RESUMEN
Sixty female Wistar rats were submitted to a daily intake of ration doped with uranium from weaning to adulthood. Uranium in bone was quantified by the SSNTD (solid state nuclear track detection) technique, and bone mineral density (BMD) analysis performed. Uranium concentration as a function of age exhibited a sharp rise during the first week of the experiment and a drastic drop of 70% in the following weeks. Data interpretation indicates that uranium mimics calcium. Results from BMD suggest that radiation emitted by the incorporated Uranium could induce death of bone cells.
Asunto(s)
Huesos/metabolismo , Huesos/efectos de la radiación , Uranio/efectos adversos , Uranio/farmacocinética , Envejecimiento/metabolismo , Animales , Densidad Ósea/efectos de la radiación , Huesos/patología , Calcio/metabolismo , Muerte Celular/efectos de la radiación , Femenino , Ratas , Ratas WistarRESUMEN
Since the great discovery of Furchgott, Ignarro and Murad in the late 90's, nitric oxide (NO) is considered one of the most versatile endogenous molecules, which is involved in important signaling biochemistry pathways of the human body. Thus, it is directly related to pathological processes and its over- or low-production is able to cause damage in systems that are involved. By using certain functional groups present in molecules that already have potential therapeutic value, hybrid compounds, by means of inclusion of NO-donors (e.g., ester nitrates, furoxans, benzofuroxans, NONOates, S-nitrosothiols, metal complexes), can be generated that have a NO release benefit along with maintaining the activity of the native drug. This approach has proved to be useful in many spheres of Medicinal Chemistry, such as cardiovascular, inflammatory, bacterial, fungal, viral, parasitic, ocular diseases and cancer. Potent and selective nitric oxide synthase inhibitors are being designed, mainly through enzyme structure based process, however, due to high homology between the isoforms, these studies have proved to be very difficult. The objective of the research is to achieve a balance between the release of therapeutic amounts of NO, especially in specific site of action, and maintaining the native drug activity. The search for new and effective NO-donor hybrid drugs, as well as selective nitric oxide synthase inhibitors, is an important focus in modern drug design in order to manipulate biochemical pathways involving NO that influence many dysfunctions of the human organism.
Asunto(s)
Diseño de Fármacos , Óxido Nítrico/metabolismo , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antiinfecciosos/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Oftalmopatías/tratamiento farmacológico , Humanos , Neoplasias/tratamiento farmacológico , Donantes de Óxido Nítrico/química , Donantes de Óxido Nítrico/farmacología , Donantes de Óxido Nítrico/uso terapéutico , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
In this work, the uranium (U) content in sediment and soil samples collected near the Santos and São Vicente estuaries was determined using the fission track registration technique (SSNTD). The sediment and soil samples after oven-dried and pulverised were prepared in the solution form. About 10 microl of this solution was deposited on a plastic detector and irradiated at the IPEN-IEA-R1 (3.5 MW) nuclear reactor. After the irradiation and chemical etching of the plastic foils, the fission tracks were counted with a system consisting of an optical microscope together with a video camera and a PC. The U content in the analysed samples ranged from 3.12 +/- 0.55 to 18.3 +/- 1.2 ppm for sediments and from 3.21 +/- 0.63 to 11.5 +/- 1.1 ppm for soils or in terms of (238)U equivalent activity from 38.5 +/- 6.8 to 226 +/- 15 and 39.6 +/- 7.8 to 142 +/- 14 Bq kg(-1) for sediments and soils, respectively. These results were compared with other values reported in the literature for sediments and soils collected in environments similar to the ones studied in this work. Most of the values obtained in this work are higher than the world mean and are in reasonable agreement with results found by other authors for sediments and soils from regions considered as polluted or with a high level of radioactivity.