RESUMEN
A novel class of glycopeptidolipids is described, which potentially can be used as a novel antigen-delivery system. The compounds have been prepared by a combination of solid-supported and solution-based methods. The use of the orthogonally protected FmocLysDde derivative provided an opportunity to incorporate two different types lipids. It was found that the model compound 1 forms aggregates in aqueous media which can be described as rod or tubelike structures. The aggregates can be stabilized by topotactic photopolymerization. Studies on the structural analogues 2-5 revealed the effect of the carbohydrate, peptide, and lipid moiety on the aggregation properties. It is concluded that none of the structure elements can lay claim to be exclusively important for the formation of highly organized aggregates such as tubes, fibers, or helical ribbons from 1, but the presence of all of these structural elements afforded the most uniformly shaped extended structures.
Asunto(s)
Vacunas Bacterianas/química , Monosacáridos/química , Tensoactivos/química , Secuencia de Carbohidratos , Grabado por Congelación , Técnica de Fractura por Congelación , Lipopolisacáridos/química , Espectroscopía de Resonancia Magnética , Microscopía Electrónica , Datos de Secuencia Molecular , Difracción de Rayos XRESUMEN
The effects of cadmium exposure during pregnancy (by means of daily subcutaneous injections of 4.4 mumol/kg to the mother) on the neonates were investigated. No effect was observed on fetal or neonatal body weights, nor on neonatal liver weights. These parameters were examined up to 5 weeks after birth. The weight of neonatal thymuses was decreased 7 and 14 days after birth due to cadmium exposure of the mothers as compared with controls. This may be caused by zinc deficiency, because zinc concentrations in fetal and neonatal livers after cadmium exposure were found to be very low 20 days after conception and 5 h after birth. Cadmium concentration in neonatal liver decreased; however, cadmium in malignant liver increased as age increased. In the mother, cadmium was transferred to the milk, as it was demonstrated in the stomach contents of the pups. Simultaneous administration of zinc in amounts equimolar to cadmium did not have any noticeable effect on the amount of cadmium transferred to the fetus or on cadmium concentrations in any of the organs investigated. It could not prevent zinc deficiency in fetal and neonatal liver. In addition, growth retardation of the thymus from exposed pups could not be prevented by zinc administration.
Asunto(s)
Cadmio/toxicidad , Hígado/metabolismo , Zinc/metabolismo , Animales , Animales Recién Nacidos , Peso Corporal/efectos de los fármacos , Cadmio/metabolismo , Cadmio/farmacocinética , Femenino , Masculino , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas , Ratas Endogámicas , Distribución TisularRESUMEN
When 2 inbred rat strains, the Brown-Norway rat and the Lewis rat were exposed to the same amount of CdCl2 for 15 days, a completely different immunological reaction pattern could be demonstrated. Despite the same amount of intrathymic cadmium in both strains, the Brown-Norway rat showed a significant decrease in thymocytes in the S-phase and a significant increase of thymocytes in the G2 phase and mitosis, in contrast with findings in the Lewis rats. A new method for estimating subtle forms of thymus atrophy showed a slight decrease in the number of the smallest thymocytes in the Brown-Norway rat after exposure to cadmium, in contrast with that in the Lewis rat. Evidence is presented that the approximately 1.7 times larger number of thymocytes/mg thymus in the Lewis rat, compared to the Brown-Norway rat, as well as the approximately 2.5 times lower proliferation rate of the thymocytes, and an approximately 1.5 times higher metallothionein content of the thymus medulla epithelial cells in the Lewis rat, might be responsible for the observed difference in toxicity. The zinc content of the thymus was not significantly decreased by exposure to CdCl2, and did not differ significantly between both strains.
Asunto(s)
Cadmio/toxicidad , ADN/biosíntesis , Linfocitos T/efectos de los fármacos , Timo/efectos de los fármacos , Animales , Cadmio/análisis , Femenino , Citometría de Flujo , Inmunoquímica , Hígado/análisis , Metalotioneína/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Especificidad de la Especie , Organismos Libres de Patógenos Específicos , Linfocitos T/metabolismo , Timo/metabolismo , Zinc/análisisRESUMEN
Cadmium (Cd) and zinc (Zn) concentrations were determined by solid sampling atomic absorption spectrometry (AAS) in rat maternal and fetal tissues after exposure to cadmium. Cadmium was administered subcutaneously as CdCl2 in saline daily during pregnancy. Two experiments were performed. In expt. I we investigated the tissue concentration at day 19 (gestational age) after administration of several doses: 0, 1.1, 2.2, 4.4, and 8.8 mumol Cd/kg/day. In expt. II the course of the Cd and Zn concentrations during pregnancy was investigated by collecting samples at days 14, 16, 18 and 20, after daily injections of 4.4 mumol Cd/kg. Cadmium concentrations in blood, maternal liver, placenta and fetal liver increased with dose and duration of exposure. Cadmium was heavily accumulated in the liver and transferred to the fetus only in small amounts. The zinc concentration in the maternal liver was positively correlated with the cadmium concentration. In the placenta the zinc concentration was not affected. Zinc in fetal liver was decreased from day 18 onward. Despite relatively high cadmium levels and decreased zinc levels in the fetus, we observed no adverse effects on various reproduction parameters, such as birth weights and obvious malformations.
Asunto(s)
Intoxicación por Cadmio/metabolismo , Cadmio/metabolismo , Feto/metabolismo , Complicaciones del Embarazo/metabolismo , Zinc/metabolismo , Animales , Cadmio/sangre , Femenino , Hígado/embriología , Hígado/metabolismo , Masculino , Placenta/metabolismo , Embarazo , Ratas , Zinc/sangreRESUMEN
Quantitative data are presented of the glycogen contents in the placental labyrinth, fetal liver and maternal liver of 14-, 16-, 18-, 19- and 20-day pregnant rats exposed to cadmium during pregnancy. The values are obtained from periodic acid-Schiff-stained sections by microdensitometry. No changes due to cadmium exposure were observed in the glycogen content of maternal and fetal livers. However, at 18, 19 and 20 days of pregnancy, significantly higher amounts of glycogen were observed in the trophoblastic labyrinth of cadmium-exposed rats compared with control animals.
Asunto(s)
Cadmio/farmacología , Glucógeno/análisis , Hígado/análisis , Placenta/análisis , Animales , Cloruro de Cadmio , Femenino , Edad Gestacional , Inyecciones Subcutáneas , Hígado/embriología , Glucógeno Hepático/análisis , Embarazo , Ratas , Ratas EndogámicasRESUMEN
Cadmium was administered subcutaneously to pregnant Wistar rats: 0.49 mg/kg as CdCl2 in saline daily, starting at the day of conception. Placentas and fetal livers were collected on day 14, 16, 18, 19 and 20 of gestation. Livers and thymuses from the newborns were collected 5 hours after delivery (day 22) and 1, 2 and 5 weeks after delivery. In these tissues concentrations of cadmium and zinc were determined by solid sampling ETA-AAS. Furthermore, the effect of cadmium administration on the glycogen content of the trophoblastic labyrinth and the fetal liver was studied. The concentration of cadmium in the placenta increased with time of exposure, indicating accumulation of cadmium in this organ. In the fetal liver, cadmium was present in a very low concentration, which slightly increased with longer exposure. The concentration of zinc in the placenta tends to decrease between day 14 and day 20. This decrease was observed both in control and in cadmium-exposed animals. Zinc levels increased in fetal livers from control dams, whereas this rise was markedly reduced in fetuses from cadmium-exposed animals. Placentas from cadmium-exposed animals had a changed glycogen pattern as compared to the controls, namely higher glycogen contents of the labyrinth at the end of pregnancy. However, notwithstanding lower zinc levels in the fetus and changed glycogen deposition in the placenta, it is not quite clear whether cadmium affects fetal development. No changes were observed in fetal weights or birthweights, nor in glycogen deposition of the fetal liver. Indications were obtained for reduced neonatal thymic weights.
Asunto(s)
Cadmio/administración & dosificación , Metabolismo de los Hidratos de Carbono , Desarrollo Embrionario y Fetal/efectos de los fármacos , Glucógeno/metabolismo , Placenta/efectos de los fármacos , Animales , Animales Recién Nacidos/crecimiento & desarrollo , Peso al Nacer/efectos de los fármacos , Femenino , Hígado/anatomía & histología , Hígado/efectos de los fármacos , Hígado/embriología , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Ratas , Ratas Wistar , Timo/anatomía & histología , Timo/efectos de los fármacos , Factores de TiempoRESUMEN
Female Wistar rats were injected subcutaneously with CdCl2 (0.49 mg Cd/kg/day) daily during pregnancy. Placentae, fetal livers and maternal livers were prepared for histological investigation of the glycogen content 14, 16, 18, 19 and 20 days after mating. The glycogen content was estimated semiquantitatively in periodic acid-Schiff-(PAS-)stained sections. The development of the glycogen content of the placenta and the fetal liver from days 14 to 20 of pregnancy in control animals is described and compared with the development of the glycogen content of these tissues from cadmium-exposed animals. No clear changes due to cadmium exposure were observed in the glycogen content of maternal and fetal livers, nor in the spongiotrophoblast and the islets of glycogen in the placenta. The glycogen content in the placental labyrinth increased from day 14 up to day 18 in both control and cadmium-exposed animals. In control animals, the glycogen content decreased after day 18, whereas it remained high in the placental labyrinth of cadmium-exposed animals; this might be considered as a feature of retarded maturation. Regulating mechanisms and similarities between the effects of cadmium exposure and the diabetic state are discussed.
Asunto(s)
Cadmio/toxicidad , Feto/efectos de los fármacos , Glucógeno/análisis , Glucógeno Hepático/análisis , Hígado/química , Placenta/química , Animales , Cloruro de Cadmio , Femenino , Feto/patología , Hígado/efectos de los fármacos , Hígado/patología , Placenta/efectos de los fármacos , Placenta/patología , Embarazo , Ratas , Ratas EndogámicasRESUMEN
When cadmium is chronically administered to rats, an increase by more than 10% of protein bound disulphides and cadmium-thiolate clusters appears to be an indicator for non-toxic accumulation of cadmium in liver and kidney and probably in other organs as well. Using enzyme histochemistry, no damage could be observed in these livers, on the contrary, even signs of increased cellular activity could be demonstrated with specific staining for single stranded RNA. It is clearly demonstrated that in the case of 2 livers with the same quantity of accumulated cadmium morphological damage is completely dependent on dose and schedule of administration. However, despite the fact that cadmium is retained very well in rat livers showing an increase in protein-bound disulphides and cadmium-thiolate clusters, there are still small morphological changes, especially in cells and tissues that appear to have a relatively small potency for producing cadmium-binding proteins.
Asunto(s)
Cadmio/análisis , Hígado/análisis , Metalotioneína/análisis , Animales , Cadmio/farmacología , Núcleo Celular/efectos de los fármacos , Núcleo Celular/ultraestructura , Cromatina/efectos de los fármacos , Cromatina/ultraestructura , Relación Dosis-Respuesta a Droga , Femenino , Hígado/efectos de los fármacos , Hígado/ultraestructura , Ratas , Ratas EndogámicasRESUMEN
Female Wistar rats were injected daily with different doses of CdCl2 during the first 19 days of pregnancy. The placentas of highly exposed animals showed reduced weights as well as some light microscopic changes with respect to the amount of collagen in the basal membranes around fetal blood vessels and to the relative volume densities of the fetal blood vessels. These results are in accordance with changes, found in the placentas of smoking mothers, probably due to cadmium in cigarette smoke.