The effects of up to 240 days of tacrolimus therapy on the gingival tissues of rats - A morphological evaluation

Background: Tacrolimus, an immunosuppressive drug used in organ transplantation, has been reported not to induce gingival overgrowth. However, prevalence studies are limited, and the methods used for assessing gingival overgrowth varies among studies. Objective: The purpose of this study was to evaluate the effects of up to 240 days of tacrolimus therapy on gingival tissues of rats. Materials and methods: Rats were treated for 60, 120, 180 and 240 days with daily subcutaneous injections of 1 mg/kg body weight of tacrolimus. After histological processing, the oral and connective tissue, volume densities of fibroblasts (Vf), collagen fibers (Vcf) and other structures (Vo) were assessed in the region of the lower first molar. Results: After 60 and 120 days of treatment with tacrolimus, gingival overgrowth was not observed. The gingival epithelium, connective tissue, as well as the values for Vf, Vcf, and Vo were similar to those of the control rats (P > 0.05). After 180 and 240 days of the treatment, gingival overgrowth was associated with a significant increase in the gingival epithelium and connective tissue as well as an increase in the V f and Vcf (P < 0.05). Conclusions: Within the limits of the experimental study, it may be concluded that the deleterious side effects of tacrolimus on the gingival tissues of rats may be time-related. © 2007 Blackwell Munksgaard All rights reserved.

Nicotine-Induced Damage Affects Gingival Fibroblasts in the Gingival Tissue of Rats

Background: Very limited information is available from in vivo studies about whether smoking and/or nicotine affect gingival tissues in the absence of plaque. The purpose of this study is to evaluate the effect of the systemic administration of nicotine in the proliferation and counting of fibroblast-like cells in the gingival tissue of rats.Methods: Thirty adult male Wistar rats were randomly assigned into two groups to receive subcutaneous injections of a saline solution (control group = group C) or nicotine solution (group N; 3 mg/kg) twice a day. The animals were euthanized 37, 44, or 51 days after the first subcutaneous injection. Specimens were routinely processed for serial histologic sections. Five fields of view in the connective tissue adjacent to the gingival epithelium and above the alveolar bone crest of the maxillary first molar were selected for the counting of fibroblast-like cells. Data were statistically analyzed (P<0.05).Results: The intergroup analysis detected a lower number of fibroblast-like cells in group N compared to group C on days 37 (2.65 +/- 1.41 and 6.67 +/- 3.25, respectively), 44 (2.70 +/- 1.84 and 8.57 +/- 2.37, respectively), and 51(2.09 +/- 1.41 and 7.49 +/- 2.60, respectively) (P<0.05). The quantification of fibroblast-like cells showed no significant difference (P >0.05) in the intragroup analysis of control and nicotine throughout experimental periods. In the intergroup analysis, group N had reduced proliferating cell nuclear antigen positive fibroblasts compared to group C in all periods (P<0.05).Conclusion: The daily systemic administration of nicotine negatively affected, in vivo, the number and proliferation of fibroblast-like cells in the gingival tissue of rats. J Periodontol 2011;82:1206-1211.

Functional Aesthetic Treatment of Patient With Phenytoin-Induced Gingival Overgrowth

Gingival overgrowth (GO) may be related to the frequent use of certain medications, such as cyclosporin, phenytoin (PHT), and nifedipine, and is therefore denominated drug-induced GO. This article reports a case of a patient who with chronic periodontitis made use of PHT and presented generalized GO. A 30-year-old man with GO was referred to the clinic of the Universidade Estadual Paulista, Brazil. The complaint was poor aesthetics because of the GO. The patient had a medical history of a controlled epileptic state, and PHT was administered as an anticonvulsant medication. The clinical examination showed generalized edematous gingival tissues and presence of bacterial plaque and calculus on the surfaces of the teeth. The diagnosis was GO associated with PHT because no other risk factors were identified. Treatment consisted of meticulous oral hygiene instruction, scaling, root surface instrumentation, prophylaxis, and daily chlorhexidine mouth rinses. After this stage, periodontal surgery was performed, and histopathologic evaluation was made. The patient has been under control for 3 years after the periodontal surgery, and up to the present time, there has been no recurrence. It can be concluded that PHT associated with the presence of irritants favored gingival growth and that the association of nonsurgical and surgical periodontal therapies was effective in the treatment of GO. Besides, motivating the patient to maintain oral hygiene is a prerequisite for the maintenance of periodontal health.

Influence of a Parafunctional Oral Habit on Root Fracture Development After Trauma to an Immature Tooth

Root fractures in immature teeth are rare because the resilience of the alveolar bone is more favorable to the occurrence of luxation. This article reports a case of traumatic injury in an immature permanent tooth that progressed to root fracture, having a parafunctional oral habit as the possible modifying factor of case evolution. A 12-year-old boy presented for treatment complaining of a defective restoration and mild pain on the maxillary right central incisor. The patient had a history of crown fracture in this tooth due to trauma 2 years before. The clinical examination showed healthy gingival tissues and no abnormal tooth mobility, whereas radiographic projections revealed healthy periradicular tissues, incomplete root formation, and no visible root fracture. As pulp necrosis was diagnosed, calcium hydroxide therapy was started for canal disinfection and subsequent obturation. However, after 4 weeks of treatment, a horizontal fracture line was observed radiographically in the root's middle third. The patient denied a new traumatic injury, but revealed the habit of chewing on a pencil. Refraining from the deleterious oral habit was strongly advised, and root canal filling with mineral trioxide aggregate was performed to treat the root fracture. After 4 years of follow-up, the tooth has normal function and no abnormal mobility. Images suggestive of remodeling at the apical end of the coronal segment and replacement resorption of the apical segment are seen radiographically. This case demonstrates the need of following cases of dental trauma and the possible influence of parafunctional oral habits as modifying factors of case progression.

Removable Partial Denture in Combination with a Milled Fixed Partial Prosthesis as Interim Restorations in Long-Term Treatment

Interim restorations are frequently used in prosthodontic treatments. Many complex situations require the combination of fixed and removable partial prostheses. An appropriate interim restoration design that accurately implements the treatment plan is necessary to prepare the oral cavity for the prostheses, and to contribute to the preservation and health of remaining natural teeth, bone support, and gingival tissues. This report describes a modified technique for construction of interim restorations with a combination of fixed and removable partial prostheses. The technique consists of the construction of a milled fixed prosthesis and removable partial denture with metallic framework for use during extensive treatment, improving masticatory function and esthetics and preserving the periodontal health of supporting structures. This interim restoration can also serve as a template for the definitive restoration, allowing patient and dentist to evaluate appearance and function and helping to ensure the success of the definitive restoration.

Aesthetic Approach in Single Immediate Implant-Supported Restoration

The aim of this study was to analyze the main aspects that influence the aesthetics of single immediate implant-supported restorations through a literature review on the MEDLINE database. It was observed that immediate implant-supported restorations present clinical success with aesthetic predictability demonstrated by the literature. Proper patient selection and diagnostic and multidisciplinary planning are essential and should be associated to technical ability of professional and knowledge concerning the biology of peri-implant tissues. It is suggested that provisional restoration should be immediately inserted after implant fixation to guide healing of gingival tissues with a proper emergence profile besides psychologic comfort for a patient due to immediate aesthetic reestablishment.

Curcumin modulates the immune response associated with LPS-induced periodontal disease in rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Potent anti-inflammatory effects of systemically administered curcumin modulate periodontal disease in vivo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

LPS Induces Greater Bone and PDL Loss in SPARC-null Mice

Individuals with periodontal disease have increased risk of tooth loss, particularly in cases with associated loss of alveolar bone and periodontal ligament (PDL). Current treatments do not predictably regenerate damaged PDL. Collagen I is the primary component of bone and PDL extracellular matrix. SPARC/Osteonectin (SP/ON) is implicated in the regulation of collagen content in healthy PDL. In this study, periodontal disease was induced by injections of lipopolysaccharide (LPS) from Aggregatibacter actinomycetemcomitans in wild-type (WT) and SP/ON-null C57/B16 mice. A 20-mu g quantity of LPS was injected between the first and second molars 3 times a week for 4 weeks, whereas PBS control was injected into the contralateral maxilla. LPS injection resulted in a significant decrease in bone volume fraction in both genotypes; however, significantly greater bone loss was detected in SP/ON-null maxilla. SP/ON-null PDL exhibited more extensive degradation of connective tissue in the gingival tissues. Although total cell numbers in the PDL of SP/ON-null were not different from those in WT, the inflammatory infiltrate was reduced in SP/ON-null PDL. Histology of collagen fibers revealed marked reductions in collagen volume fraction and in thick collagen volume fraction in the PDL of SP/ON-null mice. SP/ON protects collagen content in PDL and in alveolar bone in experimental periodontal disease.

Análise quantitativa dos tecidos gengivais de ratos tratados com fenitoína e ciclosporina

Os aumentos gengivais podem ser decorrentes de reações teciduais a estímulos idiopáticos, patológicos e farmacológicos. O objetivo desse trabalho foi avaliar morfometricamente e estereologicamente a ação da fenitoína (Fen) e ciclosporina (CsA) sobre os tecidos gengivais de ratos. Dez ratos receberam, por via intraperitonial, Fen na dose inicial de 2 mg/kg de peso corporal/dia, aumentando 2 mg a cada duas semanas, durante 60 dias. em outros 10 ratos, administraram-se, por via subcutânea, 10mg/kg de peso corporal/dia de CsA, durante o mesmo período do grupo anterior. Os valores morfométricos e estereométricos dos tecidos gengivais dos ratos tratados com CsA foram significativamente maiores quando comparado com os valores dos tecidos gengivais do grupo tratado com Fen. Esses resultados sugerem que a CsA na dose utilizada é mais eficaz no desenvolvimento do aumento gengival em ratos, podendo estar atuando na proliferação de fibroblastos e no desequilíbrio fisiológico da síntese de fibras colágenas.

Fluoxetine Inhibits Inflammatory Response and Bone Loss in a Rat Model of Ligature-Induced Periodontitis

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

COX-2 inhibition decreases VEGF expression and alveolar bone loss during the progression of experimental periodontitis in rats

Background: Vascular endothelial growth factor (VEGF) is a macromolecule of importance in inflammation that has been implicated in periodontitis. The aims of this study were to investigate VEGF expression during the progression of periodontal disease and to evaluate the effect of a preferential cyclooxygenase (COX)-2 inhibitor meloxicam on VEGF expression and alveolar bone loss in experimentally induced periodontitis.Methods: A total of 120 Wistar rats were randomly separated into groups 1 (control) and 2 (meloxicam, 3 mg/kg/day, intraperitoneally, for 3, 7, 14, or 30 days). Silk ligatures were placed at the gingival margin level of the lower right first molar of all rats. VEGF expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR), Western blot (WB), and immunohistochemical (IHC) analyses. The hemiarcades were processed for histopathologic analysis. RT-PCR and WB results were submitted to analysis of variance, the Tukey test, and Pearson correlation analysis (P<0.05).Results: A reduction in alveolar bone resorption was observed in the meloxicam-treated group compared to the control group at all periods studied. There was a positive correlation between COX-2 mRNA and VEGF mRNA in the gingival tissues and periodontal disease (R = 0.80; P = 0.026). Meloxicam significantly reduced the increased mRNA VEGF expression in diseased tissues after 14 days of treatment (P = 0.023). Some alterations in VEGF receptor I mRNA expression were observed, but these were not statistically significant. VEGF protein expression in WB experiments was significantly higher in diseased sites compared to healthy sites (P<0.05). After 14 days of treatment with meloxicam, an important decrease in VEGF protein expression was detected in diseased tissues (P = 0.08). Qualitative IHC analysis revealed that VEGF protein expression was higher in diseased tissues and decreased in tissues from rats treated with meloxicam.Conclusions: The present data suggest an important role for VEGF in the progression of periodontal disease. Systemic therapy with meloxicam can modify the progression of experimentally induced periodontitis in rats by reducing VEGF expression and alveolar bone loss.

Proteinase-activated receptor-2 (PAR2) agonist causes periodontitis in rats

Proteinase-activated receptor-2 (PAR2) is a G-protein-coupled receptor that mediates cellular responses to extracellular proteinases. Since PAR2 is expressed by oral epithelial cells, osteoblasts, and gingival fibroblasts, where its activation releases interleukin-8, we hypothesized that PAR2 activation may participate in periodontal disease in vivo. We investigated the role of PAR2 activation in periodontal disease in rats. Radiographic and enzymatic (myeloperoxidase) analysis revealed that topical application of PAR2 agonist causes periodontitis but also exacerbates existing periodontitis, leading to significant alveolar bone loss and gingival granulocyte infiltration. Inhibition of matrix metalloproteinase (MMP) and cyclo-oxygenase (COX) decreased PAR2 agonist-induced periodontitis. More specifically, the overexpression of COX-1, COX-2, MMP-2, and MMP-9 in gingival tissues suggests that they are involved in PAR 2-induced periodontitis. In conclusion, PAR2 agonist causes periodontitis in rats through a mechanism involving prostaglandin release and MMP activation. Inhibition of PAR2 may represent a novel approach to modulate host response in periodontitis.

Diltiazem não induziu crescimento gengival em ratos. Análise clínica, histológica e histométrica

The administration of calcium channel blockers has been associated with gingival overgrowth. However, there are few studies in humans or animals that evaluated the effect of diltiazem on gingival tissues. The present study assessed the influence of diltiazem, at different dosages and treatment duration, on gingival tissues of rats, using clinical, histological and histometric analyses. Eighty young male rats were separated into eight groups according to the dosage and duration of treatment. Rats were treated for 20 or 40 days with a daily subcutaneous injection of 5, 20 or 50 mg/kg of body weight of diltiazem. The results confirmed that diltiazem did not induce gingival overgrowth in rats. For all animals, the evaluation did not show gingival alterations regardless of the dosages and periods of treatment. The histometric analysis showed no significant change in the area of epithelium and connective tissues, although after 40 days of treatment a decrease in the area of connective tissue was observed, without statistically significant difference from control groups. Within the limits of this study, we suggest that diltiazem did not induce gingival overgrowth.

Six-year follow-up of maxillary anterior rehabilitation with forced orthodontic extrusion: Achieving esthetic excellence with a multidisciplinary approach

Orthodontic extrusion with multidisciplinary treatment can provide predictable outcomes in selected situations, reducing the costs and the adaptation times of gingival tissues after implant integration. Forced orthodontic extrusion is strongly related to interactions of teeth with their supportive periodontal tissues. This article reports a case of orthodontic extrusion of the maxillary incisors for later implant rehabilitation in a patient with periodontal disease. Slow forces were applied for 14 months. After this time, the teeth were extracted, and the implants were placed on the same day. Also in the same session, the provisional crown was fabricated for restoration of the anterior maxillary interdental papillae loss and for gingival contouring. Clinical and radiographic examinations at the 6-year follow-up showed successful tooth replacement and an improved esthetic appearance achieved by this multidisciplinary treatment. The decision to perform orthodontic extrusion for implant placement in adult patients should be multidisciplinary. Copyright © 2013 by the American Association of Orthodontists.