Effectiveness of periodontal therapies on the treatment of different aetiological factors induced gingival overgrowth in puberty

OBJECTIVES: The aim of the present study was to compare oral improvement achieved by different periodontal therapies (surgical and non-surgical) for different aetiological factors induced gingival overgrowth in 60 subjects (mean age +/- SD = 12.33 +/- 1.05 years; age range = 12-15 years). METHODS: Subjects received oral hygiene instructions, scaling, surgical treatment (if necessary) and periodontal maintenance therapy. Clinical parameters were taken at baseline, after initial treatment and after periodontal surgery. RESULTS: The decrease in the clinical index values after all treatments compared to the initial values is found to be statistically significant (P < 0.05). Although there was a statistically significant difference in all aspects of the clinical index values of the study groups after initial treatments, for drug-induced gingival overgrowth subjects full improvement was seen only after periodontal surgery. CONCLUSION: Attention to plaque control and removal of local irritants is very important for the gingival health of the patients in puberty. In puberty, plaque-induced gingival overgrowth can be treated with plaque removal. However, these approaches alone do not prevent drug-induced gingival overgrowth and surgical therapy often becomes the treatment of choice.     

Non-surgical periodontal treatment of cyclosporin A-induced gingival overgrowth: immunohistochemical results

Aim:  The present study was planned to analyze the effects of a 12-month non-surgical periodontal treatment on histologic and immunohistochemical features of cyclosporin A (CsA)-induced gingival overgrowth (GO).
Materials and methods:  Gingival samples were collected from 21 liver transplant subjects exhibiting CsA-induced GO prior to, and 12 months after non-surgical periodontal therapy including oral hygiene instructions, scaling and 2-month recall appointments, and also from 18 healthy control subjects. Gingival biopsy specimens were stained with hematoxylin–eosin and monoclonal antibodies for vimentin, CD3 (T-lymphocytes), CD20 (B-lymphocytes), CD34 (endothelium) and Ki-67 (fibroblasts proliferation rate), using a streptavidin-biotin-peroxidase complex method.
Results:  Total inflammatory cells, gingival vessels and fibroblast proliferation rate demonstrated significant reduction after non-surgical periodontal treatment ( P  < 0.0001) in overgrown gingiva, while B- and T-lymphocytes remained nearly unchanged ( P  = 0.61 and 0.33, respectively). At the 12-month evaluation no significant differences were found when comparing the gingival biopsies from CsA-treated patients and those from healthy controls ( P  > 0.05).
Conclusions:  Control of clinical inflammation by means of non-surgical periodontal treatment results both in lowering of inflammatory infiltrate and in changes in connective tissue composition. Thus, plaque-induced inflammation would seem to modulate the drug-gingival tissue interaction.
Clinical relevance:  A strict plaque control program play a pivotal role in the management of transplant patients exhibiting cyclosporin A-GO.     

Gingival tissue proteoglycan and chondroitin-4-sulphate levels in cyclosporin A-induced gingival overgrowth and the effects of initial periodontal treatment

OBJECTIVES: Cyclosporin A (CsA) is a potent immunosuppressive drug used in organ transplant patients to prevent graft rejection. CsA-induced gingival overgrowth is one of the side effects of this drug and its pathogenesis is still unclear. The present study was planned to comparatively analyse total proteoglycan (PG) and chondroitin-4-sulphate (C4S) levels in CsA-induced overgrown gingival tissue samples obtained before and after initial periodontal treatment and to compare these findings with the situation in healthy gingiva. MATERIAL AND METHODS: Gingival tissue samples were obtained from nine patients with CsA-induced gingival overgrowth before and 4 weeks after initial periodontal treatment including oral hygiene instruction and scaling and also from 10 healthy control subjects. Total PG and C4S levels were determined by biochemical techniques. PG levels were analysed using modified Bitter and Muir method. C4S assay was carried out using chondroitin sulphate lyase AC and chondroitin-6 sulphate sulphohydrolase enzymes. The results were tested statistically using non-parametric tests. RESULTS: All clinical measurements in the CsA-induced gingival overgrowth group demonstrated significant reductions 4 weeks after initial periodontal treatment (p<0.05). There was no significant difference between the levels of baseline total PG in CsA-induced gingival overgrowth and healthy control groups (p>0.05). The gingival tissue levels of PG in CsA-induced gingival overgrowth group decreased significantly 4 weeks after treatment (p=0.043). Gingival tissue C4S levels in the overgrowth group were significantly higher than the healthy control group at baseline (p=0.000). C4S levels of the overgrowth group were significantly reduced after treatment (p=0.033), but these levels were still significantly higher than the healthy control group (p=0.000). CONCLUSION: The observed prominent increase in gingival tissue C4S levels may be interpreted as a sign of an increase in C4S synthesis in CsA-induced gingival overgrowth. Furthermore, remission of clinical inflammation by means of initial periodontal treatment had a positive effect on tissue levels of these extracellular matrix molecules.     

Stereologic study of cyclosporin A-induced gingival overgrowth in renal transplant patients

Gingival biopsies were taken from 13 renal transplant patients (mean age 26.5 yr), 11 of whom exhibited cyclosporin A (CsA)-inditced gingival overgrowth. Control material was obtained from seven volunteers (mean age 28 yr). Gingival tissue components were analyzed by quantitative microscopy (stereology) on 5-(μm-thick sections of interdental papillae. The volume density (Vv) of different tissue components and the surface density of epithelial ridges were calculated by conventional point and intersection counting. The study showed that the volume density of oral epithelium and the surface density of the epithelial ridges in the CsA-induced gingival overgrowth were significantly increased compared to normal gingival tissue. The connective tissue of the lesion exhibited a significant increase in volume density of cells, blood vessels and non-collagenous matrix with a corresponding decrease in the collagenous matrix. These results indicate that CsA-induced gingival overgrowth represents a tissue with an altered composition characterized by increased thickness of oral epithelium and relatively-increased amount of cells, vessels, non-collagenous matrix and decreased collagenous matrix in the connective tissue.     

环孢菌素A导致牙龈过度生长机理的研究近况

牙龈过度生长是环孢菌素A的重要的不良反应之一,其病理特征是牙龈组织上皮层的增厚和胞外基质的蓄积,但其确切的病理机制仍不清楚。该文就环孢菌素A导致的牙龈过度生长的病因及病理机制的研究现状做一综述。     

The prevalence and severity of cyclosporin and nifedipine-induced gingival overgrowth

Abstract The gingival health of 32 renal transplant patients who were medicated with cyclosporin was compared with a similar cohort of 23 renal transplant patients medicated with both cyclosporin and nifedipine. Both groups of patients had been taking the above medication for at least 3 months. Plaque scores, gingival inflammation and probing depths were similar for both groups. Patients medicated with the combination of nifedipine and cyclosporin had a significantly higher gingival overgrowth score (p= <0.046) when compared with the group receiving cyclosporin alone. The incidence of clinically significant overgrowth (i.e., overgrowth >30% which would require surgical intervention) was similar in both groups. Gingival overgrowth was not related to cyclosporin dosage. It is concluded that patients taking cyclosporin or cyclosporin and nifedipine experience gingival overgrowth and that the severity of the overgrowth is greater in patients taking the combined therapy. The levels of plaque and gingival inflammation appear to be associated with this phenomenon.     

Morphological evaluation of combined effects of cyclosporin and nifedipine on gingival overgrowth in rats

It has previously been shown that, while cyclosporin A (CsA) and nifedipine both cause gingival overgrowth in the rat, the combined use of these drugs increases the severity of overgrowth. The aim of this study was to describe the histometry and densities of fibroblasts, collagen fibers and vessels in the gingival tissue of rats that were treated with CsA and nifedipine, either alone or in combination. Rats were treated for 60 days with a daily subcutaneous injection of 10 mg/kg body weight of CsA and/or with 50 mg/kg body weight of nifedipine added to the chow. The results confirmed that CsA causes a more severe overgrowth than nifedipine, and that the combined use of these drugs increases the overgrowth severity. All the rat groups that were studied showed that, as the severity of overgrowth increased, there was a parallel increase in fibroblasts and collagen, and a decrease in vessel content. Therefore, independently of whether the gingival overgrowth was caused by CsA alone, nifedipine alone, or both treatments in combination, the fibroblast and collagen density increased in parallel with the severity of the overgrowth.     

Reduction in gingival overgrowth associated with conversion from cyclosporin A to tacrolimus

BACKGROUND: Unsightly gingival overgrowth affects many individuals immunosuppressed with cyclosporin A (CsA). Current management involves repeated periodontal surgery and intensive hygienist support. Tacrolimus is an effective alternative immunosuppressive agent for renal transplantation which does not appear to produce gingival enlargement. AIMS: The purpose of the present study was to monitor the gingival response of 4 renal transplant patients (RTPs), with clinically significant CsA-induced gingival overgrowth, after their immunosuppressive therapy was switched to tacrolimus. METHODS: Intra-oral photographs and alginate impressions were taken both prior to the drug conversion and again, 6 to 9 months later. Gingival overgrowth scores were determined, from plaster models on both these occasions. RESULTS: All of the RTPs experienced significant resolution of their gingival enlargement within the time period studied; however, only one had complete regression. CONCLUSION: It is concluded that conversion of RTPs with gingival overgrowth from CsA to tacrolimus may provide an effective management strategy for this clinical problem.     

The calcium channel blocker used with cyclosporin has an effect on gingival overgrowth

BACKGROUND/AIMS: To investigate whether the choice of calcium channel blocker, used in conjunction with cyclosporin A, affected the prevalence of gingival overgrowth. METHOD: A cohort of 135 renal transplant recipients who had been medicated with cyclosporin A in combination with either nifedipine (89) or amlodipine (46) since transplant, took part in the study. The inclusion criteria were that eligible subjects had been in receipt of a kidney transplant for at least 12 months, had at least 10 teeth and had not received specialist periodontal treatment. The age, gender, current drug regimen and dosage were recorded for each participant and alginate impressions taken of both arches. The presence and severity of gingival overgrowth were scored from plaster models. RESULTS: A higher proportion (72%) of the amlodipine group were categorised as having gingival overgrowth compared with only 53% of the nifedipine group, chi square=4.5, p<0.05. Logistic regression analysis was used to explore the relationship between the presence or absence of gingival overgrowth (dependent variable) and age, gender, time since transplant, dose of cyclosporin A, centre in which the patient was treated, and the calcium channel blocker used (independent variables). Independent predictors of gingival overgrowth in this multivariate analysis were whether the individual was treated with amlodipine or nifedipine (p=0.01) and whether the individual was young or old (p=0.01). Within the multivariate analysis, the odds ratio for amlodipine to be associated with gingival overgrowth compared with nifedipine was 3.0 (confidence interval 1.3-6.9). CONCLUSIONS: The prevalence of gingival overgrowth in renal transplant recipients maintained on cyclosporin A and nifedipine is lower than those treated with cyclosporin A and amlodipine.     

Morphometric evaluation of gingival overgrowth and regression caused by cyclosporin in rats

Cyclosporin A is a selective immunosuppressant, used in organ transplants to prevent graft rejection. Cyclosporin A can cause various side effects including gingival overgrowth. The aim of this work was to evaluate gingival overgrowth of rats treated daily with 10 mg/kg bodyweight of cyclosporin A for 60 days, as well as the regression after the interruption of treatment. All rats treated with cyclosporin A developed gingival overgrowth, with increased thickness of the epithelium, height and width of the connective tissue. The density of fibroblasts and collagen fibers also increased. Five to 90 days after the interruption of treatment with cyclosporin A, there was a progressive reduction of the gingival volume and of collagen fibers and fibroblast densities. The reduction was more pronounced in the initial periods and after 90 days did not return to the normal values.     

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目的评价吸烟与非吸烟药物性牙龈增生患者单纯牙周非手术治疗1个月后的临床疗效。方法2007年3月至2007年12月收集河北省人民医院口腔科钙拮抗剂类药物导致的牙龈增生男性患者20例,其中吸烟组9例,非吸烟组11例,两组患者基线时的临床参数具有可比性。观察的牙龈增生牙齿,探诊深度5~7mm,吸烟组78个位点,非吸烟组80个位点。在未停药的情况下进行牙周非手术治疗,观察这些位点在治疗前、后1个月菌斑指数(PLI)、探诊深度(PD)、附着丧失(AL)、牙龈增生指数(HI)和出血指数(BI)的变化。结果治疗前两组PLI、BI、PD、AL以及HI差异无统计学意义,牙周非手术治疗1个月后,两组临床指标均有明显改善,吸烟组改善程度明显低于非吸烟组,但只有PD、PLI和HI的变化有统计学意义(P<0.05),AL和BI变化无统计学意义(P>0.05)。结论药物性牙龈增生患者,牙周非手术治疗效果吸烟者差于非吸烟者。     

Combined effects of cyclosporin and nifedipine on gingival overgrowth in rats is not age dependent

BACKGROUND: Cyclosporin A and nifedipine cause gingival overgrowth in rat, and the combined use of these drugs increases the overgrowth severity. OBJECTIVE: The purpose of this study was to compare gingival overgrowth of rats of differents ages treated with cyclosporin A and nifedipine alone or given concurrently. MATERIALS AND METHODS: Rats 15, 30, 60 and 90 d old were treated with 10 mg/kg body weight of cyclosporin A and/or 50 mg/kg body weight of nifedipine in the chow. RESULTS: Young rats showed evident gingival overgrowth with nifedipine, cyclosporin A, and cyclosporin A and nifedipine given concurrently. Adult rats did not show significant gingival alterations when treated with cyclosporin A and nifedipine alone. Nevertheless evident gingival overgrowth with alterations of the epithelium and connective tissue were observed when treated simultaneously with cyclosporin A and nifedipine. CONCLUSION: These results suggest that the combined effects of cyclosporin A and nifedipine on gingival overgrowth in rat is not age dependent.     

牙周基础治疗对药物性牙龈增生疗效的纵向观察

目的评价单纯牙周基础治疗对钙拮抗荆类药物导致的牙龈增生的治疗效果。方法选取钙拮抗荆类药物导致的牙龈增生患者13例，男8例，女5例，其中6例进行纵向观察，，在未停药的情况下进行牙周基础治疗，在治疗前和龈下刮治后1个月、3个月、6．5～29个月后记录牙龈增生指数、茵斑指数、出血指数和探诊深度。6名患者完成了纵向观察。结果在纵向观察期间，牙龈增生逐步减轻。在153个增生位点中，龈下刮治1个月后有69个位点痊愈，其中包括17个位点从2度、3度增生变为痊愈。3个月后痊愈的位点为105个，从2度、3度牙龈增生变为痊愈的位点数上升到41个。半年以上痊愈的位点数为122个，从2度、3度牙龈增生变为痊愈的位点数达50个。结论牙周基础治疗可改善钙拮抗剂药物引起牙龈增生的程度，其效果至少可保持半年以上。     

牙周基础治疗对药物性牙龈增生的疗效观察

目的：评价牙周基础治疗对钙拮抗剂导致的药物性牙龈增生的治疗效果。方法：纳入钙拮抗剂导致的牙龈增生患者24例,在基线和牙周基础治疗后1个月、3个月、6个月各时点分别记录菌斑指数（plaqueindex,PLI）,出血指数（bleedingindex,BI）,探诊深度（probingdepth,PD）和牙龈增生指数（Gingivalovergrowthindex,GO）。18例患者共240个位点完成了6个月的观察。结果：在观察期间,PLI、BI、PD和GO指数持续改善（P〈0.01）,GO指数为0级的位点基线为0,治疗后6个月则上升到45.83%,GO指数为1、2、3级的位点逐渐下降,GO指数为3级的位点在治疗后6个月降为0。结论：牙周基础治疗可改善钙拮抗剂药物引起的牙龈增生的程度。     

Elevation of collagen type I in fibroblast-keratinocyte cocultures emphasizes the decisive role of fibroblasts in the manifestation of the phenotype of cyclosporin A-induced gingival overgrowth

Background and Objective: Collagen type I elevation in cyclosporin A‐induced gingival overgrowth supports evidence that gingival fibroblasts play a decisive role in the manifestation of the phenotype. To analyze the role of gingival fibroblasts under more in vivo‐like conditions, we evaluated the effect of cyclosporin A on collagen type I gene and protein expression in gingival overgrowth‐derived gingival fibroblasts established as cocultures with gingival keratinocytes as well as in matched gingival fibroblast monolayers. Material and methods: Monolayers and cocultures of primary gingival fibroblasts were treated with cyclosporin A for 6 and 72 h. The expression of collagen type I mRNA was analyzed by quantitative real time polymerase chain reaction, while expression and secretion of collagen type I protein was analyzed by indirect immunofluorescence and western blotting. Results: Compared with controls, significant elevation of collagen type I mRNA was restricted to cocultures after 6 and 72 h of treatment with cyclosporin A. In keratinocytes, collagen type I remained undetectable. In monolayers and cocultures, indirect immunofluorescence showed a slightly higher level of collagen type I protein in gingival fibroblasts in response to stimulation with cyclosporin A. Semiquantitative detection of collagen type I by western blotting demonstrated a nonsignificant increase for cell extracts in monolayers and cocultures. For secreted collagen type I, western blot analysis of the supernatants revealed elevated protein levels in cultures stimulated with cyclosporin A. Compared with the corresponding monolayers, the stimulatory effect of cyclosporin A on protein secretion was significant only in coculture. Conclusion: Our results indicate that collagen type I is a target of cyclosporin A and that gingival fibroblasts are decisive for the manifestation of the gingival overgrowth‐phenotype. Furthermore, the results suggest that cocultures of gingival overgrowth‐derived gingival fibroblasts and gingival keratinocytes permit analysis of cyclosporin A‐induced effects under more in vivo‐like conditions.     

环孢素A引发牙龈过度生长过程中IL-6的表达

目的:对体外培养的牙龈上皮细胞和成纤维细胞施加环孢素A(cyclosporin,CsA)刺激,应用免疫组化方法探讨CsA引发药物性牙龈过度生长(gingival overgrowth,GO)的病理机制。方法:对体外培养的牙龈上皮细胞和成纤维细胞分别施加浓度为600、800和1000ng/mL,作用时间为48、72h的CsA刺激。在观察细胞生长曲线及其变化的基础上,通过对细胞铺片的免疫酶染色(ABC法)定量分析和对细胞培养液的酶联免疫吸附检测(ELISA法),分别对牙龈组织细胞IL-6的表达和分泌进行测定,应用SAS 6.0软件包对数据进行统计学分析。结果:牙龈上皮细胞接受CsA刺激后,细胞数量明显增加,与对照组相比具有显著差异(P<0.05)。在接受相同条件CsA刺激下,牙龈上皮细胞和成纤维细胞胞内IL-6表达无显著差异,细胞胞内IL-6表达量与CsA作用时间、浓度间相关。接受CsA刺激的最初24h内,牙龈成纤维细胞分泌IL-6的总量在各CsA浓度实验组及对照组间均无显著差异(P>0.05);牙龈成纤维细胞接受刺激超过24h后,CsA浓度为1000ng/mL的实验组与对照组间在细胞分泌IL-6总量上有显著增加...     

Gingival overgrowth induced by nifedipine and cyclosporin

Abstract. In this study, we developed a quantitative method with digital image analysis to evaluate the degree of gingival overgrowth (GO), and compared GO in kidney transplant patients treated with cyclosporin A (CsA) ( n =21) or CsA+ nifedipine ( n = 8) and a group of healthy controls ( n = 30). The method was reproducible and reliable. Our findings showed significant differences in papillary and gingival surface between controls and transplant patients treated with GO inducers. Gingival overgrowth index also differed significantly between controls and each patient group ( p < 0.01, Kruskal-Wallis test). The administration of the calcium channel blocker nifedipine potentiated the adverse effect of CsA: comparison of the morphometric findings revealed significant differences between patients treated with CsA alone and CsA+ nifedipine in papillary area, dental area, and GO index ( p < 0.01, Mann-Whitney U -test). We conclude that the method of image analysis we developed is useful in assessing the degree of GO.     

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目的    观察牙周基础治疗对钙拮抗剂导致牙龈增生的治疗效果。方法    选取2006年6月至2009年3月在沈阳市口腔医院牙周科就诊,因高血压病服用钙拮抗剂导致牙龈增生的患者16例,在不更换药物或未停药的情况下进行牙周基础治疗,在治疗前基线和治疗后1、3、6个月时记录牙龈增生指数（GO）、菌斑指数（PIL）、龈沟出血指数（SBI）和探诊深度（PD）。结果    在观察期间,各指数持续改善（P < 0.01）,牙龈炎症持续减轻,牙龈增生状况明显改善。结论    牙周基础治疗对钙拮抗剂导致的牙龈增生有效,这为不能换药或停药的高血压患者提供了较合理的治疗方法。