vessels, possibly linked at least in part to elevation in diastolic blood pressure.


Assuntos
Pressão Sanguínea , Diabetes Mellitus Tipo 1/diagnóstico , Fluorofotometria/métodos , Corpo Vítreo/metabolismo , Adolescente , Adulto , Albuminúria , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Retinopatia Diabética/diagnóstico , Diástole , Feminino , Fluoresceína , Fluoresceínas/farmacocinética , Humanos , Injeções Intravenosas , Masculino , Análise de Regressão
5.
Radiat Res ; 117(1): 59-69, 1989 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2536480

RESUMO

Based on murine survival studies, endogenous hemopoietic spleen colony formation (E-CFU), and recovery of bone marrow and splenic granulocyte-macrophage colony-forming cells (GM-CFC), it was demonstrated that the postirradiation administration of glucan, an immunomodulator and hemopoietic stimulant, enhances the radioprotective effects of WR-2721. LD50/30 dose reduction factors for mice treated with WR-2721 (200 mg/kg approximately 30 min before irradiation), glucan (250 mg/kg approximately 1 h after irradiation), or both agents were 1.37, 1.08, and 1.52, respectively. Enhanced survival in mice treated with both agents appeared to be due in part to glucan's ability to accelerate hemopoietic regeneration from stem cells initially protected from radiation-induced lethality by WR-2721. Following a 10-Gy radiation exposure, E-CFU numbers in mice treated with saline, WR-2721, glucan, or both WR-2721 and glucan were 0.05 +/- 0.03, 6.70 +/- 1.05, 0.95 +/- 0.24, and 33.90 +/- 2.96, respectively. Similarly, bone marrow and splenic GM-CFC numbers were greater in mice treated with both WR-2721 and glucan than in mice treated with either agent alone. These results demonstrated at least additive radioprotective effects when mice were given WR-2721 prior to irradiation and glucan following irradiation. These effects appeared to depend on the sequential cell protection mediated by WR-2721 and hemopoietic repopulation mediated by glucan.


Assuntos
Amifostina/uso terapêutico , Glucanos/uso terapêutico , Compostos Organotiofosforados/uso terapêutico , Protetores contra Radiação/uso terapêutico , Amifostina/administração & dosagem , Animais , Ensaio de Unidades Formadoras de Colônias , Sinergismo Farmacológico , Feminino , Glucanos/administração & dosagem , Hematopoese/efeitos dos fármacos , Hematopoese/efeitos da radiação , Camundongos , Protetores contra Radiação/administração & dosagem
6.
Radiat Res ; 143(3): 320-6, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7652171

RESUMO

To understand the effects of ionizing radiation on the production of IL-1 alpha in vivo within a hematopoietic organ, we evaluated acute changes in splenic IL-1 alpha mRNA and IL-1 alpha protein after exposing B6D2F1 mice to lethal and sublethal 60Co radiation. Results suggest that in vivo, ionizing radiation induces a time- and dose-dependent accumulation of IL-1 alpha mRNA in the mouse spleen after exposure to gamma radiation. Time-dependent increases in the level of IL-1 alpha protein were also observed, although the magnitude of increased protein expression did not complement the magnitude of the accumulation of the message. Selective concentration of cells producing IL-1 alpha does not appear to account completely for the increase in splenic IL-1 alpha mRNA observed in this in vivo system.


Assuntos
Interleucina-1/genética , Baço/metabolismo , Irradiação Corporal Total , Animais , Sequência de Bases , Feminino , Expressão Gênica/efeitos da radiação , Interleucina-1/análise , Camundongos , Dados de Sequência Molecular , RNA Mensageiro/análise
7.
Radiat Res ; 128(1 Suppl): S18-28, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1924743

RESUMO

When host antimicrobial defenses are severely compromised by radiation or trauma in conjunction with radiation, death from sepsis results. To evaluate therapies for sepsis in radiation casualties, we developed models of acquired and induced bacterial infections in irradiated and irradiated-wounded mice. Animals were exposed to either a mixed radiation field of equal proportions of neutrons and gamma rays (n/gamma = 1) from a TRIGA reactor or pure gamma rays from 60[Co sources. Skin wounds (15% of total body surface area) were inflicted under methoxyflurane anesthesia 1 h after irradiation. In all mice, wounding after irradiation decreased resistance to infection. Treatments with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) before or after mixed neutron-gamma irradiation or gamma irradiation increased survival. Therapy with S-TDCM for mice irradiated with either a mixed field or gamma rays increased resistance to Klebsiella pneumoniae-induced infections. Combined therapy with S-TDCM and ceftriaxone for K. pneumoniae infections in mice exposed to a mixed radiation field or to gamma rays was more effective than single-agent therapy. In all irradiated-wounded mice, single therapy of acquired infections with an antibiotic or S-TDCM did not increase survival. Survival of irradiated-wounded mice after topical application of gentamicin sulfate cream suggested that bacteria colonizing the wound disseminated systemically in untreated irradiated mice, resulting in death from sepsis. In lethal models of acquired infections in irradiated-wounded mice, significant increases in survival were achieved when systemic treatments with S-TDCM or gentamicin were combined with topical treatments of gentamicin cream. Therapies for sepsis in all mice exposed to a mixed field were less effective than in mice exposed to gamma rays. Nonetheless, the data show a principle by which successful therapy may be provided to individuals receiving tissue trauma in conjunction with radiation injury.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Fatores Corda/uso terapêutico , Lesões Experimentais por Radiação/complicações , Infecção dos Ferimentos/complicações , Animais , Radioisótopos de Cobalto , Feminino , Raios gama , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Camundongos , Nêutrons , Infecção dos Ferimentos/tratamento farmacológico
8.
Radiat Res ; 128(1 Suppl): S29-36, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1924744

RESUMO

Acute lethality syndromes produced by the accidental exposure of humans to mixed neutron and gamma radiation from external sources can be related to acute lethality from photon irradiation using the relative biological effectiveness (RBE) for common end points. We used the canine as a model to study injury following exposure to mixed neutron and gamma radiation from the AFRRI TRIGA reactor. Exposures from the reactor were steady-state mode (40 cGy/min, bilateral) with an average neutron energy of 0.85 MeV; tissue-air ratio = 0.59 at midline abdominal. Healthy male and female canines were irradiated free-in-air behind a 6-in. lead wall; the neutron-gamma ratio was 5.4:1 at the entrance skin surface; exposures are reported as midline tissue doses. Bilateral exposure resulted in an LD50/30 of 153 cGy without therapeutic clinical support. Addition of clinical support consisting of fluids, antibiotics, and fresh irradiated platelets/whole blood increased the bilateral LD50/30 to 185 cGy, a dose modifying factor (DMF) of 1.21. This corresponds to respective LD50/30 values for bilateral 60Co gamma exposures of 260 and 338 cGy for nonsupported and clinically supported animals, and a DMF of 1.30. The RBE based on the values determined at midline tissue is approximately 1.69. Clinical support after bilateral irradiation produced a similar DMF to those of mixed fission neutrons and gamma rays and 60Co gamma rays alone. The RBE of 1.69 for midline tissue bilateral exposures is higher than 1, an RBE often cited for large animals. Therapeutic support administered to lethally irradiated canines significantly improved survival and increased the LD50/30 independent of radiation quality.


Assuntos
Raios gama , Hematopoese/efeitos da radiação , Nêutrons , Lesões Experimentais por Radiação/fisiopatologia , Animais , Radioisótopos de Cobalto , Cães , Feminino , Hematopoese/fisiologia , Dose Letal Mediana , Masculino , Lesões Experimentais por Radiação/terapia , Eficiência Biológica Relativa
9.
Radiat Res ; 109(3): 469-78, 1987 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3031721

RESUMO

Two phosphorothioate compounds, WR-2721 and WR-151327, were examined for their radioprotective efficacies against the effects of fission neutron irradiation in male and female mice. Within sex groups no significant difference in lethality at 30 or 100 days postirradiation was found between WR-2721 or WR-151327 pretreatment. The dose modification factors (DMFs) for male mice treated with either compound were 1.29 (LD50/30) and 1.24 (LD50/100), and those for drug-treated female mice were 1.21 (LD50/30) and 1.19 (LD50/100). Both WR-2721 and WR-151327 were found to be equally radioprotective when compared using DMFs as the end point. WR-151327 (500 mg/kg, ip) was found to be significantly more toxic to both male and female B6D2F1 mice than equimolar amounts of WR-2721. Small but significant sex differences in radioprotection were found: the DMFs for female mice pretreated with either compound were lower than those for similarly treated male mice; the incidence of mortality 31-100 days postexposure in male mice pretreated with WR-151327 was greater than for female mice. In addition, sex differences were noted in drug toxicity. Toxic death in female mice given WR-151327 (500 mg/kg, ip) is 2.6 times more probable than in males.


Assuntos
Amifostina/farmacologia , Nêutrons , Compostos Organotiofosforados/farmacologia , Protetores contra Radiação , Animais , Feminino , Masculino , Camundongos , Doses de Radiação , Fatores Sexuais , Fatores de Tempo , Irradiação Corporal Total
10.
Radiat Res ; 115(3): 605-8, 1988 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2845467

RESUMO

The survival of mice after whole-body exposure to a modified fission neutron-gamma field (n: gamma = 1:1) was used to examine radiation protection by WR-2721, 16,16-dimethyl PGE2(DiPGE2), and the combination of both agents. Administration of WR-2721 (453 mg/kg) increased the LD50/30 from 5.24 to 7.17 Gy (DMF = 1.37), whereas pretreatment with DiPGE2 (1.6 mg/kg) increased the LD50/30 to 5.77 Gy (dose modification factor (DMF) = 1.10). The combination of 453 mg/kg WR-2721 and 0.4 mg/kg DiPGE2 resulted in an LD50/30 of 7.33 Gy, yielding a DMF of 1.39. However, no significant difference in protection was obtained with the combination of the two agents compared to that seen with WR-2721 alone.


Assuntos
16,16-Dimetilprostaglandina E2/uso terapêutico , Amifostina/uso terapêutico , Compostos Organotiofosforados/uso terapêutico , Prostaglandinas E Sintéticas/uso terapêutico , Lesões Experimentais por Radiação/prevenção & controle , 16,16-Dimetilprostaglandina E2/administração & dosagem , 16,16-Dimetilprostaglandina E2/toxicidade , Amifostina/administração & dosagem , Amifostina/toxicidade , Animais , Quimioterapia Combinada , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Nêutrons , Protetores contra Radiação
11.
Radiat Res ; 156(3): 283-93, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11500137

RESUMO

We showed previously that 5-androstenediol stimulates myelopoiesis, increases the numbers of circulating neutrophils and platelets, and enhances resistance to infection in gamma-irradiated mice. We have extended those studies to include monocytes, natural killer (NK) cells, eosinophils and basophils, and we have measured the activation marker CD11b using flow cytometry. Androstenediol (160 mg/kg) was administered subcutaneously to female B6D2F1 mice 24 h before whole-body gamma irradiation. Androstenediol treatments increased the blood levels of neutrophils, monocytes and NK cells in unirradiated animals; decreased the numbers of circulating eosinophils; and ameliorated radiation-induced decreases in neutrophils, monocytes, NK cells, erythrocytes and platelets. The androstenediol treatments had no significant effect on the numbers of circulating B cells or T cells. CD11b labeling intensity on monocytes was decreased slightly after androstenediol treatment. In contrast, radiation or androstenediol alone caused increases in CD11b labeling intensity on NK cells. Androstenediol and radiation combined caused a marked increase in NK cell CD11b. The results indicate that androstenediol increases the numbers of the three major cell types of the innate immune system (neutrophils, monocytes and NK cells), that androstenediol-induced changes in blood elements in irradiated animals persist for at least several weeks, and that there is a significant positive interaction between radiation and administration of androstenediol in the activation of NK cells.


Assuntos
Androstenodiol/farmacologia , Contagem de Leucócitos , Protetores contra Radiação/farmacologia , Animais , Contagem de Eritrócitos , Feminino , Citometria de Fluxo , Antígeno de Macrófago 1/sangue , Camundongos , Neutrófilos/enzimologia , Peroxidases/sangue , Irradiação Corporal Total
12.
Diabetes Res Clin Pract ; 11(3): 189-93, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2036941

RESUMO

The association of retinal changes with exercise microalbuminuria and with changes in systolic and diastolic blood pressure (BP) were evaluated in 162 young subjects with insulin-dependent (type 1) diabetes mellitus. Higher systolic and diastolic BPs at rest or after 10 or 20 min of exercise were significantly associated with more severe retinal changes in the subjects with diabetes compared to controls (P less than 0.02; global ANOVA). The mean (+/- SEM) exercise albumin excretion rate (AER) was 17.6 +/- 3.1 if there was no evidence of retinopathy compared to 81.5 +/- 23.5 when only microaneurysms were detected and 467.1 +/- 133.3 when more severe retinopathy was present. The percentage of subjects with abnormal AERs for these three retinal groups was 13, 30 and 60, respectively. (P less than 0.0001, chi-square test). It is clear that retinal changes relate to early renal changes, as monitored by exercise AERs and changes in resting and exercise BPs. It is concluded that the renal and retinal microvascular changes occur concurrently in young subjects with type 1 diabetes.


Assuntos
Albuminúria , Pressão Sanguínea , Diabetes Mellitus Tipo 1/fisiopatologia , Retinopatia Diabética/fisiopatologia , Esforço Físico , Retina/fisiopatologia , Adulto , Nefropatias Diabéticas/fisiopatologia , Feminino , Humanos , Cinética , Masculino , Valores de Referência
13.
Int J Radiat Biol ; 76(2): 261-71, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10716647

RESUMO

PURPOSE: To determine the efficacy of WR-151327 (WR) [S-3-(3-methylaminopropylamino) propylphosphorothioic acid; (CH3-HN-(CH2)3-NH-(CH2)3-S-PO3H2)] in increasing resistance to bacterial infection after a sublethal dose of gamma-photons or mixed-field neutrons plus gamma-photons. MATERIALS AND METHODS: B6D2F1/J female mice received 200 mg/kg WR i.p. or saline vehicle 20-30 min before or after sham (0 Gy) or 7.0 Gy 60Co gamma-photon irradiation. WR or saline vehicle was given only before 3.5 Gy TRIGA-reactor-produced mixed-field [n/(n+y) = 0.67] irradiation. Four days after drug treatment or drug treatment and irradiation, graded doses of Klebsiella pneumoniae were injected s.c. into mice, and 30-day survival was recorded. To assess haemopoietic changes other unirradiated and irradiated mice not injected with bacteria were given WR or saline. Peripheral blood (PB) and femoral bone marrow (BM) cells were measured 1, 3 or 4, 7, 10 and 14 or 15 days later. RESULTS: WR pretreatment increased resistance to infection in irradiated but not in unirradiated mice. Bacterial CFU-LD50/30 values for 0 Gy saline-treated mice were 1.20x10(6); for 0 Gy WR-treated mice 1.16x10(6); for gamma-photon-irradiated saline-treated mice 3.02x10(1); for gamma-photon-irradiated WR-treated mice 1.24x10(4); for mixed-field-irradiated saline-treated mice 1.94x10(2); and for mixed-field-irradiated WR-treated mice 6.13x10(3). WR-induced resistance to infection paralleled increased numbers of PB white cells, neutrophils, platelets, femoral BM cells and granulocyte macrophage colony-forming cells (GM-CFC) in irradiated mice not given bacteria. CONCLUSIONS: These studies quantify the resistance to bacterial infection in mice treated with WR before sublethal irradiation. The findings suggest that WR treatment increases resistance to infection in immunocompromised hosts.


Assuntos
Imunidade Inata/efeitos da radiação , Infecções por Klebsiella/imunologia , Klebsiella pneumoniae , Compostos Organotiofosforados/farmacologia , Protetores contra Radiação/farmacologia , Animais , Contagem de Células Sanguíneas , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/efeitos da radiação , Feminino , Raios gama , Imunidade Inata/efeitos dos fármacos , Infecções por Klebsiella/mortalidade , Camundongos , Eficiência Biológica Relativa
14.
Laryngoscope ; 102(1): 88-9, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1731163

RESUMO

The bacterial flora of 20 headset devices were evaluated before and after they were worn for 1 hour. Bacteria were recovered from all headsets, and their number increased from a mean (+/- standard deviation) of 60 +/- 5 organisms per device to 650 +/- 51 organisms per device (P less than .001). The predominant organisms recovered were Staphylococcus spp, Streptococcus spp, Propionibacterium spp, and Peptostreptococcus spp. This study demonstrates the presence of potential pathogens in headset devices, as well as the increase in the number of these pathogens after the headsets have been worn for 1 hour.


Assuntos
Aeronaves/instrumentação , Bactérias/isolamento & purificação , Contaminação de Equipamentos , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Peptostreptococcus/isolamento & purificação , Propionibacterium/isolamento & purificação , Staphylococcus/isolamento & purificação , Streptococcus/isolamento & purificação , Fatores de Tempo
15.
J Radiat Res ; 41(3): 259-77, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11210828

RESUMO

Irradiation increases susceptibility to bacterial infection. Exogenous proinflammatory cytokines can alter the response of mice to gamma radiation, but the role of endogenous inflammatory cytokines after bacterial infection in irradiated animals is not known. Gene expression of hematopoietic (GM-CSF) and proinflammatory (IL-1 beta, IL-6 and TNF-alpha) cytokines were examined in spleens of B6D2F1/J female mice after irradiation alone (1.0- and 7.0-Gy), and after irradiation followed by Klebsiella pneumoniae s.c. challenge 4 days postirradiation by using the reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridization. At 4, 8, and 24 h after bacterial challenge in 7.0-Gy-irradiated mice, GM-CSF mRNA increased (p < 0.05). TNF-alpha mRNA in irradiated mice were slightly decreased, whereas after bacterial challenge, TNF-alpha mRNA elevated at 30 h in 7.0-Gy-irradiated mice; at 4, and 8 h in 1.0-Gy-irradiated mice, and at 1 h in sham-irradiated mice (p < 0.05). IL-6 mRNA displayed a biphasic response in 7.0-Gy-irradiated mice, and, after bacterial challenge, in both irradiated mice (1.0- and 7.0-Gy) and sham-irradiated mice. IL-1 beta mRNA remained at or below normal for 8 h and increased at 24 h after bacterial challenge on day 4 in 7.0-Gy-irradiated mice. These results indicate that sublethal gamma radiation alters the patterns of the hematopoietic and proinflammatory cytokine responses to bacterial challenge in vivo. Consequently, treatment protocols may need to take into account changes in cytokine gene responses to resolve infection after irradiation.


Assuntos
Citocinas/imunologia , Regulação da Expressão Gênica/efeitos da radiação , Infecções por Klebsiella/imunologia , Klebsiella pneumoniae , Baço/imunologia , Baço/efeitos da radiação , Animais , Citocinas/genética , Regulação da Expressão Gênica/imunologia , Infecções por Klebsiella/genética , Camundongos , Baço/microbiologia
16.
Food Chem Toxicol ; 21(1): 49-58, 1983 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-6681792

RESUMO

[14C]Acrylamide and [14C]betaine hydrochloride were administered in a single iv dose to pregnant rats, rabbits, beagle dogs and miniature pigs late in gestation (1-2 days before expected parturition). Dosages used were 10 mg/kg for rats and 5 mg/kg for the other species. The compounds were allowed to equilibrate in the animal (for 1 hr in rats and for 2 hr in the other species); the dam was then killed and the foetuses were removed by caesarean section. Each foetus was weighed and analysed for radioactivity, either by homogenization of the whole foetus (rat and rabbit) or by determining separately the radioactivity in individual organs and tissues (dog and pig). Foetal uptake of the polar compound betaine hydrochloride was much lower than that of the more lipophilic acrylamide. The sex of the foetus did not appear to affect uptake of either compound. There were no significant differences in total uptake of isotope attributable to the position of the foetus within the uterus in any of the four species given either acrylamide or betaine. Similarly, uterine position did not affect the uptake of acrylamide or betaine by individual tissues of foetal dogs or pigs. Since the distributions of 14C-labelled acrylamide and betaine hydrochloride were essentially uniform throughout a litter, it would not be necessary to sample all of the members of a litter to obtain a representative picture of foetal distribution.


Assuntos
Acrilamidas/metabolismo , Betaína/metabolismo , Feto/metabolismo , Animais , Radioisótopos de Carbono , Cães , Feminino , Masculino , Gravidez , Coelhos , Ratos , Fatores Sexuais , Especificidade da Espécie , Suínos , Porco Miniatura , Distribuição Tecidual
17.
Ann Clin Lab Sci ; 23(6): 439-47, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8291898

RESUMO

Intestinal and testicular toxicity in groups of nonirradiated and irradiated mice were investigated after intraperitoneal injection of aminothiol compounds or saline. Four aminothiols were studied. Three were prodrugs: WR-2721, WR-3689, and WR-151327 and one was the active form of WR-2721: WR-1065. Thirty minutes after injection, the mice were sham-irradiated or bilaterally exposed (whole body) to 60Co gamma-irradiation at a dose rate of 1 Gy per min to a total dose of 15 Gy. Four days after injection, mice were euthanised, and the intestines and testes were removed and histologically examined. The intestinal crypt cell number was increased in all the irradiated mice given WR-compounds compared to controls (P < 0.05). Interestingly, the crypt cell number in nonirradiated mice given WR-1065 was also greater than control or WR-2721 (P < 0.05) treated mice. Germinal cell numbers from testes of mice administered aminothiols prior to radiation decreased or did not change. Some swelling of the seminiferous tubules was also observed. The germinal cell numbers in sham-irradiated mice were also less than the controls. Thus, aminothiol addition can provide limited protection to intestinal crypt cells but not to germinal cells of the testes in response to gamma-irradiation. There is also evidence that aminothiols are toxic to the germinal cell layer of the seminiferous tubules when given to sham-irradiated mice.


Assuntos
Enteropatias/induzido quimicamente , Mercaptoetilaminas/toxicidade , Protetores contra Radiação/toxicidade , Doenças Testiculares/induzido quimicamente , Irradiação Corporal Total , Amifostina/análogos & derivados , Amifostina/toxicidade , Animais , Enteropatias/patologia , Masculino , Camundongos , Compostos Organotiofosforados/toxicidade , Doenças Testiculares/patologia
18.
Adv Space Res ; 30(4): 945-55, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12572532

RESUMO

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d-1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d-1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (>1 yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d-1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d-1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation.


Assuntos
Medula Óssea/efeitos da radiação , Raios gama , Hematopoese/efeitos da radiação , Células-Tronco Hematopoéticas/efeitos da radiação , Sistema Hematopoético/efeitos da radiação , Animais , Cães , Relação Dose-Resposta à Radiação , Leucemia Induzida por Radiação , Leucócitos/efeitos da radiação , Longevidade/efeitos da radiação , Neoplasias Induzidas por Radiação , Lesões Experimentais por Radiação/mortalidade , Tolerância a Radiação , Medição de Risco , Voo Espacial , Irradiação Corporal Total
19.
Mil Med ; 166(12 Suppl): 88-9, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11778450

RESUMO

The combined effects of injury from exposure to ionizing radiation and the potential biological warfare agent Venezuelan equine encephalitis (VEE) virus remain largely unknown. To study these effects, 4- to 5-week-old B6D2F1/J female mice were given a sublethal whole-body 7 Gy dose of 60Co gamma-photon radiation followed 48 hours later by aerosol or intraperitoneal challenge with enzootic VEE IIIA virus. Survival was observed for 30 days. A single sublethal 7 Gy dose of gamma radiation reduced the LD50/30 of VEE IIIA virus, in intraperitoneal challenged mice by a factor of 10(4) from 1.1 x 10(6) plaque-forming units (pfu) to 1 x 10(2) pfu, and in aerosol challenged mice, by a factor of 5 from 70 pfu to 14 pfu. These findings further confirm there is a combined effect of exposure to ionizing radiation and biological warfare agents, which could be devastating to unprotected populations and thus should be investigated further.


Assuntos
Vírus da Encefalite Equina Venezuelana/patogenicidade , Raios gama/efeitos adversos , Animais , Feminino , Camundongos , Projetos Piloto
20.
Mil Med ; 166(12 Suppl): 85-7, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11778449

RESUMO

The Biodosimetry Assessment Tool software application under development will equip health care providers with diagnostic information (clinical signs and symptoms, physical dosimetry, etc.) germane to the management of human radiation casualties. Designed primarily for prompt use after a radiation incident, the user-friendly program facilitates collection, integration, and archiving of data obtained from exposed persons. Data collected in templates are compared with established radiation dose responses obtained from the literature to provide multiparameter dose assessments. The program archives clinical information (e.g., extent of contamination, wounds, infection, etc.) useful for casualty management, displays relevant diagnostic information in a concise format, and can be used to manage both military and civilian radiation accidents. In addition, monitoring of diagnostic information of individuals using this program could potentially minimize the severity of psychological casualties by making a marked impact on the way that both radiation casualties and the worried well view their exposure, dose, and future risk for the development of disease.


Assuntos
Sistemas Computadorizados de Registros Médicos/tendências , Radiometria/métodos , Software , Humanos
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