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1.
Public Health ; 221: 150-159, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37454405

RESUMO

OBJECTIVES: We reviewed environmental public health practice at a local level (roles, responsibilities, interaction with partner agencies) to establish what and how an integrated approach to the service, as found in Cheshire and Merseyside, North West England, should be delivered, if at all, and at what footprint. STUDY DESIGN: Mixed methods approach. METHODS: We triangulated: qualitative interviews with relevant professionals to gain an in-depth understanding of their interest and vision for any health protection input to health risks and outcomes from environmental issues; an electronic questionnaire assessing experience, interest, vision and comfort zones of a wider range of professionals involved in environmental health issues; a half-day workshop to review study findings and agree ways forward. RESULTS: Stakeholders value their local health protection team's input, but environmental public-health knowledge and skills also exist in local authority teams. Regional health protection teams can provide environmental public-health expertise to local partners and agencies. They harness national input and evidence with local frontline professionals practice, enabling locally grounded approaches, integrating science into local contexts, to answer difficult, often incorrigible, problems. CONCLUSIONS: Specialist leadership by experienced Consultants in Health Protection is of value to local authority public health and environmental teams and should be based on a footprint that is appropriate to enhance local relationships without compromising available expert knowledge and skills.


Assuntos
Prática de Saúde Pública , Saúde Pública , Humanos , Inquéritos e Questionários , Liderança , Inglaterra
2.
J Hosp Infect ; 111: 89-95, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33453349

RESUMO

BACKGROUND: COVID-19 care home outbreaks represent a significant proportion of COVID-19 morbidity and mortality in the UK. National testing initially focused on symptomatic care home residents, before extending to asymptomatic cohorts. AIM: The aim was to describe the epidemiology and transmission of COVID-19 in outbreak free care homes. METHODS: A two-point prevalence survey of COVID-19, in 34 Liverpool care homes, was performed in April and May 2020. Changes in prevalence were analysed. Associations between care home characteristics, reported infection, prevention and control interventions, and COVID-19 status were described and analysed. FINDINGS: No resident developed COVID-19 symptoms during the study. There was no significant difference between: the number of care homes containing at least one test positive resident between the first (17.6%, 95% confidence interval (CI) 6.8-34.5) and second round (14.7%, 95% CI 5.0-31.1) of testing (p>0.99); and the number of residents testing positive between the first (2.1%, 95% CI 1.2-3.4) and second round (1.0%, 95% CI 0.5-2.1) of testing (P=0.11). Care homes providing nursing care (risk ratio (RR) 7.99, 95% CI 1.1-57.3) and employing agency staff (RR 8.4, 95% CI 1.2-60.8) were more likely to contain test positive residents. Closing residents shared space was not associated with residents testing positive (RR 2.63, 95% CI 0.4-18.5). CONCLUSIONS: Asymptomatic COVID-19 care homes showed no evidence of disease transmission or development of outbreaks; suggesting that current infection prevention and control measures are effective in preventing transmission. Repeat testing at two to three weeks had limited or no public health benefits over regular daily monitoring of staff and residents for symptoms. These results should inform policies calling for regular testing of asymptomatic residents.


Assuntos
Teste para COVID-19/estatística & dados numéricos , COVID-19/prevenção & controle , COVID-19/transmissão , Portador Sadio/diagnóstico , Surtos de Doenças/prevenção & controle , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Casas de Saúde/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Assintomáticas/epidemiologia , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Avaliação de Sintomas , Reino Unido/epidemiologia
3.
Int J Tuberc Lung Dis ; 24(2): 150-164, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32127098

RESUMO

BACKGROUND: Indoor and ambient air pollution exposure is a major risk to respiratory health worldwide, particularly in low- and middle-income countries (LMICs). Interventional trials have mainly focused on alternatives to cooking stoves, with mixed results. Beyond cooking, additional sources of particulate matter also contribute to the burden of air pollution exposure. This review explores evidence from current randomised controlled trials (RCTs) on the clinical effectiveness of interventions to reduce particulate matter in LMICs.METHODS: Twelve databases and the grey literature (e.g., Government reports and policy papers) were searched. Eligible studies were RCTs conducted in LMICs aiming to reduce particulate exposure from any source and reporting on at least one clinical respiratory outcome (respiratory symptoms, lung function or clinical diagnoses). Data from relevant studies were systematically extracted, the risk of bias assessed and narrative synthesis provided.RESULTS: Of the 14 included studies, 12 tested 'improved' cookstoves, most using biomass, but solar and bioethanol cookers were also included. One trial used solar lamps and another was an integrated intervention incorporating behavioural and environmental components for the treatment and prevention of chronic obstructive pulmonary disease. Of the six studies reporting child pneumonia outcomes, none demonstrated significant benefit in intention-to-treat analysis. Ten studies reported respiratory symptom outcomes with some improvements seen, but self-reporting made these outcomes highly vulnerable to bias. Substantial inter-study clinical and methodological heterogeneity precluded calculation of pooled effect estimates.CONCLUSION: Evidence from the RCTs performed to date suggests that individual household-level interventions for air pollution exposure reduction have limited benefits for respiratory health. More comprehensive approaches to air pollution exposure reduction must be developed so their potential health benefits can be assessed.


Assuntos
Poluição do Ar em Ambientes Fechados , Poluição do Ar , Poluição do Ar/efeitos adversos , Poluição do Ar/prevenção & controle , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise , Criança , Culinária , Poeira , Características da Família , Humanos , Material Particulado
4.
Water Sci Technol ; 69(6): 1326-33, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24647201

RESUMO

Combined sewer overflows (CSOs) represent a common feature in combined urban drainage systems and are used to discharge excess water to the environment during heavy storms. To better understand the performance of CSOs, the UK water industry has installed a large number of monitoring systems that provide data for these assets. This paper presents research into the prediction of the hydraulic performance of CSOs using artificial neural networks (ANN) as an alternative to hydraulic models. Previous work has explored using an ANN model for the prediction of chamber depth using time series for depth and rain gauge data. Rainfall intensity data that can be provided by rainfall radar devices can be used to improve on this approach. Results are presented using real data from a CSO for a catchment in the North of England, UK. An ANN model trained with the pseudo-inverse rule was shown to be capable of predicting CSO depth with less than 5% error for predictions more than 1 hour ahead for unseen data. Such predictive approaches are important to the future management of combined sewer systems.


Assuntos
Drenagem Sanitária , Chuva , Redes Neurais de Computação , Radar
5.
Eur J Cardiothorac Surg ; 25(1): 116-22, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14690742

RESUMO

OBJECTIVE: Following cardiac surgery, patients are transferred from the operating theatre to intensive care. This clinical environment has one nurse per patient and facilities for mechanical ventilation. Patients are kept in this setting until the following day. This practice has been challenged with early extubation of patients. At our institution we have established a fast-track policy including the following features: (1) patient selection; (2) operating list scheduling with fast-track patients first; (3) anaesthetic tailored to early extubation; (4) methodical procedure with warm cardiopulmonary bypass; (5) removal of the arterial line; (6) transfer from intensive care to a separate high dependency unit ('step-down') on the day of operation, where the ratio of nurse to patient is one to three and there are no ventilatory facilities and no invasive monitoring; or (7) to keep these patients on ICU but decrease the nurse to patient ratio. METHOD: The case notes of 572 patients who predominantly had myocardial revascularisation, undergoing this process from July 1996 to July 2000 at our institution were reviewed. RESULTS: Mean EUROSCORE for the study group was 1.42. The 30-day mortality rate for the study group was 0.34%, mean intensive care time was 5 h 52 min, mean time to extubation was 3 h 10 min, mean readmission rate to intensive care was 0.34% and mean hospital stay from day of operation (inclusive) was 5.65 days. This process increased our throughput by 14.6% (compared to standard practices). COMMENT: This study demonstrates that transfer of appropriate patients to a high dependency area from intensive care following cardiac surgery is safe. It allows intensive care beds to be used by more than one patient each day and allows significant cost savings by reducing the nursing ratio per patient.


Assuntos
Cuidados Críticos/organização & administração , Revascularização Miocárdica , Adulto , Idoso , Ponte de Artéria Coronária/métodos , Ponte de Artéria Coronária/mortalidade , Feminino , Indicadores Básicos de Saúde , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Prognóstico , Medição de Risco
6.
Water Sci Technol ; 47(7-8): 343-50, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12793699

RESUMO

Combined sewer systems contain a large number of organic and inorganic pollutants from both domestic and industrial sources. These pollutants are often retained within the combined sewer system for significant lengths of time before entering sewage treatment works, or being spilt to a watercourse via a combined sewer overflow (CSO) during storm conditions. Currently little knowledge exists concerning the effects of in sewer processes on pollutants. Understanding of in-sewer processes is important for the effective and efficient design of treatment works and CSO chambers and for impact assessments on receiving waters. A series of studies covering storm and dry weather flow conditions were undertaken with the aim of investigating the nature of in-sewer processes. These studies consisted of marking a body of water with a fluorescent tracer. The tracer was then monitored at a series of downstream sites, and discrete samples collected from the body of water as it progressed through the sewer. The samples were analysed for water quality parameters and these results investigated in tandem with the detailed hydraulic information gained through the tracer studies. The results highlight the hydraulic differences between storm and dry weather conditions such as increased travel times and mixing under storm conditions. The Advection Dispersion Equation (ADE) and Aggregated Dead Zone (ADZ) model parameters have been quantified for the tracer data. The ADE mixing coefficient is shown to increase by an order of magnitude for storm conditions. The ADZ dispersive fraction parameter is shown to be approximately constant with flow. Chemical reactions and decay within the sewer system were found to be consistent with oxygen limitation.


Assuntos
Monitoramento Ambiental/estatística & dados numéricos , Modelos Teóricos , Esgotos , Poluentes da Água/análise , Conceitos Meteorológicos , Oxigênio , Chuva , Valores de Referência , Movimentos da Água
7.
J Digit Imaging ; 12(2 Suppl 1): 195-6, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10342210

RESUMO

To improve radiology access to full uncompressed Digital Imaging and Communications in Medicine (DICOM) data sets, we evaluated satellite access to a DICOM server. Radiologists' home computers were connected by satellite to a Medweb DICOM server (Medweb, San Francisco, CA). A 10.2-kb data set containing a 19-image head computed tomography (CT) scan was transferred using DirecPC (Hughes Electronics Corp, Arlington, VA) at three different times of the day; 6 AM, 3 PM, and 8 PM. The average transfer time for all 19 images from the DICOM server was 4 minutes and 17 seconds (257 seconds). The slowest transfer rate of 670 seconds (121 kbps) was obtained at 8 PM. The best transfer rate of 2 minutes, 54 seconds (467 kbps) was obtained at 6 AM. The full 16-bit DICOM images were viewed with bone, brain, and soft tissue windows. The Medweb plug-in viewer loaded the first image within 30 seconds of selecting the case for satellite transfer. In conclusion, satellite internet transfer of radiology studies is suitable for timely review of full DICOM data sets and can expand the range of teleradiology consultation.


Assuntos
Redes de Comunicação de Computadores , Diagnóstico por Imagem , Sistemas de Informação em Radiologia , Comunicações Via Satélite , Encéfalo/diagnóstico por imagem , Sistemas Computacionais , Face/diagnóstico por imagem , Humanos , Internet , Crânio/diagnóstico por imagem , Telerradiologia , Fatores de Tempo , Tomografia Computadorizada por Raios X
8.
Ocul Immunol Inflamm ; 6(1): 13-8, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9798189

RESUMO

The purpose of this study was to compare the efficacy and safety of diclofenac-gentamicin (DR 1352/1) combination eye drops with gentamicin eye drops in the postoperative management of patients undergoing extracapsular cataract surgery and lens implantation. This was a prospective, randomised, double-masked, parallel-group, four-week, multicentre study with patient visits preoperatively, on the day of surgery, and postoperatively on days 1, 5-8, 12-16, and 26-32. Of the 196 patients (diclofenac-gentamicin 99, gentamicin 97) recruited into the study, 161 (diclofenac-gentamicin 83, gentamicin 78) were available for per-protocol analyses. The two treatment groups were clinically similar at baseline. On days 12-16 postoperatively, diclofenac-gentamicin was significantly more effective (p = 0.002) than gentamicin in reducing intraocular inflammation as assessed by the sum of grades of anterior chamber cells and flare. The level of conjunctival hyperaemia was significantly less in the diclofenac-gentamicin group compared with the gentamicin group on postoperative days 5-8 and 12-16. There was no significant difference between the two study groups in the global assessment of local tolerance. Possibly drug-related adverse events were slightly more in the diclofenac-gentamicin group (22,22%) compared with gentamicin (17,17%); however, all affected study patients normalised with appropriate therapy except one patient with endophthalmitis. In conclusion, diclofenac-gentamicin (DR1352/1) eye drops were more effective than gentamicin eye drops and appeared to be as safe in the control of post-cataract surgery inflammation.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Extração de Catarata , Diclofenaco/uso terapêutico , Endoftalmite/prevenção & controle , Gentamicinas/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/efeitos adversos , Diclofenaco/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Gentamicinas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Estudos Prospectivos
9.
J Exp Biol ; 200(Pt 1): 65-81, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9023994

RESUMO

The primary skeletal structure used by dolphins to generate the dorsoventral bending characteristic of cetacean swimming is the vertebral column. In the vertebral column of the saddleback dolphin Delphinus delphis, we characterize the static and dynamic mechanical properties of the intervertebral joints, describe regional variation and dorsoventral asymmetries in mechanical performance, and investigate how the mechanical properties are correlated with vertebral morphologies. Using a bending machine that applies an external load (N m) to a single intervertebral segment, we measured the resulting angular deformation (rad) of the segment in both dorsal extension and ventral flexion. Intervertebral segments from the thoracic, lumbar and caudal regions of the vertebral column were tested from five individuals. Using quasi-static bending tests, we measured the initial (low-strain) bending stiffness (N m rad-1) as a function of segment position, direction of bending (extension and flexion) and sequential cutting of intervertebral ligaments. We found that initial bending stiffness was significantly greater in the lumbar region than in adjacent thoracic and caudal regions, and all joints were stiffer in extension than is predicted (r2 = 0.554) by the length and width of the intervertebral disc and the length of the cranial vertebral body in the segment. Stiffness in flexion is predicted (r2 = 0.400) by the width of the nucleus pulposus, the length of the caudal vertebral body in the segment and the height of the transverse processes from the ventral surface of the vertebral body. We also performed dynamic bending tests on intervertebral segments from the lumbo-caudal joint and the joint between caudal vertebrae 7 and 8. Dynamic bending stiffness (N m rad-1) increases with increasing bending amplitude and is independent of bending frequency. Damping coefficient (kg m2 rad-2 s-1) decreases with increasing bending amplitude and frequency. Resilience (% energy return) increases from approximately 20% at low bending amplitudes (+/-0.6 degree) to approximately 50% at high bending amplitudes (+/-2.9 degrees). Based on these findings, the dolphin's vertebral column has the mechanical capacity to help control the body's locomotor reconfigurations, to store elastic energy and to dampen oscillations.


Assuntos
Golfinhos/fisiologia , Locomoção , Coluna Vertebral/fisiologia , Animais , Fenômenos Biomecânicos , Feminino , Articulações/fisiologia , Ligamentos/fisiologia , Masculino , Músculos/fisiologia
10.
Toxicol In Vitro ; 10(5): 643-7, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20650247

RESUMO

The expression of multiple recessive genes by aberrant mitotic lesions plays a major part in carcinogenesis. These lesions include intragenic mutations as well as chromosomal lesions. An in vitro model for studying carcinogenesis should respond to all these lesions. Mutagenesis studies that target hemizygous loci may not be useful in studying chromosomal mechanisms because lesions incorporating essential genes already missing on the inactive, homologous chromosome may be lethal to the cell. Cells heterozygous at the selectable gene may survive. Using L5178Y mouse cells, we compared the mutagenic responses at the heterozygous tk and hemizygous hprt loci to four chemicals-benzidine dihydrochloride, diglycidylresorcinol ether, nitrofen and p-benzoquinone dioxime. None of the compounds induced clear positive responses at the hprt locus. In contrast, all the compounds induced clear or marginal mutagenic responses at the tk locus. These data are consistent with the expectation that heterozygous loci can detect lesions that are refractory to hemizygous loci.

13.
Vaccine ; 9(1): 60-6, 1991 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1901187

RESUMO

Twenty five adult male volunteers were given a vaccine composed of the capsular B polysaccharide non-covalently complexed to serotype 6 outer membrane proteins (OMP) of Neisseria meningitidis. Subjects were divided into three dose groups receiving 50, 100 or 150 micrograms vaccine in aluminium hydroxide in each of three injections spaced 4 weeks apart. Systemic signs/symptoms considered clinically significant were recorded on 6% (4/70) of occasions and were succeeded by withdrawal of two volunteers from the study. Local injection site reactions, mostly mild to moderate, were reported after all vaccinations with one such reaction leading to a third volunteer withdrawing from the study. Geometric mean anti-B responses before immunization and 1 week after the third immunization (9 weeks) were 3.60 and 7.12 micrograms ml-1 in the 50 micrograms group (p less than 0.05) 2.05 and 12.19 micrograms ml-1 in the 100 micrograms group (p less than 0.001), and 3.68 and 14.20 micrograms ml-1 in the 150 micrograms group (p less than 0.001). The anti-B response was predominantly of the IgM isotype and persistence above prevaccination levels was evident for at least 12 months. Anti-type 6 OMP responses were also evidenced with geometric mean multiplicative increases over prevaccination levels at 9 weeks and 6 months of 7.8 and 4.2 for the 50 micrograms group, 11.6 and 5.6 for the 100 micrograms group and 6.8 and 3.4 for the 150 micrograms group. The bulk of this response was of the IgG isotype. Passive protection of mice was achieved with both pre- and post-vaccination (9 weeks; 100 and 150 micrograms groups) pools of sera.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Vacinas Bacterianas/imunologia , Neisseria meningitidis/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/biossíntese , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/efeitos adversos , Humanos , Imunoglobulina M/biossíntese , Masculino , Meningite Meningocócica/prevenção & controle , Pessoa de Meia-Idade , Polissacarídeos Bacterianos/imunologia
14.
Environ Mol Mutagen ; 17(2): 122-9, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-2009867

RESUMO

A new protocol for testing vapors and gases in the L5178Y mouse lymphoma assay is presented. Four chemicals, propylene, 1,2-propylene oxide, 1,3-butadiene, and vinylidene chloride, were tested for their mutagenic potential. Cultures were exposed to the chemicals, which were delivered as vapors or gases, for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 microgram/ml. Each chemical was tested at least twice. Significant responses were obtained with 1,2-propylene oxide and vinylidene chloride, but neither cytotoxicity nor mutagenicity was induced by 1,3-butadiene; propylene could not be classified as either mutagenic or non-mutagenic in the assay. Rat liver S9 mix was not a requirement for the mutagenic activity of 1,2-propylene oxide, whereas the liver preparation markedly enhanced both the cytotoxicity and mutagenicity of vinylidene chloride.


Assuntos
Testes de Mutagenicidade/métodos , Mutagênicos , Células Tumorais Cultivadas/efeitos dos fármacos , Poluentes Atmosféricos/toxicidade , Alcenos/toxicidade , Animais , Butadienos/toxicidade , Dicloroetilenos/toxicidade , Compostos de Epóxi/toxicidade , Metanossulfonato de Etila/toxicidade , Linfoma/patologia , Metanossulfonato de Metila/toxicidade , Metilcolantreno/toxicidade , Camundongos , Timidina Quinase/genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-18267636

RESUMO

The electrical and reliability characteristics of ferroelectric capacitors fabricated using sol-gel derived 50/50 lead-zirconate-titanate (PZT) thin films have been examined for ULSI DRAM (dynamic random access memory) applications. Various electrode materials, film thicknesses (200 nm to 600 nm) and capacitor areas were used. A large stored-energy density (Q(c)) of 15 muC/cm(2) (at 125 kV/cm) was measured using different methods. The results indicate that PZT thin films exhibit material properties which might satisfy the requirements of ULSI DRAMs.

16.
Cornea ; 9(3): 234-7, 1990 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1695562

RESUMO

A series of 160 consecutive penetrating keratoplasties was analysed for patterns of graft rejection. All surgery was performed between January 1981 and December 1987. The incidence of homograft rejection was 34% (54 grafts). The site of the initial rejection episode was analysed. It was found that when grafts with either preexisting vascularisation or loose sutures were removed from our analysis, the site of initial graft rejection was from the superior limbus in one case and from the inferior limbus in 17 cases. In eight others, there was diffuse corneal oedema at initial appearance. We feel that the increased incidence of graft rejection occurring inferiorly is significant and probably relates to the presence of some factor(s) present in the tears. By bathing the inferior corneal surface and, more importantly, the inferior graft-host interface, the risk of rejection occurring at this site is increased.


Assuntos
Rejeição de Enxerto , Ceratoplastia Penetrante/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Edema da Córnea/etiologia , Feminino , Rejeição de Enxerto/imunologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Fatores de Risco , Técnicas de Sutura , Lágrimas/imunologia
17.
Acta Anaesthesiol Scand ; 34(4): 282-5, 1990 May.
Artigo em Inglês | MEDLINE | ID: mdl-2343729

RESUMO

Intraocular pressure (IOP) was measured in four groups of patients receiving isoflurane or halothane in consecutively increasing or decreasing concentrations (1.0, 2.0 and 3.0 MAC in 70% nitrous oxide). IOP decreased significantly in all groups irrespective of whether the higher or the lower concentration of the volatile agent was used first. There were no further significant changes in IOP whether the concentrations were increased or decreased, suggesting no dose-relation. Maximum reductions in IOP were slightly greater in those receiving the higher concentrations of the volatile agents first (64 and 66% with isoflurane and halothane, respectively) in comparison to those receiving the lower concentrations first (54 and 46%, respectively).


Assuntos
Halotano/farmacologia , Pressão Intraocular/efeitos dos fármacos , Isoflurano/farmacologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Distribuição Aleatória
19.
Mutagenesis ; 5 Suppl: 35-44, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2184319

RESUMO

As part of the third UKEMS collaborative trial, ethylmethane sulphonate (EMS), benzo[a]pyrene (B[a]P) and benzidine (BZD) were assayed for mutagenicity using the L5178Y mouse lymphoma TK +/- forward mutation system. Exogenous metabolic activation was achieved with two different sources of rat liver S9 which were used under optimized conditions for B[a]P and BZD, the latter being tested also without S9. EMS was assayed in the absence of S9 only. Mutants were selected for trifluorothymidine (TFT) resistance after 48 and 72 h expression time. Mutant frequency (MF) data were subjected to ANOVA analysis and t-tests for differences between replicate cultures, linear trend and differences from solvent controls. Large TFT resistant colonies are believed to be due to induction of small amounts of genetic damage (point mutations, small deletions) at the tk locus, whilst small colonies are thought to be a result of larger effects. The relative proportions of the two colony types were determined in some experiments. All three compounds induced dose-related increases in MF under all conditions. B[a]P induced equal proportions of large and small colonies at all doses. EMS induced predominantly large colonies at all doses. The effect of BZD on colony size was variable. The source of S9 did not exert any consistent effect on toxicity, mutagenicity or mutant colony size. Maximum MF values occurred at 72 h for B[a]P and BZD but the results with EMS were variable. No consistent differences were apparent between estimates of toxicities made either by cloning immediately after treatment (day 0 cloning) or by estimating the relative total growth (RTG) at expression time.


Assuntos
Benzidinas/toxicidade , Benzo(a)pireno/toxicidade , Metanossulfonato de Etila/toxicidade , Testes de Mutagenicidade/métodos , Mutagênicos , Animais , Benzidinas/metabolismo , Benzo(a)pireno/metabolismo , Biotransformação , Contagem de Células , Técnicas In Vitro , Leucemia L5178 , Camundongos , Microssomos Hepáticos/metabolismo , Ratos , Ratos Endogâmicos F344 , Timidina Quinase/genética , Fatores de Tempo , Células Tumorais Cultivadas
20.
Carcinogenesis ; 10(11): 2003-8, 1989 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2478309

RESUMO

5-Azacytidine (5-aza-CR) and six of its analogs were examined for their ability to induce trifluorothymidine (TFT) and/or 6-thioguanine (6TG) resistance in L5178Y mouse lymphoma cells. These analogs were 5-aza-2'-deoxycytidine (5-aza-CdR), 5-fluoro-2'-deoxycytidine (5-FCdR), 5,6-dihydro-5-azacytidine (dH-aza-CR), 6-azacytidine (6-aza-CR), cytidine (CR) and 1-b-D-arabinofuranosylcytosine (ara-C). 5-Aza-CR and 6-aza-CR were examined for their ability to induce 6TG-resistant colonies and results demonstrated no effect. At least a 5-fold increase in TFT resistance was observed for 5-aza-CR, 5-aza-CdR, 5-FCdR, dH-aza-CR and ara-C. The concentration at which these compounds induced TFT resistance correlated well with the potential of the nucleoside analogs to induce differentiation in C3H10T1/2 cells as determined by Constantinides et al. (Nature, 267, 364-366, 1977). In L5178Y mouse lymphoma (MOLY) cells, 5-aza-CR induced TFT resistance and produced both small and large colonies. Previous studies using mammalian cells showed the absence of mutagenic activity with 5-aza-CR and some of its analogs at the ATPase and hgprt loci. However, the different spectrum of DNA lesions detected at the tk locus may be responsible for the response of MOLY cells to 5-aza-CR.


Assuntos
Azacitidina/farmacologia , Resistência a Medicamentos , Animais , Diferenciação Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hipoxantina Fosforribosiltransferase/genética , Leucemia L5178 , Camundongos , Mutação , Tioguanina , Timidina Quinase/genética , Trifluridina , Células Tumorais Cultivadas
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