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1.
Heliyon ; 5(5): e01664, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31193100

RESUMO

Short-term wind speed forecasting for Colonia Eulacio, Soriano Department, Uruguay, is performed by applying an artificial neural network (ANN) technique to the hourly time series representative of the site. To train the ANN and validate the technique, data for one year are collected by one tower, with anemometers installed at heights of 101.8, 81.8, 25.7, and 10.0 m. Different ANN configurations are applied for each site and height; then, a quantitative analysis is conducted, and the statistical results are evaluated to select the configuration that best predicts the real data. This method has lower computational costs than other techniques, such as numerical modelling. For integrating wind power into existing grid systems, accurate short-term wind speed forecasting is fundamental. Therefore, the proposed short-term wind speed forecasting method is an important scientific contribution for reliable large-scale wind power forecasting and integration in Uruguay. The results of the short-term wind speed forecasting showed good accuracy at all the anemometer heights tested, suggesting that the method is a powerful tool that can help the Administración Nacional de Usinas y Transmissiones Eléctricas manage the national energy supply.

2.
Indian J Med Microbiol ; 33 Suppl: 97-101, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25657165

RESUMO

BACKGROUND: The incidence of Candida tropicalis less susceptible to fluconazole (FLC) has been reported in many parts of the world. OBJECTIVES: The aim of this study was to examine the changes of putative virulence attributes of Candida tropicalis accompanying the development of resistance to FLC in vitro and in vivo. MATERIALS AND METHODS: A FLC-resistant strain (FLC-R) was obtained after sequential exposure of a clinical isolate FLC-sensitive (FLC-S) to increasing concentrations of the antifungal. The course of infection by both strains was analyzed in BALB/c mice. Analyses of gene expression were performed by real-time polymerase chain reaction PCR. The cell surface hydrophobicity, adhesion and biofilm formation were also determined. RESULTS: Development of resistance to FLC could be observed after 15 days of subculture in azole-containing medium. Overexpression of MDR1 and ERG11 genes were observed in FLC-R, and this strain exhibited enhanced virulence in mice, as assessed by the mortality rate. All mice challenged with the FLC-R died and FLC-treatment caused earlier death in mice infected with this strain. All animals challenged with FLC-S survived the experiment, regardless of FLC-treatment. Overall, FLC-R derivatives strains were significantly more hydrophobic than FLC-S strains and showed greater adherence and higher capacity to form biofilm on polystyrene surface. CONCLUSIONS: The expression of virulence factors was higher in FLC-R-C. tropicalis and it was enhanced after FLC-exposure. These data alert us to the importance of identifying microorganisms that show resistance to the antifungals to establish an appropriate management of candidiasis therapy.


Assuntos
Antifúngicos/farmacologia , Biofilmes , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/fisiologia , Candidíase/microbiologia , Farmacorresistência Fúngica , Fluconazol/farmacologia , Animais , Candidíase/tratamento farmacológico , Candidíase/mortalidade , Membrana Celular/química , Interações Hidrofóbicas e Hidrofílicas , Masculino , Camundongos , Virulência
3.
Artigo em Inglês | MEDLINE | ID: mdl-23983800

RESUMO

In this study, the antimalarial and toxicity potentials of husk fibre extracts of five Nigerian varieties of Cocos nucifera were evaluated in vitro. The only active extract fraction, West African Tall (WAT) ethyl acetate extract fraction, was then evaluated for its phytochemical constituents, antimalarial and toxicity potentials at varying doses (31.25-500 mg/kg body weight) using various organ function indices. The results revealed that WAT ethyl acetate extract fraction (WATEAEF) contained alkaloids, tannins, and flavonoids and was active against Plasmodium falciparum W2 strain maintained in continuous culture, with a selectivity index of 30.3. The same extract fraction was active in vivo against Plasmodium berghei NK65, causing more than 50% reduction in parasitaemia on days 4 and 6 after inoculation at various doses administered. WATEAEF did not significantly alter (P > 0.05) function indices of the liver and cardiovascular system at all doses administered but significantly increased (P < 0.05) plasma creatinine concentration at 250 and 500 mg/Kg body weight compared to controls. The results of this study suggest that WATEAEF possesses antimalarial activity and may not adversely affect normal liver function nor predispose subjects to cardiovascular diseases but may impair normal kidney function at higher doses. Further studies are underway to isolate the active principles.

4.
Rev. SOBECC ; 7(4): 25-30, out.-dez. 2002. tab, graf
Artigo em Português | LILACS, BDENF - Enfermagem | ID: lil-339970

RESUMO

O presente trabalho teve comoobjetivo identificar o conhecimento geral que permeia os traços de liderança desenvolvidos nos currículos de graduação em Enfermagem. Uma breve revisão bibliográfica possibilitou uma reflexão a respeito de como essa característica vem sendoarticulada nas reformas curriculares. Considerando a qualidade da assitência deEnfermagem e a satisfação do trabalho em equipe como o ápice da liderança, os órgãos formadores precisam explicitar e operacionalizar conteúdos e estratégias de ensino-aprendizagem que permitam experiências concretas nos acadêmicos.


Assuntos
Humanos , Enfermagem , Currículo , Liderança
5.
Alcohol Clin Exp Res ; 25(6): 935-43, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11410731

RESUMO

BACKGROUND: The mechanisms of liver sensitization by alcohol to Gram-negative bacterial lipopolysaccharide (LPS) remain elusive. The purpose of this study was two-fold: (1) to test the hypothesis that alcohol-enhanced liver apoptosis may be a sensitizing mechanism for LPS and (2) to further characterize the liver apoptotic response to alcohol. METHODS: Rats were fed a high-fat, alcohol-containing liquid diet for 14 weeks, treated with LPS (1.0 mg/kg of body weight, intravenously) or saline, followed by injection of a pan-caspase inhibitor IDN1965; N-[(1,3-dimethylindole-2-carbonyl)-valinyl]-3-amino-4-oxo-5-fluoropentanoic acid; 10 mg/kg of body weight, intraperitoneally or vehicle, and killed. The following parameters were assessed: plasma aspartate: 2-oxoglutarate aminotransferase activity (AST); liver histology and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) response; caspase-3, -8, and -9 activity; and mRNA and protein expression for two apoptosis-signaling molecules: Fas receptor and Fas ligand; and three apoptosis adaptors: Bax, Bcl-XL, and Bcl-2. RESULTS: Alcohol-feeding-induced liver steatosis, slightly increased caspases' activity, the number of TUNEL-positive nuclei, and facilitated the LPS necrotic effect without affecting mRNA expression of apoptosis signals and adaptors. LPS induced a significant increase in AST and the number of TUNEL-positive nuclei, both effects being more pronounced in alcohol-treated rats. LPS produced hepatic necrosis only in alcohol-treated rats. LPS effects were associated with up-regulation of mRNA expression for both apoptosis adaptors and signaling molecules. IDN1965 administration 3 hr after LPS injection strongly inhibited caspases' activity, particularly that of caspase-3. IDN1965 also abolished the increase in TUNEL-positive nuclei, reversed the effect of LPS on plasma AST in alcohol-treated rats, and prevented LPS-induced necrosis. CONCLUSIONS: (1) Alcohol-enhanced liver apoptosis may not involve regulatory steps at the transcriptional level. LPS-induced liver apoptosis seems to involve transcriptional regulation of several apoptosis adaptors. Therefore, alcohol and LPS may enhance liver apoptosis through different mechanisms. (2) Alcohol-enhanced liver apoptosis precedes and may facilitate the hepatic effects of LPS. LPS superimposed on alcohol further elevates the rate of apoptosis in the liver. This may exceed the phagocytosing capacity of the liver so that all the apoptotic cells are not phagocytosed, but rather die of necrosis.


Assuntos
Apoptose/efeitos dos fármacos , Inibidores de Caspase , Inibidores Enzimáticos/farmacologia , Etanol/efeitos adversos , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Animais , Aspartato Aminotransferases/sangue , Caspase 3 , Caspase 8 , Caspase 9 , Caspases/metabolismo , Etanol/administração & dosagem , Proteína Ligante Fas , Fígado Gorduroso/induzido quimicamente , Marcação In Situ das Extremidades Cortadas , Indóis/farmacologia , Fígado/patologia , Hepatopatias Alcoólicas/patologia , Masculino , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/genética , Necrose , Oligopeptídeos/farmacologia , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Receptor fas/análise , Receptor fas/genética
6.
Hepatol Res ; 19(3): 306-324, 2001 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-11251313

RESUMO

Background/aims: The liver apoptotic response to chronic alcohol consumption remains poorly characterized. The purpose of this study was to determine in rats the effects of chronic alcohol consumption on the relative magnitude of apoptosis in two major targets of alcohol-induced liver injury: the hepatocyte (Hep) and sinusoidal endothelial cell (SEC). Methods: Rats were fed a liquid diet containing either alcohol or isocaloric amounts of maltose-dextrin for 14 weeks. Hep and SEC were isolated by liver perfusion with collagenase followed by centrifugal elutriation. The state of the liver was assessed on the basis of light microscopic appearance, plasma liver enzymes (alanine and aspartate:2-oxoglutarate amino transferases), and the content of malondialdehyde in Hep. Apoptosis was assessed on the basis of DNA fragmentation in the whole organ (TUNEL), and caspase-3 and -8 activity in isolated cells. A mechanistic approach was also undertaken by measuring mRNA expression and the amount of protein for Fas/CD95, Fas ligand, caspase-3, Bax, Bcl-X(L), and Bcl-2 in the isolated Hep and SEC. Results: The livers of alcohol-fed rats displayed prominent steatosis. Oxidative stress was also present as reflected by an increase in the malondialdehyde content of Hep. Alcohol consumption increased apoptosis in the whole liver assessed on the basis of TUNEL procedure and in Hep and SEC as reflected by significant increase in caspase-3 activity. Of the multiple pro- and anti-apoptotic factors determined in this study, significant changes as assessed by both mRNA expression and the amount of proteins, were observed only in the SEC compartment. Conclusions: The data presented in this study indicate that: (1) chronic alcohol consumption in rats leads to a moderate augmentation of apoptosis in the whole liver and in two liver cell types which are targets for injury in alcoholic liver disease: Hep and SEC; (2) the mechanisms recruited/activated by these two types of liver cells to initiate and execute apoptosis in response to alcohol vary with the cell type.

7.
J Hepatol ; 30(2): 213-21, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10068098

RESUMO

BACKGROUND/AIMS: Functional and morphological alterations of the hepatic sinusoidal endothelial cell occur in several models of experimental liver injury and in clinical settings. The causes of these alterations are multiple. The aim of this study was to test the hypothesis that the early functional impairment and morphological alterations of the sinusoidal endothelial cell and hepatic sinusoid associated with liver injury are mediated by free radical species, such as superoxide anion and nitric oxide. METHODS: Isolated rat livers were perfused by recirculation with hemoglobin-free, Krebs-Henseleit bicarbonate buffer and presented with a source of superoxide anion (xanthine oxidase+hypoxanthine) or nitric oxide (S-nitroso-N-acetyl penicillamine). Hyaluronan uptake (an index of sinusoidal endothelial cell scavenging function), thiobarbituric acid-reactive substances content of the tissue (a marker of lipid peroxidation), reduced and oxidized glutathione (a marker of the thiol system oxidation/reduction state), lactate dehydrogenase and alanine aminotransferase activities (markers of cytolysis), as well as scanning and transmission electron microscopic appearance of the sinusoid were evaluated. RESULTS: At the high concentrations used, both free radical generating systems suppressed hyaluronan uptake, increased malondialdehyde content of the tissue, enhanced the release of both liver enzymes, decreased the total glutathione content of the liver, and altered the ratio of reduced/oxidized glutathione. Both free radical species induced dose-dependent morphological alterations of the sinusoid, consisting of the appearance of large gaps replacing the sieve-plated fenestration. CONCLUSIONS: The free radical species-induced functional impairment and morphological alterations of the liver sinusoid, presented in this study, closely resemble the early in vivo changes associated with liver injury under a variety of conditions, such as preservation and reperfusion, or administration of hepatotoxicants such as D-galactosamine, Gram-negative bacterial lipopolysaccharides, acetaminophen, alcohol and others. Therefore, we suggest that early liver sinusoid injury, observed under these conditions, can be attributed to the action of free radicals, such as superoxide anion and nitric oxide.


Assuntos
Endotélio Vascular/fisiologia , Fígado/irrigação sanguínea , Óxido Nítrico/farmacologia , Superóxidos/farmacologia , Alanina Transaminase/metabolismo , Animais , Endotélio Vascular/metabolismo , Endotélio Vascular/ultraestrutura , Glutationa/metabolismo , Ácido Hialurônico/farmacocinética , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Masculino , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Perfusão , Ratos , Ratos Sprague-Dawley , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Xantina Oxidase/farmacologia
8.
Alcohol Clin Exp Res ; 23(2): 349-56, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10069567

RESUMO

The purpose of this study was to determine if exacerbation of apoptosis precedes liver injury during chronic exposure of rats to alcohol. After 7 weeks of feeding an alcohol- or dextrin-containing liquid diet, the animals were treated with gram-negative bacterial lipopolysaccharide (1 mg x kg(-1) body weight, intravenously) or sterile saline and sacrificed 3 hr after the treatment. Alanine:2-oxoglutarate aminotransferase (ALT) and lactate:NAD oxidoreductase [lactate dehydrogenase (LDH)] were measured in plasma. The caudate lobe of the liver was resected for histology, while the rest of the organ was perfused with collagenase to isolate hepatocytes, Kupffer cells (KCs), and sinusoidal endothelial cells (SECs) by centrifugal elutriation. Hepatocyte mitochondria were isolated by differential centrifugation of the cell homogenate. Reduced and oxidized glutathione (GSH and GSSG) in isolated hepatocytes and hepatocyte mitochondria, and malondialdehyde in hepatocytes were assayed. Caspase-3 activity and Fas ligand mRNA expression were determined in hepatocytes, KCs, and SECs. Plasma ALT and LDH activity, liver histology, GSH, GSSG and their ratio, and malondialdehyde content were not affected by alcohol treatment Caspase-3 activity was significantly increased in alcohol-treated rats in all three cell types, with the lowest response observed in hepatocytes and the highest in KCs. Fas ligand mRNA expression, which had the highest level in SECs, followed by KCs and hepatocytes, was not affected by alcohol administration. Lipopolysaccharide had the following effects: an increase in ALT in both pair- and alcohol-fed rats, and LDH only in alcohol-fed rats, a decrease in GSH + GSSG levels in both mitochondria and hepatocytes, an elevation of malondialdehyde content in hepatocytes, a raise in caspase-3 activity in all groups and cell types, and an augmentation of Fas ligand expression in hepatocytes and KCs, but not in SECs. These data suggest that, during chronic alcohol consumption, an exacerbated apoptosis precedes alcohol-induced liver injury.


Assuntos
Caspases/metabolismo , Depressores do Sistema Nervoso Central/farmacologia , Precursores Enzimáticos/metabolismo , Etanol/farmacologia , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , RNA Mensageiro/biossíntese , Receptor fas/metabolismo , Alanina Transaminase/sangue , Animais , Caspase 3 , Glutationa/metabolismo , Técnicas In Vitro , L-Lactato Desidrogenase/sangue , Fígado/citologia , Fígado/enzimologia , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
9.
Braz J Med Biol Res ; 31(5): 647-54, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9698769

RESUMO

The submucous plexus of the normal small and large intestine of Calomys callosus was studied by NADH and AChE histochemical techniques and by transmission and scanning electron microscopy. The plexus contains (X +/- SD) 7,488 +/- 293 neurons/cm2 in the duodenum, 5,611 +/- 836 in the jejunum, 2,741 +/- 360 in the ileum, 3,067 +/- 179 in the cecum, and 3,817 +/- 256 in the proximal colon. No ganglia or nerve cell bodies were seen in the esophagus, stomach, distal colon or rectum. The neurons are pear-shaped with a round or oval nucleus and the neuronal cell profile areas were larger in the large intestine than in the small intestine. Most of the neurons display intense AChE activity in the cytoplasm. AChE-positive nerve fibers are present in a primary meshwork of large nerve bundles and in a secondary meshwork of finer nerve bundles. At the ultrastructural level, the ganglia are irregular in shape and covered with fibroblast-like cells. The nucleoplasm of the neurons is finely granular with a few condensations of chromatin attached to the nuclear envelope. In the neuropil numerous varicosities filled with vesicles of different size and electron densities are seen. The pre- and post-synaptic membrane thickenings are asymmetric. Characteristic glial cells with oval nuclei and few organelles are numerous. These data provide a detailed description of this submucosal meshwork.


Assuntos
Intestino Grosso/inervação , Intestino Delgado/inervação , Roedores , Plexo Submucoso/ultraestrutura , Acetilcolinesterase/análise , Animais , Animais Selvagens , Gânglios/ultraestrutura , Masculino , Microscopia Eletrônica , Neurônios/ultraestrutura , Oxirredutases
10.
Alcohol ; 16(2): 125-33, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9665314

RESUMO

Internalization and degradation of human recombinant [125I]TNF-alpha was studied in hepatocytes isolated from rats exposed to ethanol (EtOH) either acutely (i.p. injection, 2.2 g kg(-1) b.wt.) or chronically (14-16 weeks of EtOH feeding in liquid diet). Both acute and chronic EtOH exposure diminished cytokine binding to the cell-surface receptors. In the acute group, EtOH increased internalization of the cytokine, accelerated its disappearance from the cell surface, and markedly reduced its conversion into acid-soluble 125I-containing compounds. In the chronic group, EtOH did not markedly affect these parameters. Internalization and degradation of the cytokine in the chronic group was much lower than in the acute group. It is concluded that EtOH interferes not only with the cytokine binding to the cell-surface receptors, as demonstrated in previous studies, but also with postbinding events, such as internalization and intracellular degradation of TNF-alpha. Possible mechanisms of action of EtOH are discussed.


Assuntos
Etanol/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Membrana Celular/metabolismo , Meios de Cultivo Condicionados , Etanol/administração & dosagem , Etanol/sangue , Humanos , Radioisótopos do Iodo , Cinética , Masculino , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/metabolismo
11.
Braz. j. med. biol. res ; 31(5): 647-54, May 1998. ilus
Artigo em Inglês | LILACS | ID: lil-212402

RESUMO

The submucous plexus of the normal small and large intestine of Calomys callosus was studied by NADH and AChE histochemical techniques and by transmission and scanning electron microscopy. The plexus contains (X + SD) 7,488 + 293 neurons/cm2 in the duodenum, 5,611 + 836 in the jejunum, 2,741 + 360 in the ileum, 3,067 + 179 in the cecum, and 3,817 + 256 in the proximal colon. No ganglia or nerve cell bodies were seen in the esophagus, stomach, distal colon or rectum. The neurons are pear-shaped with a round or oval nucleus and the neuronal cell profile areas were larger in the large intestine than in the small intestine. Most of the neurons display intense AChE activity in the cytoplasm. AChE-positive nerve fibers are present in a primary meshwork of large nerve bundles and in a secondary meshwork of finer nerve bundles. At the ultrastructural level, the ganglia are irregular in shape and covered with fibroblast-like cells. The nucleoplasm of the neurons is finely granular with a few condensations of chromatin attached to the nuclear envelope. In the neuropil numerous varicosities filled with vesicles of different size and electron densities are seen. The pre- and post-synaptic membrane thickenings are asymmetric. Characteristic glial cells with oval nuclei and few organelles are numerous. These data provide a detailed description of this submucosal meshwork.


Assuntos
Animais , Masculino , Intestino Grosso/inervação , Intestino Delgado/inervação , Roedores , Plexo Submucoso/ultraestrutura , Acetilcolinesterase/análise , Animais Selvagens , Gânglios/ultraestrutura , Microscopia Eletrônica , Neurônios/ultraestrutura , Oxirredutases
12.
Alcohol Clin Exp Res ; 21(6): 1128-36, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9309327

RESUMO

Increasing evidence implicates injury of hepatic sinusoidal endothelial cells as an important component in the development of several forms of liver injury. The purpose of this study was to test the hypothesis that alcohol [ethanol (EtOH)]-induced pathological changes of the sinusoidal endothelial cell of the liver precede, and may lead to, hepatocyte injury. BALB/c mice were treated with EtOH either acutely (1.5 or 3.0 g.kg-1 body weight, i.p.) or chronically [by feeding an EtOH-containing (4%, w/v) liquid diet]. Acutely treated animals were killed 3, 6, and 12 hr after EtOH administration, whereas chronically treated animals were killed 12, 28, and 56 days after the initiation of EtOH feeding. The levels of plasma EtOH, hyaluronan (a functional marker for sinusoidal endothelial cell), and alanine-2: oxoglutarate aminotransferase (ALT) activity (a marker for hepatocyte damage) were measured in all groups. The livers were examined by electron and light microscopy. Between 3 and 6 hr after intraperitoneal injection of EtOH, the plasma EtOH levels were relatively stationary (5 and 11 mM for the low- and high-dose groups, respectively). At 12 hr, EtOH was almost completely cleared from the plasma. Hyaluronan levels were increased 3 hr after EtOH exposure at both doses and reached a peak at 6 hr after EtOH administration. In the low EtOH dose animals, the hyaluronan level declined toward normal values at 12 hr. In the high EtOH dose group, hyaluronan levels were still above normal values 12 hr after EtOH administration. No changes in the plasma ALT level were observed in either acutely EtOH-treated groups. In animals treated chronically, plasma hyaluronan levels were markedly increased at 12, 28, and 56 days of EtOH feeding. Plasma ALT levels were elevated at 28 and 56 days, but not at 12 days, of EtOH feeding. Scanning electron microscopy of the liver sinusoid in the acutely treated animals showed the presence of large gaps co-existing with normal sieve-plate fenestrations in sinusoidal endothelial cells. Such changes were seen 3 hr after the high dose and 6 hr after the low dose of EtOH. They disappeared 12 hr after low dose, but lasted well beyond this time point after the high dose of EtOH. Twelve days after the start of EtOH feeding, no changes in the electron microscopic appearance of the sinusoid could be observed. However, 26 days after the initiation of EtOH feeding, the sinusoidal endothelial cells displayed a reduced number of fenestrae. Moreover, the remaining fenestrae were distributed uniformily rather than in organized sieve plates. In addition, at these latter time points, transmission electron microscopy demonstrated the presence of fibrous material in the space of Disse. Both light and transmission electron microscopy demonstrated the presence of lipids within the hepatocyte. The picture observed 56 days after the start of EtOH feeding was essentially the same as at 28 days, except that the reduction in the number of fenestrae was more accentuated. These data document EtOH-induced pathological changes in sinusoidal endothelial cell before either biochemical or histological hepatocyte damage.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Etanol/toxicidade , Hepatopatias Alcoólicas/patologia , Testes de Função Hepática , Fígado/irrigação sanguínea , Animais , Relação Dose-Resposta a Droga , Endotélio Vascular/patologia , Fígado Gorduroso Alcoólico/patologia , Técnica de Fratura por Congelamento , Fígado/patologia , Cirrose Hepática Alcoólica/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica , Microscopia Eletrônica de Varredura
13.
Biochem Pharmacol ; 52(6): 891-9, 1996 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-8781508

RESUMO

The effects of chronic (16-week) alcohol consumption by rats on [125I] tumor necrosis factor (TNF)-alpha and [125I]interleukin (IL)-6 plasma clearance and organ distribution in vivo and uptake and metabolism by the isolated, perfused liver were studied. Alcohol was administered to rats in a liquid diet for 16 weeks, and caused a decreased (48%) plasma clearance rate of IL-6 and converted the plasma clearance kinetics of the cytokine from a biphasic exponential in normal rats to a monophasic exponential decay. Alcohol feeding significantly increased (101%) plasma clearance of TNF-alpha, which followed a biphasic exponential decay and decreased the T1/2 for both the alpha (67%) and beta (76%) elimination components. The distribution of both cytokines in trichloroacetic acid precipitable and non-precipitable fractions of liver, spleen, stomach, small intestine (ileum), lung, kidney, and blood was also studied. The only effect of alcohol treatment was a significant decrease in IL-6 uptake and metabolism by the small intestine. Perfused livers, isolated from alcohol-fed rats, took up and metabolized larger amounts of IL-6 than did livers isolated from pair-fed rats. TNF-alpha uptake and metabolism by the isolated, perfused liver were not affected by chronic alcohol consumption. Regardless of the animal treatment, the isolated perfused liver took up and metabolized significantly larger (17-fold) amounts of TNF-alpha than IL-6, in spite of identical concentrations of cytokines (6 nM) in the perfusion medium. The data presented in this study along with our previous results demonstrating the effects of alcohol consumption on TNF-alpha and IL-6 receptors on various liver cells suggest that the effects of chronic alcohol treatment on cytokine clearance cannot be ascribed to changes in the receptors for the two cytokines. Also, no correlation was found between the effects of alcohol treatment on plasma cytokine clearance and uptake and metabolism of cytokines by the isolated, perfused liver. Experimental data and theoretical considerations suggest that cytokine receptor recycling may play an important role in mediating alcohol effects on cytokine clearance.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Etanol/farmacologia , Interleucina-6/metabolismo , Fígado/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Doença Crônica , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley
14.
Alcohol Clin Exp Res ; 20(6): 973-9, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8892514

RESUMO

Electron microscopic appearance of the liver sinusoid was examined in rats fed alcohol chronically in a complete liquid diet or in sucrose-containing drinking water. The animals were kept on liquid diet (+/- alcohol) for 14 weeks or on sucrose-containing drinking water (+/- alcohol) for 12.5 weeks and sacrificed thereafter. To rule out possible artifact induced by fixation procedure, livers were fixed by immersion (no perfusion), immersion preceded by perfusion, and by perfusion with glutaraldehyde and examined with both scanning and transmission electron microscopy. Regardless of the mode of its administration, and of the fixation procedure used, alcohol induced similar changes in liver sinusoid ultrastructure. Such changes included disruption of the sieve-plate pattern of the sinusoidal endothelial cell fenestrations with the appearance of large gaps and resulting in a meshwork lining, wherein large areas of the sinusoid communicated freely with the underlying hepatocytes. Transmission electron microscopy complemented these findings. The results reported in this study demonstrate that alcohol-induced structural changes of the liver sinusoid in the rat are similar whether alcohol is fed via a liquid diet or in drinking water. Therefore, alcohol administration in drinking water may provide a simple, inexpensive, and convenient method of inducing structural changes in the rat liver sinusoid.


Assuntos
Consumo de Bebidas Alcoólicas/patologia , Alcoolismo/patologia , Modelos Animais de Doenças , Endotélio Vascular/patologia , Etanol/administração & dosagem , Cirrose Hepática Alcoólica/patologia , Fígado/irrigação sanguínea , Animais , Etanol/toxicidade , Masculino , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Ratos , Ratos Sprague-Dawley
15.
Alcohol Clin Exp Res ; 20(2): 293-301, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8730220

RESUMO

Plasma clearance and organ distribution of intravenously injected human recombinant [125I]interleukin (IL)-6 and [125I]tumor necrosis factor (TNF)-alpha were studied in male rats, 2 hr after intravenous alcohol (ethanol) administration (single dose, 2.2 g.kg-1 body weight). Also, the rate of uptake and degradation of the two cytokines by the isolated, perfused rat liver was studied in the absence or in the presence of ethanol (35 mM) in the perfusate. Acute ethanol administration significantly increased plasma clearance rate for both cytokines (36% and 72%, for IL-6 and TNF-alpha, respectively), decreased the t1/2 alpha (30% and 11%, for IL-6 and TNF-alpha, respectively), abolished the slow (beta)-phase component for TNF-alpha, and increased t1/2 beta for IL-6 (31%). Although alcohol did not affect organ distribution of TNF-alpha, it increased the IL-6 content in the liver, kidney, and blood. IL-6 uptake rate by the isolated, perfused rat liver was 2-fold higher than TNF-alpha uptake, whereas the rate of degradation was larger for TNF-alpha than for IL-6, despite the fact that both cytokines were presented to the liver at the same concentration (6 nM). Ethanol addition to the perfusate (35 mM, final concentration) significantly increased TNF-alpha uptake (24%), without affecting IL-6 uptake or the degradation rate of either cytokine. Also, the kinetics of degradation by the isolated, perfused rat liver was linear for TNF-alpha, but exponential for IL-6. Data presented in this study demonstrate that: (1) acute alcohol consumption can alter the kinetic behavior of IL-6 and TNF-alpha in the bloodstream, mainly by accelerating their clearance which, in turn, may counteract the outcome of cytokine secretion and delivery to the blood; and (2) short exposure of liver to ethanol levels commonly seen in humans after binge drinking may alter its capacity to take up cytokines.


Assuntos
Intoxicação Alcoólica/imunologia , Interleucina-6/sangue , Fígado/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Relação Dose-Resposta a Droga , Masculino , Taxa de Depuração Metabólica/fisiologia , Perfusão , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/sangue , Distribuição Tecidual
16.
Hepatology ; 23(4): 788-96, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8666333

RESUMO

Scanning and transmission electron-microscopic examination of the rat liver sinusoid was performed in this study after in vivo treatment of rats with gram-negative bacterial lipopolysaccharide (LPS, 1 mg/Kg(-1) body weight), with or without pretreatment with gadolinium chloride (GdCl3 10 mg(Kg(-1) body weight). Twenty-seven and 48 hours after GdCl3 administration, to inactivate/eliminate part of the Kupffer cell population, a decrease in the number of visualized Kupffer cells was observed, without evident effects on the sinusoidal endothelial cell or on the hepatocyte. Three and 24 hours after its administration, LPS produced ultrastructural changes in the sinusoid characterized by morphological evidence of Kupffer cell activation (i.e., swelling and expanded philopodia anchoring the Kupffer cell to the luminal surface of the sinusoidal wall), and a marked decrease in the population of endothelial cell fenestration. The reduction in the number of fenestrae was associated with a change in the diameter of fenestrae and can be interpreted as a component of the "capillarization" process of the hepatic sinusoid. Such ultrastructural changes were prevented by the administration of GdCl3 24 hours before LPS injection. Hence, these findings suggest that LPS-induced structural changes in the liver sinusoid are mediated by an LPS-induced Kupffer cell activation. Coupled with previous experimental data, showing similar effects of GdCl3 on one of the hepatic sinusoidal endothelial cell (SEC) functions, i.e., hyaluronan scavenging, the data presented in this study strongly support the view that Kupffer cells modulate both the hepatic SEC's functional as well as ultrastructural properties.


Assuntos
Gadolínio/farmacologia , Macrófagos do Fígado/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Fígado/efeitos dos fármacos , Animais , Endotélio/efeitos dos fármacos , Endotélio/ultraestrutura , Macrófagos do Fígado/fisiologia , Fígado/ultraestrutura , Masculino , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley
17.
Alcohol Clin Exp Res ; 20(1): 156-63, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8651446

RESUMO

We investigated the effect of alcohol (ethanol) on the ability of the alveolar macrophage to produce tumor necrosis factor-alpha (TNF-alpha), superoxide anion (O2-), and nitric oxide (NO)--three critical components of pulmonary host defense. Male rats were treated with alcohol either acutely (priming dose 175 mg/100 g of body weight, followed by a 7-hr continuous intravenous infusion of 30 mg/100 g of body weight/hr) or chronically (12-14 weeks of feeding ethanol in a liquid diet). Three hours before sacrifice, the rats received an intravenous injection of saline or lipopolysaccharide (LPS; Escherichia coli, 026:B6, 100 micrograms/100 g of body weight). Alveolar macrophages (AMs) were then isolated by bronchoalveolar lavage and assessed for their in vitro capacity to produce TNF-alpha, O2-, and NO spontaneously and in response to different stimuli. Acute alcohol administration suppressed in vitro LPS-stimulated AM TNF-alpha secretion by 52%. AMs from both pair-and alcohol-fed rats secreted TNF-alpha spontaneously in culture. However, the AMs from chronic alcohol-fed group secreted 42-53% less TNF-alpha spontaneously and in response to LPS, interferon-gamma (IFN-gamma) or IFN-gamma + LPS compared with the AMs from pair-fed group. Systemic LPS treatment inhibited in vitro LPS-stimulated AM TNF-alpha secretion (50%) only in the control rats. Acute alcohol administration enhanced significantly in vitro phorbol 12-myristate 13-acetate (PMA)- and opsonized zymosan (OPZ)-induced AM O2- secretion (4-and 1.8-fold, respectively). Systemic LPS treatment primed the AMs from control rats to secrete 83% more O2- in response to PMA but not OPZ; however, in the acute alcohol-treated group, it suppressed both PMA (54%)- and OPZ (66%)-induced AM O2- release (loss of priming effect of LPS). Chronic alcohol feeding suppressed PMA-induced AM O2- secretion (40%) without affecting the OPZ-induced release. Although systemic LPS treatment had no significant effect on PMA or OPZ-induced AM O2- secretion in the pair-fed group, it enhanced the PMA-stimulated AM O2- release (88%) in the alcohol-fed group. AMs recovered from control or acute alcohol-treated rats did not secrete NO spontaneously in vitro. However, AMs from both pair and chronic alcohol-fed rats secreted NO spontaneously with AMs from chronic alcohol-fed group secreting 34% less. Both acute and chronic alcohol treatment inhibited AM NO secretion in response to IFN-gamma, LPS, and IFN-gamma + LPS significantly. Systemic LPS had no effect on AM NO production in response to different in vitro stimuli in any of the treatment groups. These data suggest that (1) both acute and chronic alcohol administration to rats inhibit AM TNF-alpha and NO secretion; (2) acute and chronic alcohol treatment have differential effects on AM O2- secretion; and (3) alcohol-induced alteration in AM TNF-alpha, O2-, and NO secretion may in part explain the increased susceptibility of alcohol-consuming individuals to pulmonary infections.


Assuntos
Intoxicação Alcoólica/imunologia , Alcoolismo/imunologia , Macrófagos Alveolares/imunologia , Óxido Nítrico/metabolismo , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Etanol/toxicidade , Radicais Livres , Tolerância Imunológica/efeitos dos fármacos , Tolerância Imunológica/imunologia , Masculino , Ratos , Ratos Sprague-Dawley
18.
Alcohol Clin Exp Res ; 19(5): 1219-25, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8561294

RESUMO

Pulmonary infection with Pneumocystis carinii, an opportunistic pathogen, is associated with a variety of immunosuppressive states, including human immunodeficiency virus infection. We hypothesized that alcohol ingestion might compromise host defenses against this pathogen and, in an immunocompromised host, increase the severity of infection. This hypothesis was tested in both acute and chronic ethanol-treated normal and CD4+ T-cell-depleted mice challenged with P. carinii organisms. Normal and CD4+ T-cell-depleted mice were given an intraperitoneal injection of ethanol or saline 0.5 hr before P. carinii challenge and killed 3 hr later for bronchoalveolar lavage. Acute alcohol treatment decreased significantly tumor necrosis factor (TNF) activity and the number of polymorphonuclear leukocytes (PMNLs) recovered in the lavage in response to the pathogen. Depletion of CD4+ T-cells did not potentiate the effect of alcohol on the early inflammatory response to the pathogen any further. In normal animals, in vivo interferon (IFN)-gamma pretreatment augmented significantly the P. carinii-stimulated lung TNF response and PMNL recruitment. However, IFN-gamma pretreatment prevented the alcohol-induced suppression of TNF secretion without affecting the PMNL recruitment. The effect of chronic alcohol consumption on the severity of infection was studied in long-term, alcohol-fed normal and CD(4+)-depleted mice challenged with P. carinii organisms. Lung histopathology showed that P. carinii infection was present in > 60% of the alcohol-fed mice and in none of the controls. Also, a significantly higher number of PMNLs were recovered in the lavage fluid of alcohol-fed mice with persistent infection.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Alcoolismo/imunologia , Infecções Oportunistas/imunologia , Pneumonia por Pneumocystis/imunologia , Consumo de Bebidas Alcoólicas/imunologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Linfócito CD4 , Citocinas/sangue , Tolerância Imunológica/imunologia , Interferon gama/sangue , Macrófagos Alveolares/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator de Necrose Tumoral alfa/metabolismo
19.
Am J Respir Crit Care Med ; 151(4): 1233-8, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7697258

RESUMO

We hypothesized that therapy with granulocyte-macrophage colony stimulating factor (GM-CSF) would decrease intensity of murine Pneumocystis carinii pneumonia by upregulating alveolar macrophage function. Mice were depleted of CD4+ T lymphocytes and then inoculated intratracheally with P. carinii. Four weeks later, they received recombinant murine GM-CSF (rmGM-CSF) 5 micrograms/d subcutaneously for 7 and 14 d. At the end of therapy lung tissue was scored for intensity of P. carinii infection by silver methenamine stain and for inflammation by hematoxylin-eosin stain. We found that rmGM-CSF therapy significant decreased the intensity scores of PCP infection in comparison to control mice (1.88 +/- 0.47 vs 3.06 +/- 0.12, p < 0.001). Inflammation scores were not significantly different in the rmGM-CSF group compared with the control group (1.83 +/- 0.47 vs 2.83 +/- 0.67). Alveolar macrophages from mice treated with rmGM-CSF released significantly more tumor necrosis factor-alpha (TNF-alpha) than cells from control mice after in vitro stimulation with lipopolysaccharide (LPS) alone (2.65 +/- 0.30 vs 1.45 +/- 0.26 ng/ml, p = 0.01) or with LPS plus murine recombinant interferon-gamma (4.16 +/- 0.51 vs 2.25 +/- 0.34 ng/ml, p = 0.01). We conclude that GM-CSF therapy reduces the intensity of PCP and this effect is associated with an enhanced alveolar macrophage TNF-alpha production.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Pneumonia por Pneumocystis/tratamento farmacológico , Animais , Pulmão/patologia , Macrófagos Alveolares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia por Pneumocystis/patologia , Proteínas Recombinantes/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo
20.
Alcohol Clin Exp Res ; 19(2): 291-8, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7625560

RESUMO

Transmission and scanning electron microscopic studies were performed on the liver sinusoid, with emphasis on sinusoidal endothelial cells, in rats fed a liquid diet containing either alcohol or dextrin (control) for 14 weeks. Animals were also treated with either Gram-negative bacterial lipopolysaccharide (LPS; 100 micrograms/100 g body weight, intravenously) or sterile saline (control). All specimens were prepared after perfusion fixation of the liver. Livers of rats fed dextrin-containing liquid diet displayed the ultrastructural features typical of the sinusoid and its endothelial cells. Livers from alcohol-fed animals, however, were characterized by massive loss of sieve-plate architecture of the sinusoidal endothelium, which was virtually replaced with a meshwork of enlarged openings with diameters frequently exceeding 1 micron. Morphological evidence of Kupffer cell activation could also be seen along with significant fatty infiltration of the hepatocyte. Conversely, LPS administration to dextrin-fed animals induced an apparent decrease in fenestration of the sinusoidal endothelial cell, accompanied by morphological evidence of enhanced endocytotic activity and cytoplasmic swelling. The changes seen 3 hr after LPS administration were markedly advanced at 24 hr. LPS administration to alcohol-fed rats accentuated the alterations observed after alcohol treatment alone. Additionally, the presence of platelets in the sinusoid as well as adhering to the hepatocyte microvilli in the space of Disse, along with the presence of Ito and Kupffer cell activation, greater than that observed in the alcohol-treated rats, is morphological evidence consistent with the disruption of vascular integrity in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Hepatopatias Alcoólicas/patologia , Fígado/irrigação sanguínea , Animais , Endocitose/efeitos dos fármacos , Endotélio Vascular/patologia , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Ratos , Ratos Sprague-Dawley
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