Biomedical subjects

P M Mandalunis

Publications and source records attributed to P M Mandalunis.

7 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↗

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↗

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

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

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↗

PubMed1997

Effect of compressive forces on a bone modelling surface.

The work presented herein, is an experimental study on the effect of an orthodontic appliance with a helicoidal spring designed to exert force toward palatine--i.e. in the opposite direction to the natural vestibular drift--on a bone remodelling surface. The appliance consists of two stainless steel molar bands, with a horizontal bracket tube welded to their palatal aspect through which the arms of the helicoidal spring are passed. Wistar rats, 250 g body weight, were fitted with the device for 48 and 96 hours. One group of rats was administered two doses of tetracycline hydrochloride prior to device placement, in order to label mineralizing fronts. Histomorphometric studies of the periodontal wall of the palatine alveolar bone showed a marked increase of bone resorption at both experimental time points together with an increase in the number of osteoclasts, and no tetracycline labelling after 48 hours. The results show that compressive forces are capable of stimulating resorption, even on bone modelling surfaces. The pressure applied would stimulate osteoblasts to send out signals for osteoclast recruitment and activity.

Alveolar Bone Loss↗