RESUMO
BACKGROUND: Obesity is a public health problem in Micronesia. The objective of the study was to assess obesity, the relationship between body mass index (BMI) and body fat percentage (BF%) among adults, and determine the appropriate BMI cut-points in Kiribati. METHODS: A cross-sectional study was undertaken among 483 adults randomly selected from South Tarawa (ST) and Butaritari (BT). Weight, height, BF% and physical activity level (PAL) was measured using standard methods. Linear and quadratic regression analyses were conducted to assess the association between BF% and BMI whilst controlling for age and gender. Receiver operating characteristics (ROC) curve analyses were used to assess whether for the Kiribati population alternative BMI cut-off points for obesity are needed. RESULTS: Approximately 75% of participants were obese using standard BMI and BF% cut-offs, with the highest prevalence observed in South Tarawa. BF% was significantly (p < 0.001) and positively associated with age (males, r = 0.78; females, r = 0.67; p < 0.001) and BMI. Based on ROC-curve analyses the BMI cut-offs for predicting high BF% among I-Kiribati people were 24.5 kg/m2 for males and 32.9 kg/m2 for females. CONCLUSIONS: In conclusion, the majority of adults in Kiribati were either obese or overweight and had high BF%. We suggest that ethnic-specific BMI cut-points to define obesity for the population of Kiribati may be more appropriate than the currently used international cut-points.
Assuntos
Tecido Adiposo , Índice de Massa Corporal , Exercício Físico , Obesidade/epidemiologia , Adulto , Composição Corporal , Peso Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Micronésia , Pessoa de Meia-Idade , Prevalência , Saúde Pública , Curva ROC , Valores de Referência , Análise de Regressão , Razão Cintura-EstaturaRESUMO
The histone variant, macroH2A1, has an important role in embryonic stem cell differentiation and tumor progression in various types of tumors. However, the regulatory roles of macroH2A1 on bladder cancer progression have not been fully elucidated. Here, we show that macroH2A1 knockdown promotes stem-like properties of bladder cancer cells. The knockdown of macroH2A1 in bladder cancer cells increased tumorigenicity, radioresistance, degeneration of reactive oxygen species, increased sphere formation capability and an increase in the proportion of side populations. We found that macroH2A1 is required for the suppression of Lin28B identified as a novel downstream target of macroH2A1 in bladder cancer. Loss of macroH2A1 expression significantly correlated with the elevated levels of Lin28B expression and subsequently inhibited the mature let-7 microRNA expression. Furthermore, the stable overexpression of Lin28B enhances the several phenotypes, including tumorigenicity and sphere-forming ability, which are induced by macroH2A1 depletion. Importantly, Lin28B expression was regulated by macroH2A1-mediated reciprocal binding of p300 and EZH2/SUV39H1. Our results suggest that Lin28B/let-7 pathway is tightly regulated by macroH2A1 and its cofactors, and have a pivotal role in the bladder tumor progression and the regulation of stem-like characteristics of bladder cancer cells.
Assuntos
Regulação para Baixo , Histonas/genética , Células-Tronco Neoplásicas/patologia , Proteínas de Ligação a RNA/genética , Ativação Transcricional , Neoplasias da Bexiga Urinária/patologia , Animais , Carcinogênese , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Regiões Promotoras Genéticas/genética , Tolerância a Radiação , Regulação para Cima , Neoplasias da Bexiga Urinária/genéticaRESUMO
The extension of both median and maximum lifespan and the suppression of age-related diseases in laboratory animals by reduced food intake, i.e., calorie restriction (CR) are regarded as hallmarks of CR's anti-aging action. The diverse efficacy of CR to counteract aging effects and its experimental reproducibility has made it the gold standard of many aging intervention studies of recent years. Although CR originally was used as a tool to perturb the aging process of laboratory animals as to uncover clues of underlying mechanisms of aging processes, current CR research interests have shifted to the retardation of aging-related functional decline and the prevention of age-related diseases. Advances in CR research on non-human primates and recent endeavors using human subjects offer a promising outlook for CR's beneficial effects in healthy human aging. In this review, several major issues related to CR's anti-aging mechanisms are discussed by highlighting the importance of modulating deleterious chronic inflammation at molecular levels and the impact of epigenetic chromatin and histone modifications by CR at the ultimate control sites of gene expression. The recent research on rapamycin as a CR mimetic is summarized and a brief description of intermittent feeding patterns is reviewed in comparison to the CR effect.
Assuntos
Envelhecimento/fisiologia , Restrição Calórica , Envelhecimento/efeitos dos fármacos , Animais , Epigênese Genética/fisiologia , Comportamento Alimentar/fisiologia , Humanos , Imunossupressores/farmacologia , Modelos Animais , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fatores de Transcrição/fisiologiaRESUMO
Aging is a biological process characterized by time-dependent functional declines that are influenced by changes in redox status and by oxidative stress-induced inflammatory reactions. An organism's pro-inflammatory status may underlie the aging process and age-related diseases. In this review, we explore the molecular basis of low-grade, unresolved, subclinical inflammation as a major risk factor for exacerbating the aging process and age-related diseases. We focus on the redox-sensitive transcription factors, NF-κB and FOXO, which play essential roles in the expression of pro-inflammatory mediators and anti-oxidant enzymes, respectively. Major players in molecular inflammation are discussed with respect to the age-related up-regulation of pro-inflammatory cytokines and adhesion molecules, cyclo-oxygenase-2, lipoxygenase, and inducible nitric oxide synthase. The molecular inflammation hypothesis proposed by our laboratory is briefly described to give further molecular insights into the intricate interplay among redox balance, pro-inflammatory gene activation, and chronic age-related inflammatory diseases. The final section discusses calorie restriction as an aging-retarding intervention that also exhibits extraordinarily effective anti-inflammatory activity by modulating GSH redox, NF-κB, SIRT1, PPARs, and FOXOs.
Assuntos
Envelhecimento/fisiologia , Restrição Calórica , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Estresse Oxidativo/fisiologia , Animais , Aterosclerose/metabolismo , Moléculas de Adesão Celular/metabolismo , Periodontite Crônica/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Lipoxigenase/metabolismo , Síndrome Metabólica/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoporose/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Transdução de SinaisRESUMO
The coarsening kinetics of the stepped-and-terrace groove structure formed on a vicinal Si(111) surface was investigated by in-situ synchrotron x-ray scattering. The time evolution of the groove period L at various temperatures below the (1 x 1)-to-(7 x 7) transition falls onto a universal curve when the annealing time is scaled by a scale factor. Distinctive stages of spinodal decomposition, coarsening, and saturation are identified in the evolution of the groove period. L increases following a power law, L approximately t;{n} with n = 1/6 and 0.29 in the initial stage and the late stage of coarsening, respectively. The initial coarsening proceeds via collective motion of step bunches while the late stage is dominated by the diffusion of individual steps.
RESUMO
OBJECTIVE: To compare the effect of short-term calorie restriction (CR) on aging with that of already known long-term CR, the anti-inflammatory efficacy of 10-day CR was explored in aged rat kidney. TREATMENT: Two different age groups, 6 months (young) and 24 months (old) were used. In the old group, one sub-group was control, fed ad libitum (AL) and the other was fed CR for 10 days with 40 % of the food intake of the AL subgroup (n = 5). METHODS: Reactive species (RS), lipid peroxides and COX-2 activity were measured. The activities of proinflammatory transcription factors NF-kB and AP-1 were measured by electro-mobility shift assay (EMSA). Upstream signaling cascades of NF-kB and AP-1 as well as proinflammatory gene expression were detected by Western blot. RESULTS: 10-day CR suppressed RS, lipid peroxides, and COX-2 activity in aged rat kidney. CR also inhibited upstream signaling cascades and DNA binding activity of NF-kB and AP-1, and thioredoxin/Ref-1 pathway. CR blocked expression of NF-kB-and AP-1-responsive gene COX-2, iNOS, VCAM-1 and ICAM-1. CONCLUSIONS: We report for the first time that 10-day CR can attenuate the altered signaling transduction for inflammatory processes which is mediated through RS-induced NF-kB and AP-1 in aged kidney.
Assuntos
Envelhecimento/fisiologia , Restrição Calórica , Inflamação/imunologia , Rim/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Fator de Transcrição AP-1/metabolismo , Animais , Dieta , Peroxidação de Lipídeos , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oxirredução , Estresse Oxidativo , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Ratos Endogâmicos F344 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologiaRESUMO
Horticultural soils can contain elevated concentrations of selected trace elements and organochlorine pesticides as a result of long-term use of agrichemicals and soil amendments. A glasshouse study was undertaken to assess the uptake of weathered SigmaDDT {sum of the p, p'- and o, p-isomers of DDT [1,1,1-trichloro-2,2- bis( p-chlorophenyl)ethane], DDE [1,1-dichloro-2,2- bis( p-chlorophenyl)ethylene] and DDD[1,1-dichloro-2,2- bis( p-chlorophenyl)ethane]}, arsenic (As), cadmium (Cd), copper (Cu), and lead (Pb) residues by lettuce ( Lactuca sativa) and radish ( Raphanus sativus) from field-aged New Zealand horticultural soils. Concentrations of SigmaDDT, DDT, DDE, Cd, Cu, and Pb in lettuce increased with increasing soil concentrations. In radish, similar relationships were observed for SigmaDDT, DDE, and Cu. The bioaccumulation factors were less than 1 with the exception of Cd and decreased with increasing soil concentrations. Lettuce Cd concentrations for plants grown on four out of 10 assayed soils were equivalent to or exceeded the New Zealand food standard for leafy vegetables of 0.1 mg kg (-1) fresh weight. Concentrations of As, Pb, and SigmaDDT did not exceed available food standards. Overall, these results demonstrate that aged residues of SigmaDDT, As, Cd, Cu, and Pb in horticultural soils have remained phytoavailable. To be protective of human health, site-specific risk assessments and soil guideline derivations for residential settings with vegetable gardens need to consider the produce consumption pathway.
Assuntos
DDT/metabolismo , Lactuca/metabolismo , Resíduos de Praguicidas/metabolismo , Raphanus/metabolismo , Poluentes do Solo/metabolismo , Oligoelementos/metabolismo , Arsênio/metabolismo , Cádmio/metabolismo , Cobre/metabolismo , Diclorodifenil Dicloroetileno/metabolismo , Diclorodifenildicloroetano/metabolismo , Chumbo/metabolismo , Lactuca/química , Raphanus/química , Oligoelementos/análiseRESUMO
Panax ginseng is widely used as herbal medicine in East Asia and the pharmacological effects of P. ginseng against certain chronic diseases might be explained by its antioxidative effects. Here, we show that ginsenoside Rd significantly increases both cellular glutathione (GSH) contents and the protein level of gamma-glutamylcysteine ligase (gamma-GCL) heavy chain in H4IIE cells (a rat hepatocyte cell line). Subcellular fractionation and Western blot analysis revealed that ginsenoside Rd increased the nuclear level of p65, but not of Nrf2. Moreover, ginsenoside Rd increased luciferase reporter gene activity in cells transfected with nuclear factor-kappaB (NF-kappaB) binding site-containing -1088 bp gamma-GCL promoter. However, ginsenoside Rd-inducible reporter activity was abolished when cells were transfected with NF-kappaB deletion mutant. These effectsof ginsenoside Rd are suggested to underlie the putative anti-oxidative effect of Panax ginseng.
Assuntos
Antioxidantes/farmacologia , Ginsenosídeos/farmacologia , Glutamato-Cisteína Ligase/biossíntese , Glutationa/metabolismo , NF-kappa B/fisiologia , Animais , Western Blotting , Linhagem Celular , Indução Enzimática , Genes Reporter/efeitos dos fármacos , Glutamato-Cisteína Ligase/genética , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fator 2 Relacionado a NF-E2/biossíntese , Fator 2 Relacionado a NF-E2/genética , Ratos , Fator de Transcrição RelA/biossíntese , Fator de Transcrição RelA/genéticaRESUMO
The long-term routine use of agrichemicals can result in elevated levels of trace elements and persistent organic pollutants in soils. Trace element concentrations and SigmaDDT levels were measured in soil (0-7.5 cm) samples collected from horticultural and grazing properties in 3 regions of New Zealand (Auckland, Tasman and Waikato). Elevated levels of arsenic (<2 to 58 mg kg(-1)), cadmium (<0.1 to 1.5 mg kg(-1)), copper (5 to 523 mg kg(-1)), lead (5 to 243 mg kg(-1)) and SigmaDDT (<0.03 to 34.5 mg kg(-1)) were detected in soils from all 3 regions. With the exception of cadmium and zinc, significantly higher levels of contaminants were generally detected in horticultural soils than in grazing soils. Our results have implications for the on-going use of agrichemicals as concentrations of cadmium, copper, tin and zinc in some samples exceeded ecotoxicity based soil criteria. The p,p'-DDE:DDT ratios indicate that the degradation of DDT in NZ horticultural soils may be inhibited by the co-contamination with trace elements.
Assuntos
Arsênio/análise , DDT/análise , Metais Pesados/análise , Resíduos de Praguicidas/análise , Poluentes do Solo/análise , Agricultura , Monitoramento Ambiental , Nova Zelândia , Praguicidas/análise , NicotianaRESUMO
We investigate the kinetic roughening of Ar+ ion-sputtered Pd(001) surface both experimentally and theoretically. In situ real-time x-ray reflectivity and in situ scanning tunneling microscopy show that nanoscale adatom islands form and grow with increasing sputter time t. Surface roughness W(t) and lateral correlation length xi(t) follow the scaling laws W(t) approximately t(beta) and xi(t) approximately t(1/z) with the exponents beta approximately 0.20 and 1/z approximately 0.20, for an ion beam energy epsilon=0.5 keV, which is inconsistent with the prediction of the Kuramoto-Sivashinsky (KS) model. We thereby extend the KS model by applying the coarse-grained continuum approach of the Sigmund theory to the order of O(inverted Delta(4),h(2)), where h is the surface height, and derive a new term of the form inverted Delta(2)(inverted Delta h)(2) which plays a decisive role in describing the observed morphological evolution of the sputtered surface.
RESUMO
In the statistical interpretation of forensic glass evidence it is standard practice to make the assumption of homogeneity of the refractive index (RI) of the source glass, or of localized homogeneity. However, the work of Locke and Hayes showed that, for toughened windscreen glass, this assumption might not be true. This work is well cited, but there appears to have been little follow-on published research. Furthermore, the toughening process is something known to affect the refractive index, and is a process that float glass does not undergo. Float glass is a major component of casework in New Zealand and for that reason it would be interesting to know whether the findings of Locke and Hayes apply when dealing with float glass. In this paper we describe an experiment similar to that of Locke and Hayes, systematically examining the variation of RI in a pane of float window glass. It was found that, although there were no systematic differences in refractive index, there were observable differences across the pane.
RESUMO
Orchards (n=13) were sampled as part of a larger survey investigating agrichemical residues (pesticides and trace elements) in cropping soils in the Auckland region, New Zealand. SigmaDDT concentrations in orchard soils ranged from <0.03 to 24.41 mg kg(-1). DDT (o,p'- and p,p'-) comprised at least 40% of the SigmaDDT residues in 67% of orchards in which DDT residues were detected. There was a highly significant negative correlation (-0.924, P<0.001) between copper concentration (21-490 mg kg-1) and the ratio of DDE:DDT (0.4-5.2) in pip and stonefruit orchard soils. In further investigations involving five pip and stone fruit orchard sites and one grazing paddock it was found that soil respiration and the ratio of soil microbial carbon to soil carbon (%Cmic/Org-C) in orchard soils decreased with increasing copper concentration. These findings are consistent with the conclusion that elevated soil copper concentrations in pip and stone fruit orchard soils in the Auckland region may have reduced the ability of the indigenous soil microbial community to degrade DDT to DDE
Assuntos
Cobre/metabolismo , DDT/metabolismo , Diclorodifenil Dicloroetileno/metabolismo , Inseticidas/metabolismo , Solo/análise , Agricultura , Biodegradação Ambiental/efeitos dos fármacos , Frutas , Resíduos de Praguicidas/metabolismo , Microbiologia do Solo , Poluentes do Solo/análise , Poluentes do Solo/metabolismoRESUMO
We find that foreign adsorbates acting as local impurities can induce a metal-insulator transition by pinning a charge-density wave (CDW) on the quasi-1D metallic In/Si(111)-(4x1) chain system. Our scanning tunneling microscopy image clearly reveals the presence of a new local 4x2 structure nucleated by Na adatoms at room temperature, which turns out to be insulating with a doubled periodicity along the chains. We directly determine a CDW gap energy Delta = 105+/-8 meV by identifying a characteristic loss peak in our high-resolution electron-energy-loss spectra. We thus report the first observation of a local impurity-derived Peierls-like reconstruction of a quasi-1D system.
RESUMO
Along with five known triterpene glycosides, a new triterpene glucosyl ester, named crataegioside, was isolated from the roots of Rubus crataegifolius Bunge. The structure was established as ilexosapogenin A 28-O-beta-D-glucopyranosyl ester by chemical and spectroscopic methods.
Assuntos
Plantas Medicinais/química , Rosaceae/química , Saponinas/síntese química , Saponinas/isolamento & purificação , Triterpenos , Remoção de Radical Alquila , Hidrólise , Coreia (Geográfico) , Espectroscopia de Ressonância Magnética , Raízes de Plantas/química , Espectrofotometria InfravermelhoRESUMO
The utilization of the lanthanide shift reagent tris (6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato) europium (III) [Eu(fod)3] as a simple one-step reagent for the luminescent visualization of latent fingerprints has been investigated. UV excitation of Eu(fod)3-treated prints, achieved by using a hand-held UV lamp or a Polilight, results in an orange emission at 614 nm. Time-resolved imaging is not required for visualization. Visualization of latent fingerprints on paper under the conditions used, although good, was found to be inferior to that obtained by standard DFO (1,8-diazafluoren-9-one) treatment, whereas visualization of prints obtained on aluminum drink cans and galvanized iron proved superior to that obtained by Superglue/panacryl treatment. Eu(fod)3 treatment can also be used first without compromising subsequent ninhydrin or DFO treatment, making it a 'nothing-to-lose" reagent.
Assuntos
Dermatoglifia/classificação , Medicina Legal/métodos , Indicadores e Reagentes/química , Compostos Organometálicos/química , Alumínio , Humanos , Medições Luminescentes , PapelRESUMO
PURPOSE: To study whether the synthetic ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) derivatives, which we have synthesized and have reported their apoptosis-inducing effect, have the effect on the proliferation of retinal pigment epithelial cells. METHODS: UDCA, CDCA, and their synthetic derivatives were administered in culture to the human retinal pigment cell line, ARPE-19. The effect on cell viability and growth was assessed by trypan blue dye exclusion. In order to evaluate the type of cell death, mitochondrial membrane potential assay, DNA electrophoresis, TUNEL assay, nuclear staining and Western blotting for caspase-3 and poly(ADP-ribose) polymerase (PARP) activities were conducted. RESULTS: Unlike UDCA and CDCA, which did not exhibit a significant effect on viability, their synthetic derivatives decreased the viability of ARPE-19 cells in a concentration-dependent manner. The cells treated with the synthetic derivatives did not demonstrate the characteristic findings of apoptosis, such as DNA ladder, DNA fragmentation, nuclear condensation or fragmentation, and caspase-3 and PARP activation. The reduction of mitochondrial membrane potential was shown. In electron microscopical study nuclear condensation was not shown. CONCLUSIONS: The synthetic UDCA and CDCA derivatives induced nonapoptotic death of ARPE-19 cells.
Assuntos
Morte Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Ácido Quenodesoxicólico/farmacologia , Epitélio Pigmentado Ocular/patologia , Ácido Ursodesoxicólico/farmacologia , Western Blotting , Caspase 3 , Caspases/metabolismo , Células Cultivadas , Ácido Quenodesoxicólico/análogos & derivados , DNA/análise , Fragmentação do DNA , Relação Dose-Resposta a Droga , Humanos , Marcação In Situ das Extremidades Cortadas , Potenciais da Membrana/fisiologia , Mitocôndrias/efeitos dos fármacos , Epitélio Pigmentado Ocular/efeitos dos fármacos , Epitélio Pigmentado Ocular/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Azul Tripano/metabolismo , Ácido Ursodesoxicólico/análogos & derivadosRESUMO
Several studies have demonstrated that inhibitors of cyclooxygenase (COX) attenuate various neuronal injuries and age-dependent demented conditions. From these findings, we proposed to test the effect of age on COX activity and its possible suppression by the antiaging action of dietary restriction in the rat brain. The status of reactive oxygen species (ROS) was also assessed to correlate with COX activity to delineate the underlying mechanism of the altered COX activity during aging. These results showed that COX activity significantly increased in 24-month-old rats compared with 6-month-old rats in an ad libitum group. Interestingly, mRNA and protein levels of COX-2 showed little corresponding age-related change. The formation of ROS was found to increase gradually with age in ad libitum fed rats. However, dietary restriction suppressed the increase at the age of 24 months. To substantiate the relationship between ROS and COX activity when the rats were 24 months of age, we conducted in vitro experiments with a C6 glioma cell line. Together, it is concluded that increased COX activity with age is due to the activation of COX catalytic reaction by ROS without increased gene expression of COX-2 and that it is related to the increased pro-oxidant status in aged rats.
Assuntos
Envelhecimento/fisiologia , Dieta , Dinoprostona/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Telencéfalo/enzimologia , Fatores Etários , Animais , Sequência de Bases , Western Blotting , Técnicas de Cultura , Masculino , Modelos Animais , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Ratos , Ratos Wistar , Sensibilidade e EspecificidadeRESUMO
Exposure to nitrosamines may be the occupational risk factor for liver cirrhosis. 2-(Allylthio)pyrazine, a chemopreventive agent, inhibits CYP2E1 and induces phase II enzymes. We examined the effects of 2-(allylthio)pyrazine on hepatic fibrosis, a prepathologic state of cirrhosis, and on the expression of transforming growth factor-beta1 induced by dimethylnitrosamine. Treatment of rats with dimethylnitrosamine for 4 weeks increased plasma alanine/aspartate amino-transferase and y-glutamyl transpeptidase activities, and bilirubin content, whereas the total plasma protein and albumin levels were decreased. 2-(Allylthio)pyrazine inhibited dimethylnitrosamine-induced increases in the enzyme activities and bilirubin, and restored the plasma protein and albumin contents. Masson's trichrome staining showed that dimethylnitrosamine induced liver fibrosis, the extent of which was reduced by 2-(allylthio)pyrazine treatments. Reverse transcription-polymerase chain reaction analysis revealed that 2-(allylthio)pyrazine inhibited production of transforming growth factor-beta1 mRNA by dimethylnitrosamine. These results demonstrated that 2-(allylthio)pyrazine might inhibit dimethylnitrosamine-induced liver fibrosis due to suppression of CYP2E1 expression and transforming growth factor-beta1 production.
Assuntos
Dimetilnitrosamina/antagonistas & inibidores , Inibidores Enzimáticos/uso terapêutico , Cirrose Hepática/prevenção & controle , Pirazinas/uso terapêutico , Fator de Crescimento Transformador beta/efeitos dos fármacos , Animais , Dimetilnitrosamina/toxicidade , Fígado/efeitos dos fármacos , Fígado/enzimologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transaminases/sangue , Fator de Crescimento Transformador beta1RESUMO
A rapid method for determining paracetamol (acetaminophen) in whole blood and liver tissue samples is described. Blank plus single-point calibration gives reliable quantitation at therapeutic and higher concentrations. Whole blood and liver tissue samples containing a deuterated internal standard were extracted using Bond Elut Certify columns. Butyl derivatives were formed using n-iodobutane and tetramethyl ammonium hydroxide under mild conditions and were extracted into ethyl acetate as a cleanup step. Recovery was better than 90%, and sample preparation time was less than 2 h. Gas chromatograph run time was less than 20 min. SIM of two ion pairs formed by electron impact ionization resulted in intraday coefficients of variation (CV) less than 3.03% (7.48% in liver) and interday CVs less than 8.93% (for midtherapeutic concentrations in whole blood). Linearity was observed from subtherapeutic to high, fatal levels. This method has been applied to forensic cases and has significantly reduced analytical time while improving casework quality. Results of a case study involving paracetamol are given.
Assuntos
Acetaminofen/análise , Analgésicos não Narcóticos/análise , Acetaminofen/sangue , Analgésicos não Narcóticos/sangue , Calibragem , Deutério , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Fígado/química , Padrões de Referência , Reprodutibilidade dos TestesRESUMO
An investigation was conducted to assess the chemopreventive effects of 2-(allylthio)pyrazine (2-AP), synthesized for potential use as a chemopreventive agent, after administration during the pre-initiation and post-initiation stages in a rat colon carcinogenesis model with azoxymethane (AOM). One hundred, 5-week-old, male F344 rats were randomly divided into two experiments (n = 50 each). Experiment 1 rats were randomly divided into three groups: Group 1 rats were pre-treated with 2-AP (25 or 50 mg/kg body weight, 3 consecutive days through the route of intragastric intubations) before AOM (20 mg/kg body weight, single subcutaneous (s.c.) injection) initiation. Group 2 rats were treated with AOM alone. Group 3 rats were given 2-AP alone without AOM initiation. The animals were killed at the end of each experiment (week 5) and the aberrant crypt foci (ACF) of the colonic mucosa were assessed after staining with methylene blue. Experiment 2 rats were randomly divided into three groups: Group 1 rats were given 2-AP (10, 25 or 50 mg/kg body weight, five-times intragastric intubations per week for 5 weeks from week 3) after AOM (15 mg/kg body weight, three s.c. injections) initiation for 2 weeks. Group 2 rats were treated with AOM alone. Group 3 rats were given 2-AP alone without AOM initiation. The animals were killed at the end of the experiment (week 8) and the ACF of the colonic mucosa were quantified. Total numbers of ACF/colon in Group 1 rats (pre-treated with 2-AP) tended to decrease (2-AP, 50 mg/kg body weight) or increase (2-AP, 100 mg/kg body weight) depending on the dose level. Total numbers of ACF/colon in Group 1 rats (treated with AOM followed by 2-AP, all subgroups; 160.8 +/- 38.0; 161.8 +/- 38.1; 137.1 +/- 48.4) were decreased significantly compared with the values in Group 2 rats (AOM alone; 214.8 +/- 48.1) (P < 0.05 or 0.01). The highest dose group (2-AP, 50 mg/kg body weight) had the lowest levels of total numbers of ACF/colon among the three subgroups. Total numbers of aberrant crypts (AC)/colon of the highest dose group (340.1+/- 117.9) decreased significantly compared with the value for Group 2 rats (AOM alone; 545.1 +/- 38.3). These results thus suggest that 2-AP may have potential as a chemopreventive agent against rat colon carcinogenesis after administration of AOM during the post-initiation stage.