RESUMO
We have determined the specificity of mutations produced by nickel(II), a known human carcinogen, in a forward mutation assay and also used a sensitive reversion assay to show that Ni(II), like iron and copper, can produce tandem double CC-->TT mutations, a hallmark of damage to DNA by either UV irradiation or oxygen free radicals. A reduction in mutation frequencies by the addition of oxygen radical scavengers also supports the involvement of reactive oxygen species in DNA damage and mutagenesis by Ni(II). Mutagenesis by Ni(II) is enhanced by the addition of both hydrogen peroxide and a tripeptide glycyl-glycyl-L-histidine. The enhancement of mutagenesis of Ni(II) by the tripeptide indicates that these complexes could serve to localize Ni(II) in nuclei and mediate DNA damage and mutagenesis via the generation of short-lived oxygen free radicals. These data suggest that Ni(II) carcinogenesis may proceed via the generation of active oxygen species and furthermore provide a model for nickel carcinogenesis based on the binding of Ni(II) to nuclear proteins.
Assuntos
Dano ao DNA , Mutação , Níquel/toxicidade , Espécies Reativas de Oxigênio/toxicidade , Sequência de Aminoácidos , Sequência de Bases , Radicais Livres , Dados de Sequência MolecularRESUMO
Therapeutic intervention for atherosclerosis has predominantly concentrated on regulating cholesterol levels; however, these therapeutics are not efficacious for all patients, suggesting that other factors are involved. This study was initiated to identify mechanisms that regulate atherosclerosis predisposition in mice other than cholesterol level regulation. To do so we performed quantitative trait locus analysis using two inbred strains that each carry the atherosclerosis phenotype-sensitizing Apoe deficiency and that have been shown to have widely disparate predilection to atherosclerotic lesion formation. One highly significant locus on chromosome 10 (LOD = 7.8) accounted for 19% of the variance in lesion area independent of cholesterol. Two additional suggestive loci were identified on chromosomes 14 (LOD = 3.2) and 19 (LOD = 3.2), each accounting for 7-8% of the lesion variance. In all, five statistically significant and suggestive loci affecting lesion size but not lipoprotein levels were identified. Many of these were recapitulated in an independent confirmatory cross. In summary, two independently performed crosses between C57BL/6 and FVB/N Apoe-deficient mice have revealed several previously unreported atherosclerosis susceptibility loci that are distinct from loci linked to lipoprotein levels.
Assuntos
Apolipoproteínas E/deficiência , Arteriosclerose/genética , Predisposição Genética para Doença , Animais , Apolipoproteínas E/genética , Colesterol/sangue , Feminino , Frequência do Gene , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Característica Quantitativa HerdávelRESUMO
Metallosis is a well-documented phenomenon in hip and knee arthroplasty from metal on metal bearing joint replacements. However, few cases of metallosis of metacarpophalangeal joint replacements have been reported. We present the case of a 49-year-old lady with rheumatoid arthritis who had previously undergone MCP joint replacements over 20 years ago. The decision was taken to revise her middle MCP joint after she developed pain and ulnar drift. At revision, the joint exhibited severe metallosis presumably arising from the grommet component of the replacement. This required considerable debridement and removal of the components and revision to a new upsized implant without grommets. It is of note that there were no external signs of metallosis with full flexion of the finger and a good roll up.
Assuntos
Artrite Reumatoide/cirurgia , Artroplastia de Substituição/métodos , Dimetilpolisiloxanos , Artropatias/etiologia , Prótese Articular/efeitos adversos , Articulação Metacarpofalângica/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Artropatias/diagnóstico , Artropatias/cirurgia , Pessoa de Meia-Idade , Falha de Prótese , ReoperaçãoRESUMO
This case report demonstrates and emphasises the unusual radiographic appearance of silver nitrate treatment in a 30-year-old patient, who subsequently underwent excision biopsy of a presumed potentially malignant lesion.
Assuntos
Dedos , Corpos Estranhos/diagnóstico por imagem , Granuloma Piogênico/diagnóstico , Nitrato de Prata/efeitos adversos , Úlcera Cutânea/tratamento farmacológico , Adulto , Feminino , Dedos/diagnóstico por imagem , Humanos , Anamnese , Ossificação Heterotópica/diagnóstico por imagem , Radiografia , Nitrato de Prata/uso terapêuticoRESUMO
Four-corner fusion is an accepted surgical treatment for established SLAC and SNAC wrist. We describe a technique of bone grafting to be used in conjunction with any of the standard fusion techniques. A step by step, illustrated approach allows the easy placement of an autograft which is in contact with all surfaces of the bones involved in the fusion.
Assuntos
Artrodese/métodos , Transplante Ósseo/métodos , Ossos do Carpo/cirurgia , Articulação do Punho/cirurgia , HumanosRESUMO
INTRODUCTION: Hip fractures are common injuries in elderly patients presenting to the trauma surgeon. Mortality following such injuries approaches 10% at one month, rising to 30% at one year. Of those who survive, most experience a decrease in mobility and independence. The authors believe that the general public are not aware of these facts and in particular do not perceive hip fractures to be injuries of serious consequence. SUBJECTS AND METHODS: This study aims to assess the perception of hip fractures amongst the general public. Subjects were recruited from a population attending a general orthopaedic clinic in a district general hospital during March 2008. All participants were asked to fill out a questionnaire relating to their perception of hip fracture epidemiology, aetiology, presentation, treatment and both physical and social outcomes. RESULTS: A total of 142 people completed a questionnaire. Of those, 27 (19%) had been filled out by either hip fracture patients or their relatives. A significant majority of subjects underestimated both the hospital length of stay and mortality figures; however, most people did know that some form of surgery would be required. CONCLUSIONS: This study underlines the need for detailed counselling of the patient and relatives following a hip fracture in order to create realistic expectations and to allow those involved to prepare for potential outcomes. Written patient information may also be useful to allow patients and relatives the opportunity to digest relevant information and to pose questions relating to what they have read.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Fraturas do Quadril/psicologia , Adolescente , Adulto , Feminino , Fraturas do Quadril/mortalidade , Fraturas do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
The blue-winged teal (Anas discors L.), an abundant waterfowl species in North America, winters primarily in Mexico, Central America, and South America. Its transcontinental migratory behavior provides the opportunity to examine contaminant acquisition across a diverse biogeographic landscape that has varied environmental regulations and wildlife laws. We determined concentrations of arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), and selenium (Se) in liver samples of blue-winged teal migrating through southern Texas during autumn 1998 (n = 47) and spring 1999 (n = 46). Concentrations for As (range 0.006 to 0.22 microg/g wet weight [ww]), Cd (range 0.007 to 8.14 microg/g ww), and Pb (range 0.012 to 1.79 microg/g ww) were at background levels for birds, whereas Cu (8.1 to 227.3 microg/g ww) and Se (0.36 to 5.07 microg/g ww) were increased in several individuals. All 24 hatch-year (HY) blue-winged teal had detectable levels of Cd, Cu, Pb, and Se, and eight had detectable levels of As. A seasonal effect was found for Cd, in which the mean Cd concentration in autumn was lower (p < 0.015) than in spring. Comparisons between autumn-collected HY and autumn-collected after-hatch-year (AHY) blue-winged teal found the mean concentration of Cd was higher (p < 0.001) in AHY birds. A seasonal effect occurred for Cu, in which the mean concentration was higher (p < 0.001) in autumn than in spring. Comparisons between seasons using only AHY blue-winged teal found that the mean concentration of Cu was higher (p < 0.001) in autumn than in spring. No sex effects (p > 0.05) were found for the five elements examined. Results indicated that blue-winged teal were acquiring all five elements; that HY blue-winged teal were exposed to these elements in North America; and that increased Se concentrations in 15% of the 93-bird sample were at levels known to cause impairment in birds.
Assuntos
Arsênio/análise , Aves/metabolismo , Cádmio/análise , Cobre/análise , Monitoramento Ambiental/métodos , Poluentes Ambientais/análise , Chumbo/análise , Selênio/análise , Fatores Etários , Animais , Emigração e Imigração , Feminino , Masculino , Estações do Ano , Caracteres SexuaisRESUMO
Oxygen free radicals are highly reactive species that damage DNA and cause mutations. We determined the mutagenic spectrum of oxygen free radicals produced by the aerobic incubation of single-stranded M13mp2 DNA with Fe2+. The Fe2(+)-treated DNA was transfected into component Escherichia coli, and mutants within the nonessential lac Z alpha gene for beta-galactosidase were identified by decreased alpha-complementation. The frequency of mutants obtained with 10 microM Fe2+ was 20- to 80-fold greater than that obtained with untreated DNA. Mutagenesis was greater after the host cells were exposed to UV irradiation to induce the SOS "error-prone" response. The ability of catalase, mannitol, and superoxide dismutase to diminish mutagenesis indicates the involvement of oxygen free radicals. The sequence data on 94 of the mutants establish that mutagenesis results primarily from an increase in single-base substitutions. Ninety-four percent of the mutants with detectable changes in nucleotide sequence were single-base substitutions, the most frequent being G----C transversions, followed by C----T transitions and G----T transversions. The clustering of mutations at distinct gene positions suggests that Fe2+/oxygen damage to DNA is nonrandom. This mutational spectrum provides evidence that a multiplicity of DNA lesions produced by oxygen free radicals in vitro are promutagenic and could be a source of spontaneous mutations.
Assuntos
Dano ao DNA , DNA Viral/efeitos dos fármacos , Proteínas de Escherichia coli , Escherichia coli/genética , Ferro/farmacologia , Mutagênese , Sequência de Bases , Colífagos/genética , DNA Viral/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos) , Desoxirribonuclease IV (Fago T4-Induzido) , Endodesoxirribonucleases/metabolismo , Radicais Livres , Teste de Complementação Genética , Células HeLa/enzimologia , Humanos , Dados de Sequência Molecular , Oxigênio , Resposta SOS em Genética , TransfecçãoRESUMO
Infusions of 50 mg of sulbactam per kg per day and 400 mg of ampicillin per kg per day in divided doses to infants and children with bacterial meningitis produced levels in cerebrospinal fluid approximately one-third those in serum. Concentrations in cerebrospinal fluid of 5.5 micrograms of sulbactam per ml and 16.0 micrograms of ampicillin per ml declined within a few days of therapy to 1.9 microgram of sulbactam per ml and 5.2 micrograms of ampicillin per ml.
Assuntos
Ampicilina/líquido cefalorraquidiano , Meningite/tratamento farmacológico , Sulbactam/líquido cefalorraquidiano , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Meningite/líquido cefalorraquidiano , PermeabilidadeRESUMO
Reactive oxygen species are generated by a variety of cellular processes. These endogenously generated, reactive intermediates produce a multiplicity of DNA alterations and mutations and have been implicated in the pathogenesis of several human diseases. We report here that treatment of single-stranded M13mp2 bacteriophage DNA with methylene blue and white light generates increased levels of 8-hydroxydeoxyguanosine and that mutagenesis is both highly specific and dependent on the SOS response. Lesions produced block the progression of DNA synthesis one base preceding template guanines. In SOS-induced Escherichia coli, 97% of all methylene blue-induced mutations in the lacZ alpha gene of M13mp2 DNA are single-base substitutions opposite template guanines. The most frequent mutations are G----C transversions. The G----T transversions expected from the presence of 8-hydroxydeoxyguanosine in the template strand occur, but at a lower frequency. Sequence data together with SOS dependency and the presence of replication blockage demonstrate that while 8-hydroxydeoxyguanosine may serve as an important marker to monitor oxygen-induced DNA damage in humans, it does not account for either the observed blockage to replication or the mutagenesis by methylene blue plus light in SOS-induced E. coli. Instead, an as yet unidentified lesion generated by active oxygen species is a more potent mutagenic event.
Assuntos
Colífagos/genética , DNA de Cadeia Simples/genética , Desoxiguanosina/análogos & derivados , Escherichia coli/genética , Luz , Azul de Metileno/farmacologia , Mutagênese , Resposta SOS em Genética , 8-Hidroxi-2'-Desoxiguanosina , Sequência de Bases , Colífagos/efeitos dos fármacos , Colífagos/efeitos da radiação , DNA Bacteriano/efeitos dos fármacos , DNA Bacteriano/genética , DNA Bacteriano/efeitos da radiação , DNA de Cadeia Simples/efeitos dos fármacos , DNA de Cadeia Simples/efeitos da radiação , Desoxiguanosina/análise , Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , Dados de Sequência Molecular , TransfecçãoRESUMO
Extracts of Heliotropium indicum Linn. (Boraginaceae) showed significant activity in several experimental tumor systems. The active principle is isolated and shown to be the N-oxide of the alkaloid, indicine, previously isolated from this plant. Supporting structural data and anti-tumor data are provided.