Mycobacterium bovis is the causative agent of bovine tuberculosis and is a member of Mycobacterium tuberculosis complex, which causes tuberculosis in a number of mammals including humans. Previous studies have shown that the genes encoding the two-component system PhoPR, which regulates several genes involved in the virulence of M. tuberculosis, are polymorphic in M. bovis, when compared to M. tuberculosis, which results in a dysfunctional two-component system. In this study we investigated the role of PhoPR in two M. bovis strains with differing degrees of virulence. We found that the deletion of phoP in an M. bovis isolate reduced its capacity of inducing phagosomal arrest in bovine macrophages. By gene expression analysis, we demonstrated that, in both M. bovis strains, PhoP regulates the expression of a putative lipid desaturase Mb1404-Mb1405, a protein involved in redox stress AhpC, the sulfolipid transporter Mmpl8 and the secreted antigen ESAT-6. Furthermore, the lack of PhoP increased the sensitivity to acidic stress and alteration of the biofilm/pellicle formation of M. bovis. Both these phenotypes are connected to bacterial redox homeostasis. Therefore, the results of this study suggest a role of PhoPR in M. bovis to be linked to the mechanisms that mycobacteria display to maintain their redox balance.

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.

Distraction osteogenesis (DO) is a surgical technique producing bone lengthening by distraction of the fracture callus. Although a large number of experimental studies on the events associated with DO of craniofacial skeleton have been reported, the few employing rat mandibular bone DO used complicated designs and produced a small volume of newly formed bone. Thus, this study aims to present an original experimental model of mandibular DO in edentulous rats that produces a sufficient quantity and quality of intramembranous bone. Eight male Wistar rats, weighing 75 g, underwent extraction of lower molars. With rats weighing 350 g, right mandibular osteotomy was performed and the distraction device was placed. The distraction device was custom made using micro-implants, expansion screws, and acrylic resin. Study protocol: latency: 6 days, distraction: ¼ turn (0.175 mm) once a day during 6 d, consolidation: 28 d after distraction phase, sacrifice. DO-treated and contralateral hemimandibles were dissected and compared macroscopically and using radiographic studies. Histological sections were obtained and stained with H&E. A distraction gap filled with newly formed and mature bone tissue was obtained. This model of mandibular DO proved useful to obtain adequate quantity and quality of bone to study bone regeneration

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.