RESUMEN
Among the first events after immersion of surfaces in the ocean is surface 'conditioning'. Here, the accumulation and composition of the conditioning films formed after immersion in the ocean are analyzed. In order to account for different surface chemistries, five self-assembled monolayers that differ in resistance to microfouling and wettability were used. Water samples from two static immersion test sites along the east coast of Florida were collected at two different times of the year and used for experiments. Spectral ellipsometry revealed that conditioning films were formed within the first 24 h and contact angle goniometry showed that these films changed the wettability and rendered hydrophobic surfaces more hydrophilic and vice versa. Infrared reflection adsorption spectroscopy showed that the composition of the conditioning film depended on both the wettability and immersion site. Laboratory and field assays showed that the presence of a conditioning film did not markedly influence settlement of microorganisms.
Asunto(s)
Organismos Acuáticos/fisiología , Biopelículas/crecimiento & desarrollo , Incrustaciones Biológicas , Agua de Mar/química , Florida , Interacciones Hidrofóbicas e Hidrofílicas , Espectrofotometría Infrarroja , Propiedades de Superficie , HumectabilidadRESUMEN
AIM: the authors conducted an open-label investigation examining the effects of modafinil in reducing fatigue in patients with cancer, undergoing cancer treatment, and receiving opioid therapy. METHODS: after approval by the local Ethics Committee and informed consent cancer patients who reported fatigue - defined as persistent tiredness interfering with usual functioning - were enrolled in the study. Once daily, patients received 100 mg open-label modafinil. The Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and a visual analogue scale (VAS, 0-10) were performed at baseline (t1), day 7 (t2), and day 28 (t3). Further assessment comprised the d2 Test of Attention (d2), the Hamilton Depression Scale (HAMD), the Eastern Cooperative Oncology Group-Score (ECOG), side effects, and patients' satisfaction with modafinil treatment. RESULTS: of the 37 patients who were enrolled, 29 completed all assessments in the study. Modafinil had a significant effect on the FSS (t1 44.6+/-12.2, t2 39+/-12.4, t3 35.3+/-13.8 (p=0.015), on the VAS (t1 6+/-3.1), t2 4.5+/-2.8, t3 3.7+/-2.8 (p=0.005), and an insignificant effect on d2 parameters of neurophysiological functioning and ESS. No differences were seen for ECOG and patients' satisfaction. No severe adverse effects were detected. CONCLUSION: modafinil improved alertness and cognitive skills in patients receiving cancer pain treatment by enhancing vigilance and cognitive performance. Although confirmation of this preliminary result is needed, these findings suggest that modafinil may improve quality of life in this patient population. However, in Germany the use of modafinil for fatigue is off-label and careful assessment of fatigue is needed prior to treatment. Randomized controlled trials are needed to confirm this evidence.
Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Fatiga/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/fisiopatología , Actividades Cotidianas/psicología , Adulto , Anciano , Anciano de 80 o más Años , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/psicología , Evaluación de la Discapacidad , Método Doble Ciego , Fatiga/etiología , Fatiga/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modafinilo , Neoplasias/psicología , Pruebas Neuropsicológicas/estadística & datos numéricos , Dimensión del Dolor/estadística & datos numéricos , Determinación de la Personalidad/estadística & datos numéricos , Psicometría , Calidad de Vida/psicología , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Results of several animal bioassays have demonstrated the carcinogenic potential of polychlorinated biphenyl (PCB) mixtures. Although PCBs are no longer manufactured, cancer risk assessment for PCBs remains an important issue because of continued potential human exposure from many sources. The existing cancer risk estimate for PCBs used by the U.S. EPA is based on liver tumors observed in female Sprague-Dawley rats in a lifetime bioassay. Liver cancer has been observed in other long-term bioassays as well. In this case study, experimental designs and biological characteristics of the data from these studies were evaluated to determine whether a combination of the data sets is scientifically reasonable. A statistical analysis of the data sets based on likelihood ratio theory was used to assess the compatibility of individual data sets to a common multistage dose-response model. The results from these biological and statistical assessments suggest that at least two data sets could be combined to derive a quantitative risk estimate for PCBs. Increased confidence in the quantitative estimate would result from such combination because more data are being used to assess the dose-response relationship.
Asunto(s)
Pruebas de Carcinogenicidad/estadística & datos numéricos , Carcinógenos/toxicidad , Neoplasias Hepáticas/inducido químicamente , Bifenilos Policlorados/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Neoplasias Hepáticas/patología , Ratas , RiesgoRESUMEN
There are often several data sets that may be used in developing a quantitative risk estimate for a carcinogen. These estimates are usually based, however, on the dose-response data for tumor incidences from a single sex/strain/species of animal. When appropriate, the use of more data should result in a higher level of confidence in the risk estimate. The decision to use more than one data set (e.g., representing different animal sexes, strains, species, or tumor sites) can be made following biological and statistical analyses of the compatibility of the these data sets. Biological analysis involves consideration of factors such as the relevance of the animal models, study design and execution, dose selection and route of administration, the mechanism of action of the agent, its pharmacokinetics, any species- and/or sex-specific effects, and tumor site specificity. If the biological analysis does not prohibit combining data sets, statistical compatibility of the data sets is then investigated. A generalized likelihood ratio test is proposed for determining the compatibility of different data sets with respect to a common dose-response model, such as the linearized multistage model. The biological and statistical factors influencing the decision to combine data sets are described, followed by a case study of bromodichloromethane.
Asunto(s)
Carcinógenos/toxicidad , Hidrocarburos Halogenados , Neoplasias Experimentales/inducido químicamente , Animales , Relación Dosis-Respuesta a Droga , Femenino , Funciones de Verosimilitud , Masculino , Ratones , Ratas , Factores de Riesgo , TrihalometanosRESUMEN
Quantitative risk assessments for carcinogens conducted by the U.S. EPA have most frequently been based on results of a bioassay from a single sex/strain/species of animal. In some cases, more than one data set derived from different sexes, strains, or species of animals is suitable for quantitative risk assessment. When there is no apparent difference among the data sets in sensitivity to the carcinogen, use of more of the available data should result in a higher level of confidence in the risk estimate. Several biological factors must be considered before combining data from different animal sexes, strains, species, or tumor sites. The relevance of the animal models, study design and execution, dose selection, and route of administration are factors which influence whether data from separate studies should be combined. The decision to combine data sets is also based on what is known of the mechanism of action of the agent, its pharmacokinetics, any species/sex specificity of the effect, and considerations regarding tumor site specificity. Statistical analysis also indicates whether the data sets may be described by the same multistage model. The evaluation of these factors in the decision to combine or not combine data sets is discussed.
Asunto(s)
Pruebas de Carcinogenicidad/métodos , Interpretación Estadística de Datos , Acrilatos/toxicidad , Animales , Árboles de Decisión , Nitrilos/toxicidad , Factores de RiesgoRESUMEN
BACKGROUND AND PURPOSE: Platelet behavior of Sprague Dawley (SD), Wistar (WI), Wistar-Kyoto (WKY), spontaneously hypertensive (SHR), and stroke-prone spontaneously hypertensive rats (SHRSP) was studied in vivo to evaluate the importance of hypertension-related hemostatic disorders. METHODS: The study was based on the model of stimulus-induced pulmonary microembolization of labeled platelets. After injection of 51Cr-labeled homologous platelets into urethane-anesthetized rats, the organ distribution of the platelets was continuously monitored by gamma detectors. Count rates of two detectors--one placed above the animals' thoraxes (C1), the other above their abdomens (C2)-and the ratio of C1:C2 were calculated. The following platelet activators were applied intravenously: adenosine diphosphate (ADP; 50 micrograms/kg), collagen (100 micrograms/kg), and thrombin (50 IU/kg). RESULTS: All three substances caused a reversible pulmonary accumulation of the labeled platelets and hence an increase in C1/C2 (delta C1/C2%). ADP induced a shift of 75% in SD, 52% in WI, 32% in WKY, 30% in SHR, and 31% in SHRSP. Thrombin-mediated shift was 79% in SD, 64% in WI, 58% in WKY, 48% in SHR, and 54% in SHRSP. Collagen induced a shift of 85% in SD, 96% in WI, 84% in WKY, 56% in SHR, and 62% in SHRSP. CONCLUSIONS: Because indistinguishable results were observed in both hypertensive strains, we conclude that impaired platelet aggregation is not specific for SHRSP. Hence, it may not primarily be responsible for the increased occurrence of stroke in these animals.
Asunto(s)
Activación Plaquetaria , Ratas Endogámicas SHR/sangre , Adenosina Difosfato/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Trastornos Cerebrovasculares/sangre , Trastornos Cerebrovasculares/genética , Radioisótopos de Cromo , Colágeno/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Técnicas In Vitro , Cinética , Masculino , Activación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Probabilidad , Ratas , Ratas Endogámicas WKY/sangre , Ratas Sprague-Dawley/sangre , Ratas Wistar/sangre , Especificidad de la EspecieRESUMEN
The metabolism of DMBA by microsomes and various cell cultures has been widely studied. However, the biotransformation of this compound by intact organs has not been well characterized. In order to compare the metabolism of DMBA in the whole liver with that in subcellular preparations, we used an in situ single-pass rat liver perfusion system and rat liver microsomes. [14C]DMBA was infused into the livers of Sprague-Dawley rats during the first 60 min of a 120 min perfusion. HPLC analysis of extracts of perfusate samples indicated that DMBA was rapidly oxidized in this system to a series of metabolites. The major products were polar metabolites including the trans-5,6- and the trans-10,11-dihydrodiols (46%), the trans-3,4-dihydrodiol (5%) and the 7-OHM-12-MBA and the 12-OHM-7-MBA metabolites (12%) of DMBA. Microsomes prepared from livers of corn oil treated rats were incubated with [14C]DMBA for 60 min, then extracted. In the microsomal system the major DMBA metabolites were the trans-8,9-dihydrodiol (6%), the 7- and 12-hydroxymethyl (20%), and the 3- and 4-hydroxy (11%) of DMBA with the more polar metabolites and the trans-3,4-dihydrodiol present at lower levels (12 and 3% respectively). This is the first report of DMBA metabolism in a whole liver preparation and the results are clearly different from those obtained in subcellular preparations in our laboratory and in cell culture systems elsewhere. These results have important implications for understanding DMBA biotransformation in vivo.
Asunto(s)
9,10-Dimetil-1,2-benzantraceno/metabolismo , Hígado/metabolismo , Microsomas Hepáticos/metabolismo , 9,10-Dimetil-1,2-benzantraceno/análogos & derivados , Animales , Masculino , Oxidación-Reducción , Perfusión , Ratas , Ratas EndogámicasRESUMEN
Dimethylbenz(a)anthracene (DMBA) is a potent inducer of mammary tumors in intact female Sprague-Dawley rats, but not in males or ovariectomized females (OVX). Qualitative and quantitative aspects of hepatic metabolism of DMBA were examined in these three groups of rats, using the nonrecirculating perfused liver, to determine whether the production of proximate carcinogenic metabolites of DMBA by the liver differed among these groups in the same manner as does sensitivity to tumor induction. DMBA was infused into the liver at a constant rate for 60 min. Rates of appearance of DMBA and its metabolites were measured in perfusate and bile during the infusion period and the first 60 min thereafter. The maximum rate of appearance of total metabolites in the perfusate, seen at the end of the infusion period, was highest in the intact female [2.6 +/- 0.3 nmol/(g x min)], slightly lower in the OVX [2.3 +/- 0.2 nmol/(g x min)] and significantly lower in the male [1.0 +/- 0.1 nmol/(g x min)]. The rates of appearance of metabolites in the bile showed the same order as those seen in the perfusate. The major metabolites extracted from the perfusate in all three groups were dihydrodiols, hydroxymethyl metabolites, and several unidentified metabolites. The 3,4-dihydrodiol, a proximate carcinogenic metabolite, appeared in the perfusate at higher rates in the intact female and OVX than in the male. Hydrolysis of bile samples showed that glucuronidation was a major pathway in the excretion of DMBA metabolites in bile. High performance liquid chromatographic analysis indicated that hydrolysis of DMBA glucuronides yielded the 7- and 12-hydroxymethyl metabolites and an unidentified metabolite designated X. The major hydrolysis product in the male was 12-hydroxymethyl while X was found to be the major product in the intact female and OVX. Under the conditions of this study, there were differences in the metabolic activation of DMBA by male and female rat liver. Ovariectomy, followed by DMBA perfusion 7 days later, did not result in significant changes in DMBA metabolism relative to the intact female, except for a decreased rate of excretion of metabolites in bile.