苯妥英钠性牙龈增生的病理机制

苯妥英钠具有抗癫痫,治疗三叉神经和坐骨神经痛、发作性舞蹈手足徐动症、肌强直症,抗心律失常,降压等作用;但其所导致的牙龈增生不仅影响患者容貌的美观,还影响患者的口腔功能。本文就苯妥英钠性牙龈增生中的成纤维细胞增殖和程序性死亡,胶原的合成和降解,细胞外基质的积聚以及炎症反应等研究进展作一综述。     

综合治疗苯妥英钠致牙龈增生的体会

长期服用苯妥英钠者约40％～50％发生牙龈纤维性增生,尤其是年轻人居多。对于此类牙龈增生最好的治疗方法是牙龈切除术。以往笔者曾作过多例此类手术,往往在术后1年或更短时间就复发。究其原因是术后未对患者进行洁治和口腔卫生维护、牙龈按摩、消除牙龈炎症等综合性防治。近几年来,笔者对因口服苯妥英钠引起牙龈增生的患者采取综合性治疗,取得了一定效果,现报告如下。 临床资料和方法 1.临床资料 本组13例患者均因患癫痫病,长期服用苯妥英钠而引起牙龈增生。增生牙龈覆盖到牙冠的切((牙合))缘,妨碍咀嚼功能,影响美观和口腔卫生,有的患者曾经作过牙龈切除术再     

单纯牙周基础治疗对苯妥英钠所致药物性牙龈增生疗效评价

目的 评价单纯牙周基础治疗对苯妥英钠（PHT）所致药物性牙龈增生的治疗效果。方法 选择佛山市禅城区向阳医院·禅城区口腔医院2011年1月至2013年6月因服用PHT导致牙龈增生的患者16例,在不停药亦不换药的情况下行牙周基础治疗,并于治疗前及治疗后1、3、6个月进行牙龈增生指数（GHI）、菌斑指数（PLI）、龈沟出血指数（SBI）、探诊深度（PD）等临床指标检查。结果 单纯牙周基础治疗后1、3、6个月的GHI、PLI、SBI、PD各项临床指标逐步改善,牙龈炎症逐步减轻,牙龈增生状况持续好转;与治疗前基线相比,差异均有统计学意义（均P < 0.05）。结论 单纯牙周基础治疗对PHT所致药物性牙龈增生有效。     

药物性牙龈增生发病机制的研究进展

药物性牙龈增生是指服用抗癫痫药、钙通道阻滞剂和免疫抑制剂等某些特定药物引起的牙龈增生和体积增大,具有共同的病理组织学特点,其发病机制目前仍无定论。下面就药物性牙龈增生在胶原的合成与降解失衡、上皮细胞的增殖和程序性细胞死亡以及上皮下炎症浸润机制上取得的研究进展作一综述。     

钙离子拮抗剂诱导牙龈增生发病机理的研究进展

钙离子拮抗剂广泛应用于治疗高血压和冠心病,但该类药物可以导致部分病人牙龈增生。该文分别从组织病理、组织代谢、药物浓度、牙龈上皮凋亡以及遗传免疫学等角度对钙离子拮抗剂导致牙龈增生的发病机理的研究进展做一综述。     

硝苯吡啶诱导牙龈增生发病机理研究进展

本文从组织病理、组织代谢、遗传与免疫、口腔卫生状况及微生和学方面,对近年来国内外关于硝苯吡啶诱导龈增生发病机理的研究现状进行了综合分析。建议进一步从宏观及微观角度作深入探讨。     

苯妥英钠所致牙龈增生的发病因素与免疫组化探讨(附20例报告)

对苯妥英钠所致牙龈增生的致病因素和机理做一分析．对２０例病人临床检查和处理资料，部分病例做常规组织病理学观察和免疫组化研究．尤其是当患者处于性腺内分泌不稳定的青春期而又口腔卫生欠佳并伴有牙龈炎症时，三者协同作用最易导致本病发生．免疫组化检测发现，本病牙龈增生组织主要由新生幼稚的Ⅲ型胶原所构成，成熟的Ⅰ型胶原较少．牙龈组织持续合成大量新生胶原是导致临床牙龈增生的一个重要原因     

硝苯吡啶致牙龈增生的治疗

硝苯吡啶 (硝苯地平等 )是一种有效的钙离子通道拮抗剂 ,作为抗心绞痛及降压药在临床广泛应用。而硝苯吡啶引起的牙龈增生也日益引起重视 ,国内报道患病率为2 0 .8%。我科自 1998年起治疗此类患者多例 ,追踪治疗16例 ,疗效显著 ,现总结如下 :1　临床资料1.1　病例选择16例牙龈增生患者男 7例 ,女 9例 ,年龄 41～ 62岁 ,服用硝苯地平 (心痛定 ) 3个月～ 4年 ,排除糖尿病、癫痫、器官移植者 ,职业为干部及离退休人员 ,医从性好 ,能正确地按照医生的要求进行口腔清洁维护。1.2　临床检查16例病例口腔卫生普遍较差 ,牙石 +- ,牙周袋深度 5～ 10…     

尼群地平致牙龈增生1例

尼群地平作为治疗高血压药物在临床上已广泛使用，但由其引起的药物性牙龈增生却少有报道。本文作者遇到1例，并成功治愈，现报告如下。     

青少年局限性海绵状牙龈增生的诊疗进展

青少年局限性海绵状牙龈增生(localized juvenile spongiotic gingival hyperplasia,LJSGH)是一种具有特殊病理表现的牙龈增生性疾病,近年来引起了学者们的广泛关注,但是国内尚未有相关文献和报道,且该病的诊治仍然存在诸多难点,其诊断标准尚未达成一致.本文将从该病的病因、发病...     

Quantitative histopathologic assessment of developing phenytoin-induced gingival overgrowth in the cat

Abstract Phenytoin (Dilantin®) induces gingival overgrowth characterized by an accumulation of connective tissue. The cell-to-matrix ratio in the mature lesion is normal, yet there must be more fibroblasts per oral cavity if there is excessive tissue mass. Using a mongrel cat model system, we studied the early, developing phenytoin-induced lesion by quantitating fibroblasts per unit of tissue in papilla biopsies collected over a 3-month period of daily drug administration. At 6 and 8 weeks, the number of fibroblasts per unit of tissue increased dramatically. By 3 months, as the lesions matured, the fibroblast-to-matrix ratio returned to normal. We suggest that the drug interacts with resident gingival fibroblasts, causes them to proliferate and thus induces a true, but transient, hypercellularity. Cell division then appears to slow or cease, and rapid production of connective tissue matrix ensues, returning the cell-to-matrix ratio to normal.     

Regression of phenytoin-induced gingival overgrowth after withdrawal of medication

The regression of phenytoin-induced gingival overgrowth after withdrawal of medication was studied in 10 children. After only one month a statistically significant (p less than 0.05) in buccolingual dimension of the marginal gingiva was observed in both the maxillary and mandibular incisor areas. Children diagnosed as responders (i.e. exhibiting pseudopockets) showed a more rapid and significantly greater decrease (p less than 0.05) in buccolingual dimension at 1 and 3 months after withdrawal of PHT medication than non-responders. Compared to a control group of children on other antiepileptic drugs, no significant differences could be found in the thickness of the marginal gingiva six months after withdrawal of medication.     

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.     

Subpopulations of lymphocytes in connective tissue from phenytoin-induced gingival overgrowth

The presence of mononuclear cells was studied in gingival biopsies from seven children exhibiting phenytoin(PHT)-induced gingival overgrowth, three children with gingivitis and a control group consisting of three children without clinical signs of inflammation. The mononuclear cells were detected using monoclonal antibodies defining functional T-lymphocyte subpopulations, B-lymphocytes and monocytes. Gingival biopsies from the individuals in the PHT-group showed a substantial number of mononuclear cells. The distribution of mononuclear cells in separate individuals were as follows: 69-95% OKT3 +/Leu4+ cells (T-lymphocytes), 50-64% OKT4 +/Leu3+ cells (T-helper phenotype) and 29-46% OKT8+ cells (T-suppressor/cytotoxic phenotype). None of the biopsies in the PHT-group contained more than a few scattered plasma cells. The vast majority of all mononuclear cells present in the biopsies reacted with OKIa1, a monoclonal antibody defining the HLA-DR framework. In contrast, biopsies from the control group and the gingivitis group contained few mononuclear cells, the majority of which were T-cells. This suggests that immunologic reactions mediated by T-cells may play a role in the pathogenesis of the PHT-induced lesion.     

Subpopulations of lymphocytes in connective tissue from phenytoin-induced gingival overgrowth

The presence of mononuclcar cells was studied in gingival biopsies from seven children exhibiting phenyloin(PHT)-induced gingival overgrowth, three children with gingivitis and a control group consisting of three children without clinical signs of inflammation. The mononucle-ar cells were detected using monoclonal antibodies defining functional T-lymphocytc subpopulations, B-lymphocytes and monocytes. Gingival biopsies from the individuals in the PHT-group showed a substantial number of mononuclear cells. The distribution of mononuclear cells in separate individuals were as follows: 69-95% OKT3 +/Leu4+ cells (T-lymphocytes), 50-64% OKT4 +/Leu3 + cells (T-helper phenotype) and 29-46% OKT8 + cells (T-suppressor/cytotoxic phenotype). None of the biopsies in the PHT-group contained more than a few scattered plasma cells. The vast majority of all mononuclear cells present in the biopsies reacted with OKIal, a monoclonal antibody defining the HLA-DR framework. In contrast, biopsies from the control group and the gingivitis group contained few mononuclear cells, the majority of which were T-cells. This suggests that immunologic reactions mediated by T-cells may play a role in the pathogenesis of the PHT-induced lesion.     

Increased bFGF level in the serum of patients with phenytoin-induced gingival overgrowth

Abstract. To elucidate the involvement of bFGF (basic fibroblast growth factor) in the pathogenesis of phenytoin-induced gingival overgrowth, we measured the concentration of bFGF in the serum of 36 epileptic patients taking phenytoin and in 94 normal volunteers by enzyme-linked immunosorbent assay technique. The concentration of phenytoin in serum was determined by high-performance liquid chromatography. In 34 of 36 patients taking phenytoin in this investigation, apparent gingival overgrowth was noticed. The mean concentration of bFGF was 33.9±18.5 pg/ml in the overgrowth group and 10.6±5.2 pg/ml in the volunteer group ( p <0.01). The serum phenytoin level did not correlate ( r =0.22, p = 0.2) with the degree of gingival overgrowth but there was a significant correlation ( r =0 38, p =0.023) between the degree of gingival overgrowth and the serum bFGF level. However, no correlation was observed among age, daily phenytoin dose, total phenytoin dose, duration of phenytoin therapy, serum phenytoin level, or serum bFGF level. The results suggested that enhanced serum bFGF level was implicated in the pathogenesis of phenytoin-induced gingival overgrowth.     

Synthesis of sulfated glycosaminoglycans by human gingival fibroblasts from phenytoin-induced gingival overgrowth in vitro

Abstract – The in vitro synthesis of sulfated glycosaminoglycans (GAGs) was studied in gingival fibroblasts from two patients exhibiting phenytoin(PHT)-induced gingival overgrowth, i.e. pseudopockets, which required surgical excision, from one patient on PHT medication not exhibiting pseudopockets and from two normal controls. The results showed that the newly synthesized GAGs were distributed to the culture medium, to a pericellular pool and to the cell fraction. Gingival fibroblasts from the PHT-induced gingival overgrowth showed a significantly increased incorporation of ³⁵SO₄^2- into GAGs compared to the other strains, and this, increase was mainly confined to the dermatan sulfate fraction. These results are in accordance with our previous biochemical studies where increased amounts of GAGs were found in gingival biopsies from the PHT-induced lesion.     

Synthesis of sulfated glycosaminoglycans by human gingival fibroblasts from phenytoin-induced gingival overgrowth in vitro

The in vitro synthesis of sulfated glycosaminoglycans (GAGs) was studied in gingival fibroblasts from two patients exhibiting phenytoin(PHT)-induced gingival overgrowth, i.e. pseudopockets, which required surgical excision, from one patient on PHT medication not exhibiting pseudopockets and from two normal controls. The results showed that the newly synthesized GAGs were distributed to the culture medium, to a pericellular pool and to the cell fraction. Gingival fibroblasts from the PHT-induced gingival overgrowth showed a significantly increased incorporation of 35SO4(2-) into GAGs compared to the other strains, and this increase was mainly confined to the dermatan sulfate fraction. These results are in accordance with our previous biochemical studies where increased amounts of GAGs were found in gingival biopsies from the PHT-induced lesion.     

Lack of pathogenic mutations in SOS1 gene in phenytoin-induced gingival overgrowth patients

ObjectiveGingival overgrowth is a side effect associated with some distinct classes of drugs, such as anticonvulsants, immunosuppressants, and calcium channel blockers. One of the main drugs associated with gingival overgrowth is the antiepileptic phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. It has been shown that mutation of human SOS1 gene is responsible for a rare hereditary gingival fibromatosis type 1, a benign gingival overgrowth. The aim of the present study is to evaluate the possible contribution of SOS1 mutation to gingival overgrowth-related phenotype.DesignWe selected and screened for mutations a group of 24 epileptic patients who experienced significant gingival overgrowth following phenytoin therapy. Mutation scanning was carried out by denaturing high-performance liquid chromatography analysis of the entire coding region of the SOS1 gene. Novel identified variants were analyzed in-silico by using Alamut Visual mutation interpretation software, and comparison with normal control group was done.ResultsMutation scanning of the entire coding sequence of SOS1 gene identified seven intronic variants and one new exonic substitution (c.138G > A). The seven common intronic variants were not considered to be of pathogenic importance. The exonic substitution c.138G > A was found to be absent in 100 ethnically matched normal control chromosomes, but was not expected to have functional significance based on prediction bioinformatics tools.ConclusionsThis study represents the first mutation analysis of the SOS1 gene in phenytoin-induced gingival overgrowth epileptic patients. Present results suggest that obvious pathogenic mutations in the SOS1 gene do not represent a common mechanism underlying phenytoin-induced gingival overgrowth in epileptic patients; other mechanisms are likely to be involved in the pathogenesis of this drug-induced phenotype.     

Effect of folic acid on recurrence of phenytoin-induced gingival overgrowth following gingivectomy

This study examined the effect of folic acid supplementation on the recurrence of phenytoin-induced gingival overgrowth following gingivectomy. 8 residents of an institution for the developmentally disabled were randomly assigned to a treatment (N = 4) or control (N = 4) group. Subjects in the treatment group received an oral supplementation of 5 mg of folic acid daily during the study; those in the control group did not. A gingivectomy with an external beveled incision made to the crest of the alveolus was completed by quadrants. The following data were obtained prior to gingivectomy, 2 weeks following the last quadrant of surgery, and at 3 and 6 months post-surgery: plaque and gingival index scores, red blood cell folic acid levels, free phenytoin blood levels, photographs, and impressions. % change in overgrowth was determined from cross-sectional area measurements made on dies obtained from bucco-lingual cuts on stone models. Differences across time between and within groups were tested by a two-factor repeated measure analysis of variance. The groups did not differ in plaque and gingival index scores or free phenytoin blood levels. The treatment group had significantly higher red blood cell folic acid levels (p less than or equal to 0.0001). Reduction in gingival overgrowth as a result of surgery was similar in both groups. Although the treatment group had significantly less recurrence of gingival overgrowth (p less than or equal to 0.05), the mean differences amounted to only 6-7% at 3 and 6 months.