Hypusine Modification of the Ribosome-binding Protein eIF5A, a Target for New Anti-Inflammatory Drugs: Understanding the Action of the Inhibitor GC7 on a Murine Macrophage Cell Line

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

High intensity exercise training worsens alveolar destruction in pulmonary emphysema rats

OBJECTIVE: Investigation of standard intensities of physical exercise is important to better comprehend and develop rehabilitation programs for emphysema. We aimed to evaluate the effects of different intensities (moderate and high-intensity) of physical exercise on the development of a protease-induced (papain intratracheal instillation) emphysema in rats. METHODS: Male Wistar rats were randomly separated into five groups that received intratracheal instillation of papain solution or vehicle: (i) papain high intensity exercise, (ii) papain moderate exercise, (iii) saline high intensity exercise, (iv) saline sedentary and (v) papain sedentary. Forty days after intratracheal instillation, the exercise groups were submitted to an exercise-training protocol on a treadmill during 10 weeks, 5 days/week, at 0.9 km/h (Papain and saline high exercise), or at 0.6 km/h (papain moderate exercise).We measured respiratory system elastance and resistance, the collagen fiber lung parenchyma, and the pulmonary mean linear intercept. RESULTS: All animal groups that received papain instillation presented higher alveolar wall destruction compared to animals that received only saline solution. The papain high intensity exercise group presented higher values of mean linear intercept compared to emphysema groups that were trained at a moderate intensity or not submitted to exercise. CONCLUSION: High intensity exercise training worsened alveolar destruction in an experimental model of emphysema in rats when compared to moderate intensity exercise, or to no exercise.

Macrophage Cell Activation with Acute Apical Abscess Contents Determined by Interleukin-1 Beta and Tumor Necrosis Factor Alpha Production

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hard and soft tissue changes around implants installed in regular-sized and reduced alveolar bony ridges. An experimental study in dogs

Objective: To study bony and soft tissue changes at implants installed in alveolar bony ridges of different widths.Material and methods: In 6 Labrador dogs, the mandibular premolars and first molars were extracted, and a buccal defect was created in the left side at the third and fourth premolars by removing the buccal bone and the inter-radicular and interdental septa. Three months after tooth extraction, full-thickness mucoperiosteal flaps were elevated, and implants were installed, two at the reduced (test) and two at the regular-sized ridges (control). Narrow or wide abutments were affixed to the implants. After 3 months, biopsies were harvested, and ground sections prepared for histological evaluation.Results: A higher vertical buccal bony crest resorption was found at the test (1.5 +/- 0.7 mm and 1.0 +/- 0.7 mm) compared to the control implants (1.0 +/- 0.5 mm and 0.7 +/- 0.4 mm), for both wide and narrow abutment sites. A higher horizontal alveolar resorption was identified at the control compared to the test implants. The difference was significant for narrow abutment sites. The peri-implant mucosa was more coronally positioned at the narrow abutment, in the test sites, while for the control sites, the mucosal adaptation was more coronal at the wide abutment sites. These differences, however, did not reach statistical significance.Conclusions: Implants installed in regular-sized alveolar ridges had a higher horizontal, but a lower vertical buccal bony crest resorption compared to implants installed in reduced alveolar ridges. Narrow abutments in reduced ridges as well as wide abutments in regular-sized ridges yielded less soft tissue recession compared to their counterparts.

A digital evaluation of alveolar ridge preservation at implants placed immediately into extraction sockets: an experimental study in the dog

Objective: To compare with pristine sites bone resorption and soft tissue adaptation at implants placed immediately into extraction sockets (IPIES) in conjunction with deproteinized bovine bone mineral (DBBM) particles and a collagen membrane.Material and methods: The mesial root of the third premolar in the left side of the mandible was endodontically treated (Test). Flaps were elevated, the tooth hemi-sectioned, and the distal root removed to allow the immediate installation of an implant into the extraction socket in a lingual position. DBBM particles were placed into the defect and on the outer contour of the buccal bony ridge, concomitantly with the placement of a collagen membrane. A non-submerged healing was allowed. The premolar on the right side of the mandible was left in situ (control). Ground sections from the center of the implant as well as from the center of the distal root of the third premolar of the opposite side of the mandible were obtained. The histological image from the implant site was superimposed to that of the contralateral pristine distal alveolus, and dimensional variation evaluated for the hard tissue and the alveolar ridge.Results: After 3 months of healing, both histological and photographic evaluation revealed a reduction of hard and soft tissue dimensions.Conclusion: The contour augmentation performed with DBBM particles and a collagen membrane at the buccal aspects of implants placed IPIES was not able to maintain the tissue volume.

Influence on alveolar resorption of the buccal bony plate width in the edentulous ridge expansion (ERE) - an experimental study in the dog

Objective: To compare the hard tissue changes at implants installed applying edentulous ridge expansion (E.R.E.) at sites with a buccal bony wall thickness of 1 or 2 mm.Material and methods: In six Labrador dogs, the first and second maxillary incisors were extracted, and the buccal alveolar bony plates and septa were removed. After 3 months of healing, partial-thickness flaps were dissected, and the E.R.E. was applied bilaterally. Hence, an expansion of the buccal bony crest was obtained in both sides of the maxilla with a displacement of either a 1- or a 2-mm-wide buccal bony plate at the test and control sites, respectively. After 3 months of healing, biopsies were obtained for histological analyses.Results: A buccal vertical resorption of the alveolar crest of 2.3 +/- 0.8 and 2.1 +/- 1.1 mm, and a coronal level of osseointegration at the buccal aspect of 2.7 +/- 0.5 and 2.9 +/- 0.9 mm were found at the test (1 mm) and control (2 mm) sites, respectively. The differences did not reach statistical significance. The mean values of the mineralized bone-to-implant contact (MBIC%) ranged from 62% to 73% at the buccal and lingual sites. No statistically significant differences were found. Horizontal volume gains of 1.8 and 1.1 mm were observed at the test and control sites, respectively, and the difference being statistically significant.Conclusions: Implants installed using the E.R.E. technique yielded a high degree of osseointegration. It is suggested that the displacement of buccal bony plates of 1 mm thickness is preferable compared with that of wider dimensions.

Cimetidine Reduces Alveolar Bone Loss in Induced Periodontitis in Rat Molars

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alveolar ridge augmentation with the perforated and nonperforated bone grafts

Purpose: Autogenous bones are frequently used because of their lack of antigenicity, but good osteoconductive and osteoinductive properties. This study evaluated the biological behavior of perforated and nonperforated cortical block bone grafts.Methods: Ten nonsmoking patients who required treatment due to severe resorption of the alveolar process and subsequent implant installation were included in the study. The inclusion criteria was loss of one or more teeth; the presence of atrophy of the alveolar process with the indication of reconstruction procedures to allow rehabilitation with dental implants; and the absence of systemic disease, local infection, or inflammation. The patients were randomly divided into two groups based on whether they received a perforated (inner surface) or nonperforated graft. After a 6-month healing period, a biopsy was performed and osseointegrated implants were installed in the same procedure.Results: Fibrous connective tissue was evident at the interface in patients who received nonperforated grafts. However, full union between the graft and host bed was visible in those who had received a perforated graft.Conclusions: We found that cortical inner side perforations at donor sites increased the surface area and opened the medullary cavity. Our results indicate an increased rate of graft incorporation in patients who received such perforated grafts.

Treatment with tacrolimus enhances alveolar bone formation and decreases osteoclast number in the maxillae: A histomorphometric and ultrastructural study in rats

Recent studies have suggested that tacrolimus monotherapy is a beneficial therapeutic alternative for the normalization of cyclosporin- induced bone loss in animal models and humans. The mechanism accounting for this action is unclear at present. In the present study, we attempted to determine the effect of tacrolimus monotherapy on alveolar bone using histological, histomorphometrical and transmission electron microscopy (TEM).Groups of rats (n= 10 each) were treated with either tacrolimus (1mg/ kg/ day, s.c.) or drug vehicle for 60 days. Fragments containing maxillary molars were processed for light microscopy to investigate the alveolar bone volume, trabecular separation, number of osteoclasts and osteoblasts, and transmission electron microscopy to investigate their ultrastructural basic phenotype.Treatment with tacrolimus monotherapy during 60 days may induce increases in alveolar bone volume (BV/ TV,%; P < 0.05) and a non- significant decrease in trabecular separation (Tb. Sp, mm; P > 0.05), represented by a decrease in osteoclast number (N. Oc/ BS; P < 0.05) and maintenance of osteoblast number (N. Ob/ BS; P > 0.05). Osteoblasts were often observed as a continuous layer of active cells on the bone surface. Osteoclasts appeared to be detached from the resorbed bone surface, which was often filled by active osteoblasts and collagen- rich matrix. Moreover, osteoclasts in the treated group were frequently observed as inactive cells (without ruffled border, clear zone and detached from the bone surface).Within the limits of the present study, we conclude that tacrolimus leads to an increase in alveolar bone formation, which probably exerts action on osteoclasts. Tacrolimus could, therefore, play a crucial role in the control of both early osteoclast differentiations from precursors, as well as in functional activation.

Data collection on bone density of mandibular alveolar bone on a Hounsfield scale of the dental apex of the cranial root of the first inferior molar in dogs using computed tomography at FMVZ-UNESP

The head is the most important and specialized region in the body because it contains a range of specialized organs and, because it has interconnections between specialized organs, there is a great overlap of images. Thus, computed tomography (CT) helps in diagnosing diseases in this region, such as oral conditions, as they provide millimetric slices or cuts and demonstrate the relationship between the various anatomical structures involved, in volume and depth. Within dentistry, CT helps in the identification of pathological processes such as infection, tumors, visualization of embedded teeth and bone bed. This study aimed to assess the density of the mandibular alveolar bone at a determined point to later predict how periodontal disease is involved in bone resorption. For this, we performed a blind retrospective study (n = 124) of the CT scan files of dog skulls at FMVZ-UNESP in order to determine the density of the jaw bone using a Hounsfield scale, in the region of the dental apex of the cranial root of the first molar tooth in dogs. The results obtained were evaluated using mean and standard deviation (27.28 +/- 9.53 HU) in order to predict the normal density of the mandibular alveolar bone in the studied region. Thus, this data analysis allows a more concise evaluation of bone resorption of mandibular alveolar bone and, therefore, provides an adequate surgical planning in cases of osteosynthesis given mainly by the presence of installed periodontal disease.

Estudio histológico del processo de reparación alveolar después de la aplicación tópica de la solucioón anestésica prilocaína 3 % con felipressina o,o3 ui/ml

The aim of this study was to evaluate the local anesthetic solution, composed by Prilocaine 3% and felipressin 0,03 UI/ml, influence on the alveolar repair process in rats after dental extraction. This research was previously approved by the Ethic Committee in Research of the Masters Degree Program in Oral and Maxillofacial Surgery of the Marília University (UNIMAR), Marília, São Paulo, Brazil. It was an experimental, randomly controlled study, with bifactorial analysis (group control versus experimental group, in function of the postoperative times (2 X 4)). For the accomplishment of this study 32 rats were used (Rattus norvegicus, albinus, Wistar), males, adults, weighing between 280 and 320 grams. The animals were selected and divided into Group I (control) and Group II (Citocain 3%® - Prilocaine 3% with felipressin 0,03UI/ml) with 16 rats each; being four animals of the Group I and four of the Group II, destined to the euthanasia in the postoperative periods of 3rd, 7th, 15th and 24th days. The histological analysis with base in the developed methodology, allowed us to conclude that the anesthetic solution of Citocain 3%® applied with gauze compress on the surgical dental wound, produced tissue events that committed the basic biological principles, that are responsible for the regeneration of the gingival epithelium and the alveolar process repair in rats. The Group I presented better results in the alveolar repair when compared to the Group II.

Periodontal disease-associated compensatory expression of osteoprotegerin is lost in type 1 diabetes mellitus and correlates with alveolar bone destruction by regulating osteoclastogenesis

Alveolar bone resorption results from the inflammatory response to periodontal pathogens. Systemic diseases that affect the host response, such as type 1 diabetes mellitus (DM1), can potentiate the severity of periodontal disease (PD) and accelerate bone resorption. However, the biological mechanisms by which DM1 modulates PD are not fully understood. The aim of this study was to determine the influence of DM1 on alveolar bone resorption and to evaluate the role of receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) in osteoclastogenesis in rats. PD was induced by means of ligature in nondiabetic and in streptozotocyn-induced DM1 rats. Morphological and morphometric analyses, stereology and osteoclast counting were performed. RANKL and OPG mRNA levels, protein content, and location were determined. PD caused alveolar bone resorption, increased the number of osteoclasts in the alveolar bone crest and also promoted changes in RANKL/OPG mRNA expression. DM1 alone showed alveolar bone destruction and an increased number of osteoclasts at the periapical and furcal regions. DM1 exacerbated these characteristics, with a greater impact on bone structure, resulting in a low OPG content and a higher RANKL/OPG ratio, which correlated with prominent osteoclastogenesis. This work demonstrates that the effects of PD and DM1 enhance bone destruction, confirms the importance of the RANKL signaling pathway in bone destruction in DM1 in animal models and suggests the existence of alternative mechanisms potentiating bone degradation in PD.

Alveolar ridge and maxillary sinus augmentation using rhBMP-2: a systematic review

Purpose: The aim of this systematic review was to evaluate clinical and safety data for recombinant human bone morpho-genetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier when used for alveolar ridge/maxillary sinusaugmentation in humans.Materials and Methods: Clinical studies/case ser ies published 1980 through June 2012 using rhBMP-2/ACS were searched.Studies meeting the following criteria were considered eligible for inclusion: >10 subjects at baseline and maxillary sinus oralveolar ridge augmentation not concomitant with implant placement.Results: Seven of 69 publications were eligible for review. rhBMP-2/ACS yielded clinically meaningful bone formationfor maxillary sinus augmentation that would allow placement of regular dental implants without consistent differencesbetween rhBMP-2 concentrations. Never theless, the statistical analysis showed that sinus augmentation following autog-enous bone graft was significantly greater (mean bone height: 1.6 mm, 95% CI: 0.5–2.7 mm) than for rhBMP-2/ACS(rhBMP-2 at 1.5 mg/mL). In extraction sockets, rhBMP-2/ACS maintained alveolar ridge height while enhancing alve olarridge width. Safety reports did not represent concerns for the proposed indications.Conclusions: rhBMP-2/ACS appears a promising alternative to autogenous bone grafts for alveolar ridge/maxillary sinusaugmentation; dose and carrier optimization may expand its efficacy, use, and clinical application.

Osteotomia sagital da crista alveolar para instalação de implantes Bicon

This case report presents details of a new surgical technique for mandibular ridge sagittal osteotomy and expansion associated to immediate dental implants in atrophic ridges. The bone atrophies represents a challenge for the surgeons that intends to modify this situation. In the past, the only viable option was the onlay bone graft. However, the bone graft requests a second surgical site that certainly increases the postoperative morbidity, without mentioning the longer treatment time required. The sagittal osteotomy of the alveolar crest represents a faster option, because it eliminates the time requested for bone graft integration, providing rehabilitation of edentulous areas with thin alveolar crests that otherwise would need additi onal surgical procedures for a satisfactory result. The authors report a clinical case in which this technique was used with the installation of a Bicon dental implant in the same surgical time, showing all the steps for this single-tooth rehabilitation.

The H2S-releasing naproxen derivative, ATB-346, inhibits alveolar bone loss and inflammation in rats with ligature-induced periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)