Biomedical subjects

A M Ubios

Publications and source records attributed to A M Ubios.

At least 19 recordsLinked to original sources

PubMed2006

Ultrastructural and metabolic changes in osteoblasts exposed to uranyl nitrate.

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.

Alkaline Phosphatase↗

PubMed2005

Effect of ethane-1-hydroxy-1,1-bisphosphonate (EHBP) on endochondral ossification lesions induced by a lethal oral dose of uranyl nitrate.

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.

Administration, Oral↗

PubMed2005

Bone response to different strength orthodontic forces in animals with periodontitis.

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.

Alveolar Bone Loss↗

PubMed2005

Root resorption in deciduous teeth after applying orthodontic forces.

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.

Case-Control Studies↗

PubMed2003

Rheological properties and biocompatibility of endodontic sealers.

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.

Analysis of Variance↗

PubMed2003

Exposure to oral uranyl nitrate delays tooth eruption and development.

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.

Animals↗

PubMed2003

Renal function in mice poisoned with oral uranium and treated with ethane-1-hydroxy-1,1-bisphosphonate (EHBP).

Exposure to uranium is a risk for the workers involved in uranium mining, purification, and manufacture, principally by its ingestion or inhalation. It is also a risk for the population at large in case of intake of contaminated water or food. Uranium induces nephropathy that is characteristic of heavy metals, which can lead to death. The toxic effects of uranium can be prevented by a biphosphonate, ethane-1-hydroxy-1,1-bisphosphonate (bisodic etidronate), administered orally or subcutaneously. Employing bisodic etidronate, our laboratory obtained satisfactory results in terms of survival in adult mice, adult rats, and suckling rats. The aim of the present study was to evaluate the efficacy of bisodic etidronate for preventing renal dysfunction induced by a lethal dose of uranyl nitrate, employing serum levels of urea and creatinine as end-points. Two experiments were performed over different time periods, i.e., Experiment A: 48 h, Experiment B: 14 d. Each experiment was performed with 4 groups of 20 male Balb/c mice each, 25 g average body weight. Three of these groups received 350 mg kg(-1) of body weight of uranyl nitrate by gavage (forced oral administration). Two of the three exposed groups were treated with bisodic etidronate either by gavage in a dose of 500 mg kg(-1) body weight or with a subcutaneous injection of 50 mg kg(-1) body weight. The fourth group served as control. Survivors of the experimental groups were sacrificed at the end of the experiment by overdose of inhalation anesthetic (ether). The kidneys were routinely processed for histological analysis. Blood samples were taken by cardiac puncture to assess urea and creatinine serum levels. Urea and creatinine serum levels were markedly lower at 48 h in exposed animals treated with bisodic etidronate than in untreated exposed animals. On day 14 these values in exposed and treated animals did not differ significantly from control values. The renal function of animals treated with orally or subcutaneous bisodic etidronate that survived uranyl nitrate exposure was markedly improved compared to the controls of untreated exposed animals at 48 h. At 14 days, treatment with bisodic etidronate averted renal damage. At this time, the histologic study of kidneys showed images of tissue recovery. These results suggest that the use of EHBP may be of great value in reducing the renal damage.

Administration, Cutaneous↗

PubMed2001

Root resorption in elderly patients.

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.

Adolescent↗

PubMed2001

Early osteocyte response to bone resorption stimuli.

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.

Alveolar Process↗

PubMed2000

Percutaneous toxicity of uranyl nitrate: its effect in terms of exposure area and time.

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.

Administration, Topical↗

PubMed2000

Orally administered ethane-1-hydroxy-1,1-biphosphonate reduces the lethal effect of oral uranium poisoning.

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%.

Administration, Oral↗

PubMed2000

Effects of uranium poisoning on cultured preimplantation embryos.

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.

Animals↗

PubMed2000

Enlargement of periosteocytic lacunae associated to mechanical forces.

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.

Alveolar Bone Loss↗

PubMed1999

Iron overloading inhibits dentine mineralization.

The present study reveals the inhibitory effect of iron intoxication on the process of dentine mineralization. Wistar rats were injected intraperitoneally with iron dextran at 0.88 g/kg body weight per day for 10 days during the period of odontogenesis. An age-matched group was injected intraperitoneally with bisodium etidronate (EHBP) at 20 mg/kg body weight per day for 10 days. Another age-matched group was treated with similar amounts of saline intraperitoneally and considered as control. At the end of the experimental period the animals intoxicated with iron exhibited non-mineralized dentine and mineralized bone. The animals treated with EHBP showed non-mineralized dentine and bone. These findings would suggest the existence of different mineralization mechanisms for bone and dentine.

Alveolar Process↗

PubMed1998

Effect of biphosphonates on abnormal mandibular growth of rats intoxicated with uranium.

Intoxication with uranium induces severe alterations in kidneys and in acute intoxications inhibits bone formation and bone growth. Administered at high doses, uranium leads to death, an event that can be prevented by the administration of ethane-1-hydroxy-1,1 biphosphonate (EHBP), which would presumably exert its effect via its chelating properties. Based on this information, the aim of the present study was to determine the best therapeutic method for treatment using biphosphonates to prevent mandibular growth alterations in animals that survive uranyl nitrate poisoning. Seven groups of Wistar rats weighing 14 g were used as follows: I, untreated control; II, one intraperitoneal injection (IPI) of 2 mg Kg(-1) of body weight of uranyl nitrate (238U). In groups III to VII animals were intoxicated as in Group II and in addition were given a single injection of 10 mg Kg(-1) of ethane-1-hydroxy-1, 1-biphosphonate (EHBP), or 3-amine-1, 1-hydroxypropylene-1, 1 biphosphonate (APD) as follows; Group III, IPI of EHBP given immediately after poisoning (0 h); IV, IPI of EHBP given at 24 h; V, subcutaneous injection (SCI) of EHBP at 0 h; VI, SCI of EHBP at 48 h; VII SCI of APD at 0 h. Survivors were killed on the sixtieth day. Body weight increase, survival rate, and biometric parameters of mandibular growth (Eratalay's method) were studied. Student's "t" test was used for statistical analysis. On day 60 there was only one survivor in Group II and none in Group IV. All animals in the other groups survived. Mandibular growth parameters showed the worst results in Group VII and the best in Group V for which no difference with the controls was observed. These results show that a single subcutaneous injection of EHBP given immediately after uranium poisoning, apart from preventing death, is capable of preventing undesirable alterations in mandibular growth.

Animals↗

PubMed1998

Dynamics of bone loss in experimental periodontitis.

A dynamic histomorphometric study of bone loss in periodontitis induced by inserting a thread ligature around the neck of the lower first molar of Wistar rats weighing 300 g. was performed. Bone formation fronts were labelled twice by tetracycline injection (day 1 and day 14). On day 16 the animals were divided into 4 groups: Two experimental (ligature in place) and two controls (no ligature). Animals in one experimental and one control groups were killed 72 hours post insertion, and the other two groups 96 hours post-insertion. Grinding sections of the first molar were obtained to perform histomorphometric studies on microphotographs taken under fluorescence microscopy. At 72 hours results showed total loss of the double labeling in the mesial wall, partial loss in the top of the crest and no loss in the distal wall. At 96 hours, loss of the double labeling at the top of the crest was greater, while only one label (the first) could be observed in the distal wall. These results show that in this periodontitis experimental model, bone loss is initiated and is more rapid in the bone remodeling (mesial) wall than in the modeling (distal) wall. This understanding of bone loss dynamics enables the characterization of the model employed herein, contributing to further studies on the course of periodontal disease under different experimental conditions.

Alveolar Bone Loss↗

PubMed1997

Skin alterations induced by long-term exposure to uranium and their effect on permeability.

The skin is a probable route of incorporation of uranium by percutaneous absorption. The changes in epidermal thickness and their effect on skin permeability after uranium exposure are reported herein. Two experiments (A and B) were performed in Wistar rats weighing 60 g. In experiment A the animals were exposed to U3O8 (0.012 g d(-1)) in 30 daily topical applications. In experiment B the animals were treated as in experiment A, followed by a period of non-exposure of 60 d. Samples of the treated area of skin were taken for histologic studies and for the study of the skin permeability. The epidermal thickness was measured on the histological sections. Epidermis was thinner in experimental than in control animals in both experiments. The values in the control groups were 41.05 +/- 14.03 microm (A) and 38.92 +/- 16.50 microm (B) and 21.35 +/- 10.29 microm (A) and 24.06 +/- 16.50 microm (B) in the experimental groups, the differences being statistically significant. Skin permeability was measured placing skin samples in a diffusion cell, in which the upper compartment was filled with a staining solution. The determinations were made with a spectrophotometer. The results revealed that the skin permeability in both experimental groups was higher than in the respective controls, 65% in experiment A and 77% in experiment B. The results revealed that a long term uranium exposure leads to an epidermal atrophy which in turn results in an increased permeability of the skin.

Administration, Topical↗

PubMed1997

Iron overloading inhibits endochondral ossification.

The development of bone disease in patients with chronic renal failure is well known. Renal patients frequently suffer anemia and iron oral therapy and/or transfusions are used to treat them. Recent findings show that iron could be a factor that provokes bone lesions but the alterations it causes are not well known. The aim of this work was to study the effect of iron intoxication on endochondral ossification, a recognized model for bone growth evaluation. Male Wistar rats weighing 250-300 g were used. They received 88 mg of dextran-iron per day intraperitoneally during 34 days. The experimental and control groups were killed on day 34. A histomorphometric study of the endochondral plate was performed on histologic sections of tibiae. The results obtained show that iron overloading inhibits endochondral ossification.

Animals↗