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1.
BioTech (Basel) ; 12(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36648834

RESUMO

The prospect of humans inhabiting planetary bodies is gaining interest among research and development communities, with the moon being considered as a transitory base camp and Mars the next planet humans will inhabit. NASA's Mission to Mars program is set to have humans inhabiting Mars within on-planet space camps by the Year 2030, which has tremendously increased research and development for space exploration-including research oriented toward human life support in long-term planetary lodging camps. The sustenance of human life on Mars will not be trivial due to the unavailability of an appropriate atmosphere and usable water. This situation requires a self-sustaining human life support system that can provide the basic needs such are breathable air, potable water, food, and energy. The feasibility of sending a payload with resources adequate to support long-term human inhabitation is not reasonable, which means every resource within a Mars space camp is valuable, including human-produced wastes. A biorefinery system that treats wastewater and can also produce valuable products such as oxygen, food, and energy offers a form of circular utilization of valuable resources. To conduct research for such systems requires a wastewater influent that is representative of the wastewater to be generated by the space crew within this isolated, confined environment, which is different from what is generated on Earth due to limited variability in diet, human activity, and lifestyle in this confined area. Collection of actual wastewater influent from an isolated environment supporting humans is challenging. Additionally, to ensure a safe working environment in the laboratory and avoid the imposed threat of handling actual human feces, the proposed synthetic, non-human feces containing wastewater influent formulation offers an easy-to-produce and safer-to-handle option. This paper reviews several synthetic wastewater compositions that have been formulated for space exploration purposes. None of the formulations were found to be realistic nor adequate for a space-camp-type scenario. Thus, the formulation of a synthetic wastewater for simulating a wastewater influent from a human space-based camp is proposed in this paper. In addition, the physical, chemical, and biodegradation characteristics of the final formulation designed are presented to illustrate the value of the proposed influent formulation.

2.
Nat Hazards (Dordr) ; 105(2): 1923-1944, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33132533

RESUMO

Disaster preparedness plans reduce future damages, but may lack testing to assess their effectiveness in operation. This study used the state-designed Local Government Unit Disaster Preparedness Journal: Checklist of Minimum Actions for Mayors in assessing the readiness to natural hazards of 92 profiled municipalities in central Philippines inhabited by 2.4 million people. Anchored on the Hyogo Framework for Action 2005-2015, it assessed their preparedness in 4 criteria-systems and structures, policies and plans, building competencies, and equipment and supplies. Data were analyzed using statistical package for social sciences, frequency count, percentage, and weighted mean. The local governments were found highly vulnerable to tropical cyclone and flood while vulnerable to earthquake, drought, and landslide. They were partially prepared regardless of profile, but the coastal, middle-earning, most populated, having the least number of villages, and middle-sized had higher levels of preparedness. Those highly vulnerable to earthquake and forest fire were prepared, yet only partially prepared to flood, storm surge, drought, tropical cyclone, tornado, tsunami and landslide. The diverse attitude of stakeholders, insufficient manpower, and poor database management were the major problems encountered in executing countermeasures. Appointing full-time disaster managers, developing a disaster information management system, massive information drive, organizing village-based volunteers, integrating disaster management into formal education, and mandatory trainings for officials, preparing for a possible major volcanic eruption and crafting a comprehensive plan against emerging emergencies like the COVID-19 pandemic may lead to a 360° preparedness.

3.
Chemosphere ; 248: 126078, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32041070

RESUMO

The surface properties of graphene oxide (GO) have been identified as the key effects on the adsorption of Pb(II) from aqueous solutions in this study. This study reveals the effect of the surface reactivity of GO via Carbon Disulfide (CS2) functionalization for Pb(II) adsorption. After successfully preparing CS2 functionalized GO (GOCS), the specific techniques were applied to investigate Pb(II) adsorption onto GOCS. Results indicated that the new sulfur-containing functional groups incorporated onto GOCS significantly enhanced Pb(II) adsorption capacity on GOCS than that of GO, achieving an improvement of 31% in maximum adsorption capacity increasing from 292.8 to 383.4 mg g-1. The equilibrium adsorption capacity for GOCS was 280.2 mg g-1 having an improvement of 83.2% over that of 152.97 mg g-1 for GO at the same initial concentration of 150 mg L-1 under the optimal pH of 5.7. Moreover, the results of adsorption experiments showed an excellent fit to the Langmuir and Pseudo-Second-Order models indicating the monolayer and chemical adsorption, respectively. The mechanism for Pb(II) adsorption on GOCS was proposed as the coordination, electrostatic interactions, cation-pi interactions, and Lewis acid-base interactions. The regeneration study showed that GOCS had an appreciable reusability for Pb(II) adsorption with the adsorption capacity of 208.92 mg g-1 after five regeneration cycles. In summary, GOCS has been proved to be a novel, useful, and potentially economic adsorbent for the high-efficiency removal of Pb(II) from aqueous solutions.


Assuntos
Dissulfeto de Carbono/química , Grafite/química , Chumbo/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Cinética , Propriedades de Superfície
4.
Water Environ Res ; 91(9): 865-876, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31004529

RESUMO

The main objective of this study was to demonstrate a computational approach of global sensitivity analysis (GSA) integrated with functional principal component analysis (fPCA) for activated sludge models through aggregation of time-dependent model response patterns into time-independent coefficients of functional principal components (PCs). This proposed approach addresses the main issue of time-varying character of GSA indices when calculated solely on the time-dependent model outputs. The GSA-fPCA methodology was implemented using the rigorous model Activated Sludge Model No. 3 (ASM3) as case study. The approach transforms the time-dependent model outputs into functional PCs prior to calculation of GSA indices to remove the time-varying character of the calculated GSA indices. This work focused on the evaluation of the following key computational factors that may significantly influence the performance of the GSA-fPCA methodology: (a) model parameter sampling range, (b) model simulation period, (c) basis functions system, and (d) state of the system being modeled-batch or continuous activated sludge process. Results show that first few functional PCs capture up to 100% of the curve patterns in the time-dependent model outputs. The sensitivity indices calculated from the PC scores via Morris' GSA technique elucidated parameter sensitivity patterns inherent to the complex mathematical structure of ASM3. PRACTITIONER POINTS: Functional principal components-mediated GSA technique to remove time-varying character of sensitivity indices derived from time-dependent dynamical models. Technique amenable to improving efficiency of capturing response patterns into few functional principal components through various basis functions. Identifying priority parameters for ASM3 model calibration requires specification of target model outputs to which parameter sensitivities are calculated. GSA-fPCA offers a comprehensive numerical approach to manipulating models depending on the intended applications: simple fast-responding models to complex models.


Assuntos
Esgotos , Calibragem , Análise de Componente Principal
5.
Med Eng Phys ; 47: 210-213, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28651855

RESUMO

This paper describes the quantitative assessment of a robotic testing platform, consisting of an industrial robot and a universal force-moment sensor, via the design of fixtures used to hold the tibia and femur of cadaveric knees. This platform was used to study the contributions of different soft tissues and the ability of implants and reconstruction surgeries to restore normal joint functions, in previously published literature. To compare different conditions of human joints, it is essential to reposition specimens with high precision after they have been removed for a surgical procedure. Methods and experiments carried out to determine the pose repeatability and measure errors in repositioning specimens are presented. This was achieved using an optical tracking system (fusion Track 500, Atracsys Switzerland) to measure the position and orientation of bespoke rigid body markers attached to the tibial and femoral pots after removing and reinstalling them inside the rigs. The pose repeatability was then evaluated by controlling the robotic platform to move a knee joint repeatedly to/from a given pose while tracking the position and orientation of a rigid body marker attached to the tibial fixture. The results showed that the proposed design ensured a high repeatability in repositioning the pots with standard deviations for the computed distance and angle between the pots at both ends of the joint equal to 0.1mm, 0.01mm, 0.13° and 0.03° for the tibial and femoral fixtures respectively. Therefore, it is possible to remove and re-setup a joint with high precision. The results also showed that the errors in repositioning the robotic platform (that is: specimen path repeatability) were 0.11mm and 0.12°, respectively.


Assuntos
Articulações/fisiologia , Posicionamento do Paciente/métodos , Postura/fisiologia , Amplitude de Movimento Articular/fisiologia , Robótica/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
6.
Vet Parasitol ; 190(1-2): 95-103, 2012 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-22763348

RESUMO

Taeniid tapeworms which include Echinococcus and Taenia spp. are obligatory parasites of mammals with pathogenicity usually related to the larval stages of the life cycle. Two species (or genotypes) of Echinococcus, E. granulosus sensu stricto and E. equinus, as well as several Taenia spp. are endemic in the UK. Here we report on the occurrence of larval cystic stages of Echinococcus and Taenia spp. in captive mammals in the UK. Using molecular techniques we have identified E. granulosus (G1 genotype) in a guenon monkey and a Philippine spotted deer; E. equinus in a zebra and a lemur; E. ortleppi in a Philippine spotted deer; E. multilocularis in a macaque monkey and Taenia polyacantha in jumping rats. To the best of our knowledge this is the first report of E. multilocularis in a captive primate translocated to the UK. As far as we know these are the first reports of E. equinus in a primate (lemur) and in a zebra; as well as E. granulosus (G1 genotype) and E. ortleppi in a cervid translocated to the UK. These infections and implications of the potential establishment of exotic species of cestodes are discussed.


Assuntos
Animais de Zoológico/parasitologia , Equinococose/veterinária , Echinococcus/isolamento & purificação , Mamíferos/parasitologia , Taenia/isolamento & purificação , Teníase/veterinária , Animais , Sequência de Bases , Cercopithecus/parasitologia , DNA de Helmintos/genética , Cervos/parasitologia , Equinococose/epidemiologia , Equinococose/parasitologia , Equinococose/patologia , Echinococcus/genética , Equidae/parasitologia , Feminino , Genótipo , Lemuridae/parasitologia , Fígado/parasitologia , Fígado/patologia , Pulmão/parasitologia , Pulmão/patologia , Macaca/parasitologia , Masculino , Dados de Sequência Molecular , Doenças dos Primatas/epidemiologia , Doenças dos Primatas/parasitologia , Doenças dos Primatas/patologia , Roedores , Análise de Sequência de DNA , Taenia/genética , Teníase/epidemiologia , Teníase/parasitologia , Teníase/patologia , Reino Unido/epidemiologia
7.
Curr Oncol ; 18(5): e227-37, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21980254

RESUMO

BACKGROUND: Many women with symptoms suggestive of a breast cancer diagnosis delay presentation to their family physician. Although factors associated with delay have been well described, there is a paucity of data on strategies to mitigate delay. OBJECTIVES: We conducted a qualitative research project to examine factors related to delay and to identify health care system changes that might encourage earlier presentation. METHODS: Individual semi-structured interviews were conducted with women who sought care 12 weeks or more after self-detection of breast cancer symptoms and with family physicians whose practices included patients meeting that criterion. RESULTS: The women and physicians both suggested a need for clearer screening mammography guidelines for women 40-49 years of age and for better messaging concerning breast awareness. The use of additional hopeful testimonials from breast cancer survivors were suggested to help dispel the notion of cancer as a "death sentence." Educational initiatives were proposed, aimed at both increasing awareness of "non-lump" breast cancer symptoms and advising women that a previous benign diagnosis does not ensure that future symptoms are not cancer. Women wanted empathic nonjudgmental access to care. Improved methods to track compliance with screening mammography and with periodic health exams and access to a rapid diagnostic process were suggested. CONCLUSIONS: A list of "at-risk situations for delay" in diagnosis of breast cancer was developed for physicians to assist in identifying women who might delay. Health care system changes actionable both at the health policy level and in the family physician's office were identified to encourage earlier presentation of women with symptomatic breast cancer.

8.
J Neurooncol ; 101(1): 25-32, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20490612

RESUMO

To describe the morphologic magnetic resonance imaging (MRI) findings in histologically proven therapy-induced cerebral necrosis. We retrospectively reviewed the morphologic MRI findings in patients with therapy-induced cerebral necrosis. Images were reviewed for size, location, and characteristics of signal intensity abnormalities and T1-contrast enhancement. Images were also assessed for mass effect, necrosis, cyst, atrophy, cortical thinning, and leukoencephalopathy. The individual imaging characteristics were correlated with clinical and treatment variables. There were 44 patients. Seventy percent had a glioma, all patients had received radiation, and 57% had received chemotherapy in close proximity to radiation. All images demonstrated contrast enhancement, predominantly in the white matter. Enhancement was present in the periventricular/subependymal region in 50% of cases and the corpus callosum in 27%. The most common pattern of lesion peripheral enhancement was "spreading wavefront" and of interior enhancement was "Swiss cheese/soap bubble." The enhancing lesion was single in 60% of cases. Mass effect was present in 93% of patients. Location and patterns of enhancement were significantly associated with the interval from brain radiation to the diagnosis of therapy-induced cerebral necrosis, tumor histology, patient age, type of radiation, and administration of systemic chemotherapy. This is the largest study of the morphologic conventional MRI findings in pathologically confirmed therapy-induced cerebral necrosis. We characterized the imaging findings in a variety of tumor types following a variety of radiation treatments and other antineoplastic therapy. These findings may be of value in identifying therapy-induced cerebral necrosis in patients treated for a brain tumor.


Assuntos
Neoplasias Encefálicas/terapia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Necrose , Lesões por Radiação/patologia , Radioterapia/efeitos adversos , Estudos Retrospectivos
9.
J Small Anim Pract ; 52(1): 46-50, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21175625

RESUMO

This case report describes congestive heart failure with pleural effusion in two middle-aged, pet house rabbits. Both had a history of acute onset dyspnoea, weakness and weight loss. Bi-atrial enlargement was seen on echocardiography in both rabbits. One rabbit had atrial fibrillation and ventricular premature complexes identified on electrocardiography. There was a radiographically evident pleural effusion in both rabbits and thoracocentesis was undertaken in one rabbit. These findings were confirmed on post-mortem examination. The aetiology for the underlying heart disease was not found, but the potential types of cardiomyopathies are discussed.


Assuntos
Cardiomiopatias/veterinária , Insuficiência Cardíaca/veterinária , Derrame Pleural/veterinária , Coelhos , Animais , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Diagnóstico Diferencial , Ecocardiografia/veterinária , Evolução Fatal , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Masculino , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia
10.
Vet Rec ; 167(25): 961-5, 2010 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-21262711

RESUMO

To establish a well-tolerated technique for recording electrocardiograms (ECGs) and a reference range for the normal pet rabbit ECG, 46 healthy pet rabbits were studied. The following reference ranges were calculated. Heart rate was 198 to 330 bpm. P waves had a duration of 0.01 to 0.05 seconds and an amplitude of 0.04 to 0.12 mV. The P-R interval was 0.04 to 0.08 seconds and the duration of the QRS complex was 0.02 to 0.06 seconds. The amplitude of the R wave was 0.03 to 0.39 mV. The Q-T interval was 0.08 to 0.16 seconds. The amplitude of the T wave was 0.05 to 0.17 mV. Mean electrical axis was found to be -43° to +80°. Evidence of variation due to breed or bodyweight was not found to be significant, except for a quadratic relationship between R wave amplitude and bodyweight. The ECG recording technique used in this study for pet rabbits was well tolerated and shown to be both reliable and repeatable.


Assuntos
Eletrocardiografia/veterinária , Animais de Estimação , Coelhos/fisiologia , Animais , Eletrocardiografia/métodos , Coração/fisiologia , Valores de Referência , Reprodutibilidade dos Testes
11.
Emerg Med J ; 26(2): 123-7, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19164628

RESUMO

OBJECTIVE: To identify any association between the response priority code generated during calls to the ambulance communication centre and patient reports of pain severity. METHODS: A retrospective analysis of patient care records was undertaken for all patients transported by paramedics over a 7-day period. The primary research interest was the association between the response code allocated at the time of telephone triage and the initial pain severity score recorded using a numeric rating scale (NRS). Univariate and multivariate logistic regression methods were used to analyse the association between the response priority variable and explanatory variables. RESULTS: There were 1246 cases in which both an initial pain score using the NRS and a response code were recorded. Of these cases, 716/1246 (57.5%) were associated with a code 1 ("time-critical") response. After adjusting for gender, age, cause of pain and duration of pain, a multivariate logistic regression analysis found no significant change in the odds of a patient in pain receiving a time-critical response compared with patients who had no pain, regardless of their initial pain score (NRS 1-3, odds ratio (OR) 1.11, 95% CI 0.7 to 1.8; NRS 4-7, OR 1.12, 95% CI 0.7 to 1.8; NRS 8-10, OR 0.84, 95% CI 0.5 to 1.4). CONCLUSION: The severity of pain experienced by the patient appeared to have no influence on the priority (urgency) of the dispatch response. Triage systems used to prioritise ambulance calls and decide the urgency of response or type of referral options should consider pain severity to facilitate timely and humane care.


Assuntos
Ambulâncias/estatística & dados numéricos , Manejo da Dor , Triagem/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Coleta de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/estatística & dados numéricos , Estudos Retrospectivos
12.
Biochem Pharmacol ; 73(8): 1084-96, 2007 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-17129577

RESUMO

The successful cloning and functional expression of the histamine H(3) receptor in the late 1990 s has greatly facilitated our efforts to identify small molecule, non-imidazole based compounds to permit the evaluation of H(3) antagonists in models of CNS disorders. High-throughput screening identified several series of lead compounds, including a series of imidazopyridines, which led to JNJ-6379490, a compound with high affinity for the human H(3) receptor. Analysis of structural features common to several series of non-imidazole H(3) receptor ligands resulted in a pharmacophore model. This model led to the design of JNJ-5207852, a diamine-based H(3) antagonist with good in vitro and in vivo efficacy but with an undesirable long half-life. However, further modifications of the template provided an understanding of the effect of structural modifications on pharmacokinetic properties, ultimately affording several additional series of compounds including JNJ-10181457, a compound with an improved pharmacokinetic profile. These compounds allowed in vivo pharmacological evaluation to show that H(3) antagonists promote wakefulness, but unlike modafinil and classical psychostimultants, they do not increase locomotor activity or produce any alteration of the EEG power spectral activity in rats. H(3) antagonists also increase extracellular acetylcholine and norepinephrine but not dopamine in rat frontal cortex and show efficacy in various models of learning-memory deficit. In addition, cFos immunoreactivity studies show H(3) antagonists activate neuronal cells in restricted rat brain regions in contrast to widespread activation after modafinil or amphetamine treatment. Therefore, H(3) antagonists are promising clinical candidates for the treatment of excessive day time sleepiness and/or cognitive disorders.


Assuntos
Antagonistas dos Receptores Histamínicos/farmacologia , Piperidinas/farmacologia , Receptores Histamínicos H3/metabolismo , Animais , Clonagem Molecular , Transtornos Cognitivos/tratamento farmacológico , DNA Complementar/isolamento & purificação , DNA Complementar/metabolismo , Diaminas/química , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Masculino , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Narcolepsia/tratamento farmacológico , Piperidinas/uso terapêutico , Ratos , Ratos Wistar , Receptores Histamínicos H3/genética , Receptores Histamínicos H3/fisiologia
13.
Br J Pharmacol ; 143(5): 649-61, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15466448

RESUMO

1 1-[4-(3-piperidin-1-yl-propoxy)-benzyl]-piperidine (JNJ-5207852) is a novel, non-imidazole histamine H3 receptor antagonist, with high affinity at the rat (pKi=8.9) and human (pKi=9.24) H3 receptor. JNJ-5207852 is selective for the H3 receptor, with negligible binding to other receptors, transporters and ion channels at 1 microm. 2 JNJ-5207852 readily penetrates the brain tissue after subcutaneous (s.c.) administration, as determined by ex vivo autoradiography (ED50 of 0.13 mg kg(-1) in mice). In vitro autoradiography with 3H-JNJ-5207852 in mouse brain slices shows a binding pattern identical to that of 3H-R-alpha-methylhistamine, with high specific binding in the cortex, striatum and hypothalamus. No specific binding of 3H-JNJ-5207852 was observed in brains of H3 receptor knockout mice. 3 In mice and rats, JNJ-5207852 (1-10 mg kg(-1) s.c.) increases time spent awake and decreases REM sleep and slow-wave sleep, but fails to have an effect on wakefulness or sleep in H3 receptor knockout mice. No rebound hypersomnolence, as measured by slow-wave delta power, is observed. The wake-promoting effects of this H3 receptor antagonist are not associated with hypermotility. 4 A 4-week daily treatment of mice with JNJ-5207852 (10 mg kg(-1) i.p.) did not lead to a change in body weight, possibly due to the compound being a neutral antagonist at the H3 receptor. 5 JNJ-5207852 is extensively absorbed after oral administration and reaches high brain levels. 6 The data indicate that JNJ-5207852 is a novel, potent and selective H3 antagonist with good in vitro and in vivo efficacy, and confirm the wake-promoting effects of H3 receptor antagonists.


Assuntos
Antagonistas dos Receptores Histamínicos/farmacologia , Piperidinas/farmacologia , Receptores Histamínicos H3/efeitos dos fármacos , Vigília/efeitos dos fármacos , Administração Oral , Animais , Autorradiografia , Temperatura Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , AMP Cíclico/metabolismo , Eletrodos , Eletroencefalografia/efeitos dos fármacos , Eletromiografia/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/farmacocinética , Humanos , Injeções Intravenosas , Masculino , Camundongos , Camundongos Knockout , Camundongos Obesos , Atividade Motora/efeitos dos fármacos , Piperidinas/administração & dosagem , Piperidinas/farmacocinética , Polissonografia , Ratos , Ratos Sprague-Dawley , Receptores Histamínicos H3/genética , Sono/efeitos dos fármacos , Transdutores
14.
Mutat Res ; 501(1-2): 13-7, 2002 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-11934433

RESUMO

Preconception paternal irradiation (PPI) modifies haemopoietic and stromal tissues of offspring and increases risk of generating lympho-haemopopietic malignancy if those offspring are then exposed to a leukaemogen. We hypothesised that this increased risk was related to inherited damage which had caused increased stem cell proliferation rates. To test for this link, in vivo, rapid stem cell proliferation was established by giving sub-lethal irradiation (3Gy gamma-rays) and allowing 3 days recovery. At this stage, 60% of haemopoietic spleen colony-forming units (CFU-S) were in DNA-synthesis, compared to <10% in unirradiated controls. Two groups of mice, unirradiated controls and irradiated animals, were then injected with 50mg/kg methyl nitrosourea (MNU) and observed daily for onset of lympho-haemopoietic malignancy. In a further control group of 60 mice, irradiated but not injected with MNU, only one leukaemia developed. In unirradiated controls, 20% of the mice developed malignancies between 3 and 8 months later: in the irradiated, MNU-treated groups, 95% developed malignancies between 2 and 7 months later. Thus, at least one powerful potentiating mechanism for induction of lympho-haemopoietc malignancy following inherited damage can be related to haemopoietic stem cell proliferation. Genomic instability is exposed by cell proliferation and has been implicated in this type of damage. However, a regulatory stromal microenvironment plays a part in inducing that proliferation. Thus, the microenvironment is the effective "bystander" which is thought to promote and amplify genomic instability, and thereby influence the induction of malignancy both in PPI offspring and in mice with induced stem cell proliferation.


Assuntos
Alquilantes/farmacologia , Efeito Espectador , Metilnitrosoureia/farmacologia , Células-Tronco/fisiologia , Animais , Divisão Celular/efeitos dos fármacos , Divisão Celular/genética , Feminino , Leucemia Experimental/induzido quimicamente , Leucemia Experimental/genética , Camundongos , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/efeitos da radiação , Irradiação Corporal Total
15.
Radiat Res ; 156(5 Pt 1): 488-94, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11604061

RESUMO

The conjecture that germline mutations induced by radiation exposure before conception may predispose subsequent offspring to cancer remains contentious. Previous experimental studies have shown that preconception paternal irradiation with (239)Pu induces perturbations in the hemopoietic systems of offspring and influences sensitivity to a secondary carcinogen. In the present study, male DBA2 mice were injected intravenously with the Auger electron emitter (55)Fe (4 kBq g(-1)) 18 or 84 days before mating with normal females. Comet analysis showed an increased incidence of DNA strand breaks in sperm from contaminated animals after 84 days, but not after 18 days, indicating spermatogonial rather than spermatid damage. Offspring were either assayed for changes in bone marrow stem cells and committed progenitors or challenged with the chemical carcinogen methyl nitrosourea (MNU, 50 mg/kg) at 10 weeks of age and monitored for the onset of malignancy. Offspring from irradiated fathers had normal peripheral blood profiles, although the stem cell population was amplified in offspring arising from those exposed to (55)Fe at 84 days before conception. Exposure to MNU significantly increased the incidence of lympho-hemopoietic malignancies in offspring from the 84-day group, but not in those from the 18-day group. These findings support the hypothesis that aberrations that are potentially leukemogenic may be transmitted to offspring after radiation damage to the paternal germline.


Assuntos
Feto/efeitos da radiação , Radioisótopos de Ferro/efeitos adversos , Leucemia Induzida por Radiação/etiologia , Exposição Paterna , Animais , Contagem de Células Sanguíneas , Dano ao DNA , Masculino , Metilnitrosoureia/toxicidade , Camundongos , Camundongos Endogâmicos DBA , Espermatozoides/efeitos da radiação , Testículo/efeitos da radiação
16.
Clin Cancer Res ; 7(7): 2085-90, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11448927

RESUMO

Filgrastim G-CSF has a short, biologically active half-life, and its effective use depends on repeated inoculations. A major aim, therefore, has been to develop a once-per-chemotherapy cycle formulation. To this end, a polyethylene glycolylated form of Filgrastim, known as SD/01, has been developed. In this study, we compared the cellular kinetics of granulocyte production in mice stimulated with SD/01 and granulocyte colony-stimulating factor (G-CSF). Mice were injected with a single dose of SD/01 (1 mg/kg) or G-CSF (125 microg/kg) twice per day for 4 days. Mice rendered leukopenic with a single injection of cyclophosphamide (200 mg/kg) and temozolomide (90 mg/kg) were similarly treated at their 3-day neutrophil nadir. Tritiated thymidine was injected for autoradiographic labeling studies. Bone marrow labeling indices and the release of labeled neutrophils and monocytes into the peripheral blood were assessed. Granulocytopoiesis was stimulated similarly by both SD/01 and G-CSF in both normal and neutropenic animals, with counts rising to >20 x 10(9) polymorphonuclear neutrophils/l in both cases. Bone marrow thymidine labeling indices were increased, indicating a greater proportion of cells in DNA synthesis and an elevated proliferative activity. Compared with the normally slow release of neutrophils into the peripheral blood, labeled neutrophils (and monocytes) were rapidly released, increasing to peak levels at approximately 24 h. The peripheral half-life of neutrophils was not significantly different from normal, and the mitotic amplification factors for increase in granulocytopoiesis, accounted for by 3-3.9 extra cell divisions, were comparable for both factors. We conclude that neutrophil kinetics are stimulated in the same way and to the same extent by both SD/01 and G-CSF.


Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Neutropenia/fisiopatologia , Neutrófilos/efeitos dos fármacos , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Divisão Celular/efeitos dos fármacos , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/química , Cinética , Contagem de Leucócitos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Endogâmicos , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Neutropenia/patologia , Neutrófilos/citologia , Neutrófilos/metabolismo , Polietilenoglicóis/química , Proteínas Recombinantes , Timidina/metabolismo , Fatores de Tempo , Trítio
17.
Int J Radiat Biol ; 77(6): 665-78, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11403706

RESUMO

PURPOSE: To study the temporal change in microdistribution of plutonium-239, americium-241 and uranium-233 in the mouse distal femur and to compare and combine calculated radiation doses with those obtained previously for the femoral shaft. Also, to relate doses to relative risks of osteosarcoma and acute myeloid leukaemia. MATERIALS AND METHODS: Computer-based image analysis of neutron-induced and alpha-track autoradiographs of sections of mouse femora was used to quantify the microdistribution of (239)Pu, (241)Am and (233)U from 1 to 448 days after intraperitoneal injection. Localized dose-rates and cumulative doses over this period were calculated for different regions of the marrow spaces in trabecular bone. The results were then combined with previous data for doses to the cortical marrow of the femoral shaft. A morphometric analysis of the distal femur was carried out. RESULTS: Initial deposition on endosteal surfaces and dose-rates near to the trabecular surfaces at 1 day were two to four times greater than corresponding results for cortical bone. Burial was most rapid for (233)U, about twice the rate in cortical bone. As in cortical bone, subsequent uptake into the marrow was seen for (239)Pu and (241)Am but not (233)U. Cumulative doses to 448 days for different regions of trabecular marrow were greater than corresponding values for cortical marrow for each radionuclide. Combined doses reflected the greater overall volume of cortical marrow. CONCLUSIONS: Cumulative radiation doses to the 10 microm thick band of marrow adjacent to all endosteal surfaces were in the ratio of approximately 7:3:1 for (239)Pu:(241)Am:(233)U. This ratio is not inconsistent with observed incidences of osteosarcoma induction by the three nuclides. Analysis of doses to different depths of marrow, however, showed that although ratios were probably not significantly different to that for a 10 microm depth, better correlations with osteosarcomagenic risk were obtained with 20-40 microm depths. For acute myeloid leukaemia, the closest relationship between relative risk and doses was obtained by considering only the central 5-10% of marrow, which gave a dose ratio of approximately 12:11:1 for (239)Pu:(241)Am:(233)U respectively.


Assuntos
Amerício/toxicidade , Medula Óssea/efeitos da radiação , Plutônio/toxicidade , Urânio/toxicidade , Amerício/farmacocinética , Animais , Autorradiografia , Medula Óssea/metabolismo , Relação Dose-Resposta à Radiação , Fêmur/metabolismo , Fêmur/efeitos da radiação , Humanos , Leucemia Mieloide Aguda/etiologia , Masculino , Camundongos , Camundongos Endogâmicos CBA , Neoplasias Induzidas por Radiação/etiologia , Osteossarcoma/etiologia , Plutônio/farmacocinética , Radiometria , Fatores de Risco , Distribuição Tecidual , Urânio/farmacocinética
18.
Soc Work Health Care ; 34(1-2): 177-93, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-12219766

RESUMO

Australian Social Work, over recent years, has been challenged to develop a standardised and accurate classification system for social work interventions. The need for such a system arose through changes in funding arrangements based on the Diagnosis Related Groups (DRGs) treated within hospitals. In Australian hospitals, the mix of DRGs treated became known as its 'casemix.' These new funding arrangements made it necessary for Social Work to classify and measure activity with each patient to ensure continuing resource allocation to social work services in hospitals. A national Casemix Network was formed under the auspice of the Australian Association of Social Workers to develop a classification system. The Network worked collaboratively with other allied health professions to produce a generic framework for professional activities and also developed a classification of social work interventions. These activity classifications have been incorporated into procedure coding in Australian hospitals. The challenges associated with casemix funding required Social Work to address a number of philosophical and methodological issues related to classification of professional activities to ensure an outcome that recognised the unique contribution of Social Work to health care.


Assuntos
Administração de Caso , Grupos Diagnósticos Relacionados , Serviço Social/classificação , Serviço Social/organização & administração , Austrália , Humanos , Avaliação de Resultados em Cuidados de Saúde
20.
J Exp Clin Cancer Res ; 20(4): 505-10, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11876543

RESUMO

Clinical trials with autologous indium-114m-labelled lymphocytes have revealed significant anti-tumour effects in chronic lymphocytic leukaemia patients with highly resistant disease. Substitution of the lymphocyte vector with heat-damaged red blood cells (HDRBC) may make this treatment more universally applicable and reduce the dose-limiting myelosuppression encountered with labelled lymphocytes. Therefore, the bone marrow localization and toxicities of indium-labelled lymphocytes or HDRBC have been investigated in BDFI mice. At 24 hours approximately 4% and 1.2% of 114In(m) administered as labelled lymphocytes or HDRBC respectively was localized within the bone marrow and remained constant for 57 days thereafter. Toxicity towards bone marrow stem cells, measured as CFU-S, was equivalent for both cellular vectors. However, at clinically relevant activities, 114In(m) HDRBC were less toxic than labelled lymphocytes towards committed progenitors, assayed as in vitro-CFC and CFU-Meg. These data suggest that substitution of HDRBC for lymphocytes as the 114In(m) vector may be beneficial in reducing the myelosuppression associated with this technique.


Assuntos
Medula Óssea/efeitos da radiação , Eritrócitos/metabolismo , Células-Tronco Hematopoéticas/efeitos da radiação , Radioisótopos de Índio/efeitos adversos , Baço/metabolismo , Animais , Ensaio de Unidades Formadoras de Colônias , Fêmur/patologia , Hipertermia Induzida , Leucemia Linfocítica Crônica de Células B/radioterapia , Transfusão de Linfócitos , Megacariócitos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Baço/efeitos da radiação , Linfócitos T/citologia , Distribuição Tecidual
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