RESUMEN
Bisphosphonates (BPs) are widely used to treat several bone pathologies. Their action on bone cells depends on cell lineage, promoting or preventing apoptosis in osteoclastic and osteoblastic lineage respectively. Bone cells and bone marrow (BM) are closely related. Bone marrow megakaryocytes regulate bone turn-over. The objective of this in vivo experimental work was to evaluate the effect of olpadronate (OPD) on osteoclasts (Ocs) and megakaryocytes (Mks) using histomorphometric, histochemical, and immunohistochemical methods. Healthy female Wistar rats were used: experimental and Sham animals received OPD or vehicle during five weeks. After sacrifice, kidneys, liver, spleen, femurs and tibiae were dissected and fixed for histological processing. H and E, histochemical detection of TRAP and immunohistochemical detection of TUNEL and RANKL were performed. Results showed increased bone volume and number of Ocs, larger Ocs with more nuclei, increase in Oc apoptosis, and loss of polarity in OPD-treated animals. Statistically significant association was found between apoptotic morphology and RANKL expression in Ocs. BM and spleen showed a significant increase in Mk number. The number of RANKL+Ocs and MKs per unit area increased. The increase in Oc apoptosis did not counteract the increase in Oc recruitment thus resulting in an increase in Oc number. Ocs recruitment could be associated with RANKL expression in Mks and apoptotic Ocs. The effect of OPD and other BPs on Mks should be investigated further to elucidate the mechanism by which BPs act on the bone-bone marrow functional unit, and understand the therapeutic implications of BPs.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Difosfonatos/farmacología , Megacariocitos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Fosfatasa Ácida/efectos de los fármacos , Fosfatasa Ácida/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Femenino , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Isoenzimas/efectos de los fármacos , Isoenzimas/metabolismo , Megacariocitos/metabolismo , Osteoclastos/metabolismo , Ligando RANK/efectos de los fármacos , Ligando RANK/metabolismo , Ratas , Ratas Wistar , Fosfatasa Ácida TartratorresistenteRESUMEN
The population at large is at risk of oral exposure to uranium. Previous studies performed at our laboratory showed delayed tooth eruption 7 d post-administration of a single oral dose of uranyl nitrate in newborn rats. Rat kidney exhibiting severe damage 2 d post-acute uranyl nitrate exposure showed signs of recovery after 7 d; however, tooth eruption and development were significantly lower as compared with their age-matched controls. The aim of the present work was to establish whether tooth eruption and development, delayed by uranium exposure, can catch up to normal values at longer experimental times. In addition, since it is well documented that uranium intoxication by other routes of entry causes alterations in bone growth, we also aimed to evaluate the effect of oral exposure to uranium on mandibular growth. An experimental group of 16 1-d-old Wistar rats received a single 90 mg kg-1 body weight oral dose of uranyl nitrate. Another group of 16 age-matched rats received an equal volume of saline solution and served as the control. Eight animals in each group were killed 7 d post-treatment, and the remaining animals were killed 27 d after the onset of the experiment. Morphometric measurements of mandibular growth were performed on radiographs. Tooth eruption and development were evaluated histomorphometrically on histologic sections obtained at the level of the mesial root of the first molar. Our results showed that the tooth eruption, dental development, and mandibular growth retardation observed 7 d post-acute uranyl nitrate exposure caught up completely after 27 d.
Asunto(s)
Desarrollo Óseo/efectos de la radiación , Erupción Dental/efectos de la radiación , Nitrato de Uranilo/toxicidad , Administración Oral , Animales , Animales Recién Nacidos , Cintigrafía , Ratas , Ratas Wistar , Factores de Tiempo , Resorción Dentaria/diagnóstico por imagen , Resorción Dentaria/patología , Resorción Dentaria/veterinariaRESUMEN
Exposure to uranium is an occupational hazard to workers who continually handle uranium and an environmental risk to the population at large. Since the cellular and molecular pathways of uranium toxicity in osteoblast cells are still unknown, the aim of the present work was to evaluate the adverse effects of uranyl nitrate (UN) on osteoblasts both in vivo and in vitro. Herein we studied the osteoblastic ultrastructural changes induced by UN in vivo and analyzed cell proliferation, generation of reactive oxygen species (ROS), apoptosis, and alkaline phosphatase (APh) activity in osteoblasts exposed to various UN concentrations (0.1, 1, 10, and 100 microM) in vitro. Cell proliferation was quantified by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, ROS was determined using the nitro blue tetrazolium test, apoptosis was morphologically determined using Hoechst 3332 and APh activity was assayed spectrophotometrically. Electron microscopy revealed that the ultrastructure of active and inactive osteoblasts exposed to uranium presented cytoplasmic and nuclear alterations. In vitro, 1-100 microM UN failed to modify cell proliferation ratio and to induce apoptosis. ROS generation increased in a dose-dependent manner in all tested doses. APh activity was found to decrease in 1-100 microM UN-treated cells vs. controls. Our results show that UN modifies osteoblast cell metabolism by increasing ROS generation and reducing APh activity, suggesting that ROS may play a more complex role in cell physiology than simply causing oxidative damage.
Asunto(s)
Osteoblastos/efectos de los fármacos , Osteoblastos/ultraestructura , Nitrato de Uranilo/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Retículo Endoplásmico Rugoso/ultraestructura , Femenino , Investigación Fetal , Humanos , Inyecciones Intraperitoneales , Masculino , Microscopía Electrónica , Osteoblastos/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Acetato de Tetradecanoilforbol/administración & dosificación , Acetato de Tetradecanoilforbol/farmacología , Acetato de Tetradecanoilforbol/toxicidad , Tibia/citología , Tibia/metabolismo , Tibia/ultraestructura , Factores de Tiempo , Nitrato de Uranilo/administración & dosificación , Nitrato de Uranilo/toxicidadRESUMEN
BACKGROUND: Occlusal alterations resulting from tooth movements caused by periodontitis-related bone loss are often corrected with orthodontic treatments. Although the outcome is usually satisfactory, a quantitative histomorphometric study of bone response would contribute to improving treatment planning and optimizing results. METHODS AND RESULTS: This study is a histomorphometric analysis of alveolar bone response to 51 and 75-g orthodontic forces applied to rat molars subjected to experimental periodontitis by placing a ligature around the neck of the molar during 48 h. The orthodontic device consisted of two bands with a tube welded to their palatine aspect, through which the arms of a helicoidal spring were threaded so as to exert force toward palatine. The device was placed immediately and 48 h after removing the ligatures. When applied 48 h post-removal of the ligature, both orthodontic forces caused an increase in bone volume in the periodontitis group. CONCLUSIONS: Our study shows that application of orthodontic forces once periodontal infection has been controlled contributes to increasing alveolar bone volume, consequently improving bone quality.
Asunto(s)
Pérdida de Hueso Alveolar/complicaciones , Proceso Alveolar/patología , Periodontitis/complicaciones , Técnicas de Movimiento Dental , Pérdida de Hueso Alveolar/fisiopatología , Proceso Alveolar/fisiopatología , Animales , Densidad Ósea/fisiología , Encía/patología , Encía/fisiopatología , Tejido de Granulación/patología , Masculino , Diente Molar , Necrosis , Osteoclastos/patología , Ligamento Periodontal/patología , Ligamento Periodontal/fisiopatología , Periodontitis/fisiopatología , Ratas , Ratas Sprague-Dawley , Estrés Mecánico , Factores de Tiempo , Migración del Diente/etiología , Migración del Diente/terapia , Técnicas de Movimiento Dental/instrumentaciónRESUMEN
The relation between orthodontic forces applied to deciduous teeth and the occurrence of root resorption, as a possible outcome of these forces, has not been studied to date. The aim of this work was to study root resorption in deciduous teeth of patients receiving orthodontic treatment. Twenty-four deciduous molars extracted for therapeutic purposes were studied: nineteen molars treated with light orthodontic forces and five untreated molars that served as control. Histological and histomorphome tric studies were performed to determine the magnitude of root resorption. Location of root resorption in treated deciduous teeth was different from that of physiological root resorption. Extent and volume of root resorption were more extensive and deeper in treated than in untreated teeth. These results suggest that radiographic follow-up of deciduous teeth subjected to orthodontic forces would be useful to prevent root fractures.
Asunto(s)
Diente Molar , Ortodoncia Correctiva/efectos adversos , Resorción Radicular/etiología , Diente Primario , Estudios de Casos y Controles , Niño , Humanos , Resorción Radicular/patologíaRESUMEN
A 350 mg/kg body weight (b.w.) oral dose of uranyl nitrate (UN) caused 100% mortality in mice three days after administration, due to resulting kidney lesions. Mortality decreased 50% after an oral (o) or subcutaneous (sc) dose of bisodic etidronate (EHBP). Given that bone is also a target organ for uranium (U) in acute intoxication, the aim of this work was to study the effect of exposure to a lethal oral dose of UN on endochondral ossification, and the latter's response to EHBP treatment. One hundred male Balb/c mice weighing 25 g were assigned to one of ten groups. Group I served as control. Group II received a lethal 350 mg/kg b.w. oral dose of UN by gavage. Groups III, IV, VII, and VIII received an equal dose of UN immediately followed by a single 500 mg/kg oral dose of EHBP in groups III and VII and a single 50 mg/kg subcutaneous dose of EHBP in groups IV and VIII. Groups V and IX only received a single 500 mg/kg oral dose of EHBP, and groups VI and X received a single 50 mg/kg subcutaneous dose of EHBP. The animals in groups II, III, IV, V, and VI were sacrificed 48 h after the onset of the experiment, whereas those in groups VII, VIII, IX, and X were killed at 14 days. Histologic and histomorphometric studies were performed on the femurs to determine growth cartilage width, bone volume, and metaphyseal bone activity. Our results showed that all growth cartilage and metaphyseal bone histomorphometric parameters were significantly lower in animals exposed to UN at 48 h than in controls. EHPB administration was found to prevent this condition at 48 h reaching similar values to those of controls. Although histomorphometric values did not reach control values at 14 days, they were higher than those of animals exposed to UN at 48 h not treated with EHBP. It is noteworthy that these values also decreased in animals only receiving EHBP at 14 days. Our results show that EHBP effectively ameliorates the adverse effects of a lethal dose of UN on endochondral ossification.
Asunto(s)
Condrogénesis/efectos de los fármacos , Difosfonatos/farmacología , Fémur/efectos de los fármacos , Placa de Crecimiento/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Nitrato de Uranilo/toxicidad , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Fémur/patología , Placa de Crecimiento/patología , Inyecciones Subcutáneas , Longevidad/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
AIM: To determine the flow characteristics and subcutaneous tissue reactions to five endodontic sealers. METHODOLOGY: The materials used were Procosol, AH26, Endomethasone, Sealapex and Endion. The sealers were prepared following the manufacturers' instructions, and 0.075 mL of each material was placed on a glass surface, which was then rotated 90 degrees. The samples were stored at 37 degrees C and 95% humidity. The displacement of the sealer was recorded by measuring the difference between its original position and the position recorded at 15 and 60 min. Three samples of each material were used. Two pockets were created in the back of Wistar rats, and one silicone tube, 1 mm in diameter and 1 cm in length, was implanted in each. One was filled with one of the materials under study, and the other empty tube was implanted as a control. Fourteen days after implantation, the animals were sacrificed, and samples of the skin containing the tubes were histologically processed. Histological and histomorphometric evaluations of the tissues adjacent to the open end of the tube were carried out the volume of tissue reaction was measured histomorphometrically according to standard stereological principles. Results were statistically analysed using analysis of variance and Duncan's test. RESULTS: The highest flow values were obtained with Sealapex and AH26. Time significantly affected the flow and the material (P < (1001). Procosol and Endion produced the most severe histological reactions: these were outlined by fibrous tissue; AH26. Endomethasone and Sealapex produced reactions of smaller size and with more moderately defined limits. CONCLUSIONS: The flow did not correlate with the degree of inflammatory response. Procosol and Endion produced the most severe tissue reactions, whereas Endomethasone, Sealapex and AH26 produced only minimum reactions.
Asunto(s)
Materiales de Obturación del Conducto Radicular/química , Materiales de Obturación del Conducto Radicular/toxicidad , Timol/análogos & derivados , Análisis de Varianza , Animales , Bismuto/química , Bismuto/toxicidad , Hidróxido de Calcio/química , Hidróxido de Calcio/toxicidad , Dexametasona/química , Dexametasona/toxicidad , Combinación de Medicamentos , Resinas Epoxi/química , Resinas Epoxi/toxicidad , Fibroblastos/efectos de los fármacos , Reacción a Cuerpo Extraño/inducido químicamente , Formaldehído/química , Formaldehído/toxicidad , Cementos de Ionómero Vítreo/química , Cementos de Ionómero Vítreo/toxicidad , Hidrocortisona/química , Hidrocortisona/toxicidad , Ensayo de Materiales , Ratas , Ratas Wistar , Resinas Sintéticas/química , Resinas Sintéticas/toxicidad , Reología , Salicilatos/química , Salicilatos/toxicidad , Plata/química , Plata/toxicidad , Piel/efectos de los fármacos , Estadísticas no Paramétricas , Timol/química , Timol/toxicidad , Titanio/química , Titanio/toxicidad , Viscosidad , Óxido de Zinc/química , Óxido de Zinc/toxicidad , Cemento de Óxido de Zinc-Eugenol/química , Cemento de Óxido de Zinc-Eugenol/toxicidadRESUMEN
The risk of oral exposure to uranium potentially involves the population at large. Tooth eruption and development are ongoing processes that begin during fetal development and continue until the age of 18 y. Since one of the mechanisms involved in tooth eruption is bone formation and it is well documented that uranium inhibits bone formation, the aim of the present work was to study the effect of oral administration of uranyl nitrate (UN) on tooth eruption and development. Wistar rats aged 1 and 7 d were orally administered a single dose of 90 mg kg(-1) body weight of uranyl nitrate. Two age matched groups received an equal volume of saline and served as controls. The animals were killed at 7 and 14 d of age, respectively. Mandibles were resected and processed to obtain bucco-lingual sections oriented at the level of the mesial root of the first mandibular molar, and histomorphometric studies were performed. Results showed that an acute high dose of uranyl nitrate delays both tooth eruption and development, probably due to its effect on target cells.
Asunto(s)
Exposición a Riesgos Ambientales/efectos adversos , Odontogénesis/efectos de la radiación , Erupción Dental/efectos de la radiación , Nitrato de Uranilo/toxicidad , Animales , Animales Recién Nacidos , Desarrollo Óseo/efectos de la radiación , Resorción Ósea/etiología , Ratas , Ratas Wistar , Diente/crecimiento & desarrollo , Diente/efectos de la radiaciónRESUMEN
Root resorption in permanent teeth is a frequently observed pathology that may originate in various causes. Life expectancy is progressively rising, odontological preventive care is becoming more widespread and professionals are educating their patients in the importance of preventive practices. Because senior citizens are thus losing fewer teeth prematurely they will be conversely more at risk for dental problems later in life. The knowledge of the alterations that may appear in the roots of geriatric patients is particularly relevant to devising therapy and establishing prognosis. The aim of the present study was to evaluate the nature and magnitude of the histologic and histomorphometric features of root resorption and the eventual possibility of repair in elderly people. Seventy-seven uniradicular teeth of patients aged between 65 and 90 years and 18 premolars of patients aged between 14 and 20 years, were removed, fixed in 90% formalin, decalcified in EDTA and embedded in paraffin. Vestibulo-lingual sections were stained with hematoxylin-eosin and employed to perform histological and histomorphometric studies. The results showed that 30% of the teeth of younger patients and 94% of the teeth of elderly patients exhibited areas of root resorption. From the 416 resorptive areas found in elderly patients, 173 exhibited signs of repair being the volume/surface ratio of these areas 0.69 +/- 0.06. These data show that root resorption is a frequent finding in the older population under study. Resorptions are characterized by scarce depth, large areas and a high incidence of repair despite the old age of the patients.
Asunto(s)
Resorción Radicular/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/patología , Envejecimiento/fisiología , Colorantes , Cemento Dental/patología , Cemento Dental/fisiopatología , Colorantes Fluorescentes , Humanos , Osteoclastos/patología , Resorción Radicular/fisiopatología , Raíz del Diente/patología , Raíz del Diente/fisiopatología , Cicatrización de Heridas/fisiologíaRESUMEN
Over the last decade, increasing attention has been focused on the role of the osteocyte in bone remodeling, in view of its demonstrated ability to respond to mechanical and electric stimuli applied to bone. A previous "in vivo" study performed at our laboratory demonstrated that the application of orthodontic forces results in osteocytic lacunae enlargement. To our knowledge there are no data on cell and lacunae response to an inflammatory stimulus in the literature. The aim of this work was to determine whether osteocyte response to an inflammatory stimulus is comparable to that observed under mechanical stress and whether the ensuing cellular changes involve changes in the shape of the osteocyte and/or its lacunae. Three groups of ten male Wistar rats each, 200 to 250 g body weight, were used. Group I served as control. A cotton thread cervical ligature was placed around the first upper molars of animals in Group II, and those in Group III were fitted with an orthodontic appliance designed to exert a force toward palatine. All the animals were killed 24 hours after applying the stimuli. The histomorphometric determinations were measured on the interradicular crest between the two distal roots of the first upper molars. Osteocyte and lacunar volumes were measured and lacunar shape was analyzed. Group II exhibited a dense inflammatory infiltrate and slight resorption of the crest. Group III showed slight resorption of the vestibular wall. The lacunar volume increased in both experimental groups as compared to controls. The cell volume to lacunar volume decreased. These results suggest that osteocytes respond to inflammatory as well as to mechanical stimuli of bone resorption, enlarging lacunae without changes in cell volume.
Asunto(s)
Resorción Ósea/fisiopatología , Osteocitos/fisiología , Proceso Alveolar/patología , Animales , Matriz Ósea/patología , Resorción Ósea/patología , Tamaño de la Célula/fisiología , Masculino , Diente Molar/patología , Osteocitos/patología , Periodontitis/fisiopatología , Ratas , Ratas Wistar , Estrés Mecánico , Técnicas de Movimiento Dental/instrumentación , Raíz del Diente/patologíaRESUMEN
Root resorption in permanent teeth is a frequently observed pathology that may originate in various causes. Life expectancy is progressively rising, odontological preventive care is becoming more widespread and professionals are educating their patients in the importance of preventive practices. Because senior citizens are thus losing fewer teeth prematurely they will be conversely more at risk for dental problems later in life. The knowledge of the alterations that may appear in the roots of geriatric patients is particularly relevant to devising therapy and establishing prognosis. The aim of the present study was to evaluate the nature and magnitude of the histologic and histomorphometric features of root resorption and the eventual possibility of repair in elderly people. Seventy-seven uniradicular teeth of patients aged between 65 and 90 years and 18 premolars of patients aged between 14 and 20 years, were removed, fixed in 90
formalin, decalcified in EDTA and embedded in paraffin. Vestibulo-lingual sections were stained with hematoxylin-eosin and employed to perform histological and histomorphometric studies. The results showed that 30
of the teeth of younger patients and 94
of the teeth of elderly patients exhibited areas of root resorption. From the 416 resorptive areas found in elderly patients, 173 exhibited signs of repair being the volume/surface ratio of these areas 0.69 +/- 0.06. These data show that root resorption is a frequent finding in the older population under study. Resorptions are characterized by scarce depth, large areas and a high incidence of repair despite the old age of the patients.
RESUMEN
Over the last decade, increasing attention has been focused on the role of the osteocyte in bone remodeling, in view of its demonstrated ability to respond to mechanical and electric stimuli applied to bone. A previous [quot ]in vivo[quot ] study performed at our laboratory demonstrated that the application of orthodontic forces results in osteocytic lacunae enlargement. To our knowledge there are no data on cell and lacunae response to an inflammatory stimulus in the literature. The aim of this work was to determine whether osteocyte response to an inflammatory stimulus is comparable to that observed under mechanical stress and whether the ensuing cellular changes involve changes in the shape of the osteocyte and/or its lacunae. Three groups of ten male Wistar rats each, 200 to 250 g body weight, were used. Group I served as control. A cotton thread cervical ligature was placed around the first upper molars of animals in Group II, and those in Group III were fitted with an orthodontic appliance designed to exert a force toward palatine. All the animals were killed 24 hours after applying the stimuli. The histomorphometric determinations were measured on the interradicular crest between the two distal roots of the first upper molars. Osteocyte and lacunar volumes were measured and lacunar shape was analyzed. Group II exhibited a dense inflammatory infiltrate and slight resorption of the crest. Group III showed slight resorption of the vestibular wall. The lacunar volume increased in both experimental groups as compared to controls. The cell volume to lacunar volume decreased. These results suggest that osteocytes respond to inflammatory as well as to mechanical stimuli of bone resorption, enlarging lacunae without changes in cell volume.
RESUMEN
Over the last decade, increasing attention has been focused on the role of the osteocyte in bone remodeling, in view of its demonstrated ability to respond to mechanical and electric stimuli applied to bone. A previous [quot ]in vivo[quot ] study performed at our laboratory demonstrated that the application of orthodontic forces results in osteocytic lacunae enlargement. To our knowledge there are no data on cell and lacunae response to an inflammatory stimulus in the literature. The aim of this work was to determine whether osteocyte response to an inflammatory stimulus is comparable to that observed under mechanical stress and whether the ensuing cellular changes involve changes in the shape of the osteocyte and/or its lacunae. Three groups of ten male Wistar rats each, 200 to 250 g body weight, were used. Group I served as control. A cotton thread cervical ligature was placed around the first upper molars of animals in Group II, and those in Group III were fitted with an orthodontic appliance designed to exert a force toward palatine. All the animals were killed 24 hours after applying the stimuli. The histomorphometric determinations were measured on the interradicular crest between the two distal roots of the first upper molars. Osteocyte and lacunar volumes were measured and lacunar shape was analyzed. Group II exhibited a dense inflammatory infiltrate and slight resorption of the crest. Group III showed slight resorption of the vestibular wall. The lacunar volume increased in both experimental groups as compared to controls. The cell volume to lacunar volume decreased. These results suggest that osteocytes respond to inflammatory as well as to mechanical stimuli of bone resorption, enlarging lacunae without changes in cell volume.
RESUMEN
Root resorption in permanent teeth is a frequently observed pathology that may originate in various causes. Life expectancy is progressively rising, odontological preventive care is becoming more widespread and professionals are educating their patients in the importance of preventive practices. Because senior citizens are thus losing fewer teeth prematurely they will be conversely more at risk for dental problems later in life. The knowledge of the alterations that may appear in the roots of geriatric patients is particularly relevant to devising therapy and establishing prognosis. The aim of the present study was to evaluate the nature and magnitude of the histologic and histomorphometric features of root resorption and the eventual possibility of repair in elderly people. Seventy-seven uniradicular teeth of patients aged between 65 and 90 years and 18 premolars of patients aged between 14 and 20 years, were removed, fixed in 90
formalin, decalcified in EDTA and embedded in paraffin. Vestibulo-lingual sections were stained with hematoxylin-eosin and employed to perform histological and histomorphometric studies. The results showed that 30
of the teeth of younger patients and 94
of the teeth of elderly patients exhibited areas of root resorption. From the 416 resorptive areas found in elderly patients, 173 exhibited signs of repair being the volume/surface ratio of these areas 0.69 +/- 0.06. These data show that root resorption is a frequent finding in the older population under study. Resorptions are characterized by scarce depth, large areas and a high incidence of repair despite the old age of the patients.
RESUMEN
The toxic effect of uranium in cultured preimplantation embryos of the mouse is presented. Embryos were obtained from hybrid females CBA x C57 BL following induction of superovulation and were incubated in M16 cultured medium. Two different experiments were performed. In one, embryos in a one-cell stage were placed in culture media with final concentrations of uranyl nitrate of 104 and 208 microg/mL during 120 h in the same dish. In the other experiment, embryos in a one-cell stage were placed in culture medium with uranyl nitrate with final U concentrations of 26, 52, 104, and 208 microg/mL. At 24 h, those embryos which had reached the two-cell stage were transferred to another culture dish to which fresh solutions with uranyl nitrate were added. The percentage of embryos in two-cell stage, morula, early blastocyst, expanded blastocyst, and hatched blastocyst were recorded at 24, 72, 96 and 120 h of culture. The results obtained showed that concentrations as from 26 microg U/mL induced the delay of embryo development and the impairment of blastomere proliferation. The toxic effect of uranium increased in those experiments in which the embryos were transferred to a new medium. This embryo-culture system appears to be appropriate to evaluate the toxic effect of uranium on embryos removed from maternal influences and represents a suitable test system for environmental pollutants.
Asunto(s)
Blastocisto/efectos de los fármacos , Uranio/envenenamiento , Animales , Medios de Cultivo , Técnicas de Cultivo , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Embarazo , Factores de Tiempo , Nitrato de Uranilo/análisisRESUMEN
Intoxication with uranium compounds is both an occupational risk for the workers engaged in the different processes of the elaboration of nuclear fuel and a risk for the population at large in terms of contaminated water and food. The toxic effects of uranium can be reduced by the administration of a biphosphonate, ethane-1-hydroxy-1,1-biphosphonate (EHBP), subcutaneously or intraperitoneally. The aim of the present work was to examine whether orally administered EHBP reduces the lethal effect of a single orally administered toxic dose of uranyl nitrate. Nine groups of 20 male Balb-c mice were used. Five groups received 350 mg kg(-1) of uranyl nitrate orally administered by gavage, four were co-treated 20 min later with EHBP either by gavage (350, 500, or 700 mg kg(-1)) or by subcutaneous injection (50 mg kg(-1)), and one group was not treated. Four groups of animals received only EHBP in doses and routes the same as those used in the intoxicated animals. Survival was assessed for 14 d. On day 14 the surviving animals of all groups were killed. An additional group of uranium intoxicated animals was killed on day 2 after the start of the experiment. Kidneys were examined histologically. On day 3 all the animals treated with uranyl nitrate alone and 20% of the animals treated with 700 mg kg(-1) of EHBP alone were dead. Survival at day 14 of the groups of mice intoxicated with uranyl nitrate and treated with EHBP (50 mg kg(-1) orally or 50 mg kg(-1) subcutaneously) was 45.0 and 49.6%, respectively. Tubule necrosis lesions were present in kidneys of mice intoxicated with uranyl nitrate, whereas lesions were less severe in mice treated with EHBP. Oral administration of EHBP is effective for reducing the lethal effect of uranium, and it is at least as useful as subcutaneous administration for prompt therapy of oral uranium exposure, achieving a survival rate of almost 50%.
Asunto(s)
Difosfonatos/administración & dosificación , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Protectores contra Radiación/administración & dosificación , Uranio/envenenamiento , Administración Oral , Animales , Inyecciones Subcutáneas , Masculino , Ratones , Ratones Endogámicos BALB C , Tasa de SupervivenciaRESUMEN
Different groups have undertaken research work focusing their attention on the biological effects of uranium and have described kidney and bone to be the main target organs in uranium poisoning. In this study we used the skin as the route of entry of uranium. We carried out two sets of experiments in adult rats: in one of them topical applications with uranyl nitrate (UN) over different areas were performed; in the other topical applications with UN on a given area over different times were carried out. In the latter experiment the exposure to UN was stopped by removing it from skin with soap and water. Kidney and bone samples were removed for histological studies. This work is based on the determination of the survival rate of the exposed animals and on the effects elicited in kidney and bone. There is a relation between the area of the surface exposed to uranium and the time of exposure and the subsequent percutaneous toxicity. There were no surviving animals following topical application of UN to an 8 cm2 area nor when the time of exposure was 24 h. The survival rate of the animals increased when either the topical area or the time of exposure to UN was reduced. Although the inhibition of bone formation in metaphysical bone has been previously described by our group as a result of UN poisoning, this is the first time that such an effect is found after percutaneous exposure for such short periods of time. The general toxic effects of UN, evidenced as kidney histological alterations, increased in severity as either one of the two variables studied increased. This is a condition that could be considered as hazardous for those workers engaged in uranium processing and purification. It is noteworthy that a simple method such as washing with soap and water is an effective method to reduce the lethality of UN percutaneous intoxication.
Asunto(s)
Piel/efectos de los fármacos , Nitrato de Uranilo/envenenamiento , Administración Tópica , Animales , Desarrollo Óseo/efectos de los fármacos , Femenino , Riñón/efectos de los fármacos , Riñón/patología , Ratas , Ratas Wistar , Piel/patología , Análisis de Supervivencia , Factores de TiempoRESUMEN
Demineralization of bone has been linked to the action of osteocytes via the process of osteocytic osteolysis. The aim of this study was to assess the influence of mechanical forces produced during orthodontic movements on the osteocytic lacunae. Orthodontic movements were achieved employing a device constructed "ad hoc" for rats that exerts a force of approximately 70 gr. The experimental animals and the corresponding controls were killed 48 and 96 hours after the onset of the experiment. Histologic sections oriented along the bucco-palatine axis were employed to measure the area of osteocytic lacunae to infer information on volume in keeping with standard stereological concepts. Regions alongside resorption areas of cortical bone and resting areas of palatine bone were evaluated. Osteocytic lacunae associated to erosive surfaces were rounded and rose markedly in area after the application of the orthodontic force (58.4 +/- 6 mm2). Elongated lacunae were present in relation to resting areas (24.8 +/- 2 mm2). The present study shows an association between the increase in size of osteocytic lacunae and the resorption fronts induced by the application of orthodontic forces. This finding would suggest that the osteocyte would participate in the resorption process of bone submitted to pressure.
Asunto(s)
Pérdida de Hueso Alveolar/etiología , Osteocitos/fisiología , Técnicas de Movimiento Dental/efectos adversos , Pérdida de Hueso Alveolar/patología , Animales , Análisis del Estrés Dental , Masculino , Aparatos Ortodóncicos/efectos adversos , Periostio/patología , Ratas , Ratas Wistar , Estrés MecánicoRESUMEN
Demineralization of bone has been linked to the action of osteocytes via the process of osteocytic osteolysis. The aim of this study was to assess the influence of mechanical forces produced during orthodontic movements on the osteocytic lacunae. Orthodontic movements were achieved employing a device constructed [quot ]ad hoc[quot ] for rats that exerts a force of approximately 70 gr. The experimental animals and the corresponding controls were killed 48 and 96 hours after the onset of the experiment. Histologic sections oriented along the bucco-palatine axis were employed to measure the area of osteocytic lacunae to infer information on volume in keeping with standard stereological concepts. Regions alongside resorption areas of cortical bone and resting areas of palatine bone were evaluated. Osteocytic lacunae associated to erosive surfaces were rounded and rose markedly in area after the application of the orthodontic force (58.4 +/- 6 mm2). Elongated lacunae were present in relation to resting areas (24.8 +/- 2 mm2). The present study shows an association between the increase in size of osteocytic lacunae and the resorption fronts induced by the application of orthodontic forces. This finding would suggest that the osteocyte would participate in the resorption process of bone submitted to pressure.
RESUMEN
Demineralization of bone has been linked to the action of osteocytes via the process of osteocytic osteolysis. The aim of this study was to assess the influence of mechanical forces produced during orthodontic movements on the osteocytic lacunae. Orthodontic movements were achieved employing a device constructed [quot ]ad hoc[quot ] for rats that exerts a force of approximately 70 gr. The experimental animals and the corresponding controls were killed 48 and 96 hours after the onset of the experiment. Histologic sections oriented along the bucco-palatine axis were employed to measure the area of osteocytic lacunae to infer information on volume in keeping with standard stereological concepts. Regions alongside resorption areas of cortical bone and resting areas of palatine bone were evaluated. Osteocytic lacunae associated to erosive surfaces were rounded and rose markedly in area after the application of the orthodontic force (58.4 +/- 6 mm2). Elongated lacunae were present in relation to resting areas (24.8 +/- 2 mm2). The present study shows an association between the increase in size of osteocytic lacunae and the resorption fronts induced by the application of orthodontic forces. This finding would suggest that the osteocyte would participate in the resorption process of bone submitted to pressure.