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 transpla...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.展开更多
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 proces...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.展开更多
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 compre...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.展开更多
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 FAM...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.展开更多
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 be...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.展开更多
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 base...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.展开更多
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 gingiv...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.展开更多
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...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.展开更多
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...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’.展开更多
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 prol...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.展开更多
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 p...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.展开更多
文摘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.
基金by the Nanjing Clinical Research Center for Oral Diseases,No.2019060009the Nanjing Medical Science and Technology Development Program,No.YKK17139the Medical Innovation Team of Scientific and Educational Health in the Jiangsu Province,No.CXTDB2017014.
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China (Grant No. 81171744)the Natural Science Foundation of Heilongjiang Province of China (Grant H201418)
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
文摘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’.
文摘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.
文摘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.