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1.
Phys Rev Lett ; 124(15): 159901, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32357038

RESUMO

This corrects the article DOI: 10.1103/PhysRevLett.120.025002.

2.
Phys Rev Lett ; 120(2): 025002, 2018 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-29376698

RESUMO

This Letter presents a novel approach to study electron transport in warm dense matter. It also includes the first x-ray Thomson scattering (XRTS) measurement from low-density CH foams compressed by a strong laser-driven shock at the OMEGA laser facility. The XRTS measurement is combined with velocity interferometry (VISAR) and optical pyrometry (SOP) providing a robust measurement of thermodynamic conditions in the shock. Evidence of significant preheat contributing to elevated temperatures reaching 17.5-35 eV in shocked CH foam is measured by XRTS. These measurements are complemented by abnormally high shock velocities observed by VISAR and early emission seen by SOP. These results are compared to radiation hydrodynamics simulations that include first-principles treatment of nonlocal electron transport in warm dense matter with excellent agreement. Additional simulations confirm that the x-ray contribution to this preheat is negligible.

3.
Acta Paediatr ; 102(7): e315-20, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23560803

RESUMO

AIM: To examine in-hospital infant feeding practices, focusing on initiation and prevalence of breastmilk expression and to describe the proportion of women having a breast pump immediately after birth. METHODS: Postpartum women were recruited from three hospitals in Melbourne, Australia, between 2009 and 2011. INCLUSION CRITERIA: having had a healthy singleton term infant, intending to breastfeed and fluency in English. Data were collected using a structured questionnaire. RESULTS: Just over 1000 women were recruited at 24-48 h postpartum; 50% were primiparous. Forty-seven per cent of infants had been fully breastfeeding at the breast from birth, and another 47% had received at least some expressed breastmilk. Forty per cent of first-time mothers reported having had a problem breastfeeding, and 46% already had a breast pump prior to the birth of their infant. CONCLUSIONS: Early breastfeeding problems were common, and less than half the infants had fed only at the breast in the first days of life. Given the normalization of breastmilk expression, more evidence is needed regarding the impact of expressing on duration of breastmilk feeding and maternal health outcomes.


Assuntos
Extração de Leite , Austrália , Extração de Leite/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Período Pós-Parto , Gravidez , Estudos Prospectivos
4.
Proc Natl Acad Sci U S A ; 106(29): 12145-50, 2009 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-19581601

RESUMO

A number of distinct beta-amyloid (Abeta) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural Abeta-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic Abeta and amyloidogenic non-Abeta species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21-89 years. Antibody reactivity was most prominent against oligomeric assemblies of Abeta and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of Abeta1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant Abeta, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from Abeta toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with Abeta the monkeys developed high titers not only against Abeta peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of Abeta antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD.


Assuntos
Envelhecimento/imunologia , Doença de Alzheimer/imunologia , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/imunologia , Anticorpos/imunologia , Fármacos Neuroprotetores/imunologia , Peptídeos/imunologia , Envelhecimento/efeitos dos fármacos , Doença de Alzheimer/sangue , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/toxicidade , Animais , Anticorpos/sangue , Anticorpos/líquido cefalorraquidiano , Citoproteção/efeitos dos fármacos , Demência/complicações , Demência/imunologia , Progressão da Doença , Genes Dominantes , Imunização , Imunoglobulina G/sangue , Camundongos , Peso Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Peptídeos/química , Primatas/imunologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Estrutura Quaternária de Proteína
5.
Rev Sci Instrum ; 93(11): 113515, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36461442

RESUMO

The Opacity Platform on the National Ignition Facility (NIF) has been developed to measure opacities at varying densities and temperatures relevant to the solar interior and thermal cooling rates in white dwarf stars. The typical temperatures reached at NIF range between 150 and 210 eV, which allow these measurements to be performed experimentally. The captured opacities are crucial to validating radiation-hydrodynamic models that are used in astrophysics. The NIF opacity platform has a unique new capability that allows in situ measurement of the sample expansion. The sample expansion data are used to better understand the plasma conditions in our experiments by inferring the sample density throughout the duration of the laser drive. We present the details of the density measurement technique, data analysis, and recent results for Fe and MgO.

6.
Rev Sci Instrum ; 92(3): 033532, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33820092

RESUMO

Great strides have been made in improving the quality of x-ray radiographs in high energy density plasma experiments, enabled in part by innovations in engineering and manufacturing of integrated circuits and materials. As a consequence, the radiographs of today are filled with a great deal of detail, but few of these features are extracted in a systematic way. Analysis techniques familiar to plasma physicists tend toward brittle 1D lineout or Fourier transform type analyses. The techniques applied to process our data have not kept pace with improvements in the quality of our data. Fortunately, the field of computer vision has a wealth of tools to offer, which have been widely used in industrial imaging and, more recently, adopted in biological imaging. We demonstrate the application of computer vision techniques to the analysis of x-ray radiographs from high energy density plasma experiments, as well as give a brief tutorial on the computer vision techniques themselves. These tools robustly extract 2D contours of shocks, boundaries of inhomogeneities, and secondary flows, thereby allowing for increased automation of analysis, as well as direct and quantitative comparisons with simulations.

7.
Rev Sci Instrum ; 92(3): 033519, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33819987

RESUMO

The Opacity Platform on the National Ignition Facility (NIF) has been developed to measure iron opacities at varying densities and temperatures relevant to the solar interior and to verify recent experimental results obtained at the Sandia Z-machine, that diverge from theory. The first set of NIF experiments collected iron opacity data at ∼150 eV to 160 eV and an electron density of ∼7 × 1021 cm-3, with a goal to study temperatures up to ∼210 eV, with electron densities of up to ∼3 × 1022 cm-3. Among several techniques used to infer the temperature of the heated Fe sample, the absolutely calibrated DANTE-2 filtered diode array routinely provides measurements of the hohlraum conditions near the sample. However, the DANTE-2 temperatures are consistently low compared to pre-shot LASNEX simulations for a range of laser drive energies. We have re-evaluated the estimated uncertainty in the reported DANTE-2 temperatures and also the error generated by varying channel participation in the data analysis. An uncertainty of ±5% or better can be achieved with appropriate spectral coverage, channel participation, and metrology of the viewing slot.

8.
J Gen Virol ; 91(Pt 4): 1038-46, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20007358

RESUMO

Classical swine fever virus (CSFV) causes severe disease in pigs associated with leukopenia, haemorrhage and fever. We show that CSFV infection protects endothelial cells from apoptosis induced by the dsRNA mimic, pIpC, but not from other apoptotic stimuli, FasL or staurosporine. CSFV infection inhibits pIpC-induced caspase activation, mitochondrial membrane potential loss and cytochrome c release as well as the pro-apoptotic effects of truncated Bid (tBid) overexpression. The CSFV proteins N(pro) and E(rns) both contribute to CSFV inhibition of apoptosis. We conclude that CSFV infection can inhibit apoptotic signalling at multiple levels, including at the caspase-8 and the mitochondrial checkpoints. By supporting viral replication, endothelial cells may promote CSFV pathogenesis.


Assuntos
Apoptose/efeitos dos fármacos , Vírus da Febre Suína Clássica/patogenicidade , Células Endoteliais/fisiologia , RNA de Cadeia Dupla/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Aorta/virologia , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/fisiologia , Caspases/metabolismo , Células Cultivadas , Citocromos c/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/virologia , Ativação Enzimática , Suínos , Proteínas do Envelope Viral/fisiologia
9.
Rev Sci Instrum ; 89(10): 10F101, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30399753

RESUMO

A point-projection soft X-ray Opacity Spectrometer (OpSpec) has been implemented to measure X-ray spectra from ∼1 to 2 keV on the National Ignition Facility (NIF). Measurement of such soft X-rays with open-aperture point-projection detectors is challenging because only very thin filters may be used to shield the detector from the hostile environment. OpSpec diffracts X-rays from 540 to 2100 eV off a potassium (or rubidium) acid phthalate (KAP or RbAP) crystal onto either image plates or, most recently, X-ray films. A "sacrificial front filter" strategy is used to prevent crystal damage, while 2 or 3 rear filters protect the data. Since May 2017, OpSpec has been recording X-ray transmission data for iron-magnesium plasmas on the NIF, at "Anchor 1" plasma conditions (temperature ∼150 eV, density ∼7 × 1021 e -/cm3). Upgrades improved OpSpec's performance on 6 NIF shots in August and December 2017, with reduced backgrounds and 100% data return using filter stacks as thin as 2.9 µm (total). Photometric noise is beginning to meet requirements, and further work will reduce systematic errors.

10.
Rev Sci Instrum ; 87(11): 11E337, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27910339

RESUMO

We present synthetic transmission spectra generated with PrismSPECT utilizing both the ATBASE model and the Los Alamos opacity library (OPLIB) to evaluate whether an alternative choice in atomic data will impact modeling of experimental data from radiation transport experiments using Sc-doped aerogel foams (ScSi6O12 at 75 mg/cm3 density). We have determined that in the 50-200 eV Te range there is a significant difference in the 1s-3p spectra, especially below 100 eV, and for Te = 200 eV above 5000 eV in photon energy. Examining synthetic spectra generated using OPLIB with 300 resolving power reveals spectral sensitivity to Te changes of ∼3 eV.

11.
Int J Radiat Oncol Biol Phys ; 27(5): 1101-5, 1993 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-8262834

RESUMO

PURPOSE: Tumor radiosensitization with carbogen and nicotinamide (CON) was compared when both agents were given throughout fractionated radiotherapy with the sensitization observed when administered with only half of the fractions. The effect of overall treatment time on the local control of tumors irradiated in air or with CON was also investigated. METHODS AND MATERIALS: Local tumor control of a rodent adenocarcinoma, CaNT, was studied using eight different 20-fraction x-ray regimens. An overall time of either 10 or 20 days was used and CON was given with all, the first half or last half of the treatment. RESULTS: Relative to air, all six sensitizer combinations gave a large and significant increase in sensitization (p << 0.00001). Enhancement ratios were 1.9 and 2.1 when CON was given with all 20 fractions in either 10 or 20 days, respectively. For both overall times, enhancement ratios were reduced by 15-25% when CON was given with only half of the fractions. In air, reducing the treatment time from 20 to 10 days gave a small but significant decrease in the isoeffective doses. When CON was administered with either all or part of a schedule, varying the treatment time had little or no effect on local tumor control. No toxic side-effects were encountered when the sensitizers were administered 10 or 20 times, either once or twice per day. CONCLUSION: CON is an effective and non-toxic tumor radiosensitizer. In CaNT tumors, a significantly greater effect is seen when CON is given with every fraction of the schedule. The sensitizers reduced or abolished the sparing effect of overall time.


Assuntos
Adenocarcinoma/radioterapia , Dióxido de Carbono/uso terapêutico , Neoplasias Mamárias Experimentais/radioterapia , Niacinamida/uso terapêutico , Oxigênio/uso terapêutico , Radiossensibilizantes , Animais , Masculino , Camundongos , Camundongos Endogâmicos CBA , Radioterapia/métodos , Dosagem Radioterapêutica , Raios X
12.
Int J Radiat Oncol Biol Phys ; 34(2): 357-65, 1996 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-8567336

RESUMO

PURPOSE: To compare the radiosensitivity of mouse tumors treated in air with conventional and accelerated radiotherapy with that of tumors treated in carbogen alone or carbogen combined with nicotinamide. METHODS AND MATERIALS: CaNT mammary tumors were irradiated with either 30 x-ray fractions in 6 weeks or 40 fractions in 26 days in air, carbogen alone, or carbogen combined with 120 mg/kg of nicotinamide (NAM), the latter given intraperitonealy 30 min before each fraction. The response to treatment was assessed using local control, weight loss, and metastasis-free survival. RESULTS: Both carbogen and carbogen plus nicotinamide significantly increased tumor radiosensitivity; enhancement ratios (ERs) in the 6-week regimen were similar to those seen in the accelerated schedule. The majority of the effect was achieved by carbogen alone but the addition of NAM further enhanced tumor radiosensitization (ERs of 1.5 and 1.4 for carbogen in the conventional and accelerated schedule, respectively, were significantly lower than ERs of 1.7 and 1.6 obtained with carbogen plus nicotinamide; p < or = 0.005). Treatment protraction significantly increased radioresistance, especially when tumors were treated under air. An extra 1.5 Gy per day was required in air to counterbalance proliferation; in carbogen alone and carbogen plus nicotinamide a dose loss of 0.9 and 0.6 Gy per day was observed, respectively. Compared with treatments in air alone delivered in 6 weeks, acceleration of treatment combined with carbogen and nicotinamide gave the greatest increase in tumor radiosensitization (ER = 1.9). No toxic side effects and no detrimental changes in body weight were encountered when the sensitizers were administered 30 times (one fraction per day) or 40 times (two fractions per day). In both regimens, the incidence of metastases in mice treated with carbogen or carbogen plus nicotinamide was similar to that seen in animals treated in air. There was, however, a nonsignificant trend of a higher proportion of mice with metastasis in the accelerated schedule compared with the 6-week schedule. CONCLUSIONS: In both conventional and accelerated experimental radiotherapy, carbogen alone or combined with a small clinically relevant dose of NAM were well tolerated, achieved large and significant increases in radiosensitization, and did not affect the incidence of metastases. The sparing of damage, resulting from extending the overall treatment time, was less when the sensitizers were administered than when irradiations were performed in air. The study suggests that clinical radiotherapy regimens, which aim to reduce hypoxic and/or tumor clonogen proliferation, would benefit from the use of carbogen, especially if the gas is combined with nicotinamide and treatment acceleration.


Assuntos
Dióxido de Carbono/farmacologia , Neoplasias Mamárias Experimentais/radioterapia , Niacinamida/farmacologia , Oxigênio/farmacologia , Radiossensibilizantes/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/efeitos da radiação , Relação Dose-Resposta à Radiação , Masculino , Camundongos , Camundongos Endogâmicos CBA , Tolerância a Radiação/efeitos dos fármacos , Dosagem Radioterapêutica
13.
Int J Radiat Oncol Biol Phys ; 33(2): 399-408, 1995 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-7673027

RESUMO

PURPOSE: To determine the oxygen enhancement ratio (OER) and shape of the oxygen sensitization curve of mouse foot skin, the extent to which glutathione (GSH) depletion radiosensitized skin, and the dependence of such sensitization on the ambient oxygen tension. METHODS AND MATERIALS: The feet of WHT mice were irradiated with single doses of 240 kVp x-rays while mice were exposed to carbogen or gases with oxygen/nitrogen mixtures containing 8-100% O2. The anoxic response was obtained by occluding the blood supply to the leg of anesthetized mice with a tourniquet, surrounding the foot with nitrogen, and allowing the mice to breathe 10% O2. Further experiments were performed to assess the efficacy of this method to obtain an anoxic response. Radiosensitivity of skin was assessed using the acute skin-reaction assay. Glutathione levels were modified using two schedules of DL-buthionine sulphoximine (BSO) and diethylmaleate (DEM), which were considered to produce extensive and intermediate levels of GSH depletion in the skin of the foot during irradiation. RESULTS: Carbogen caused the greatest radiosensitization of skin, with a reproducible enhancement of 2.2 relative to the anoxic response. The OER of 2.2 is lower than other reports for mouse skin. This may indicate that the extremes of oxygenation were not produced, although there was no direct evidence for this. When skin radiosensitivity was plotted against the logarithm of the oxygen tension in the ambient gas, a sigmoid curve with a K value of 17-21% O2 in the ambient gas was obtained. Depletion of GSH caused minimal radiosensitization when skin was irradiated under anoxic or well-oxygenated conditions. Radiosensitization by GSH depletion was maximal at intermediate oxygen tensions of 10-21% O2 in the ambient gas. Increasing the extent of GSH depletion led to increasing radiosensitization, with sensitization enhancement ratios of 1.2 and 1.1, respectively, for extensive and intermediate levels of GSH depletion. In mice exposed to 100% O2, a significant component of skin radiosensitivity was due to diffusion of oxygen directly through the skin. Pentobarbitone anesthesia radiosensitized skin in mice exposed to 100% O2 by a factor of 1.2, but did not further sensitize skin in mice exposed to carbogen. CONCLUSIONS: Glutathione levels and the local oxygen tension at the time of irradiation were important determinants of mouse foot skin radiosensitivity. The extent to which GSH levels altered the radiosensitivity of skin was critically dependent on the local oxygen tension. These results have significant implications for potential clinical application of GSH depletion.


Assuntos
Dióxido de Carbono/farmacologia , Glutationa/deficiência , Misonidazol/farmacologia , Consumo de Oxigênio , Oxigênio/farmacologia , Radiossensibilizantes/farmacologia , Pele/efeitos da radiação , Animais , Butionina Sulfoximina , Hipóxia Celular/efeitos dos fármacos , Relação Dose-Resposta à Radiação , Feminino , Glutationa/efeitos dos fármacos , Masculino , Maleatos/farmacologia , Metionina Sulfoximina/análogos & derivados , Metionina Sulfoximina/farmacologia , Camundongos , Pressão Parcial , Pele/irrigação sanguínea , Pele/metabolismo , Torniquetes
14.
Int J Radiat Oncol Biol Phys ; 16(5): 1213-7, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2715072

RESUMO

Glutathione peroxidase (GSH-Px) has been implicated in mediating the radioprotective effects of glutathione (GSH). This hypothesis was tested in vivo by determining the effect of GSH-Px depletion on the radiation response of murine kidneys. Renal GSH-Px levels were depleted to 17% of control values by feeding animals a selenium deficient diet for 6 weeks; this had no significant effect on renal levels of GSH or GSH-S-transferase (GST). However, we also tested the effect of direct depletion of GSH to 3-4% of control values, using a combination of DL-buthionine sulphoximine (BSO) and diethyl maleate (DEM). Kidneys with normal or depleted levels of GSH-Px and/or GSH were irradiated with 240kVp X rays (2 fractions, 7 days apart to minimize intestinal injury). Mice breathed 7% oxygen during irradiation. Renal damage was assessed at 20, 25, and 32 weeks after the first fraction of X rays, in terms of reduced hematocrit and renal clearance of 51Cr-EDTA. Depletion of GSH-Px levels to 17% of control did not alter renal radiosensitivity, but depletion of GSH to 3-4% of control values radiosensitized the kidney by a factor of 1.4. Depletion of both GSH and GSH-Px together did not radiosensitize the kidney any more than was achieved by GSH depletion alone.


Assuntos
Glutationa Peroxidase/fisiologia , Rim/efeitos da radiação , Animais , Dieta , Feminino , Camundongos , Camundongos Endogâmicos CBA , Tolerância a Radiação , Selênio/deficiência
15.
Radiother Oncol ; 36(1): 56-64, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8525026

RESUMO

Following irradiation of the left-hind feet of mice, we measured the ability of the eccrine glands to secrete sweat following stimulation by pilocarpine. Silicone elastomer impression moulds of the foot pads gave repeatable, detailed localization of sweat ducts by retaining the impression of each emerging sweat droplet. Loss of gland function occurred rapidly following irradiation (within 2 weeks) and the rate of loss was dose-dependent, being over three times greater following a dose of 13.0 Gy than after 6.8 Gy. There was a dose-dependent nadir of function at around 8 weeks, followed by a gradual recovery that was complete by about 30 weeks after irradiation, leaving a dose-dependent residual functional deficit. Eccrine sweat glands are very radiosensitive organs compared with the epidermis. A single dose of 13 Gy resulted in complete loss of eccrine gland function at 8 weeks whilst about 23 Gy would be required to elicit transient moist desquamation, in oxygen-breathing mice. Substantial sparing was seen when two doses were split by intervals of up to 24 h.


Assuntos
Glândulas Écrinas/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Glândulas Écrinas/efeitos dos fármacos , , Membro Posterior , Hipo-Hidrose/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Pilocarpina/farmacologia , Doses de Radiação , Lesões Experimentais por Radiação/etiologia , Elastômeros de Silicone , Pele/efeitos da radiação , Suor/efeitos dos fármacos , Suor/metabolismo , Suor/efeitos da radiação , Fatores de Tempo
16.
Radiother Oncol ; 16(3): 211-20, 1989 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2587811

RESUMO

Recovery kinetics and recovery capacity were studied in a fast proliferating normal tissue, skin, and in an anaplastic mouse mammary carcinoma, CaNT. Three fractions per day of X-rays, repeated over 5 days, were given at varying interfraction intervals from 0 to 8 h. The rate of recovery in tumours (t1/2 = 0.31 +/- 0.15 h for local control) was significantly faster than in skin (t1/2 = 0.96 +/- 0.10 h). By contrast, the fractionation sensitivity of CaNT tumours was less than that of skin (alpha/beta = 43.3 +/- 8.5 Gy vs. alpha/beta = 7.9 +/- 0.2 Gy). Tissues with recovery half-times similar to or longer than that determined for skin would be at risk if interfraction intervals less than 6 h are used in regimes which involve the use of two or more fractions per day. This would be especially true for tissues that show a greater sensitivity to dose fractionation, and hence more sparing of radiation damage with hyperfractionation.


Assuntos
Adenocarcinoma/radioterapia , Neoplasias Mamárias Experimentais/radioterapia , Pele/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Feminino , Meia-Vida , Cinética , Masculino , Camundongos , Camundongos Endogâmicos CBA , Pele/fisiopatologia
17.
Radiother Oncol ; 20(2): 124-31, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1903208

RESUMO

The rate and early pattern of development of radiation-induced renal damage has been determined in the mouse by measuring reductions in both haematocrit and excretion of 51Cr-EDTA, and increases in both urination frequency and urine volume. Kidneys of CBA mice were irradiated bilaterally with 2 fractions of X-rays, one week apart. Renal function was determined immediately prior to irradiation and at 3-4 weekly intervals to 22 weeks post-irradiation. Onset of damage was detected as early as 3-6 weeks using the urination frequency assay. This was confirmed by estimating the volume of urine excreted. A significant fall in haematocrit was not detected until 6-9 weeks post-treatment and a fall in isotope clearance was not detected significantly until 12 weeks. This early detection of damage was consistent with reports using both mouse and other species. The time at which damage was detected first was independent of radiation dose for the frequency and haematocrit assays. For 51Cr-EDTA clearance, there was the suggestion of earlier functional loss for the higher doses. Following the onset of damage, a steady, dose-dependent decline in renal function was measured by all assays. The latency period is defined as the time required to reach a given level of functional damage. This time decreased with increasing radiation dose, to a minimum value set by the time of onset of damage, which varied from 3 to 12 weeks, depending on the assay used. The differences in response measured prior to 12 weeks post-irradiation represent the first occasion on which a dissociation between these 3 assays has been detected.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Rim/efeitos da radiação , Lesões Experimentais por Radiação , Animais , Relação Dose-Resposta à Radiação , Ácido Edético/metabolismo , Feminino , Hematócrito , Camundongos , Camundongos Endogâmicos CBA , Fatores de Tempo , Transtornos Urinários/etiologia
18.
Radiother Oncol ; 22(2): 81-91, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1835542

RESUMO

The ability of normobaric oxygen and carbogen (95% O2 + 5% CO2) combined with nicotinamide to enhance the radiosensitivity of two rodent adenocarcinomas and of mouse skin and kidneys, using a 10 fraction radiation schedule, was compared with the effect of radiation in air with and without the drug. Tumour response was assayed using local control and regrowth delay, and compared with acute skin reactions, decreased renal 51Cr-EDTA clearance and reduction in haematocrit. Nicotinamide increased the radiation sensitivity of CaNT tumours under all three different oxygen concentrations tested (21, 95 and 100% oxygen). The effect was statistically significant for oxygen and carbogen but not for air; the combination of nicotinamide with carbogen gave the greatest increase in tumour radiosensitivity. Relative to treatments in air without the drug, the enhancement ratios (ER) at the TCD50 level were 1.17, 1.65 and 1.83 for CaNT tumours irradiated in air, oxygen or carbogen and injected with nicotinamide 1 h before each fraction. The ER in CaRH tumours irradiated in carbogen plus the drug was 1.83, which was greater, but statistically not significantly different, to that seen with carbogen alone (ER = 1.68). In skin, relative to air without the drug, the increase in radiosensitivity by nicotinamide was greater in oxygen and carbogen than in air (1.29, 1.36 and 1.08, respectively). The ERs for both assays of renal damage were similar and lower than those in skin: less than or equal to 1.07, less than or equal to 1.13 and less than or equal to 1.16 for irradiations done in air, oxygen and carbogen plus nicotinamide, relative to air alone. A comparison of these results in the tumours and normal tissues showed that a significant therapeutic benefit was obtained with normobaric oxygen and carbogen combined with nicotinamide. This benefit is greater than observed with other radiosensitizers tested so far. Toxic side effects of the treatment are unlikely in a clinical situation, since prolonged administration of nicotinamide is well tolerated in man. The combination of normobaric carbogen with nicotinamide could be an effective method of enhancing tumour radiosensitivity in clinical radiotherapy where hypoxia limits the outcome of treatment.


Assuntos
Adenocarcinoma/radioterapia , Neoplasias Experimentais/radioterapia , Niacinamida/administração & dosagem , Animais , Carbono/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Técnicas In Vitro , Camundongos , Oxigênio/administração & dosagem , Tolerância a Radiação , Dosagem Radioterapêutica , Roedores
19.
Radiother Oncol ; 39(1): 53-64, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8735494

RESUMO

METHODS: Radiosensitisation with oxygen, carbogen or nicotinamide alone and oxygen or carbogen combined with nicotinamide was compared in early and late responding normal tissues in rodents. X-ray treatments were delivered as single doses or fractionated schedules of 2 fractions in 1 day, 2, 12 and 36 fractions in an overall time of 12 days and 10 fractions in 5 or 12 days. Acute skin reactions, survival of intestinal crypts, breathing rate, reduction in the packed red-cell volume and clearance of 51Cr-EDTA were used as assays of epidermal, gut, lung and renal damage. RESULTS: Relative to air-breathing mice, carbogen or oxygen produced a small, and not always significant, increase in sensitivity (enhancement ratios < or = 1.15) in gut, lung and kidneys; however, in skin a dose enhancement of 1.2-1.3 was observed. The effect of nicotinamide in air, carbogen or oxygen was studied only in lung and gut. The drug produced variable but generally significant increases in radiosensitisation ( < or = 1.26) in all three gases. Relative to treatments in air, enhancement ratios for nicotinamide alone were usually slightly higher than those observed when either carbogen or oxygen were administered without the drug. With all three modifiers (i.e. oxygen, carbogen, nicotinamide alone or for the drug-gas combinations) there was no significant change in the enhancement ratios observed as the number of radiation dose fractions was varied. CONCLUSIONS: Comparisons with fractionated X-ray studies done previously in rodent tumours indicate that a therapeutic benefit, relative to lung, gut and renal damage, would be observed with oxygen or carbogen alone but not with nicotinamide alone. The greatest gain would be achieved with the combination of carbogen and nicotinamide, with which a benefit was observed even relative to epidermal damage. These results indicate that some decrease in normal tissue tolerance could be observed when using these modifiers in clinical radiotherapy and, although small, the appropriate dose reductions should be considered; caution should be exercised especially when carbogen and nicotinamide are used in conjunction with the more radical accelerated schedules.


Assuntos
Dióxido de Carbono/uso terapêutico , Niacinamida/uso terapêutico , Oxigênio/uso terapêutico , Radiossensibilizantes/uso terapêutico , Animais , Dióxido de Carbono/administração & dosagem , Radioisótopos de Cromo , Relação Dose-Resposta à Radiação , Combinação de Medicamentos , Ácido Edético/metabolismo , Feminino , Hematócrito , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos da radiação , Rim/metabolismo , Rim/efeitos da radiação , Pulmão/metabolismo , Pulmão/efeitos da radiação , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos CBA , Camundongos Endogâmicos , Niacinamida/administração & dosagem , Oxigênio/administração & dosagem , Tolerância a Radiação , Radiossensibilizantes/administração & dosagem , Dosagem Radioterapêutica , Respiração/efeitos da radiação , Pele/metabolismo , Pele/efeitos da radiação , Terapia por Raios X
20.
Radiat Res ; 109(3): 456-68, 1987 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3562786

RESUMO

A further study on the response of the mouse kidney to d(4)-Be neutrons (EN = 2.3 MeV) is described. The results confirm and augment the work published previously by Stewart et al. [Br. J. Radiol. 57, 1009-1021 (1984)]; the present paper includes the data from a "top-up" design of experiment which extends the measurements of neutron RBE (relative to 240 kVp X rays) down to X-ray doses of 0.75 Gy per fraction. The mean RBE for these neutrons increases from 5.8 to 7.3 as X-ray dose per fraction decreases from 3.0 to 1.5 Gy in the kidney. This agrees with the predictions from the linear quadratic (LQ) model, based on the renal response to X-ray doses above 4 Gy per fraction. The mean RBE estimate from a single dose group at 0.75 Gy per fraction of X rays is, however, 3.9. This is below the LQ prediction and may indicate increasing X-ray sensitivity at low doses. Data from this study and from those published previously have been used to determine more accurately the shape of the underlying response to d(4)-Be neutrons; an alpha/beta ratio of 20.5 +/- 3.7 Gy was found. The best value of alpha/beta for X rays determined from these experiments was 3.04 +/- 0.35 Gy, in agreement with previous values.


Assuntos
Rim/efeitos da radiação , Nêutrons , Animais , Feminino , Camundongos , Modelos Biológicos , Doses de Radiação , Eficiência Biológica Relativa , Raios X
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