Drug-induced gingival overgrowth in cardiovascular patients

Drug-induced gingival overgrowth(DIGO)is a pathological growth of gingival tissue,primarily associated with calcium channel blockers and immunosuppressants.Consequently,it is mainly seen in cardiovascular and transplanted patients.Nifedipine remains the main calcium channel blocker related to the development of this unpleasant side-effect.As for immunosuppress-ants,cyclosporin is the leading causative agent,whereas other drugs from this druggroup,including tacrolimus,have better safety profiles.Accumulated collagen with inflammatory infiltrates is the histological hallmark of this condition.Several factors are involved in the pathogenesis and can increase the risk,such as male gender,younger age,pre-existing periodontal inflammation,and concomitant use of other DIGO-inducing medications.Patients with DIGO may experience severe discomfort,trouble with speech and mastication,pain,and teeth loss,aside from cosmetic implications.Furthermore,these patients also have an increased risk for cardiovascular diseases.The interdisciplinary approach and cooperation with dental care experts are necessary for patient management.Treatment includes discontinuing the drug and switching to one with a better profile,improving oral hygiene,and surgical removal of enlarged tissue.Recognizing the potential of commonly used medications to cause DIGO and its effect on patients'health is necessary for early detection and adequate management of this complication.

Clinical presentation and management of drug-induced gingival overgrowth: A case series

BACKGROUND We report three patients with drug-induced gingiva overgrowth(DIGO)caused by nifedipine,a calcium channel blocker,who were treated and followed up for 1–3 years.We discussed their symptoms,treatment process,treatment prognosis,and follow-up results.CASE SUMMARY All the patients had a history of nifedipine treatment to control hypertension.Besides nifedipine,Patient 1 was prescribed immunosuppressant cyclosporine A to control nephritis,which is also implicated in GO.Thus,we assumed that a synergistic effect between the drugs contributed to the severity of Patient 1’s condition.This condition has been reported to be more pronounced in patients with periodontitis.In the course of treatment,Patients 1 and 2 did not stop or change drugs.After initial periodontal treatment,periodontal surgery,and later periodontal support and better plaque control,their gingival hyperplasia was well managed and controlled.Under the guidance of a physician,Patient 3 replaced her calcium-channel blocker drug with losartan potassium and hydrochlorothiazide tablets.She received initial treatment without surgery,obtaining a good curative effect.CONCLUSION Patients’compliance,self-plaque control,and professional periodontal therapy have a vital role in treating and preventing the recurrence of DIGO.

Changes in Biomarkers after Initial Periodontal Treatment in Gingival Crevicular Fluid from Patients with Chronic Periodontitis Presenting with Drug-Induced Gingival Overgrowth

Calcium channel blocker-induced gingival overgrowth (CCB-GO) is increasing in elderly patients who have been prescribed medication for hypertension for years. The purpose of the present study was to analyze the comprehensive protein expression levels of candidate biomarkers in gingival crevicular fluid (GCF) from CCB-GO patients. Eleven GO patients (10 males and one female, mean ± SD: age: 64.4 ± 14.0 years) who had been systemically prescribed CCBs, either amlodipine or nifedipine, for hypertension for at least 12 months were recruited. Before (baseline) and 4 weeks after initial periodontal treatments, subgingival plaque and GCF samples were taken from two sites per patient: sites affected by CCB-GO and chronic periodontitis. Measurement of clinical parameters and quantitative analysis of periodontopathic bacteria using real-time PCR were performed. Biomarkers/cytokines in GCF were examined using multiplex bead immunoassays. The Mann-Whitney U test was used to compare the collected data between groups. The correlations between pairs of biomarkers were assessed using the Spearman correlation relationship. Levels of two of the 14 biomarkers, interleukin (IL)-1β and transforming growth factor (TGF)- β, were significantly decreased in CCB-GO sites after initial periodontal therapy. The intragroup comparison at baseline showed that counts of Treponema denticola in the GO group were significantly higher than those in the chronic periodontitis group (P β and TGF-β in CCB-GO patients. These factors are involved in initiation and progression of GO as well as periodontitis.

Loss of epithelial FAM20A in mice causes amelogenesis imperfecta, tooth eruption delay and gingival overgrowth

FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam2OA-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM2OA. By breeding K14-Cre mice with Fam20An^x/fl^x mice, we created K14-Cre;Fam20Af/flox/flox （conditional knock out, cKO） mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography： histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam2OA-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice, The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues.

Pattern of Gingival Overgrowth among Patients on Antihypertensive Pharmacotherapy at a Nairobi Hospital in Kenya

The objective of the study was to describe the prevalence and severity of gingival overgrowth (GO) among patients on anti-hypertensive pharmacotherapy at a Nairobi hospital in Kenya and to evaluate the relationship between GO and associated risk factors among these patients. The study design was a cross-sectional survey using a consecutive convenient sampling method. All the patients were examined for gingival enlargement by the method described by Seymour, et al. and modified by the authors to allow for measurement in millimetres. Gingival inflammatory status and plaque scores were also evaluated. The results showed that of the 164 hypertensive patients recruited, 20.7% had gingival overgrowth. Slightly over half (56.1%) of these patients were on calcium channel blockers (CCB). Patients on CCB had a higher prevalence (31.5%) of GO compared to those on non-CCB (7%). This difference was statistically significant (Yates χ2 = 13.39: 1 df: P = 0.000) with an odds ratio of 6.17 (95% CI 0.21 - 19.45). There was no statistically significant association between gender, drug dosage, plaque levels and gingivitis with GO. In conclusion, usage of CCB pharmacotherapy showed a significant association with GO.

Gingival enlargements: Differential diagnosis and review of literature

Gingival enlargement is one of the frequent features of gingival diseases. However due to their varied presentations, the diagnosis of these entities becomes challenging for the clinician. They can be categorized based on their etiopathogenesis, location, size, extent, etc. Based on the existing knowledge and clinical experience, a differential diagnosis can be formulated. Subsequently, after detailed investigation, clinician makes a final diagnosis or diagnosis of exclusion. A perfect diagnosis is critically important, since the management of these lesions and prevention of their recurrence is completely dependent on it. Furthermore, in some cases where gingival enlargement could be the primary sign of potentially lethal systemic diseases, a correct diagnosis of these enlargements could prove life saving for the patient or at least initiate early treatment and improve the quality of life. The purpose of this review article is to highlight significant findings of different types of gingival enlargement which would help clinician to differentiate between them. A detailed decision tree is also designed for the practitioners, which will help them arrive at a diagnosis in a systematic manner. There still could be some lesions which may present in an unusual manner and make the diagnosis challenging. By knowing the existence of common and rare presentations of gingival enlargement, one can keep a broad view when formulating a differential diagnosis of localized(isolated, discrete, regional) or generalized gingival enlargement.

Angiotensin Ⅱ stimulates expression of transcription factors c-Jun and c-Fos in cyclosporine induced human gingival fibroblasts

The present study demonstrates that the expression of c-Jun and c-Fos are elevated in gingival fibroblast cells treated with angiotensin Ⅱ and cyclosporine.The healthy human gingival tissues were collected and gingival fibroblasts were isolated and cultured.We used RT-PCR and Western blot analysis to identify the expression of c-Jun and c-Fos in cyclosporine and angiotensin II treated human gingival fibroblast cells.We found that angiotensin Ⅱ in combination with cyclosporine induces c-Jun and c-Fos expressions significantly;however,the angiotensin Ⅱ antagonist losartan inhibits the expression of c-Jun and c-Fos(p<0.01).The data suggest that angiotensin Ⅱ in combination with cyclosporine modulates the expression of c-Jun and c-Fos in human gingival fibroblast cells.

Phenytoin-Induced Elevation of the Intracellular Calcium Concentration by Stimulation of Calcium-Sensing Receptors in Gingival Fibroblasts

Background:The mechanism concerning gingival overgrowth as a side effect of phenytoin, a therapeutic drug for epilepsy has been still unclear. As one of mechanisms, by measuring the intracellular calcium concentration ([Ca2+]i) of the gingival fibroblasts, it has been advocated that there is relationship between gingival overgrowth and phenytoin-induced alterations in the [Ca2+]i in gingival fibroblasts. To confirm that phenytoin elevates the [Ca2+]i, and if so, to find out its mode of action. Methods: The [Ca2+]i was measured with the Ca2+-sensitive fluorescent dye fura-2/AM. Cells were soaked in a flexiperm chamber and perfused by a saline. Drugs at appropriate concentrations were added to the perfusate. Results: Phenytoin concentration-dependently elevated the [Ca2+]i. NPS2390, a calcium-sensing receptor (CaSR) blocker, significantly suppressed the phenytoin-induced [Ca2+]i elevation. U73122, a phospholipase C (PLC) inhibitor, inihibited the phenytoin-induced [Ca2+]i elevation. TMB-8, a blocker of inositol triphophate (IP3) receptors in ER, significantly depressed the phenytoin-induced [Ca2+]i elevation. m-3M3FBS, a PLC activator, enhanced the phenytoin-induced [Ca2+]i elevation. From the findings obtained, it is discussed as follows: The Ca2+-free saline and NPS2390, a CaSR antagonist, inhibited the phenytoin-induced [Ca2+]i rise;These results indicate that CaSRs exist in gingival fibroblasts and that CaSRs are involved in the phenytoin-induced [Ca2+]i rise;U73122 and TMB-8 depressed the phenytoin-induced [Ca2+]i elevation and furthermore, m-3M3FBS enhanced the phenytoin-induced [Ca2+]i elevation, showing that the Ca2+ release from the ER is involved in the phenytoin-induced [Ca2+]i elevation. Conclusion: We have concluded that phenytoin elevates the [Ca2+]i by activating CaSRs and enhancing the Ca2+ release from the Ca2+ stores in gingival fibroblasts.

Pharmacological Evidence for the Involvement of Calcium Entry through TRPV1 Channels in Nifedipine-Induced [Ca²⁺]i Elevation in Gingival Fibroblasts

Background: Among anti-hypertension drugs, calcium (Ca2+) antagonists cause gingival overgrowth as a side effect. We previously discovered that this side effect was due to elevation of the calcium concentration in the cytosol ([Ca2+]i). Ca2+ entry through non-selective cation channels (NSCCs) and Ca2+ release from intracellular Ca2+ stores are involved in this [Ca2+]i elevation. Furthermore, we discovered that calcium-sensing receptors (CaSRs) participate in nifedipine-induced [Ca2+]i elevation. Transient receptor potential (TRP) channels have been identified as NSCCs. In the present study, we undertook experiments to determine if TRPV1 channels are present in gingival fibroblasts and to ascertain if nifedipine-activated NSCCs are TRPV1 channels. Methods Normal human gingival fibroblast Gin-1 cells were used. The [Ca2+]i was measured using a video-imaging analysis system with the Ca2+-sensitive fluorescent dye fura-2/AM. Results: The NSCC inhibitor SKF96365 significantly inhibited nifedipine-induced [Ca2+]i elevation. TRPV1 channel agonists such as capsaicin, olvanil and resiniferatoxin concentration-dependently elevated the [Ca2+]i. The TRPV1 channel activator anandamide concentration-dependently increased the [Ca2+]i. The TRPV1 channel antagonists capsazepine, AMG9810, iodoresiniferatoxin, ruthenium red, and SB366791 significantly inhibited nifedipine-induced [Ca2+]i elevation. Conclusion: These results suggest that Ca2+ entry through TRPV1 channels is involved in the nifedipine-induced [Ca2+]i elevation seen in gingival fibroblasts. We describe here a modified version of our ‘calcium trigger theory’.

Phenytoin Effects on Proliferation and Induction of IL1<i>β</i>and PGE2 in Pediatric and Adults’ Gingival Fibroblasts

Background: Gingival Overgrowth (GO) is a well documented and unwanted side effect that occurs mainly as a result of certain antiseizure, phenytoin. The aim of this study was to compare the effect of phenytoin on proliferation and production of IL1β and PGE2 in cultured human gingival fibroblasts (HGF) of children and adults. Materials and Methods: Normal HGFs were obtained from 4 healthy children and 4 adult and then were cultured with phenytoin (20 mg/ml). MTT test was used to evaluate the proliferation and ELISA to determine the level of IL1β and PGE2 production by HGFs. Analysis of proliferation were assessed by Independent T-Test and ANOVA analysis was used to assess the level of IL1β and PGE2 production with an a error level less than 0.05. Results: The proliferation of HGF was not affected significantly by phenytoin in both cultured fibroblast sources (P > 0.05). Phenytoin induced a significantly higher formation of IL1β and PGE2 in child’s HGFs as compared to adult’s HGFs (P < 0.05). Conclusion: The results suggest that different inflammatory responses and cytokine formation by child’s and adult’s HGFs are the probable key elements that cause different reactions of phenytoin therapy. More advanced and systematic studies are needed to verify these findings.

牙龈肥大相关疾病的诊疗策略

牙龈肥大是临床常见的症状,严重时会影响咀嚼、发音、美观。基于2018年牙周病国际新分类,本文将牙龈肥大分为菌斑及相关因素导致的牙龈肥大和非菌斑因素导致的牙龈肥大两类,并对牙龈肥大疾病的病因、临床表现和治疗措施进行综述。

Burkitt's lymphoma of maxillary gingiva: A case report

Burkitt's lymphoma(BL) is an aggressive form of nonHodgkin's B-cell lymphoma with three variants namely endemic, sporadic, and immunodeficiency-associated types. It is endemic in Africa and sporadic in other parts of the world. While the endemic form is widely reported to occur in early childhood and commonly involves the jaw bones, the sporadic form typically presents as an abdominal mass. This presentation reports a rare case of sporadic form of BL clinically manifesting as a generalized gingival enlargement in an immunocompetent adult male which demonstrated an aggressive behavior. The patient reported with a prominent anterior gingival swelling of 6 mo duration which slowly enlarged in size and associated with multiple lymph node involvement. Microscopic examination of the lesion using H, E and immunohistochemical diagnosis confirmed the diagnosis as BL. The patient succumbed to the disease before any therapy could be instituted. Since a wide array of causes can be attributed to gingival enlargements, it is necessary to consider malignancies as one of the important differential diagnosis so as to facilitate the need for appropriate diagnosis and prompt treatment.

钙拮抗剂对牙龈成纤维细胞作用的体外实验研究

目的 :探讨钙拮抗剂硝苯地平对牙龈成纤维细胞的作用。方法 :体外培养牙龈成纤维细胞 ,细胞在不同浓度硝苯地平作用下计数观察。结果 :细胞计数在实验第 6、7天出现组间非常显著性差异。主要表现为硝苯地平 12 0 0 μg/L和 36 0 μg/L组 ,细胞计数明显高于低剂量组。 结论

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。

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剂类药物导致的牙龈增生的治疗效果。方法 选取钙拮抗剂类药物导致的牙龈增生患者1 3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 .5～2 9个月后记录牙龈增生指数、菌斑指数、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1 5 3个增生位点中,龈下刮治1个月后有6 9个位点痊愈,其中包括1 7个位点从2度、3度增生变为痊愈。3个月后痊愈的位点为1 0 5个,从2度、3度牙龈增生变为痊愈的位点数上升到4 1个。半年以上痊愈的位点数为1 2 2个,从2度、3度牙龈增生变为痊愈的位点数达5 0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。

苯妥英钠致牙龈增生机制的研究进展

苯妥英钠是临床上常用的抗癫痫药物,其主要副作用是引起牙龈增生,严重者对患者口腔的美观和功能造成影响,但是其发病机制尚不十分明确。本文从其对牙龈成纤维细胞、胶原代谢平衡以及对细胞因子的影响等方面进行综述。

服用环孢素A和他克莫司的肾移植患者药物性牙龈增生的发病情况调查

目的:调查服用环孢素A(CsA)或他克莫司(Tcr)的肾移植患者中药物性牙龈增生的发病情况。方法:研究对象为107例分别服用CsA或Tcr的肾移植患者,记录2组患者的性别、年龄、服药时间和剂量等临床资料以及牙周指数,比较2组患者中牙龈增生的发生率以及有关危险因素与牙龈增生的关系。采用SPSS13.0软件包对数据进行t检验、χ2检验、Mann-WhitneyU检验和逐步回归分析。结果:服用CsA的肾移植患者,牙龈增生的发生率(49%)显著高于服用Tcr的患者(16%),CsA组的牙龈增生评分(30.3±15.5)显著高于Tcr组(17.5±9.6),差异均有统计学意义(P<0.05);CsA组和Tcr组中牙龈增生患者的菌斑指数、龈乳头出血指数均显著高于牙龈未增生患者(P<0.05)。结论:服用CsA的肾移植患者,牙龈增生的发生率高于服用Tcr的患者;菌斑引起的感染与牙龈增生的严重程度密切相关。

硝苯吡啶所致小鼠牙龈增生的组织病理学和细胞凋亡实验研究

目的:通过动物实验来研究硝苯吡啶造成小鼠牙龈增生的发病机制和预防办法,降低临床应用硝苯吡啶的副作用。方法:采用纯系昆明种雄性小鼠为研究对象,灌喂硝苯吡啶不同时间来观察:1.牙龈增生与牙龈上皮厚度及胶原纤维的变化;2.细胞凋亡指数;3.药物作用时间对上述指标的影响;4.撤药后增生牙龈的恢复情况。结果:小鼠牙龈上皮厚度明显增加,胶原纤维致密性加大,牙龈凋亡细胞数目减少(P<0.05),硝苯吡啶撤退后一段时间,增生的牙龈恢复正常。结论:硝苯吡啶可导致小鼠牙龈增生,服药55天细胞凋亡数减少,此损害是可逆的。

环孢素对大鼠牙龈组织形态影响的定量分析

目的定量分析环孢素(CsP)对大鼠牙龈组织形态影响的部位特异性和时间依赖性。方法将80只7周龄雄性Wistar大鼠随机分为实验组和对照组,每组又分为10、20、30、40d亚组。实验组胃饲含CsP的鲜牛奶,对照组胃饲等量鲜牛奶。内固定取材后制作下颌第一磨牙颊舌向石蜡切片,HE染色,利用图像分析系统分别测量颊侧和舌侧牙龈上皮面积、结缔组织面积、最长钉突长度,行完全随机分组两因素析因设计资料的方差分析。结果实验组大鼠牙龈增厚,颊侧附着龈近膜龈联合处上皮钉突明显增生伸长。实验组大鼠颊侧和舌侧牙龈上皮面积和结缔组织面积以及颊侧最长钉突长度均显著大于对照组(颊侧P<0.01,舌侧0.01<P<0.05),2组间舌侧最长钉突长度差异无统计学意义。各时间点相比,颊侧和舌侧上皮面积、结缔组织面积以及最长钉突长度间差异无统计学意义。结论CsP对大鼠颊侧膜龈联合端附着龈上皮的影响存在部位特异性,对大鼠牙龈的影响无时间依赖性。

环孢素A作用下牙龈组织TGF-β1、PCNA蛋白的表达

目的:通过检测环孢素A(cyclosporin A,CsA)作用下牙龈组织TGF-β1和PCNA的表达情况,探讨CsA导致牙龈过度生长(gingival overgrowth,GO)可能的病理机制。方法:20只单侧拔除下颌磨牙的SD大鼠随机分为实验组(CsA,10mg.kg-1·d-1皮下注射)和对照组(等量生理盐水皮下注射)。4周后处死动物,截取下颌磨牙区组织用以检测。体视显微镜下测量牙龈宽度;标本脱钙后制片,经HE染色,行牙龈组织学镜检测量;免疫组化方法(ABC法)检测标本牙龈TGF-β1、PCNA的表达情况。以Image Pro-plus 6.0图像分析软件,对免疫组化检测结果作半定量分析,并以SAS 6.12软件包进行统计学处理。结果:实验组用药后4周,有牙侧与无牙侧牙龈TGF-β1、PCNA蛋白表达水平升高,与对照组比较具有显著差异;各组内有牙侧与无牙侧牙龈的TGF-β1、PCNA表达水平无显著差异。结论:CsA导致GO的过程中,牙龈TGF-β1表达水平上调及其作用可能独立于牙龈炎症,CsA有刺激牙龈成纤维细胞过量表达TGF-β1的作用;CsA促进牙龈上皮增殖活性的提高,可能是上皮细胞数量增加、上皮层增厚的主要原因。