RESUMO
BACK GROUND: An impalement-related injury to the oral cavity is common in pediatric patients at emergency department. A computed tomography evaluation is not always suitable in these cases. Herein, we aimed to present oral sonography findings from six pediatric patients presenting with impalement-related injury to the oral cavity. CASE SERIES: All included patients were younger than 4 years and sustained injuries with a toothbrush, chopstick, water gun, and fork to the tonsils, submandibular gland area, uvula, and under the tongue. CONCLUSION: Ultrasound imaging appeared useful in helping diagnose impalement-related injuries lateral to the midline.
Assuntos
Corpos Estranhos , Ferimentos Penetrantes , Humanos , Criança , Corpos Estranhos/diagnóstico por imagem , Boca/diagnóstico por imagem , Ultrassonografia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To analyze the influence of radiologic expertise in detecting lung tumors on chest radiographs. MATERIALS AND METHODS: We retrieved posteroanterior chest radiographs and CT examination obtained from 283 patients with solitary primary malignant lung tumors who underwent surgical resection. There were 176 men and 107 women with a mean age of 67.0±9.1 (SD) years (range: 33-88 years). Thirteen first-year post-graduate (PGY-1) trainees and nine pulmonary specialists (three radiologists, three thoracic surgeons, and three pulmonologists) interpreted the chest radiographs. Detection rates among trainees and specialists were compared using Student t test. RESULTS: The total numbers of detected tumors ranged from 103 (36.4%) to 136 (48.1%) with a mean of 127.9±9.1 (45.2±3.2%) in the trainee group, and 137 (48.4%) to 182 (64.3%) with a mean of 161.6±13.1 (57.1±4.6%) in the specialist group; the intergroup difference was statistically significant (P<0.001). Significant intergroup detectability differences of >10% were noted for tumors in the peripheral zone with (i) ground glass opacity (GGO) ratio ≥10% and <70% and any size, or (ii) GGO ratio <10% and size ≤2cm; and for tumors hidden by the mediastinum, heart, or diaphragm with (i) GGO ratio ≥10% and <30% and size >3cm, or (ii) GGO ratio <10% and size >2cm. CONCLUSION: Our study demonstrates significant differences in lung tumor detectability on chest radiographs between PGY-1 trainees and pulmonary specialists according to tumor size, extent of GGO, and tumor location.
Assuntos
Competência Clínica , Neoplasias Pulmonares/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia Torácica/normas , Estudos RetrospectivosRESUMO
The FIB-4 index is a simple formula to predict liver fibrosis based on the standard biochemical values (AST, ALT and platelet count) and age. We here investigated the utility of the index for noninvasive prediction of progression in liver fibrosis. The time-course alteration in the liver fibrosis stage between paired liver biopsies and the FIB-4 index was examined in 314 patients with chronic hepatitis C. The average interval between liver biopsies was 4.9 years. The cases that showed a time-course improvement in the fibrosis stage exhibited a decrease in the FIB-4 index, and those that showed deterioration in the fibrosis stage exhibited an increase in the FIB-4 index with a significant correlation (P < 0.001). Increase in the ΔFIB-4 index per year was an independent predictive factor for the progression in liver fibrosis with an odds ratio of 3.90 (P = 0.03). The area under the receiver operating characteristic curve of the ΔFIB-4 index/year for the prediction of advancement to cirrhosis was 0.910. Using a cut-off value of the ΔFIB-4 index/year <0.4 or ≥ 0.4, the cumulative incidence of fibrosis progression to cirrhosis at 5 and 10 years was 34% and 59%, respectively in patients with the ΔFIB-4 index/year ≥0.4, whereas it was 0% and 3% in those with the ΔFIB-4 index/year <0.4 (P < 0.001). In conclusion, measurement of the time-course changes in the FIB-4 index is useful for the noninvasive and real-time estimation of the progression in liver fibrosis.
Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Hepatite C Crônica/complicações , Cirrose Hepática/etiologia , Adulto , Fatores Etários , Idoso , Biópsia , Estudos de Coortes , Demografia , Progressão da Doença , Feminino , Hepatite C Crônica/metabolismo , Hepatite C Crônica/virologia , Humanos , Incidência , Cirrose Hepática/diagnóstico , Cirrose Hepática/metabolismo , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Fatores de TempoRESUMO
BACKGROUND: Amiodarone-induced hepatotoxicity consists of mild liver test abnormalities and rare cases of acute hepatitis and chronic hepatic lesions, and histologically resembles the whole spectrum of alcoholic liver disease, i.e., non-alcoholic steatohepatitis. Amiodarone-induced neurotoxicity, including tremor, ataxia and peripheral neuropathy, is known, and some cases of parkinsonism following amiodarone use have also been reported. OBJECTIVE: To study the pathology of amiodarone-associated parkinsonism. DESIGN: Light and electromicroscopic examinations of a patient with liver cirrhosis and amiodarone-induced parkinsonism. RESULTS: On postmortem examination, the liver showed micronodular cirrhosis. Striking steatosis and frequent Mallory bodies were present on light microscopy. There were lysosomal inclusion bodies on electron microscopy. From these findings, amiodarone-induced liver cirrhosis was diagnosed. Brain atrophy and infarcts were not observed, and pigmentation in the substantia nigra was preserved. Histologically, there was a slightly lesser degree of neuronal loss with astrocytosis in the substantia nigra, locus ceruleus, and dorsal vagal nucleus. Lewy bodies were not found. In the cerebral white matter and basal ganglia, Alzheimer Type II astrocytes, which are abundant in hepatic encephalopathy, had deposition of electron-dense materials within the lysosomes and mitochondrial matrices. The materials were compatible with the accelerated amiodarone. CONCLUSIONS: This is the first case in which the accumulation of amiodarone in the brain was morphologically observed. Amiodarone accumulation in the brain may play a role in neurotoxicity inducing parkinsonism.
Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Encéfalo/patologia , Corpos de Inclusão/ultraestrutura , Cirrose Hepática/induzido quimicamente , Transtornos Parkinsonianos/induzido quimicamente , Idoso , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Masculino , Microscopia Eletrônica de Transmissão , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/fisiopatologia , Taquicardia Ventricular/tratamento farmacológicoRESUMO
This study investigated the molecular and pharmacokinetic mechanisms of the enhanced antiviral efficacy associated with pegylated interferon (PEG-IFN) alpha-2b and ribavirin. The study involved comparing the expression of serial double-stranded RNA-activated protein kinase (PKR) before and during treatment in 26 PEG-IFN alpha-2b and 26 conventional IFN alpha-2b recipients matched for age, body weight and dose of ribavirin. The pharmacokinetics of PEG-IFN alpha-2b and ribavirin was analysed in 15 of the 26 PEG-IFN recipients. There was a rapid increase in PKR expression in both treatment groups, although expression from day 2 onwards was maintained at a significantly higher level in the PEG-IFN recipients (P < 0.05). C(max) of PEG-IFN occurred 12-48 h after the initial administration, with t(1/2) and C(min) being 49 h and 190 pg/mL, respectively. In contrast to ribavirin, accumulation of PEG-IFN was minimal. There was no association between serum PEG-IFN and ribavirin levels and virological response. Although baseline expression of PKR before treatment was marginally higher in nonresponders (NRs), from day 2 onwards, sequential PKR expression in response to PEG-IFN was higher in sustained viral responders compared with the NRs (P < 0.05). Significant correlations were found between kinetics of PKR expression and viral decline rates in each phase of hepatitis C virus dynamics (first phase, r = 0.67, P = 0.0006; second phase, r = 0.67, P = 0.001). In conclusion, improvement in pharmacokinetics following pegylation led to higher intracellular PKR expression, which was associated with enhanced virological efficacy of PEG-IFN-based combination therapy. The concentrations of both ribavirin and PEG-IFN alpha-2b were not associated with viral response and PKR expression.
Assuntos
Antivirais/farmacocinética , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/farmacocinética , Ribavirina/farmacocinética , eIF-2 Quinase/metabolismo , Administração Oral , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Células Cultivadas , Quimioterapia Combinada , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/metabolismo , Hepatite C Crônica/virologia , Humanos , Injeções Intramusculares , Injeções Subcutâneas , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Proteínas Recombinantes , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Resultado do Tratamento , Carga Viral , eIF-2 Quinase/genéticaRESUMO
We tested the hypothesis that personality plays a role in cancer outcome in a population-based prospective cohort study in Japan. In July 1990, 41 442 residents of Japan completed a short form of the Eysenck Personality Questionnaire-Revised and a questionnaire on various health habits, and between January 1993 and December 1997, 890 incident cases of cancer were identified among them. These 890 cases were followed up until March 2001, and a total of 356 deaths from all causes was identified among them. Cox proportional-hazards regression was used to estimate the hazard ratio (HR) of death according to four score levels on each of four personality subscales (extraversion, neuroticism, psychoticism, and lie), with adjustment for potential confounding factors. Multivariable HRs of deaths from all causes for individuals in the highest score level on each personality subscale compared with those at the lowest level were 1.0 for extraversion (95% CI=0.8-1.4; Trend P=0.73), 1.1 for neuroticism (0.8-1.6; Trend P=0.24), 1.2 for psychoticism (0.9-1.6; Trend P=0.29), and 1.0 for lie (0.7-1.5; Trend P=0.90). The data obtained in this population-based prospective cohort study in Japan do not support the hypothesis that personality is associated with cancer survival.
Assuntos
Neoplasias/mortalidade , Neoplasias/psicologia , Personalidade , Adulto , Estudos de Coortes , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Inventário de Personalidade , Prognóstico , Análise de SobrevidaRESUMO
BACKGROUND: The glomerular epithelial cells play an important role in glomerular filtration of the kidney. The disruption of these cells contributes to the development of glomerulosclerosis. The present study was performed to elucidate whether loss of the glomerular epithelial cells is associated with renal injury in patients with IgA nephropathy. PATIENTS AND METHODS: Thirty renal biopsy specimens from IgA nephropathy, 12 from minor glomerular abnormalities and 5 from normal controls were observed. The specimens from IgA nephropathy were divided into 2 groups: Group IgA-1, including 11 patients who had received a follow-up renal biopsy because of deterioration of renal function, and Group IgA-2, consisting of the remaining 19 patients without follow-up biopsy. Immunohistochemistry was performed using a monoclonal antibody against CD10 antigen that appears on mature epithelial cells of glomeruli. RESULTS: The average number of CD10-positive glomerular epithelial cells (GECs) was significantly lower in IgA nephropathy than in either minor glomerular abnormalities or the normal controls. In IgA nephropathy, there were significant correlations of the GECs with renal functions. The GECs were reduced along with the progression of histopathological damage. In group IgA-1, the GECs were significantly reduced at the second biopsy compared with the first biopsy, and significantly fewer in group IgA-1 than in group IgA-2 at the first biopsy. The GECs showed a significant correlation with renal prognosis during the follow-up period. CONCLUSIONS: The reduction of GECs was associated with renal dysfunction, histopathological damage and renal prognosis. The GECs may be a useful predictor of renal prognosis in IgA nephropathy.
Assuntos
Glomerulonefrite por IGA/metabolismo , Glomérulos Renais/citologia , Neprilisina/metabolismo , Adulto , Contagem de Células , Feminino , Glomerulonefrite por IGA/patologia , Humanos , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Masculino , Neprilisina/análise , Prognóstico , Urotélio/citologia , Urotélio/metabolismo , Urotélio/patologiaRESUMO
Macrophage migration inhibitory factor (MIF) is a molecule known to regulate macrophage accumulation at sites of inflammation. To elucidate the role of MIF in progression of liver fibrosis, the immunohistochemical localization of MIF and macrophages in the liver were examined. Male Wistar rats received thioacetamide (TA) injections (200 mg/kg, i.p.) for 1 or 6 weeks. In biochemical and histological tests, it was confirmed that liver fibrosis was induced. In immunohistochemical analyses, the expression of MIF protein was seen in hepatocytes in the areas extending out from the central veins to the portal tracts. In particular, at 6 weeks, immunoreactivity was detected in degenerated hepatocytes adjacent to the fibrotic areas but hardly observed in the fibrotic areas. On the other hand, a number of exudate macrophages stained by antibody ED1 were seen in the areas from the central veins to the portal tracts at 1 week and in the fibrotic areas at 6 weeks. Macrophages also showed a significant increase in number as compared with controls. These results revealed that there was a close relationship between the appearance of MIF expression and ED1-positive exudate macrophages in degenerated hepatocytes during the progression of TA-induced liver fibrosis.
Assuntos
Cirrose Hepática Experimental/induzido quimicamente , Fatores Inibidores da Migração de Macrófagos/metabolismo , Tioacetamida/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Ectodisplasinas , Técnicas Imunoenzimáticas , Injeções Intraperitoneais , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Testes de Função Hepática , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Proteínas de Membrana/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Tioacetamida/administração & dosagemRESUMO
This study was performed to investigate the correlation between clinical parameters and grading of iron deposition in renal biopsy specimens from 102 patients with various kidney diseases. Iron deposition in renal tissues was detected by Berlin blue staining. The extent of iron staining was semiquantitatively graded as negative (Fe(-)), grade 0, or positive (Fe(+)), including faint, grade 1; moderate, grade 2; or severe, grade 3, by light microscopy. Thirty-four of 102 patients (33%) showed positive iron staining. Fe(+) patients had various renal diseases, mainly consisting of 12 patients with immunoglobulin A nephropathy and 5 patients with benign nephrosclerosis. Mean arterial pressure (MAP), serum creatinine (sCr) levels, incidence of hematuria, and urinary N-acetylbeta-D-glucosaminidase (u-NAG) levels in Fe(+) patients were significantly greater than those in Fe(-) patients, and u-NAG levels correlated positively with the extent of iron deposition. Study patients were tentatively divided into two groups according to the extent of iron deposition: group A, patients with grades 2 and 3 staining, and group B, patients with grades 0 and 1 staining. In group A, MAP, sCr level, urinary protein excretion, and the incidence of hematuria were significantly greater than in group B. Our results suggest that the amount of iron deposition in renal tissue may contribute to the progression of chronic renal disease and may be an early and sensitive indicator of renal damage in certain renal diseases.
Assuntos
Ferro/metabolismo , Nefropatias/patologia , Rim/patologia , Acetilglucosaminidase/urina , Adolescente , Adulto , Análise de Variância , Biópsia , Pressão Sanguínea/fisiologia , Creatinina/sangue , Feminino , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/fisiopatologia , Humanos , Rim/metabolismo , Nefropatias/metabolismo , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nefroesclerose/metabolismo , Nefroesclerose/patologia , Nefroesclerose/fisiopatologiaRESUMO
We established a straightforward murine model of oropharyngeal candidiasis. Mice were immunosuppressed with cortisone acetate, anesthetized, and then inoculated by placing cotton wool balls saturated with Candida albicans sublingually for 2 h. A prolonged, reproducible infection was induced. This model may be useful for antifungal screening or pathogenesis studies.
Assuntos
Candidíase Bucal/microbiologia , Doenças Faríngeas/microbiologia , Animais , Antibacterianos/farmacologia , Candidíase Bucal/patologia , Contagem de Células , Cortisona/farmacologia , Modelos Animais de Doenças , Esôfago/patologia , Imunossupressores/farmacologia , Masculino , Camundongos , Doenças Faríngeas/patologia , Tetraciclina/farmacologia , Língua/patologiaRESUMO
Various types of organic compounds have been detected in Jupiter, Titan, and cometary coma. It is probable that organic compounds were formed in primitive Earth and Mars atmospheres. Cosmic rays and solar UV are believed to be two major energy sources for organic formation in space. We examined energetics of organic formation in simulated planetary atmospheres. Gas mixtures including a C-source (carbon monoxide or methane) and a N-source (nitrogen or ammonia) was irradiated with the followings: High energy protons or electrons from accelerators, gamma-rays from 60Co, UV light from a deuterium lamp, and soft X-rays or UV light from an electron synchrotron. Amino acids were detected in the products of particles, gamma-rays and soft X-rays irradiation from each gas mixture examined. UV light gave, however, no amino acid precursors in the gas mixture of carbon monoxide, nitrogen and nitrogen. It gave only a trace of them in the gas mixture of carbon monoxide, ammonia and water or that of methane, nitrogen and water. Yield of amino acid precursors by photons greatly depended on their wavelength. These results suggest that nitrogen-containing organic compounds like amino acid precursors were formed chiefly with high energy particles, not UV photons, in Titan or primitive Earth/Mars atmospheres where ammonia is not available as a predominant N-source.
Assuntos
Aminoácidos/síntese química , Evolução Química , Meio Ambiente Extraterreno/química , Prótons , Alanina/síntese química , Amônia/química , Atmosfera/química , Dióxido de Carbono/química , Dióxido de Carbono/efeitos da radiação , Monóxido de Carbono/química , Monóxido de Carbono/efeitos da radiação , Planeta Terra , Evolução Planetária , Glicina/síntese química , Marte , Metano/química , Nitrogênio/química , Nitrogênio/efeitos da radiação , Fótons , Saturno , Síncrotrons , Raios Ultravioleta , Água/químicaRESUMO
2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) is an endocrine disrupter that exerts cytotoxic effects on organisms. In this study, the influence of 2,4,5-T at low concentrations on apoptosis in PC 12 cells was investigated. Although no apoptotic features were observed in PC12 cells treated with 2,4,5-T, it inhibited the DNA fragmentation induced by serum deprivation. In addition, the cell viability of PC12 cells increased after treatment with 2,4,5-T. In conclusion, 2,4,5-T suppressed the apoptosis of the cultured cells. Since apoptosis is a morphological and biochemical description of a physiological mechanism of cell death that is commonly associated with programmed events necessary for development of individuals and organs, the inhibitory effect of 2,4,5-T on apoptosis might cause serious damage to cell homeostasis and differentiation.
Assuntos
Ácido 2,4,5-Triclorofenoxiacético/farmacologia , Apoptose/efeitos dos fármacos , Células PC12/efeitos dos fármacos , Células PC12/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura Livres de Soro/farmacologia , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletroforese em Gel de Ágar , Marcação In Situ das Extremidades Cortadas , Oxidopamina/farmacologia , Células PC12/citologia , RatosRESUMO
The combined effects of city noise and luminance of the computer display were evaluated from the changes in lymphocytes and mental activities of participants. Healthy male students were tested under the following four experimental conditions: (1) a calculating task on a video display terminal (VDT) with luminance of 90 cd m(-2) without city noise; (2) a calculating task on a VDT with luminance of 20 cd m(-2) without city noise; (3) a calculating task on a VDT with luminance of 90 cd m(-2) with city noise of 70 dB(A); and (4) a calculating task on a VDT with luminance of 20 cd m(-2) with city noise of 70 dB(A). A visual reaction test (VRT) was performed, and critical flicker fusion frequency (CFF), heart rate (HR), numbers of circulating white blood cells (WBCs), lymphocyte subsets and subjective symptoms of fatigue were measured (1) before; (2) just after; and (3) 30 min after each 60 min test. Subjective symptoms of fatigue significantly increased just after experiments conducted under the two noisy conditions. VRT and CFF showed significant changes in the case of the high-luminance display with noise. WBCs and neutrophils showed significant increases in the two quiet conditions. These results suggested that high luminance with noise had the most effect on subjective fatigue and mental activities.
Assuntos
Terminais de Computador , Fadiga/etiologia , Fadiga/imunologia , Medições Luminescentes , Ruído Ocupacional/efeitos adversos , Adulto , Análise de Variância , Catecolaminas/sangue , Humanos , Contagem de Linfócitos , Masculino , Estatísticas não ParamétricasRESUMO
We present a new detection method to measure simultaneously surface potential and fluorescence intensity distributions using a combined scanning near-field optical microscope-atomic force microscope (SNOM-AFM). A surface potential image of phospholipid monolayers was obtained in non-contact mode using the SNOM-AFM with a thin-step etched optical fibre probe. For applying this technique, a phospholipid of dipalmitoylphosphatidylethanolamine labelled at the head with a nitrobenzoxadiazole group was used as a fluorescent and single component Langmuir-Blodgett film. It is well known that aggregation of the lipid molecules and their fluorescence intensities are very sensitive to its environmental conditions such as humidity and temperature. We demonstrated for the first time the near-field optical imaging and simultaneous observation of surface potentials with Maxwell stress microscopy.
Assuntos
Oxidiazóis/química , Fosfatidiletanolaminas/química , Microscopia de Força Atômica , Microscopia de Fluorescência/métodosRESUMO
Mini rats are a transgenic rat strain carrying antisense gene for rat growth hormone (GH), resulting in retarded growth and a lower blood GH level (136 +/- 42.0 ng/mL) compared with that of age-matched parental strain Wistar rats (329 +/- 337 ng/mL). Mini rats have been used by several investigators as a GH deficiency model. In this work, we gave a single oral administration of thioacetamide (TAA), a hepatotoxicant, to both Mini rats and Wistar rats to ascertain the influence of GH deficiency on liver response to chemically induced injury and subsequent regeneration. TAA administration caused liver injury in both strains, with a greater extent of injury in Mini rats. Proliferation of bile epithelial cells and so-called oval cells was prominent at Day 3 in Mini rats only, and this change correlated well with serum total bilirubin concentrations. Antibody against Ki-67 antigen revealed that cellular proliferation after TAA-induced liver injury was suppressed but prolonged in the Mini rat liver. Although hepatic stellate cells and Kupffer cells/macrophages were more abundant in the livers of TAA-treated Mini rats, the hepatic expression patterns of hepatocyte growth factor and transforming growth factor beta 1 were comparable to those of Wistar rats. Insulin-like growth factor-I gene expression was significantly reduced in the Mini rat liver. Our results imply that a lower GH level may exacerbate chemically induced liver injury, enhance infiltration/proliferation of non-parenchymal cells, suppress regeneration of hepatocytes, and induce proliferation of bile epithelial cells and oval cells when the liver is injured by TAA.
Assuntos
Hormônio do Crescimento/deficiência , Fígado/efeitos dos fármacos , Tioacetamida/toxicidade , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Hormônio do Crescimento/sangue , Fator de Crescimento de Hepatócito/genética , Imuno-Histoquímica , Fator de Crescimento Insulin-Like I/genética , Fígado/metabolismo , Fígado/patologia , Masculino , RNA Mensageiro/análise , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta/genéticaRESUMO
The Long-Evans Cinnamon (LEC) rats, due to a genetic defect, accumulate excess copper (Cu) in the liver in a manner similar to patients with Wilson's disease and spontaneously develop acute hepatitis with severe jaundice. In this study we examined the protective effect of DL-alpha-Lipoic acid (LA) against acute hepatitis in LEC rats. LA was administered to LEC rats by gavage in doses of 10, 30 and 100 mg/kg five times per week, starting at 8-weeks-old and continuing till 12-weeks-old. Although LA had little effect against the increases in serum transaminase activities, it suppressed the loss of body weight and prevented severe jaundice in a dose-dependent manner. Antioxidant system analyses in liver showed that LA treatment significantly suppressed the inactivations of catalase and glutathione peroxidase, and the induction of heme oxygenase-1, an enzyme which is inducible under oxidative stress. Furthermore, LA showed dose-dependent suppressive effect against increase in nonheme iron contents of both cytosolic and crude mitochondrial fractions in a dose-dependent manner. Although at the highest dose, LA slightly suppressed the accumulation of Cu in crude mitochondrial fraction, it had no effect on the accumulation of Cu in cytosolic fraction. While LA completely suppressed the increase in lipid peroxidation (LPO) in the microsomal fraction at the highest dose, the suppressive effect against LPO in crude mitochondrial fractions was slight. From these results, it is concluded that LA has antioxidant effects at the molecular level against the development of Cu-induced hepatitis in LEC rats. Moreover, mitochondrial oxidative damage might be involved in the development of acute hepatitis in LEC rats.
Assuntos
Antioxidantes/farmacologia , Cobre/toxicidade , Hepatite Animal/induzido quimicamente , Hepatite Animal/tratamento farmacológico , Ácido Tióctico/farmacologia , Doença Aguda , Administração Oral , Animais , Antioxidantes/administração & dosagem , Peso Corporal/efeitos dos fármacos , Cobre/metabolismo , Citosol/efeitos dos fármacos , Citosol/enzimologia , Ingestão de Alimentos/efeitos dos fármacos , Enzimas/efeitos dos fármacos , Enzimas/metabolismo , Feminino , Heme Oxigenase (Desciclizante) , Heme Oxigenase-1 , Ferro/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/fisiopatologia , Microssomos/efeitos dos fármacos , Microssomos/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Proteínas/efeitos dos fármacos , Proteínas/metabolismo , Ratos , Ratos Endogâmicos LEC , Ratos Wistar , Ácido Tióctico/administração & dosagemRESUMO
The Long-Evans Cinnamon (LEC) rats accumulate excess copper (Cu) in the liver in a manner similar to patients with Wilson's disease (WD) and spontaneously develop acute hepatitis with severe jaundice. Although hydroxyl radicals (*OH) have been proposed to be a cause of hepatitis by the accumulation of Cu, it is not clear whether or not *OH can be produced in the liver of hepatitic LEC rats in vivo and also can be involved in the onset of hepatitis. In the present study, *OH production in plasma and liver of hepatitic LEC rats was quantified by trapping *OH with salicylic acid (SA) as 2, 3-dihydroxybenzoic acid (2, 3-DHBA). The ratios of 2, 3-DHBA/SA were significantly higher in plasma and liver of hepatitic LEC rats than those of Wistar rats and LEC rats showing no signs of hepatitis. Furthermore, the ratios of 2, 3-DHBA/SA in plasma and liver of hepatitic LEC rats were almost the same as those of Wistar rats treated orally with CuSO(4) (0.5 mmol/kg) 2 h before acetylsalicylic acid (ASA) injection. We also evaluated the protective effects of D-mannitol (a *OH scavenger) treatment against acute hepatitis in LEC rats. D-mannitol (500 mg/kg) was administered intraperitoneally to 10-week-old LEC rats for 3 weeks. D-mannitol treatment suppressed the increases in serum aspartate aminotransferase activity and total bilirubin concentration. In addition, D-mannitol treatment significantly reduced hepatic mitochondrial lipid peroxidation, which is thought to be important in the pathogenesis of Cu-induced hepatotoxicity. These observations suggest that accelerated generation of *OH catalyzed by free Cu in the liver may, at least in part, play a role in the pathogenesis of acute hepatitis in LEC rats.
Assuntos
Hepatite Animal/metabolismo , Radical Hidroxila/metabolismo , Fígado/metabolismo , Doença Aguda , Animais , Cobre/metabolismo , Sulfato de Cobre/toxicidade , Feminino , Sequestradores de Radicais Livres/farmacologia , Hepatite Animal/etiologia , Hepatite Animal/prevenção & controle , Hidroxibenzoatos/sangue , Hidroxibenzoatos/metabolismo , Manitol/farmacologia , Ratos , Ratos Endogâmicos LEC , Ratos Wistar , Ácido Salicílico/sangue , Ácido Salicílico/metabolismoRESUMO
A 55-year-old Japanese woman has been treated with various kinds of anti-rheumatic drugs under a diagnosis of rheumatoid arthritis(RA) for 18 years of disease duration. She persistently had right elbow joint pain and swelling and X-ray showed bone erosion on humerus. Thus, the synovectomy was performed with typical histopathology of RA on April 1999. On the end of February 2000, she had suddenly fatigue and anasarca with profound proteinuria of nephrotic syndrome. The renal biopsy showed minimal change glomerulopathy and no cellular infiltration in interstitial tissue by light microscopy and partial fusion of foot process by electron microscopy. Renal function was sustained normally. All of anti-rheumatic drugs including D-penicillamine(D-Pc) except NSAID were stopped and she was treated with bed rest, diet therapy, diuretics and albumin infusion without steroid therapy. Edema and proteinuria gradually disappeared. Membranous and amyloid nephropathy in RA patients associated with nephrotic syndrome are found in high incidence in literature. In low incidence, MCNS is associated with NSAID or D-Pc induced nephropathy in RA. In our case, nephrotic syndrome disappeared in 6 weeks without discontinuation of NSAID and application of steroid therapy. Thus, MCNS might be co-incidentally associated with RA.
Assuntos
Artrite Reumatoide/complicações , Nefrose Lipoide/etiologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Antirreumáticos/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Penicilamina/efeitos adversosRESUMO
The effect of trichloroethylene (TCE) on long-term potentiation (LTP) was studied using both electrical and optical recording. The hippocampi from mice injected with 300 mg/kg or 1000 mg/kg TCE were sliced 24 h after administration. The field potential from the CAI was recorded. After the application of tetanus, population spikes (PS) were potentiated in all groups, but the post-per-pre ratio of PS was smaller in TCE groups than in the control. Optical recording was also carried out in 1000 mg/kg TCE-injected mice and a new analytical method using a high speed camera was employed. After the induction of tetanus, the optical signal was potentiated in both TCE and control groups. However, the post-per-pre ratio of the optical signals and response area were smaller in the TCE groups than in the control. It was suggested that the impairment of LTP is one of the mechanisms of the impairment of immediate memory after acute exposure to TCE in humans.
Assuntos
Eletroencefalografia , Hipocampo/efeitos dos fármacos , Solventes/efeitos adversos , Percepção Espacial/efeitos dos fármacos , Percepção do Tempo/efeitos dos fármacos , Tricloroetileno/efeitos adversos , Percepção Visual/efeitos dos fármacos , Animais , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Potenciação de Longa Duração , Masculino , Camundongos , Solventes/farmacocinética , Tricloroetileno/farmacocinéticaRESUMO
PURPOSE: To evaluate the ocular hypotensive effect of topical CS-088, an angiotensin AT1 receptor antagonist, and the effect of CS-088 on aqueous humor dynamics. METHODS: The effects of CS-088 on intraocular pressure (IOP) were studied in 2 models of rabbit ocular hypertension. Experimental ocular hypertension was induced in albino rabbits by injecting alpha-chymotrypsin into the anterior chamber (alpha-chymotrypsin rabbit). The effects of the single application of CS-088 were examined. Additionally, CS-088 was repeatedly administered over a period of 3 weeks to hereditary ocular hypertensive rabbits (buphthalmic rabbits, JWHR bu/bu) and the IOPs were monitored throughout the experiment. The effects of CS-088 on aqueous humor dynamics were also examined in normal rabbits. In this study, the methods of IOP recovery rate, two-level constant pressure perfusion and fluorescein-dextran perfusion were used respectively to determine the aqueous inflow, outflow facility and uveoscleral outflow (USF). RESULTS: CS-088 at 1% and 2% significantly lowered the IOP in the alpha-chymotrypsin rabbits with a maximum IOP reduction of 10.1 mmHg. The maximum effect obtained with 2% CS-088 was no greater than that with 1% CS-088. In the buphthalmic rabbits, 2% CS-088 also lowered IOP significantly. Timolol was effective in both models. In the study on aqueous humor dynamics, a slight increase in USF (17%) was seen after a topical application of CS-088 whereas changes in aqueous inflow or outflow facility were not observed. CONCLUSIONS: Topical CS-088 can decrease IOP in rabbits. Despite the USF change, the ocular hypotensive mechanism by CS-088 was not fully determined.