RESUMEN
Horticulture has greatly increased in Argentina in recent decades mainly due to increasing greenhouse utilization and agrochemical consumption, thus representing a threat to adjacent water bodies. Riparian wetlands, however, could attenuate agrochemical contamination. The present work therefore compared insecticide concentrations in bottom sediments in addition to sediment toxicity to the amphipod Hyalella curvispina and investigated the macroinvertebrate composition upstream and downstream from a natural wetland in a small stream draining a basin undergoing intense horticultural production. The wetland surface was covered by macrophytes, mainly Thypha sp., and the insecticide concentrations measured downstream from the wetland were significantly lower, at roughly 19% of the upstream values. The growth rates of H. curvispina were significantly higher when exposed to the sediments downstream from the wetland, while the macroinvertebrate-assemblage composition was significantly different upstream and downstream: the snail Pomacea canaliculata was the dominant species upstream while the amphipod H. curvispina was dominant downstream. Pomacea canaliculata is often the dominant species in the regional streams draining agriculture and horticultural basins. Hyalella curvispina is sensitive to pesticide toxicity and is often dominant in streams draining extensive livestock basins and within a biosphere reserve. We conclude that riparian wetlands effectively attenuate horticulture contamination in pampean streams and should therefore be preserved and restored.
Asunto(s)
Insecticidas , Contaminantes Químicos del Agua , Agricultura , Animales , Argentina , Monitoreo del Ambiente , Horticultura , Insecticidas/análisis , Insecticidas/toxicidad , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , HumedalesRESUMEN
We investigated relationships among insecticides and aquatic invertebrate communities in 22 streams of two soy production regions of the Argentine Pampas over three growing seasons. Chlorpyrifos, endosulfan, cypermethrin, and lambda-cyhalothrin were the insecticides most frequently detected in stream sediments. The Species at Risk (SPEAR) pesticide bioassessment index (SPEARpesticides) was adapted and applied to evaluate relationships between sediment insecticide toxic units (TUs) and invertebrate communities associated with both benthic habitats and emergent vegetation habitats. SPEARpesticides was the only response metric that was significantly correlated with total insecticide TU values for all three averaged data sets, consistently showing a trend of decreasing values with increasing TU values (r2=0.35 to 0.42, p-value=0.001 to 0.03). Although pyrethroids were the insecticides that contributed the highest TU values, toxicity calculated based on all insecticides was better at predicting changes in invertebrate communities than toxicity of pyrethroids alone. Crustaceans, particularly the amphipod Hyalella spp., which are relatively sensitive to pesticides, played a large role in the performance of SPEARpesticides, and the relative abundance of all crustaceans also showed a significant decreasing trend with increasing insecticide TUs for two of three data sets (r2=0.30 to 0.57, p-value=0.003 to 0.04) examined. For all data sets, total insecticide TU was the most important variable in explaining variance in the SPEARpesticides index. The present study was the first application of the SPEAR index in South America, and the first one to use it to evaluate effects of pesticides on invertebrate communities associated with aquatic vegetation. Although the SPEAR index was developed in Europe, it performed well in the Argentine Pampas with only minor modifications, and would likely improve in performance as more data are obtained on traits of South American taxa, such as pesticide sensitivity and generation time.
Asunto(s)
Agricultura , Insecticidas/análisis , Invertebrados/efectos de los fármacos , Ríos , Contaminantes Químicos del Agua/análisis , Animales , Monitoreo del Ambiente , Europa (Continente) , Sedimentos Geológicos/análisis , América del Sur , Glycine max/crecimiento & desarrolloRESUMEN
Previous studies reported the presence in rat mammary tissue of a cytosolic xanthine oxidoreductase pathway for the metabolism of alcohol to acetaldehyde and hydroxyl radicals and to the microsomal biotransformation of ethanol to acetaldehyde. It was also reported that after chronic ethanol drinking stressful oxidative conditions can be observed. The present work reports that even after single doses of ethanol, given at three different levels (6.3 g kg(-1); 3.8 g kg(-1) or 0.6 g kg(-1) p.o.), acetaldehyde accumulates for prolonged periods of time in the mammary tissue to reach concentrations higher than in blood (e.g. 5.1+/-1.2 nmol g(-1) versus 0.2+/-0.1 nmol ml(-1), for 6.3 g kg(-1) dose, 6 h after intoxication). The presence in rat mammary tissue of low activities of additional enzymes able to generate acetaldehyde was established (alcohol dehydrogenase: 0.97+/-0.84 mU mg(-1) protein; CYP2E1: 1.30+/-0.12 x 10(-2) pmol 4-nitrocatechol min(-1) mg(-1) protein) and a low activity of aldehyde dehydrogenase was observed in the cytosolic, mitochondrial and microsomal fractions (0.02+/-0.04; 0.35+/-0.09 and 0.72+/-0.19 mU mg(-1) protein, respectively). After a single high dose of ethanol, an increased susceptibility to oxidative stress was observed, as evidenced by changes in the shape of t-butylhydroperoxide induced emission of chemiluminescence in mammary tissue (6.3 g kg(-1) dose; at 3 and 6 h). In summary, the results show that even after single doses of ethanol, acetaldehyde, either formed in situ or arriving via blood, tends to accumulate in mammary tissue and that this condition might decrease cell defenses against injury.
Asunto(s)
Acetaldehído/metabolismo , Depresores del Sistema Nervioso Central/farmacocinética , Depresores del Sistema Nervioso Central/toxicidad , Etanol/farmacocinética , Etanol/toxicidad , Glándulas Mamarias Animales/metabolismo , Alcohol Deshidrogenasa/metabolismo , Aldehído Deshidrogenasa/metabolismo , Animales , Depresores del Sistema Nervioso Central/sangre , Citocromo P-450 CYP2E1/metabolismo , Relación Dosis-Respuesta a Droga , Etanol/sangre , Femenino , Mediciones Luminiscentes , Estrés Oxidativo/efectos de los fármacos , Ratas , Fracciones Subcelulares/efectos de los fármacos , Fracciones Subcelulares/enzimologíaRESUMEN
Highly purified rat-liver nuclei were previously shown to have nuclear ethanol (EtOH) metabolizing system able to bioactivate alcohol to acetaldehyde and 1-hydroxyethyl radicals. These reactive metabolites were able to covalently bind to nuclear proteins and lipids potentially being able to provoke oxidative stress of nuclear components. In this study, the above-mentioned possibility was explored. Sprague Dawley male rats (125-150 g) were fed a standard Lieber and De Carli liquid diet for 28 days. Controls were pair-fed with a diet, in which EtOH was isocalorically replaced with carbohydrate. The presence of a chlorzoxazone hydroxylase activity inducible by the repetitive EtOH drinking further suggested the presence of CYP2E1 in the highly purified nuclei. Nuclei from EtOH-drinking rats evidenced significantly increased susceptibility to a t-butyl hydroperoxide challenge as detected by chemiluminescence emission, increased formation of protein carbonyls, and decreased content of protein sulfhydryls. In contrast, no significant changes in the nuclear lipid hydroperoxides formation or even decreases in the 8-oxo-7,8-dihydro-2-deoxyguanosine were observed. No significant differences were observed in different parameters of the alkaline Comet assay. In immunohistochemical studies performed, no expression of p53 was observed in the livers of the animals under the experimental conditions tested. Since nuclear proteins and lipids are known to play a role in cell growth, differentiation, repair and signaling, their alterations by either oxidative stress, or by covalent binding might be of relevance to liver tumor promotion.
Asunto(s)
Núcleo Celular/metabolismo , Etanol/administración & dosificación , Hígado/metabolismo , Estrés Oxidativo/efectos de los fármacos , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Clorzoxazona/análogos & derivados , Clorzoxazona/metabolismo , Ensayo Cometa , Citocromo P-450 CYP2E1/metabolismo , Interpretación Estadística de Datos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análisis , Hepatocitos/citología , Hepatocitos/metabolismo , Inmunohistoquímica , Peroxidación de Lípido/efectos de los fármacos , Hígado/química , Hígado/citología , Masculino , Microsomas Hepáticos/química , Microsomas Hepáticos/metabolismo , Oxigenasas de Función Mixta/metabolismo , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Compuestos de Sulfhidrilo/metabolismo , Proteína p53 Supresora de Tumor , terc-Butilhidroperóxido/metabolismoRESUMEN
Nifurtimox (Nfx) and Benznidazole (Bz) are being used for the treatment of the acute phase of Chagas' disease. Recently, they were also considered for use in the indeterminate phase. Both the nitroheterocyclic drugs have serious toxic side effects. The mechanism of Nfx toxicity is associated with the formation of reactive oxygen species (ROS) generated during nitroreduction. Potential effects on cardiac function have not been established yet, despite the well-known cardiopathy often produced by the disease itself. We describe experiments testing some acute effects of Nfx on the male Sprague Dawley rat heart. Nifurtimox was present in the heart at 1, 3 and 6 h after intragastric (i.g) treatment. In vitro studies on Nfx microsomal and cytosolic nitroreductase activities showed that only the microsomal fraction had the ability to nitroreduce it. Cytochrome P450 and cytochrome P450 reductase would be involved in the process as suggested by their response to specific inhibitors. Nifurtimox increased the cardiac protein carbonyl content at 1 and 3 h and decreased the protein sulfhydryl content at 3 h. In addition, 24 h after treatment ultrastructural alterations such as marked cytoplasmic vacuolization, separation and loss of myofibrils and mitochondrial swelling were observed. Results suggest that Nfx administration might aggravate pre-existing adverse cardiac conditions. Human & Experimental Toxicology (2007) 26, 781 -788.
Asunto(s)
Corazón/efectos de los fármacos , Miocardio/ultraestructura , Nifurtimox/toxicidad , Tripanocidas/toxicidad , Animales , Masculino , Microscopía Electrónica de Transmisión , Miocardio/metabolismo , Nitrorreductasas/metabolismo , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Previous studies showed that cytosolic and microsomal fractions from rat ventral prostate are able to biotransform ethanol to acetaldehyde and 1-hydroxyethyl radicals via xanthine oxidase and a non P450 dependent pathway respectively. Sprague Dawley male rats were fed with a Lieber and De Carli diet containing ethanol for 28 days and compared against adequately pair-fed controls. Prostate microsomal fractions were found to exhibit CYP2E1-mediated hydroxylase activity significantly lower than in the liver and it was induced by repetitive ethanol drinking. Ethanol drinking led to an increased susceptibility of prostatic lipids to oxidation, as detected by t-butylhydroperoxide-promoted chemiluminiscence emission and increased levels of lipid hydroperoxides (xylenol orange method). Ultrastructural alterations in the epithelial cells were observed. They consisted of marked condensation of chromatin around the perinuclear membrane, moderate dilatation of the endoplasmic reticulum and an increased number of epithelial cells undergoing apoptosis. The prostatic alcohol dehydrogenase activity of the stock rats was 4.84 times lower than that in the liver and aldehyde dehydrogenase activity in their microsomal, cytosolic and mitochondrial fractions was either not detectable or significantly less intense than in the liver. A single dose of ethanol led to significant acetaldehyde accumulation in the prostate. The results suggest that acetaldehyde accumulation in prostate tissue might result from both acetaldehyde produced in situ but also because of its low aldehyde dehydrogenase activity and its poor ability to metabolize acetaldehyde arriving via the blood. Acetaldehyde, 1-hydroxyethyl radical and the oxidative stress produced may lead to epithelial cell injury.
Asunto(s)
Etanol/toxicidad , Próstata/efectos de los fármacos , Próstata/ultraestructura , Acetaldehído/metabolismo , Administración Oral , Alcohol Deshidrogenasa/metabolismo , Consumo de Bebidas Alcohólicas , Aldehído Deshidrogenasa/metabolismo , Animales , Apoptosis/efectos de los fármacos , Depresores del Sistema Nervioso Central/administración & dosificación , Depresores del Sistema Nervioso Central/toxicidad , Relación Dosis-Respuesta a Droga , Retículo Endoplásmico Rugoso/efectos de los fármacos , Retículo Endoplásmico Rugoso/ultraestructura , Células Epiteliales/efectos de los fármacos , Células Epiteliales/ultraestructura , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Epitelio/ultraestructura , Etanol/administración & dosificación , Femenino , Peróxidos Lipídicos/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Microscopía Electrónica , Microsomas/clasificación , Microsomas/efectos de los fármacos , Microsomas/metabolismo , Oxigenasas de Función Mixta/metabolismo , Nitrofenoles/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
In this paper, we present a new class of quasi-Newton methods for an effective learning in large multilayer perceptron (MLP)-networks. The algorithms introduced in this work, named LQN, utilize an iterative scheme of a generalized BFGS-type method, involving a suitable family of matrix algebras L. The main advantages of these innovative methods are based upon the fact that they have an O(nlogn) complexity per step and that they require O(n) memory allocations. Numerical experiences, performed on a set of standard benchmarks of MLP-networks, show the competitivity of the LQN methods, especially for large values of n.
RESUMEN
In previous studies from our laboratory we reported the presence in highly purified liver nuclei, free of contamination with other organelles, of an ethanol metabolizing system (NEMS) able to lead to acetaldehyde and 1-hydroxyethyl free radicals (1HEt). In the present study we tested whether this NEMS is inducible by chronic alcohol administration to rats and whether these nuclei also have increased ability to bioactivate N-nitrosodimethylamine (NDMA). Sprague Dawley male rats (125-150g) were fed with a nutritionally adequate liquid diet containing alcohol to provide 36% of total energy (standard Lieber-De Carli rat diet), for 28 days. Controls received an isocaloric diet without alcohol. Animals were sacrificed, livers were excised and microsomes and purified nuclear fractions were prepared. Both microsomes and nuclei from treated animals had significantly increased ability compared to controls, to biotransform ethanol to acetaldehyde using NADPH as cofactor under an air atmosphere. Both organelles also exhibited significantly increased capacity compared to controls, to bioactivate NDMA to formaldehyde and to reactive metabolites that bind covalently to proteins. Nuclear preparations from control animals were also able to metabolize NDMA to formaldehyde and reactive metabolites. Results indicate that liver nuclei may have a CYP2E1 able to bioactivate both NDMA and EtOH and that these processes are being induced by chronic alcohol drinking. The bioactivation of these xenobiotics to reactive metabolites in the neighborhood of nuclear proteins and DNA might have significant toxicological implications.
Asunto(s)
Núcleo Celular/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Dimetilnitrosamina/metabolismo , Etanol/metabolismo , Hígado/metabolismo , N-Metilaspartato/metabolismo , Acetaldehído/metabolismo , Animales , Biotransformación , Isótopos de Carbono , Núcleo Celular/enzimología , Enfermedad Crónica , ADN/metabolismo , Dieta , Etanol/farmacocinética , Formaldehído/metabolismo , Metabolismo de los Lípidos , Masculino , Microsomas Hepáticos/metabolismo , NADP/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Recent studies from the laboratory reported the presence in highly purified liver nuclear preparations free of endoplasmic reticulum, mitochondria or cytosol, of an ethanol metabolizing group of enzymes (NEMS) leading to acetaldehyde and to hydroxyl and 1-hydroxyethyl (1HEt) free radicals. In the present study it is reported that when NEMS metabolize [14C]ethanol using NADPH as cofactor, its reactive metabolites bind covalently to nuclear proteins and lipids. No covalent binding to DNA was detected with presently used procedures. The covalent binding to nuclear proteins was acid labile and is mostly attributable to acetaldehyde. Additional evidence was attempted through studies where the acetaldehyde was identified as its 2,4-dinitrophenylhydrazone or as its pentafluorphenylhydrazone and gas chromatography (GC) analysis using electron capture detection. Values obtained were close to detection limit and of variable nature. The covalent binding to nuclear lipids involved phospholipids, fatty acids and esters and cholesterol free and esterified and it was only partially labile to acid treatment. Production of ethanol reactive metabolites such as acetaldehyde and free radicals, nearby liver nuclear DNA and nuclear proteins or lipids, might have significant toxicological consequences.
Asunto(s)
Núcleo Celular/metabolismo , ADN/metabolismo , Etanol/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismo , Proteínas Nucleares/metabolismo , Acetaldehído/metabolismo , Animales , Biotransformación , Radioisótopos de Carbono , Núcleo Celular/enzimología , Etanol/farmacocinética , Hígado/enzimología , Hígado/ultraestructura , Masculino , NADP/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
An internship program was developed for new graduate nurses hired in the critical care area. Program goals included facilitating growth and development of 21 newly graduated BSN nurses to prepare them to care for a critically ill adult. The program design included the support and guidance of university faculty for a 3-month period. The program content included planned observational, didactic, and clinical precept experiences. Interns were evaluated according to clinical logs, didactic examinations, and preceptor assessments. At completion of the program, all interns were hired by the participating hospital. Two interns elected to take medical-surgical positions. The remaining interns accepted positions within the critical care and "step-down" areas.
Asunto(s)
Cuidados Críticos , Educación Continua en Enfermería/organización & administración , Capacitación en Servicio/organización & administración , Internado no Médico/organización & administración , Práctica del Docente de Enfermería/organización & administración , Personal de Enfermería en Hospital/educación , Desarrollo de Personal/organización & administración , Adulto , Humanos , Desarrollo de Programa , Evaluación de Programas y Proyectos de SaludRESUMEN
Previous studies evidenced that garlic extracts and/or garlic components were able to prevent against chemically induced tumors or acute toxic effects of chemicals (e.g. CCl4 induced liver injury). The chemopreventive potential of garlic has been attributed to the presence in it of several bioactive organosulfur compounds. Those components might act as antioxidants able to scavenge free radicals. In the present work we describe initial studies on the antioxidative-stress properties of some garlic components such as: diallyl disulfide (DDS), diallyl sulfide (DAS), allyl mercaptan (AMT) and allyl methyl sulfide (AMS). We found that DAS, DDS and AMT but not AMS were able to trap trichloromethyl and trichloromethylperoxyl free radicals. Further, DDS but not DAS or AMT also inhibited CCl4 promoted liver microsomal lipid peroxidation. DAS, but not DDS, AMT or AMS was able to react with free radicals arised during UVC activation of hydrogen peroxide or terbutyl hydroperoxide but not with those produced during UVC activation of terbutyl peroxide. However, all garlic components tested absorbed energy from UVC and became partially destroyed in the process. AMT, but not DDS, AMS or DAS was able to destroy 4-hydroxynonenal, a key reactive aldehyde produced during lipid peroxidation. AMT and DDS were also able to prevent UVC plus CCl4 promoted oxidation of albumin in vitro, but DAS and AMS failed to do so. Results suggest that the antioxidative stress properties of garlic might result from the contributions of its sulfur component in different steps and not necessarily from the contribution of only one of them.
Asunto(s)
Compuestos Alílicos/farmacología , Tetracloruro de Carbono/toxicidad , Ajo/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Plantas Medicinales , Compuestos Alílicos/antagonistas & inhibidores , Animales , Radicales Libres , Peroxidación de Lípido/efectos de los fármacos , Masculino , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Rayos UltravioletaRESUMEN
It is well known that the main difficulties of the algorithms based on backpropagation are the susceptibility to local minima and the slow adaptivity to the patterns during the training. In this paper, we present a class of algorithms, which overcome the above difficulties by utilizing some "direct" numerical methods for the computation of the matrices of weights. In particular, we investigate the performances of the FBFBK-LSB (least-squares backpropagation) algorithms and iterative conjugate gradient singular-value decomposition (ICGSVD), respectively, introduced by Barmann and Biegler-Konig (1993) and by the authors. Numerical results on several benchmark problems show a major reliability and/or efficiency of our algorithm ICGSVD.
RESUMEN
The reaction between cholesterol (Ch) and trichloromethyl or trichloromethyl peroxyl radicals was studied. The latter were generated from CCl4 either by benzoyl peroxide (BP) catalysis or via thermal activation or by liver microsomal NADPH-dependent biotransformation of CBrCl3. The structure of the products formed was elucidated by gas chromatography-mass spectrometry (GC/MS). Under aerobic conditions and using thermal activation of CCl4, the formation of 6 products was observed. Two (I and II) were dehydrated Ch derivatives (one also having a third double bond) (I). Another product was a delta(5)-3 ketone derivative of Ch (III). Two additional reaction products were determined as ketocholesterols (IV and V). One chloro Ch was also formed (VI). At low concentrations of BP, reaction was more extensive than under thermal activation, and the formation of peaks I to IV was also observed. When the reaction was conducted anaerobically and using thermal activation of CCl4 to generate radicals, only products I and II were formed in low yield. Under anaerobic conditions, but using catalyst, compounds I and III were produced plus two new isomeric ketocholesterol derivatives (VIII and IX) and also a compound having an extra hydroxyl group on the Ch structure (X). In order to check whether similar reactions are observable under biological experimental conditions, we used activation of CBrCl3 by liver microsomes. The incubation using only microsomes (without CBrCl3 or NADPH) showed two ketocholesterol peaks (A and B). In the presence of CBrCl3 we could detect peak B and hydroxycholesterol (C) and two others, ketocholesterols (D and E). D was the only peak showing close similarity (spectrum and retention time) to one of those observed in the chemical reaction system (V). The reaction of CBrCl3 in the presence of NADPH showed peaks B, C, D and E, in low abundance and a 7-ketocholesterol (F). If some of the reaction products reported here were formed during the intoxication with these haloalkanes, significant biological consequences might be expected.
Asunto(s)
Bromotriclorometano/metabolismo , Tetracloruro de Carbono/análogos & derivados , Tetracloruro de Carbono/metabolismo , Colesterol/metabolismo , Aerobiosis , Anaerobiosis , Animales , Biotransformación , Tetracloruro de Carbono/química , Colesterol/química , Radicales Libres/metabolismo , Masculino , Espectrometría de Masas , Microsomas Hepáticos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The interaction between carbon tetrachloride (CCl4)-reactive metabolites and liver microsomal or nuclear lipids (covalent binding = CB) was studied in male rats from Osborne Mendel (OM) and Sprague Dawley (SD), strains with different cancer susceptibility. The in vitro or in vivo CB was more intense in OM than in SD. Most of the CB was with phospholipid (PL; SD > OM). The CB to cholesterol (CH) and cholesterol esters (CHE) was OM > SD. We also observed the presence of specific adducts only present in lipids from either OM or SD strains. The results were related to the well-known role of PL and CH derivatives in gene function control and cell growth.
Asunto(s)
Tetracloruro de Carbono/metabolismo , Núcleo Celular/metabolismo , Metabolismo de los Lípidos , Microsomas Hepáticos/metabolismo , Fosfolípidos/metabolismo , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Especificidad de la EspecieRESUMEN
CCl4 is a hepatic carcinogen in male Osborne-Mendel (OM) but not in Sprague Dawley (SD) male rats. We demonstrate the occurrence of NADPH-dependent CCl4-promoted lipid peroxidation processes (LP) leading to malondialdehyde (MDA) formation in liver microsomal and nuclear preparations from OM and SD rats which do not correlate with the cancer susceptibility of both strains. Our results suggest that MDA production might not be a rate determining step in the carcinogenic process. However, the formation of this reactive aldehyde proximal to DNA and nuclear proteins might play a role that remains to be elucidated.