RESUMEN
The thymus is the anatomical site where T cells undergo a complex process of differentiation, proliferation, selection, and elimination of autorreactive cells which involves molecular signals in different intrathymic environment. However, the immunological functions of the thymus can be compromised upon exposure to different infections, affecting thymocyte populations. In this work, we investigated the impact of malaria parasites on the thymus by using C57BL/6 mice infected with Plasmodium berghei ANKA and Plasmodium yoelii 17XL; these lethal infection models represent the most severe complications, cerebral malaria, and anemia respectively. Data showed a reduction in the thymic weight and cellularity involving different T cell maturation stages, mainly CD4-CD8- and CD4+CD8+ thymocytes, as well as an increased presence of apoptotic cells, leading to significant thymic cortex reduction. Thymus atrophy showed no association with elevated serum cytokines levels, although increased glucocorticoid levels did. The severity of thymic damage in both models reached the same extend although it occurs at different stages of infection, showing that thymic atrophy does not depend on parasitemia level but on the specific host-parasite interaction.
Asunto(s)
Malaria , Plasmodium yoelii , Animales , Ratones , Plasmodium berghei , Ratones Endogámicos C57BL , Atrofia , ParasitemiaRESUMEN
Cerebral malaria (CM) is a neurological complication derived from the Plasmodium falciparum infection in humans. The mechanisms involved in the disease progression are still not fully understood, but both the sequestration of infected red blood cells (iRBC) and leukocytes and an exacerbated host inflammatory immune response are significant factors. In this study, we investigated the effect of Monocyte Locomotion Inhibitory Factor (MLIF), an anti-inflammatory peptide, in a well-characterized murine model of CM. Our data showed that the administration of MLIF increased the survival and avoided the neurological signs of CM in Plasmodium berghei ANKA (PbA) infected C57BL/6 mice. MLIF administration down-regulated systemic inflammatory mediators such as IFN-γ, TNF-α, IL-6, CXCL2, and CCL2, as well as the in situ expression of TNF-α in the brain. In the same way, MLIF reduced the expression of CD31, CD36, CD54, and CD106 in the cerebral endothelium of infected animals and prevented the sequestration of iRBC and leucocytes in the brain microvasculature. Furthermore, MLIF inhibited the activation of astrocytes and microglia and preserved the integrity of the blood-brain barrier (BBB). In conclusion, our results demonstrated that the administration of MLIF increased survival and conferred neuroprotection by decreasing neuroinflammation in murine CM.
Asunto(s)
Antiinflamatorios/administración & dosificación , Malaria Cerebral/prevención & control , Fármacos Neuroprotectores/administración & dosificación , Oligopéptidos/administración & dosificación , Animales , Astrocitos/efectos de los fármacos , Astrocitos/inmunología , Encéfalo/efectos de los fármacos , Encéfalo/inmunología , Encéfalo/patología , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/inmunología , Femenino , Humanos , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Malaria Cerebral/inmunología , Malaria Cerebral/parasitología , Malaria Cerebral/patología , Ratones , Microglía/efectos de los fármacos , Microglía/inmunología , Plasmodium berghei/inmunologíaRESUMEN
Specimens of Petalophthalmus armiger Willemoes-Suhm, 1875, were collected off western Mexico during a deep-water survey. Six males and 32 females were obtained from 18 sampling localities in western Mexico. The species is redescribed in detail, including illustrations of body and appendages, and SEM photographs of the mandibles. The new material indicates that P. armiger is widely distributed in the area and more common than previously thought in the eastern Pacific. Samples indicate that P. armiger inhabits water far offshore, where total depth exceeds 1000 m. Due to the lack of discrete samplings in the water column, however, the precise depth interval where P. armiger occurs cannot be defined.
Asunto(s)
Crustáceos , Gastrópodos , Distribución Animal , Animales , Femenino , Masculino , Mandíbula , México , Manejo de EspecímenesRESUMEN
The distribution of two species of the deep-water shrimp genus Nematocarcinus A. Milne-Edwards, 1881, occurring off the west coast of Mexico is analyzed based on a large series of recently collected material. Nematocarcinus faxoni Burukovsky, 2000, is by far the most common and abundant species in the area and it is distributed throughout the central and southern Gulf of California and off the entire Baja California Peninsula south to 17º10'15"N. Based on characteristics observed in the new samples and in the type material, N. agassizii Faxon, 1893, is reinstalled as a valid species, and no longer considered a junior of N. gracilipes A. Milne-Edwards, 1881, as proposed by Cardoso & Burukovsky (2014). Along the Pacific coast of Mexico, N. agassizii exhibits a more restricted distribution and it was collected only off the Baja California Peninsula. Previous records of this species in the Gulf of California, where N. faxoni was the only representative of the genus captured during this survey, are considered doubtful.
Asunto(s)
Decápodos/clasificación , Distribución Animal , Estructuras Animales/anatomía & histología , Estructuras Animales/crecimiento & desarrollo , Animales , Tamaño Corporal , California , Decápodos/anatomía & histología , Decápodos/crecimiento & desarrollo , Ecosistema , Femenino , Masculino , México , Tamaño de los Órganos , Océano PacíficoRESUMEN
We studied the effect of vine water status on the dimethyl sulfur potential (DMSP), ammonium, and amino acid contents of the berry during the maturation of Grenache Noir grapes. Water deficit increased the accumulation of amino acids in berries and favored yeast assimilable amino nitrogen. Similarly, ammonium content was higher in berries from vines subjected to moderate water deficit. DMSP content followed the same trend as yeast assimilable amino acid content, with higher concentrations observed in the berries of vines subjected to water deficit. The high DMSP and yeast assimilable nitrogen contents of musts from vines subjected to water deficit resulted in a better preservation of DMSP during winemaking. The wines produced from these musts had a higher DMSP level and would therefore probably have a higher aroma shelf life, because the DMSP determines the rate of release of dimethyl sulfur during wine storage, and this compound enhances fruity notes.
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Aminoácidos/análisis , Compuestos de Amonio/análisis , Sulfuros/análisis , Vitis/química , Agua/análisis , Vino/análisis , Fermentación , Frutas/químicaRESUMEN
The host response against Mycobacterium tuberculosis show a wide spectrum of clinical manifestations in those patients who fail to control the infection. The course of the infection and its epidemiological consequences depend upon a complex interplay of host, environmental and bacterial factors. Experimental animal models have helped to define the influence of bacterial genetic diversity on virulence and on the immune response that is induced. For this purpose, experimental animals such as mice, guinea pigs and rabbits have been infected with selected clinical isolates obtained from outbreaks or from clinical epidemiology settings. Here we review the contribution of mouse models to defining the variability in virulence and immune response in relation to mycobacterial genetic diversity. Low dose aerosol infection in C57Bl mice or high dose intratracheal infection in BALB/c mice have demonstrated wide variability in virulence and immune responses induced by different bacterial genotypes, and each genotype has different phenotypes, with high and low virulence variants. In general, these studies have shown that high prevalent strains from big clusters are more virulent than low prevalent sporadic clinical isolates, and highly virulent strains induce non-protective immune responses with some correlation with clinical-epidemiological data. In the future selected strains from these types of studies should be analyzed with molecular technologies. These kinds of study will contribute to the identification of mycobacterial genes associated with virulence and immunogenicity.
Asunto(s)
Genotipo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidad , Tuberculosis/microbiología , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Mycobacterium tuberculosis/inmunología , Tuberculosis/epidemiología , VirulenciaRESUMEN
BACKGROUND: Polymerized-type I collagen (polymerized-collagen) is a down-regulator of inflammation and a tissue regenerator biodrug. The aim of this study was to evaluate its effect in co-cultures of cartilage and synovial tissue from patients with knee osteoarthritis (OA). MATERIALS AND METHODS: Cartilage and synovial tissue from five patients with OA were co-cultured for 7 days in the presence or absence of 1% polymerized-collagen. To determine proteoglycans content, tissues were stained with alcian blue technique. Pro- and anti-inflammatory cytokines [interleukin (IL)-1beta, IL-8, IL-10, IL-12, tumour necrosis factor (TNF)-alpha, and interferon (IFN)-gamma] and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in supernatants by ELISA and results were normalized by total protein concentration. Cartilage oligomeric matrix protein (COMP), type II collagen, TNF-alpha, IL-10 and Ki-67 expression were determined by immunohistochemistry. RESULTS: Polymerized-type I collagen induced an increase of 3- to 6fold cell proliferation (Ki-67), proteoglycans content, and COMP and type II collagen expression, whereas it inhibited IL-1beta and TNF-alpha production. IL-10 levels were up-regulated in treated vs. untreated cultures. No differences were found on IL-8 or TIMP-1 levels in supernatants from polymerized-collagen-treated co-cultures when compared with untreated cultures. IL-12 and IFN-gamma were undetectable. CONCLUSION: The addition of polymerized-type I collagen to cartilage and synovial tissue co-cultures induced up-regulation of chondrocytes proliferation and cartilage extracellular matrix proteins production (COMP, type II collagen and proteoglycans) as well as an anti-inflammatory cytokine (IL-10) and the down-modulation of pro-inflammatory cytokines (IL-1beta and TNF-alpha). It is possible that this mechanism might contribute to induce tissue regeneration and down-regulation of inflammation in OA.
Asunto(s)
Cartílago/patología , Colágeno Tipo I/metabolismo , Osteoartritis de la Rodilla/patología , Membrana Sinovial/patología , Anciano , Anciano de 80 o más Años , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Osteoartritis de la Rodilla/tratamiento farmacológicoRESUMEN
In order to assess the presence of yellow head virus (YHV) in shrimp farms along the Pacific coast of Mexico, 39 samples from 26 randomly chosen farms were analysed by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and dot-blot hybridization. Eleven samples were positive for YHV. The disease was reproduced by means of an infectivity bioassay performed with an extract of pleopods from the positive samples. Cumulative mortality reached 50% in 14 days. Four pairs of primers which amplified several YHV genome regions were designed and used to test dead and surviving shrimp from the bioassay by RT-PCR, resulting in positive results for every expected amplicon. The results of this study provide presumptive evidence of the presence of YHV in Mexican shrimp farms at least during 1999-2000.
Asunto(s)
Penaeidae/virología , Roniviridae/aislamiento & purificación , Animales , Immunoblotting , México , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Roniviridae/patogenicidadRESUMEN
Cochlear disruptions induced by toluene were shown in the rat but not in the guinea pig. To better understand the differences between species, three investigations were carried out to study (1) the blood affinity and the pulmonary uptake of the solvent, (2) its clearance and (3) its urinary elimination in both species. The blood affinity of toluene was +44% higher in the rat than in the guinea pig (14.4µg/g versus 10µg/g). Similarly, the pulmonary uptake of toluene was approximately 46.5% more efficient in the rat than in the guinea pig (75.4µg/g versus 40.3µg/g) after 3h inhalation of 1500ppm toluene. Therefore, the physicochemical composition of the blood could explain the difference in the uptake performances between rats and guinea pigs. The clearance of the toluene showed that 10min after an intravenous administration of 400µL of vehicle containing 28µL (43mgkg(-1)) of toluene, the solvent concentration was approximately threefold higher in the rat than in the guinea pig blood. The last experiment was carried out to compare the concentrations of the urinary metabolites. The concentrations of o-cresol, hippuric and benzyl mercapturic acids measured in the urines were different before and after the toluene injection. These data give evidence for large differences of toluene uptake and metabolism between rat and guinea pig. Therefore, it seems reasonable to claim that guinea pigs cochleas are not susceptible to toluene as the blood burden of solvent does not reach the concentration required to induce permanent damages.
RESUMEN
Toluene is the most widely used industrial solvent. It has been shown to cause cochlear disruptions in rats but markedly less ototoxic effects in guinea pigs. Susceptibility to the ototoxic properties of toluene is, therefore, species specific. In recent publications, an important difference in the solvent concentration in blood has been identified when rats and guinea pigs were exposed in strictly identical experimental conditions. Solvent concentrations in blood were greater in rats than in guinea pigs. The present studies were designed to compare blood affinity and toxicokinetic parameters of toluene in an attempt to understand the susceptibility differences in both species. The in vitro experiment, in which the headspace concentration of toluene was measured within a sealed vial containing blood, highlighted the greater toluene partition coefficient in rat than in guinea pig blood. The in vivo experiment showed that 10min after a single intravenous administration of 28µL of toluene, the solvent concentration is approximately two-fold lower in guinea pig than in rat blood. Based on the toxicokinetic parameters of toluene and on the relative partition coefficient of toluene in blood, it seems plausible that guinea pigs are not susceptible to organic solvents because the solvent concentration in blood does not reach the concentration required to induce permanent damage. Attempts to explain differences of vulnerability between the rat and guinea pig are addressed in the present paper.
RESUMEN
To obtain better insight into the robustness of in vitro percutaneous absorption methodology, the intra- and inter-laboratory variation in this type of study was investigated in 10 European laboratories. To this purpose, the in vitro absorption of three compounds through human skin (9 laboratories) and rat skin (1 laboratory) was determined. The test materials were benzoic acid, caffeine, and testosterone, representing a range of different physico-chemical properties. All laboratories performed their studies according to a detailed protocol in which all experimental details were described and each laboratory performed at least three independent experiments for each test chemical. All laboratories assigned the absorption of benzoic acid through human skin, the highest ranking of the three compounds (overall mean flux of 16.54+/-11.87 microg/cm(2)/h). The absorption of caffeine and testosterone through human skin was similar, having overall mean maximum absorption rates of 2.24+/-1.43 microg/cm(2)/h and 1.63+/-1.94 microg/cm(2)/h, respectively. In 7 out of 9 laboratories, the maximum absorption rates of caffeine were ranked higher than testosterone. No differences were observed between the mean absorption through human skin and the one rat study for benzoic acid and testosterone. For caffeine the maximum absorption rate and the total penetration through rat skin were clearly higher than the mean value for human skin. When evaluating all data, it appeared that no consistent relation existed between the diffusion cell type and the absorption of the test compounds. Skin thickness only slightly influenced the absorption of benzoic acid and caffeine. In contrast, the maximum absorption rate of testosterone was clearly higher in the laboratories using thin, dermatomed skin membranes. Testosterone is the most lipophilic compound and showed also a higher presence in the skin membrane after 24 h than the two other compounds. The results of this study indicate that the in vitro methodology for assessing skin absorption is relatively robust. A major effort was made to standardize the study performance, but, unlike in a formal validation study, not all variables were controlled. The variation observed may be largely attributed to human variability in dermal absorption and the skin source. For the most lipophilic compound, testosterone, skin thickness proved to be a critical variable.
Asunto(s)
Ácido Benzoico/farmacocinética , Cafeína/farmacocinética , Laboratorios/normas , Absorción Cutánea , Testosterona/farmacocinética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Ácido Benzoico/normas , Cadáver , Cafeína/normas , Cámaras de Difusión de Cultivos/métodos , Europa (Continente) , Femenino , Adhesión a Directriz/normas , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Ratas , Estándares de Referencia , Reproducibilidad de los Resultados , Grosor de los Pliegues Cutáneos , Testosterona/normasRESUMEN
OBJECTIVES: To compare the apparent urinary excretion rates of both creatinine and 1-hydroxypyrene (1-OHP) and to assess the value of creatinine normalization for both toxicokinetic analysis and the routine examination of workers. METHODS: All urine samples were collected from individuals who had been exposed to polycyclic aromatic hydrocarbons (PAHs), occupationally and non-occupationally, for at least 24 consecutive hours. Urinary creatinine and 1-OHP were determined. 1-OHP excretion rates were expressed either as a function of creatinine excretion rate or as unadjusted values. Theoretical relationships between creatinine-normalized excretion of metabolites and body weight-adjusted inhaled dose were drawn for men with a constant body mass index. RESULTS: Creatinine excretion rate paralleled 1-OHP excretion rate. The plot of creatinine excretion rate-adjusted excretion rate of 1-OHP vs time led to smooth curves for determination of toxicokinetic parameters. Creatinine normalization was adequate, even for samples with a urinary creatinine concentration below 0.5 g/l or above 3 g/l. A theoretical analysis revealed that men weighing between 50 kg and 100 kg, exposed to a constant dose of a pollutant producing a urinary metabolite excreted by the same mechanism as creatinine, would exhibit a body weight-adjusted dose span of 2 with an accompanying creatinine-normalized metabolite excretion span of 2.23-fold. CONCLUSION: The kinetics of creatinine excretion parallels that of 1-OHP, and a creatinine excretion rate-normalized excretion rate of 1-OHP appears to allow for a better determination of the toxicokinetic parameters of 1-OHP urinary excretion. At least in the case of 1-OHP, creatinine normalization seems valid, even for very dilute or very concentrated urine samples. Finally, because creatinine normalization not only compensates for variable diuresis but also correlates better with the body weight-adjusted dose of the parent compound, it should be used in biological monitoring of exposure to (PAHs) pyrene and to other substances whose urinary biomarker excretion kinetics parallel that of creatinine.
Asunto(s)
Creatinina/orina , Exposición Profesional , Compuestos Policíclicos/toxicidad , Pirenos/análisis , Humanos , Masculino , Compuestos Policíclicos/farmacocinéticaRESUMEN
The author recounts the lessons taught by single-fiber electromyography that reached him through the medium of low-frequency attenuation and a small concentric needle electrode. He concludes that it is difficult to imagine practicing electromyography today without the benefits that have flowed from the work of Erik Stålberg and his colleagues.
Asunto(s)
Electromiografía/historia , Neurofisiología/historia , Historia del Siglo XX , Humanos , Neurofisiología/instrumentación , Estados UnidosRESUMEN
This study evaluated the toxicokinetics of [(14)C]di-n-butylphthalate ([(14)C]DBP) after an intravenous administration (1 and 10 mg/kg, in Cremophor) or a topical application (10 microl/cm(2); 10 cm(2), neat) in haired male Sprague-Dawley rats. Additional in vivo and in vitro percutaneous penetration studies of [(14)C]DBP were conducted on male and female haired rats and male hairless rats. After intravenous administration, unchanged DBP disappeared rapidly from the plasma, following a two-exponential function (T1/2beta = 5-7 min). The peak levels of monobutylphthalate (MBP) and its glucuronide conjugate (MBP-Gluc) occurred 1 to 2 and 20 to 30 min after administration, respectively. These metabolites were intensively and rapidly excreted in urine (57% of the dose). However, about 35% of the dose recovered in urine was primarily excreted in bile (mainly as MBP-Gluc) and underwent hepatobiliary recycling. Unchanged DBP was barely detectable in excreta. DBP rapidly penetrated the skin, which constituted a reservoir. The absorption flux determined for 0.5 to 8 and 8 to 48 h of exposure were 43 and 156 microg/cm(2)/h, respectively. The higher flux may be due to radial diffusion of DBP in the stratum and/or epidermis. The in vivo and in vitro experiments revealed that DBP was intensively metabolized into the skin. In vivo percutaneous absorption flux was very similar in male and female haired rats. In contrast, the percutaneous absorption determined in vivo and in vitro was higher in hairless than in haired male rats. Absorption flux was accurately estimated from urinary excretion rate of MBP or MBP-Gluc.
Asunto(s)
Radioisótopos de Carbono/farmacocinética , Absorción Cutánea , Animales , Femenino , Técnicas In Vitro , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
In a previous study, it was shown that the neurotoxic compound 1,2-diethylbenzene (1,2-DEB) is mainly hydroxylated in the alkyl chain to give 1-(2'-ethylphenyl)ethanol (1,2-EPE) and excreted in urine of rats as two glucuronide compounds (GA1 and GA2). Some findings have suggested that the two enantiomers of 1,2-EPE are formed in vivo. In the present study, a chiral high-performance liquid chromatography method was developed to separate the two enantiomers of 1,2-EPE from a synthesized racemic mixture. Absolute configuration of both enantiomers was determined after esterification with (R)-(+)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetic acid and analysis of their (1)H NMR spectra in CCl(4) added with Eu (fod)(3). The two main urinary metabolites, GA1 and GA2, from [(14)C]1,2-DEB-treated Sprague-Dawley rats (80 mg/kg, i.p.) were identified, after hydrolysis with beta-glucuronidase from Escherichia coli, as (R) and (S) glucuronide conjugates of 1,2-EPE, respectively. In vitro hydroxylation of 1,2-DEB and glucuroconjugation of 1,2-EPE were under stereoselective control in S9 fraction or microsomes from male Sprague-Dawley rat liver. The V(max) and K(m) constants for (R)1,2-EPE enantiomer formation determined in S9 fraction were greater than those for the (S) enantiomer. In the plasma of bile duct-cannulated rats, the ratio was 1.2 +/- 0.02 over the 1- to 4-h period after oral administration of [(14)C]1,2-DEB (100 mg/kg). In contrast, the glucuroconjugation rate of (S)1,2-DEB enantiomer was 4 times that of (R)1,2-EPE glucuroconjugation. A similar ratio of (R) to (S)1,2-EPE glucuronide conjugates was obtained in the plasma of bile duct-cannulated rats.
Asunto(s)
Derivados del Benceno/farmacocinética , Animales , Derivados del Benceno/sangre , Derivados del Benceno/toxicidad , Espectroscopía de Resonancia Magnética , Masculino , Ratas , Ratas Sprague-Dawley , EstereoisomerismoRESUMEN
Five representative workers and two external observers were monitored by personal air and urinary 1-hydroxypyrene (PyOH) sampling for a four-shift working week in an artificial shooting target factory. The targets (clay pigeons), are made from petroleum pitch and molded at 190 degrees C. No respiratory protective mask was worn. Atmospheric concentrations of pyrene and benzo (a) pyrene (BaP) ranged from 0.66 to 5.05 microg/m(3) and 0.037 to 0.270 microg/m(3) respectively with a mean pyrene/BaP ratio of about 20 and a correlation r = 0.51. Maximum PyOH urinary excretion ranged from 1.84 to 10.9 micromol/molCreat. This occurred at the postshift for the observers but often appeared later for workers: up to 10.75 h for the person with the apparently highest dermal exposure. The apparent PyOH excretion half lives ranged from 1.9 to 12.5 h with an arithmetic mean of 6.1 h. All these data were confirmed by additional measurements taken over a weekend after the postshift. The correlation between atmospheric pyrene and urinary PyOH concentrations (increase over the shift) was poor (r = 0.37). It improve greatly (r = 0.74) if the amount of pyrene inhaled over the shift and the corresponding amount of PyOH excreted were considered. The ratio of urinary excreted PyOH to the pyrene inhaled dose (with assumed retention of 100%), ranged from 0.18 to 0.70 (arithmetic mean = 0.34). This suggests that the respiratory tract is the main entrance route for pyrene (apart from the worker who handled crude targets without gloves).
Asunto(s)
Contaminantes Ocupacionales del Aire/orina , Mutágenos/análisis , Exposición Profesional , Hidrocarburos Policíclicos Aromáticos/orina , Pirenos/análisis , Contaminantes Ocupacionales del Aire/análisis , Cromatografía Líquida de Alta Presión , Monitoreo del Ambiente/instrumentación , Femenino , Humanos , Industrias , Masculino , Hidrocarburos Policíclicos Aromáticos/análisis , UltrasonidoRESUMEN
The excretion and metabolism of neurotoxic 1,2-diethylbenzene (1, 2-DEB) was studied in male Sprague-Dawley rats after i.v. (1 mg/kg) or oral (1 or 100 mg/kg) administration of 1,2-diethyl[U-(14)C]benzene ([(14)C]1,2-DEB). Whatever the treatment, radioactivity was mainly excreted in urine (65-76% of the dose) and to a lower extent in feces (15-23% of the dose), or via exhaled air (3-5% of the dose). However, experiments with rats fitted with a biliary cannula demonstrated that about 52 to 64% of the administered doses (1 or 100 mg/kg) were initially excreted in bile. Biliary metabolites were extensively reabsorbed from the gut and ultimately excreted in urine after several enterohepatic circulations. Insignificant amounts of unchanged 1,2-DEB were recovered in the different excreta (urine, bile, and feces). As reported previously, presence of 1-(2'-ethylphenyl)ethanol (EPE) was confirmed in urine and demonstrated in bile and feces. The two main [(14)C]1,2-DEB metabolites accounted for 57 to 79% of urinary and biliary radioactivity, respectively. Beta-Glucuronidase hydrolysis and electron impact mass spectra results strongly supported their glucuronide structure. Additionally, these two main metabolites were thought to be the glucuronide conjugates of the two potential enantiomers of EPE. The results indicate that the main initial conversion step of the primary metabolic pathway of 1,2-DEB appears to be the hydroxylation of the alpha-carbon atom of the side chain. The presence of two glucuronide conjugates of EPE in the urine in a ratio different from one suggests that the metabolic conversion of 1, 2-DEB is under stereochemical control.
Asunto(s)
Derivados del Benceno/farmacocinética , Conductos Biliares/metabolismo , Administración Oral , Animales , Derivados del Benceno/toxicidad , Radioisótopos de Carbono , Cateterismo , Glucurónidos/aislamiento & purificación , Masculino , Tasa de Depuración Metabólica , Ratas , Ratas Sprague-DawleyRESUMEN
Sprague-Dawley rats were administered 1,2-diethylbenzene (1,2-DEB) by gavage on gestational days (GD) 6 through 20 at dose levels of 0 (corn oil), 5, 15, 25 or 35 mg/kg. The dams were euthanized on GD21 and the offspring were weighed and examined for external, visceral and skeletal alterations. Maternal toxicity, indicated by significant decreases in body weight gain and food consumption, was observed at doses of 15 mg/kg and above. Developmental toxicity, expressed as significantly reduced foetal body weights, was seen at doses of 15 mg/kg and higher. There was no evidence of embryolethal or teratogenic effects at any dose tested. The placental transfer of 1,2-DEB was examined after a single oral dose of 25 mg [14C]1,2-DEB/kg on GD18. Maternal and foetal tissues were collected at intervals from 1 to 48 hours. Placental and foetal tissues accounted for less than 0.35% of the administered dose. Levels of radiocarbon in foetuses were lower than those in maternal plasma and placenta at all time points. Analysis performed at 1, 2 and 4 hours indicated that ethyl acetate extractable (acidic) metabolites were predominant in the maternal plasma while n-hexane extractable (neutral) compounds represented the major part of radioactivity in the placenta and foetus. In conclusion, this study demonstrated that 1,2-DEB causes mild foetotoxicity at maternal toxic doses and that the exposure of the developing rat foetus to 1,2-DEB and/or metabolites after maternal administration of 1,2-DEB in late gestation is small.
Asunto(s)
Derivados del Benceno/farmacocinética , Derivados del Benceno/toxicidad , Desarrollo Embrionario y Fetal/efectos de los fármacos , Intercambio Materno-Fetal , Anomalías Inducidas por Medicamentos/etiología , Anomalías Inducidas por Medicamentos/metabolismo , Administración Oral , Animales , Derivados del Benceno/administración & dosificación , Transporte Biológico , Ingestión de Alimentos/efectos de los fármacos , Femenino , Absorción Intestinal , Masculino , Placenta/metabolismo , Embarazo , Ratas , Ratas Sprague-Dawley , Aumento de Peso/efectos de los fármacosRESUMEN
OBJECTIVES: The physical properties of the resin-modified composite resin Dyract (Detrey Dentsply) and the resin-modified glass ionomer cement Fuji II LC (GC) were compared, and the effect of water sorption on these properties was studied. METHODS: Compressive, diametral compressive and flexural strengths were measured using specimens aged up to three months. The Vickers hardness and the water erosion were also determined. The specimens were stored at 37 degrees C under five different conditions, chosen to vary the water sorption of the samples. The results were analyzed using a multi-factor analysis of variance. RESULTS: Dry specimens of Dyract and Fuji II LC showed similar properties. However, the two materials behaved differently when stored in presence of water. In contrast to Fuji II LC, Dyract showed very little expansion for the first 24 h (1.5 +/- 0.3 and 0.03 +/- 0.01%, respectively), leached small quantities of ions and retained its mechanical strength. Those differences are related to their chemical composition. Fuji II LC is hydrophilic, as it contains polyHEMA. In the presence of water, Fuji II LC behaves like a hydrogel, but the network resulting from the copolymerization of acidic and UDMA monomers is less hydrophilic, and the effect of water on Dyract is retarded. SIGNIFICANCE: The significant properties of Dyract are determined by its composite character. This certainly represents some advantages, for instance, a higher mechanical strength, a better protection against initial dehydration and subsequent water effects. However, Dyract shows some disadvantages over Fuji II LC, like a lower amount of fluoride release or the interference of oxygen during polymerization.
Asunto(s)
Compómeros , Resinas Compuestas/química , Cementos de Ionómero Vítreo/química , Metacrilatos/química , Resinas Sintéticas/química , Silicatos/química , Absorción , Adsorción , Análisis de Varianza , Fenómenos Químicos , Química Física , Fuerza Compresiva , Elasticidad , Dureza , Ensayo de Materiales , Solubilidad , Resistencia a la Tracción , Viscosidad , Agua/química , HumectabilidadRESUMEN
OBJECTIVES: Resin-modified glass ionomer cements (GIC) are available for clinical use as restorative materials or as liners and bases. This work was conducted to study the effect of water sorption on the physical properties of several resin-modified GIC, by changing the samples' storage conditions. METHODS: The water sorption, the flexural strength, the flexural elastic modulus, the Vickers hardness and the dimensional changes of five resin-modified GICs were measured using specimens aged for 24 h to 3 mon. The specimens were stored at 37 degrees C, either in a dry environment (A), immersed in water (B), stored in a humid environment (C), stored in a humid environment for 1 h and then immersed in water (D), or immersed in water and subsequently dried (B + A). An analysis of variance was used to compare the results. RESULTS: The resin-modified GIC absorb during the first 24 h large amounts of water (114-172 mg/cm3) compared to the conventional GIC (30-63 mg/cm3). Water alters the physical properties of resin-modified GICs: With regard to dry specimens, a decrease in the flexural strength of 20 to 80% was observed for samples immersed in water. Decreases in their flexural elastic modulus (50 to 80%) and in their hardness (approximately 50%) were also observed. Water sorption also provoked an expansion in volume of the immersed specimens, ranging from 3.4 to 11.3% after 24 h. SIGNIFICANCE: The flexural strength and Vickers hardness of the resin-modified GICs are sensitive to the water contained in the tested specimens. A correlation was established between the decrease in their physical properties and the water uptake. However, it should not be concluded that these materials are not adequate for use in applications in direct contact with oral fluids. Probably, resin-modified GIC placed in oral cavities would not be affected to the same extent as in in vitro tests. In an oral environment, the constituents of saliva will certainly decrease the rate of water sorption and will hence delay its effects.