Periodontitis as a risk factor for head and neck cancer.

BACKGROUND: Periodontitis may be associated with the development of head and neck cancer (HNC). A literature review was conducted to understand the possible association between them. MATERIAL AND METHODS: Articles published in the PubMed database from January 1999 and May 2020 were retrieved. Limitations of the studies and biological mechanisms were discussed. RESULTS: A total of 4,232 articles were found. Of these, 13 were analyzed according to inclusion criteria. Most papers found some association between periodontitis and HNC, although differences in periodontal evaluation, sample size, study design and tumor sites were observed. Porphyromonas gingivalis appears to increase the chance of both diseases, and it may be one of their main potential risk factors. Genetic predisposition is increased by exposure to environmental factors which can directly induce epigenetic changes that contribute to these diseases. CONCLUSIONS: Understanding the mechanisms related to periodontitis and HNC has increased, however, well-designed clinical studies are needed for better conclusions. Furthermore, the advent of multiple "omic" technologies will help comprehend their possible association.

One-year follow-up of the immune profile in serum and selected sites of generalized and localized aggressive periodontitis.

BACKGROUND: The local and systemic immunological profiles of important inflammatory mediators in the localized (LAgP) and generalized (GAgP) forms of aggressive periodontitis are still unknown, as well as the effect of periodontal therapy on these parameters. The aim of this prospective study was to evaluate clinical and immune responses of patients with AgP undergoing nonsurgical treatment. MATERIAL AND METHODS: Eighteen patients with GAgP, 10 with LAgP and 10 healthy participants were included in this study. AgP participants were submitted to scaling and root planing plus systemic antibiotics (amoxicillin and metronidazole). At baseline and 1-year follow-up were measured clinical parameters, such as probing depth [PD] and clinical attachment loss [CAL], and the levels of 10 immunological mediators (GM-CSF, M-CSF, MCP-1, ICAM-1, CXCL8, IL-1ß, TNF-α, IL-17, IL-4, and IL-10) in the gingival crevicular fluid (GCF) of selected sites [AgP forms: PD ≥ 6 mm or the deepest, bleeding on probing (BoP) and bone loss measured by periapical radiography; healthy individuals: PD ≤ 3 mm, no BoP, no bone loss] and serum. RESULTS: After periodontal treatment both forms of AgP presented a significant reduction of PD and CAL, an increase of GM-CSF, ICAM-1, MCP-1, TNF-α, IL-17, IL-4, and IL-10 in the GCF, as well as of GM-CSF and IL-4 in the serum, and a reduction in the serum concentration of IL-1ß. Serum levels of M-CSF, ICAM-1, and MCP-1 remained significantly below those found in healthy individuals in both forms of AgP even after therapy. An increase in the systemic or local levels of MCP-1, ICAM-1 and the anti-inflammatory profile (IL-4, IL-10) was correlated with an improvement in clinical parameters of LAgP patients. Also, a local reduction of IL-1ß levels in both forms of AgP was correlated with an increase in the clinical attachment gain. CONCLUSION: Nonsurgical periodontal therapy was successful in improving clinical parameters and modulating the immune response in both forms of AgP. However, this therapeutic approach does not seem to affect the deficient level of important serum mediators involved in mechanisms of cell transmigration.

Immunological and microbiological periodontal profiles in isolated growth hormone deficiency.

BACKGROUND: Growth hormone (GH) has been identified as an important regulator of the immune response. We have previously shown that adults with isolated GH deficiency (IGHD) due to a mutation in the GH releasing hormone receptor (GHRHR) gene, have a greater chance of having periodontitis. However, the interaction of GH with periodontal tissues is still unknown, and this population has emerged as a unique model to investigate this issue. Therefore, we evaluated the microbiological and immunological periodontal profiles of such individuals. METHODS: Nineteen IGHD and 19 controls matched by age, sex, diabetes, and smoking status, were enrolled in this case-control study. Periodontal clinical parameters (probing depth [PD] and clinical attachment loss [AL]) were measured at six sites per tooth. Immune mediators (C-reactive protein, matrix metalloproteinase [MMP]-8, MMP-9, interleukin [IL]-1α, IL-6, IL-8, tumor necrosis factor [TNF]-α, adiponectin, and leptin) were analyzed by enzyme-linked immunosorbent assay (ELISA) in the gingival crevicular fluid (GCF) in four non-adjacent sites for each participant (two with PD ≤3 mm [shallow sites] and two with PD ≥7 mm or the worst PD found in the mouth [deep sites]). Bacterial quantification (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) of subgingival biofilm samples collected from these same sites was performed by quantitative real-time polymerase chain reaction (qPCR). RESULTS: IGHD individuals presented higher values of PD and AL, and increased levels of CRP, IL-8, MMP-8, and adiponectin in the GCF. Bacterial quantification did not identify differences between the two groups. CONCLUSION: IGHD alters the local immune response in periodontal pockets leading to greater attachment loss, and GH stands out as an important hormone to be evaluated in the pathogenesis of periodontitis.

Efficacy of local phytotherapy in the nonsurgical treatment of periodontal disease: A systematic review.

Herbal drugs are commonly used in the treatment of several diseases, including periodontitis. So far, no systematic review had evaluated the evidence regarding the efficacy of these agents in the treatment of periodontal disease. Therefore, the purpose of this review was to evaluate the effect of local application of phytotherapic agents as adjuncts to scaling and root planing (SRP), compared to SRP alone, on clinical parameters of chronic periodontal patients. Only randomized controlled trials of at least 3 months follow-up, of SRP alone in association with local phytotherapic agents were included. MEDLINE (PubMed), Google Scholar and LILACS databases were searched for articles published up to October 2016. Random-effects meta-analyses were conducted for clinical attachment level and probing pocket depth (PPD) change after treatment. Of 1861 papers potentially relevant, 7 were included. All studies showed that periodontal treatment in association with local phytotherapic delivery promotes a significant PPD reduction and the majority of them showed clinical attachment level gain. The local use of phytotherapy as an adjunct to SRP may promote additional benefits in PPD reduction and clinical attachment level gain. However, these results must be interpreted with caution due to the small sample size, high risk of bias and heterogeneity of the studies.

Does the adjunctive use of statins provide additional benefits to nonsurgical periodontal treatment? A systematic review and meta-analysis.

Adjunctive therapeutic agents may be used to improve the response to nonsurgical periodontal therapy. Local delivery of statins (simvastatin, artovastatin and rosuvastatin) is a promising adjunct to scaling and root planing (SRP). Thus, the aim of this review is to evaluate if adjunctive local delivery of statins is more effective than SRP alone. Randomized clinical trials that presented a test group evaluating local delivery of statins as adjuncts in healthy, diabetic and smoking patients were included. Medline and the Cochrane library database were searched up to November 2016. Random effects meta-analyses were conducted for pocket depth change and clinical attachment gain. One hundred and twenty-five studies potentially related to the aim of this review were screened, but only 10 were included. The majority of the trials reported additional clinical benefits in the groups that were treated with adjunctive local delivery of statins. Pooled calculations showed that local delivery of statins resulted in additional reduction of pocket depth and clinical attachment gain in healthy people, smokers and diabetic patients. Local statins may offer additional clinical benefits to SRP, even in smokers and diabetics.

The Role of Proteinase-Activated Receptors 1 and 2 in the Regulation of Periodontal Tissue Metabolism and Disease.

Proteinase-activated receptors 1 (PAR1) and 2 (PAR2) are the most highly expressed members of the PAR family in the periodontium. These receptors regulate periodontal inflammatory and repair processes through their activation by endogenous and bacterial enzymes. PAR1 is expressed by the periodontal cells such as human gingival fibroblasts, gingival epithelial cells, periodontal ligament cells, osteoblasts, and monocytic cells and can be activated by thrombin, matrix metalloproteinase 1 (MMP-1), MMP-13, fibrin, and gingipains from Porphyromonas gingivalis. PAR2 is expressed by neutrophils, osteoblasts, oral epithelial cells, and human gingival fibroblasts, and its possible activators in the periodontium are gingipains, neutrophil proteinase 3, and mast cell tryptase. The mechanisms through which PARs can respond to periodontal enzymes and result in appropriate immune responses have until recently been poorly understood. This review discusses recent findings that are beginning to identify a cardinal role for PAR1 and PAR2 on periodontal tissue metabolism.

Gingival crevicular fluid levels of protease-activated receptors type 1 and type 2 in diabetic patients with periodontitis.

BACKGROUND AND OBJECTIVE: Protease activated receptor type 1 (PAR1 ) seems to play a role in periodontal repair, while PAR2 is associated with periodontal inflammation. As diabetes is a known risk factor for periodontal disease, the aim of this study was to evaluate the influence of type 2 diabetes on PAR1 and PAR2 mRNA expression in the gingival crevicular fluid of patients with chronic periodontitis before and after non-surgical periodontal treatment. MATERIAL AND METHODS: Gingival crevicular fluid samples and clinical parameters consisting of measuring probing depth, clinical attachment level, bleeding on probing and plaque index were collected from systemically healthy patients and patients with type 2 diabetes and chronic periodontitis, at baseline and after non-surgical periodontal therapy. PAR1 and PAR2 , as well as the presence of the proteases RgpB gingipain and neutrophil proteinase-3 were assessed by quantitative polymerase chain reaction in the gingival crevicular fluid. RESULTS: The periodontal clinical parameters significantly improved after periodontal therapy (p < 0.01). Diabetes led to increased expression of PAR1 in gingival crevicular fluid, and in the presence of chronic periodontitis, it significantly decreased the expression of PAR1 and PAR2 (p < 0.05). Moreover, non-surgical periodontal treatment in diabetics resulted in increased expression of PAR1 and PAR2 (p < 0.05), and decreased expression of RgpB gingipain and proteinase-3 (p < 0.05). CONCLUSION: The present data demonstrated that diabetes was associated with an altered expression of PAR1 and PAR2 in the gingival crevicular fluid cells of subjects with chronic periodontitis. Future studies are necessary to elucidate the effects of PAR1 upregulation in periodontally healthy sites and PAR2 downregulation in chronic periodontitis sites on the increased susceptibility and severity of periodontitis in diabetes.

[The Rostock Headache Questionnaire ("Rokoko")--validation of a tool to screen and to qualify primary headaches]. / Der Rostocker Kopfschmerzfragen-Komplex ("Rokoko")--Validierung einer schnellen diagnostischen Hilfe bei der Einordnung primärer Kopfschmerzen.

Primary headache disorders should be diagnosed based on the detailed history of the patient. However, only few questions are necessary to allocate the symptoms to migraine, tension-type headache or other primary headaches in most cases. The "Rostock Headache Questionnaire" (Rokoko) is suitable for being completed by the investigator or the patient him/herself within a few minutes. Validation parameters of a sample of n = 87 patients (median: 44 years), diagnosed by headache experts in a personal interview ("gold standard"), are presented. Sensitivity and specificity for migraine without aura (0.87/0.51), migraine with aura (0.71/0.95), tension-type headache (0.57/0.93), or a combination of both (0.22/0.93) are based on the parameters pain frequency (recurrent vs. permanent), and the presence or absence of aura symptoms. To differentiate tension-type headache into episodic or chronic forms, the questionnaire can be analysed individually based on the frequency of headache days. The questionnaire enables the fast acquisition of relevant data in headache diagnosis and headache research with sufficient sensitivity and specificity. In addition, further information about triggering and symptoms of headaches can be assessed. The questionnaire can be used both by neurologists or psychiatrists and by general practitioners. The questionnaire does not replace the physical examination.

[Privacy: a most important dimension for the quality of life of nursing home residents]. / Die Intimsphäre : Eine wichtige Dimension der Lebensqualität von Pflegeheimbewohnern.

BACKGROUND: A fundamental aim of social science and for practitioners is the improvement of the quality of life of inpatients residing in long-term care homes. This research aims to determine aspects of their privacy in the context of quality of life from the residents' perspective, which has long been neglected. MATERIALS AND METHOD: A total of 42 narrative interviews with nursing home residents were conducted and analyzed using the documentary method. RESULTS: Four dimensions of privacy were identified. Intimate areas concern personal hygiene and toilet matters, non-intimate areas included mainly eating and the residents' private living area. Violations of privacy are associated with unpleasant feelings such as shame and disgust and are often subject to taboos. Respondents tended to be more open to talk about taboo subjects the less the topic referred to their own body. CONCLUSION: Privacy is perceived as a significant aspect of the respondents' quality of life. To be able to address inhibition thresholds and shameful topics, a good relationship between patient and personnel is required. This postulates that the caregivers are also aware of their own inhibition threshold and negative feelings.

FLQAI - A Questionnaire on Quality of Life in Fecal Incontinence: German translation and validation of Rockwood et al.'s (2000) Fecal Incontinence Quality of Life Scale (FIQLS).

AIM: The aim of the study was to produce a German version (FLQAI) of the Fecal Incontinence Quality of Life Scale (FIQLS) by Rockwood et al., an English-language measure of quality of life in fecal incontinence 1. The FIQLS has 29 items assigned to the four subscales of lifestyle, coping/behavior, depression/self-perception and embarrassment. MATERIAL AND METHODS: The FIQLS 1 was translated into German and adapted. Indicators of test quality (convergent and discriminant validity, reliability, confirmatory factor analysis) were determined in N = 88 subjects (mean age = 71.5 years) with fecal incontinence and urinary incontinence (control group, n = 29). RESULTS: Three of the four scales of the FLQAI had an acceptable internal reliability. The scales of the FLQAI showed significant correlations with selected subscales of the SF-36 2, the ADS 3 and the FISI 4 (convergent validity). Two of the four scales of the FLQAI discriminated between patients with fecal incontinence and patients with urinary incontinence (discriminant validity). The confirmatory factor analysis did not reveal a uniform fit of the data obtained with the German version with the original four-factor solution of the original version of the questionnaire. DISCUSSION: The Questionnaire on Quality of Life in Fecal Incontinence (FLQAI) is a German-language self-rating questionnaire with satisfactory psychometric properties for measuring disease-specific quality of life in elderly patients with fecal incontinence.

Protease-activated receptor-2 (PAR(2)) in human periodontitis.

No evidence for the role of protease-activated receptor-2 (PAR(2)) in human periodontal disease has been demonstrated so far. Thus, we sought to investigate the expression of PAR(2) mRNA in chronic periodontitis, and to examine whether its expression is related to the presence of PAR(2) potential activators. Microbiological and gingival crevicular fluid samples were collected from individuals with chronic periodontitis and control individuals, and the presence of neutrophil serine proteinase 3 (P3) and Porphyromonas gingivalis was evaluated. PAR(2) mRNA expression was higher (p < 0.001) in those with chronic periodontitis compared with control individuals, and it was statistically decreased (p = 0.0006) after periodontal treatment. Furthermore, those with chronic periodontitis presented higher (p < 0.05) levels of IL-1alpha, IL-6, IL-8, and TNF-alpha, total proteolytic activity, P. gingivalis prevalence, and P3mRNA expression compared with control individuals. We conclude that PAR(2) mRNA expression and its potential activators are elevated in human chronic periodontitis, therefore suggesting that PAR(2) may play a role in periodontal inflammation.

[Patient view in the assessment of quality of life in old age: potentials and limits]. / Die Patientenperspektive in der Erfassung von Lebensqualität im Alter: Möglichkeiten und Grenzen.

Quality of life is a multidimensional construct commonly used in geriatric health care. The patient's view is increasingly incorporated in its determination. Pain and satisfaction with life are two important subjective facets of quality of life. Potentials and limits of an integration of the subjective view in seemingly heavily disadvantaged patient populations are discussed using three approaches: 1) Self-reports on pain in aphasic patients can often be obtained by means of nonverbal communication or verbal communication adapted to the disorder. 2) Even in people suffering from dementia, pain can be assessed in self-reports into the middle stages of the disease. In severe dementia, observational methods have been developed, but their significance with respect to the experience of pain is still being debated in the scientific community. 3) Differences in content and structure in the individual construction of life-satisfaction in multimorbid elderly without cognitive impairment can be reproduced by an individualized measurement tool (FLQM). It allows for determination as well of global and domain-specific life-satisfaction as of differential determinants of longitudinal changes. All three approaches highlighted potentials for an extended integration of the patient's perspective in the assessment and evaluation of their quality of life.

Smoking increases salivary arginase activity in patients with dental implants.

It is believed that an increased arginase activity may lead to less nitric oxide production, which consequently increases the susceptibility to bacterial infection. Considering the hypothesis that smoking may alter the arginase activity and that smoking is considered a risk factor to dental implant survival, the present study aimed at evaluating the effect of smoking on the salivary arginase activity of patients with dental implants. Salivary samples of 41 subjects were collected: ten non-smoking and with no dental implants (group A), ten non-smoking subjects with dental implants (group B), ten smoking subjects with implants (group C), and 11 smoking subjects with no dental implants (group D). The levels of salivary arginase activity were determined by the measurement of L-ornithine and expressed as mIU/mg of protein. A significant increase in the salivary arginase activity was verified in groups C (64.26 +/- 16.95) and D (49.55 +/- 10.01) compared to groups A (10.04 +/- 1.95, p = 0.00001 and p = 0.0110, groups C and D, respectively) and B (11.77 +/- 1.45, p = 0.00001 and p = 0.0147, groups C and D, respectively). No significant difference was found between groups C and D (p = 0.32). Within the limits of the present study, it can be concluded that salivary arginase activity is increased in smoking subjects with dental implants in contrast to non-smoking subjects with dental implants, therefore suggesting a possible mechanism by which cigarette smoking may lead to implant failure. The analysis of salivary arginase activity may represent an important tool to prevent implant failure in the near future.

Efeito do celecoxib sobre a resposta inflamatória em doença periodontal experimental: estudo histológico em ratos / Effect of celecoxib on the inflammatory response during experimental periodontal disease: a histological study in rats

Os metabólitos do ácido araquidônico exercem um reconhecido papel na patogênese da doença periodontal. O objetivo deste trabalho foi avaliar o efeito do celecoxib, um inibidor seletivo da enzima cicloxigenase-2 (COX-2), sobre o processo inflamatório durante o desenvolvimento de doença periodontal induzida por ligadura em ratos. Após a colocação de ligadura de algodão ao redor dos primeiros molares inferiores direitos, 108 ratos Wistar foram aleatoriamente subdivididos em três grupos experimentais com 36 animais cada. Nos grupos teste (Ce1 e Ce2), os animais receberam diariamente uma dose oral de celecoxib 10 mg ou 20 mg/ kg de peso corporal, respectivamente. No grupo controle, os animais receberam diariamente dose oral de 1ml/kg de peso corporal de cloreto de sódio (NaCl) a 0,9%. Aos 5, 18 e 30 dias após o início do experimento, 12 animais de cada grupo experimental foram sacrificados. As mandíbulas foram retiradas e submetidas à análise histológica. Observou-se através de análise estatística como teste não-paramétrico de Kruskal-Wallis, que o tratamento com celecoxib, em ambas as concentrações, diminuiu a magnitude do processo inflamatório agudo e, reduziu significativamente (p<0,05) a intensidade do infiltrado inflamatório crônico. Estes resultados demonstraram que, independentemente da dosagem utilizada, a inibição seletivada COX-2 através do celecoxib pode levar a um decréscimo da reação inflamatória do tecido periodontal em decorrência da presença de ligadura em ratos.

Arachidonic acid metabolites have a recognized role in the pathogenesis of periodontal disease. The purpose of this study was to evaluate the effect of a selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, on the progression of periodontal disease in a ligature-induced periodontitis model in rats. After ligature placement in the mandibular right first molars, 108, 6-week-old Wistar rats were ramdomly assigned to one of the following groups of treatment that consisted in a daily oral dose of 10mg/kg body weight of celecoxib (Ce1), 20mg/kg body weight of celecoxib (Ce2) or 10ml/kg of 0,9%NaCl (Control). At 5, 18 and 30 days later, 12 animals of each group were sacrificed and the specimens routinely processed. Treatment with celecoxib significantly (p < 0,05) decreased the acute and the chronic process, histologically observed. These results show that selective cyclooxygenase-2 (COX-2) inhibition with celecoxib, can decrease the periodontal inflammation due to ligature placement in rats.

Periodontal therapy reduces arginase activity in saliva of patients with chronic periodontitis.

This present study evaluated the salivary arginase activity (SAA) in patients with chronic periodontitis and the effect of periodontal therapy on the activity of such enzyme. Thirty-six patients (mean age, 45.97 +/- 14.52), 18 chronic periodontitis subjects (test group), and 18 periodontally healthy individuals (control group) participated in the study. Clinical periodontal examinations included measurements of probing pocket depth (PD), clinical attachment level (CAL), plaque (PI), and gingival (GI) indexes. The test group received periodontal therapy according to individual needs. The saliva sample was collected from all study population at baseline (both groups) and 30 days after periodontal therapy (test group). SAA was determined by measuring the L: -ornithine formation from L-arginine and was expressed as mU/ml. The results showed that the mean values of SAA were statistically different between control and test groups. SAA was about 2.5 times higher in test than control groups. Thirty days after periodontal therapy, enzyme levels were 1.56 times lower than before periodontal therapy. We concluded that SAA is increased in chronic periodontitis subjects when compared to periodontally healthy individuals and that periodontal therapy significantly reduced SAA levels. It was suggested that in the near future, SAA may be used as a salivary marker of periodontal status.

Role of protease-activated receptor-2 in inflammation, and its possible implications as a putative mediator of periodontitis.

Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. This receptor is widely distributed throughout the body and seems to be importantly involved in inflammatory processes. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and bacterial proteases, such as gingipain produced by Porphyromonas gingivalis. This review describes the current stage of knowledge of the possible mechanisms that link PAR2 activation with periodontal disease, and proposes future therapeutic strategies to modulate the host response in the treatment of periodontitis.

Role of protease-activated receptor-2 in inflammation, and its possible implications as a putative mediator of periodontitis

Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. This receptor is widely distributed throughout the body and seems to be importantly involved in inflammatory processes. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and bacterial proteases, such as gingipain produced by Porphyromonas gingivalis. This review describes the current stage of knowledge of the possible mechanisms that link PAR2 activation with periodontal disease, and proposes future therapeutic strategies to modulate the host response in the treatment of periodontitis.

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 PAR2-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.

Effects of long-term cyclosporin therapy on the periodontium of rats.

BACKGROUND: The treatment of cyclosporin A triggers an early bone loss and gingival overgrowth. There is a lack of studies exploring the effects of long-term cyclosporin A therapy on alveolar bone homeostasis and gingival tissue. OBJECTIVE: The purpose of this study was to evaluate the effects of long-term therapy with cyclosporin A on the gingival tissue and on the alveolar bone metabolism in rats. MATERIALS AND METHODS: Rats were treated for 60, 120, 180 and 240 days with a daily subcutaneous injection of 10 mg/kg body weight of cyclosporin A. At the end of experimental periods, animals were killed and the serum calcium (Ca(2+)) and alkaline phosphatase levels were measured in all groups. After histological processing, the oral epithelium and the connective tissue, as well as volume densities of alveolar bone (V(b)) and multinucleated osteoclasts (V(o)), were assessed at the region of the lower first molars. RESULTS: Significant increases in the serum alkaline phosphatase were observed in those groups that received cyclosporin A therapy. After 60 and 120 days of the treatment with cyclosporin A, evident gingival overgrowth associated with a significant increase of epithelium and connective tissue was observed, as well as a decrease of the densities of bone and an increase of densities of osteoclasts. After 180 and 240 days of the treatment, there was a reduction of the gingival overgrowth associated with significant decreases of epithelium and connective tissue, as well as an increase of bone densities and a decrease of osteoclasts. CONCLUSION: Within the limits of this experimental study, it can be concluded that the deleterious periodontal effects of cyclosporin A administration may be time-related side-effects.

Influence of age on combined effects of cyclosporin and nifedipine on rat alveolar bone.

BACKGROUND: There is some evidence showing that cyclosporin A (CsA) and nifedipine (NIF) affect bone metabolism. The purpose of this work was to study the effects of CsA and NIF, given alone or concurrently, on alveolar bone of rats of different ages. METHODS: Rats 15, 30, 60, and 90 days old were treated daily with 10 mg/kg body weight of CsA subcutaneously injected and/or 50 mg/kg body weight of NIF/day given orally for 60 days. Alveolar bone of the first lower molars was morphologically and stereologically evaluated in serial 5 microm bucco-lingual paraffin sections, stained with hematoxylin and eosin. Serum calcium and alkaline phosphatase levels were measured in all animals at the end of the experimental period. RESULTS: Rats treated with CsA or NIF alone or CsA and NIF concurrently showed decreased alveolar bone density. CsA was more effective than NIF. A significant decrease in serum calcium was found only in animals treated with CsA or CsA/NIF. The results were similar regardless of age. CONCLUSIONS: These results indicate that the decrease in the alveolar bone volume in rats caused by CsA and NIF alone or concurrently is not age dependent. Furthermore, NIF (50 mg/kg) did not further increase the loss of alveolar bone volume induced by CsA (10 mg/kg).