Cathepsin-L, a key molecule in the pathogenesis of drug-induced and I-cell disease-mediated gingival overgrowth: a study with cathepsin-L-deficient mice.
Drug-induced gingival overgrowth, the chronic side effect of calcium antagonists, is frequently seen due to the increase in patients with hypertension, although the etiology of the disease is largely unknown. I-cell disease, which accompanies gingival overgrowth, is characterized by a deficiency in UDP-N-acetyl-glucosamine and is classified as one of the lysosomal storage diseases. Here, we hypothesized that a common mechanism may underlie the etiology of gingival overgrowth seen in patients treated with calcium antagonist and in patients with I-cell disease. A calcium antagonist, nifedipine, specifically suppressed cathepsin-L activity and mRNA expression, but not that of cathepsin-B in cultured gingival fibroblasts. The activity of cathepsin-L was suppressed up to 50% at 24 hours after treatment of the cells with the reagent. The selective suppression of cathepsin-L activity appeared not to be dependent on Ca(2+), since treatment of the cells with thapsigargin suppressed both cathepsin-B and -L activity. Mice deficient in the cathepsin-L gene manifested enlarged gingivae. Histological observation of the gingivae demonstrated typical features of acanthosis, a phenotype very similar to that of experimentally induced gingival overgrowth. Since cathepsin-L deficiency was reported to be associated with thickening of the skin, impaired cathepsin-L activity may play a key role in the establishment of skin and gingival abnormalities seen in I-cell disease. In addition, reduced cathepsin-L activity may play an important role in inducing drug-induced gingival overgrowth. (+info)
The effect of cyclosporine with and without nifedipine on gingival overgrowth in renal transplant patients.
PURPOSE: This investigation was performed to evaluate the effect of cyclosporine alone and in combination with nifedipine on gingival overgrowth. METHODS: One hundred and nineteen patients who had undergone renal transplantation at least 12 months previously were selected for the study. The patients were divided into 2 groups according to whether they had received cyclosporine alone (group 1, n = 98) or cyclosporine with nifedipine (group 2, n = 21). Periodontal and pharmacological characteristics were assessed for all patients. RESULTS: Marked gingival overgrowth was seen in 11 (52%) of the patients in group 2 but just 6 (6%) of those in group 1. In addition, the gingival overgrowth index was significantly greater for patients who had received both nifedipine and cyclosporine (Mann-Whitney U-test, p < 0.001). However, there were no significant differences between groups with higher and lower gingival overgrowth index in terms of age, sex, cyclosporine dose, nifedipine dose or level of cyclosporine in the serum. CONCLUSION: The combination of cyclosporine and nifedipine may increase the incidence as well as the severity of gingival overgrowth in renal transplant patients. Among patients who had received both drugs, there was a clear relationship between gingival overgrowth and duration of cyclosporine and nifedipine use. (+info)
Phenytoin-induced gingival overgrowth in un-cooperated epilepsy patients.
Phenytoin-induced gingival overgrowth is a well-known and frequently reported gingival lesion, which was first detected in 1939. However, there are conflicts in the literature about the agents which affect the severity of the lesion. Un-cooperative dental patients are one of the most unsuccessfully treated periodontal patient groups because of the difficulty in maintaining their oral hygiene. This case report consists of two cases with the same characteristics: phenytoin usage, comprehension and speech defects and poor oral hygiene, but each case differs in the duration of the phenytoin therapy. Both of the cases received scaling, root planning and a gingivectomy. (+info)
High prevalence of Chlamydia pneumoniae infection in cyclosporin A-induced post-transplant gingival overgrowth tissue and evidence for the possibility of persistent infection despite short-term treatment with azithromycin.
BACKGROUND: Cyclosporin A (CsA) induces gingival overgrowth (GO) in up to a quarter of CsA-treated renal transplant recipients. A short-term therapy with azithromycin effectively reduces GO, indicating a possible involvement of microorganisms in the pathogenesis of CsA-induced GO. We aimed to determine if there could be any relationship between infection with Chlamydia pneumoniae and GO pathogenesis. In addition, we determined the long-term persistence rate of C. pneumoniae infection in residual GO tissue when azithromycin treatment failed to eliminate GO. METHODS: Chlamydia pneumoniae IgG and IgM antibody titres were measured by microimmunofluorescence technique in sera of kidney recipients with (n = 11) and without (n = 89) GO. GOs were rated and gingivectomies were performed before treatment with 500 mg of azithromycin for 3 days and at months 6 and 12 post-treatment when C. pneumoniae titres were re-evaluated. Nested polymerase chain reaction was performed to identify C. pneumoniae-specific DNA in GO tissues. Results of C. pneumoniae antibody titres from patients with GO were compared with pair-matched controls without GO. RESULTS: Chlamydia pneumoniae IgM titres were elevated in five of 11 patients with GO and in none without GO, whereas the difference of C. pneumoniae IgG titres between patients with GO and pair-matched controls did not reach significance (P<0.57). Chlamydia pneumoniae-specific DNA was found in 10 of 11 GO tissue samples pre-treatment. Azithromycin therapy effectively reduced GO and C. pneumoniae IgM titres. In residual GO, C. pneumoniae-specific DNA remained detectable after 1 year in all GO tissue samples despite azithromycin treatment. The C.pneumoniae IgM titres correlated with GO scores. CONCLUSION: Chlamydia pneumoniae infection is highly prevalent in CsA-induced GO. The infection can persist over a long period in residual GO despite short-term azithromycin therapy. The results indicate that CsA immunosuppression enhances C. pneumoniae infection rates in non-cardiovascular tissue. (+info)
The effect of basic fibroblast growth factor on cell cycle in human gingival fibroblasts from nifedipine responder and non-responder.
It has previously been demonstrated that gingival fibroblasts derived from nifedipine-reactive patients (nifedipine responders) show a greater cell proliferation rate than those from nifedipine non-reactive patients (nifedipine non-responders) in the presence of 1 microM nifedipine. The aim of the present study was to characterize cell cycle differences between nifedipine responder and non-responder fibroblast cells and determine the effect of basic fibroblast growth factor (bFGF) on cell cycle progression. Further, the effect of bFGF on cyclins A, B1, D1, E, and CDKs 1, 2, 4, 6 mRNA expression in responder and non-responder cells was investigated. A population of nifedipine responder cells underwent progression to S and G2/M phases from G0/G1 phase in the presence of 10% fetal calf serum or 10 ng/ml bFGF was greater than nifedipine non-responder cells. mRNA expression of cyclins A, B1, D1, E and CDKs 1, 2, 4, 6 in the presence of 10 ng/ml bFGF was generally greater in nifedipine responder cells than non-responder cells. These results indicate that nifedipine responder cells may be more susceptible to growth factors such as bFGF with a resultant increase in expression of cyclins and CDKs in responder compared with non-responder cells. (+info)
Risk factors of gingival overgrowth in kidney transplant recipients treated with cyclosporine A.
OBJECTIVES: Gingival overgrowth is a common side effect of cyclosporine A (CsA) therapy. The pathogenesis of CsA-induced gingival overgrowth is still debated. The influence of CsA dosage and its trough level, HLA phenotype, gender and the administered calcium channel blocker on incidence and severity of overgrowth were studied. Moreover, relationship of overgrowth with plasma level of TGF-beta I was assessed. METHODS: Degree and extent of gingival overgrowth were tested in 124 kidney transplant recipients treated with CsA, in 9 patients treated with azathioprine and in 21 patients treated with tacrolimus, and various calcium channel blockers. RESULTS: Gingival overgrowth was found in 46% of patients treated with CsA. Total yearly CsA dosage was significantly higher in patients with overgrowth. Gingival overgrowth was observed in: 86% of patients treated with nifedipin, 47% with amlodipine, 35% with verapamil. HLA-DR antigens analysis showed that half of the patients with DR-2 allele suffered from overgrowth. Gingival overgrowth was found twice as often in males than in females. Plasma level of TGF-beta I was similar in patients with or without overgrowth. Gingival overgrowth was not found in patients treated with azathioprine or tacrolimus despite that half of the patients received nifedipine or amlodipine. CONCLUSIONS: The study revealed high frequency of overgrowth in renal graft recipients treated with CsA. Overgrowth severity was larger in patients treated simultaneously with nifedipine or amlodipine. CsA dosage, male sex and HLA-DR2 phenotype were risk factors of gingival overgrowth. None of the patients treated with tacrolimus suffered from gingival overgrowth. (+info)
Connective tissue metabolism and gingival overgrowth.
Gingival overgrowth occurs mainly as a result of certain anti-seizure, immunosuppressive, or antihypertensive drug therapies. Excess gingival tissues impede oral function and are disfiguring. Effective oral hygiene is compromised in the presence of gingival overgrowth, and it is now recognized that this may have negative implications for the systemic health of affected patients. Recent studies indicate that cytokine balances are abnormal in drug-induced forms of gingival overgrowth. Data supporting molecular and cellular characteristics that distinguish different forms of gingival overgrowth are summarized, and aspects of gingival fibroblast extracellular matrix metabolism that are unique to gingival tissues and cells are reviewed. Abnormal cytokine balances derived principally from lymphocytes and macrophages, and unique aspects of gingival extracellular matrix metabolism, are elements of a working model presented to facilitate our gaining a better understanding of mechanisms and of the tissue specificity of gingival overgrowth. (+info)
Verapamil induced gingival enlargement in cluster headache.
Verapamil is an effective prophylactic treatment for cluster headaches and, therefore, is widely used. This report describes four patients with cluster headache who developed gingival enlargement after initiating treatment with verapamil. In two patients, it was possible to control this side effect adequately by optimising oral hygiene and dental plaque control. In the other two patients, lowering of the verapamil dose, in addition to optimal oral hygiene and dental plaque control, was necessary; in one patient verapamil had to be stopped completely to reverse the gingival enlargement. Doctors treating cluster headache with verapamil need to be aware of this side effect, especially as it may be preventable with good dental hygiene and dental plaque control, is reversible with reduction or cessation of verapamil, and can lead to dental loss. (+info)